TW593683B - Apparatuses containing multiple force generating elements and uses thereof - Google Patents

Abstract

This invention relates generally to the field of moiety or molecule manipulation, e.g., in a chip format. In particular, the invention provides a chip for generating fields, which chip comprises: (a) a substrate; and (b) at least two different types of structures located on said substrate, wherein each of said structures is capable of, in combination with an external energy source generating one type of physical field. Combinations and apparatuses containing single or multiple chips, and methods using the chips for manipulating a moiety or molecule are also provided.

Description

593683 A7 B7 V. Description of the Invention (i) Technical Field

The present invention relates to the field of performing solid molecules or molecular manipulations on a wafer. Specifically, the invention provides a wafer capable of generating a physical field, the wafer comprising: a) a substrate; b) at least two different built-in structures built on the substrate, any of which is such a structure Both can be combined with external energy sources to generate certain types of physics. The physical field mentioned above has the following characteristics: When a solid molecule with a property enters the field, the form of the field acting on the solid molecule appears as a certain force exerted on the solid molecule. Physical fields can include electric, magnetic, acoustic, light, velocity, and other forms of fields. Combinations, devices (which can include single or multiple wafers), and methods to manipulate physical molecules or molecules on a wafer or device are also presented in this document. Prior art

Biochips are generally divided into two categories. One type of biological wafer is a passive wafer, which does not use external physical forces to manipulate, control, or influence molecules or particles in a chemical, biochemical, or biological reaction process. This reaction process involves the thermal diffusion of molecules / particles and naturally occurring forces, such as the gravity on the particles and the geomagnetic force on the magnetic particles. The second type of biological wafer, the active wafer, uses external physical forces to promote, enhance, or accelerate the desired biochemical reaction or process, while reducing or reducing undesired effects. Examples of typical passive wafers are DNA wafers or DNA arrays (see Lockhart DJ and Winzeler EA, Nature, Vol. 405, No. 6788, Pages 827-836), oligo nucleic acid probes immobilized on the wafer, or cDNA molecules and targets in the solution covered on the wafer _ ^ _ This paper size applies the Chinese National Standard (CNS) A4 (210 X 297 mm) 593683 A7 _B7___ 5. Description of the invention (2) The hybridization reaction of This can happen when the target molecule diffuses into contact with the probe molecule. Correspondingly, examples of typical active wafers are electronic wafers (eg, US Patent No. 6,017,696 "Methods for electronic stringency control f? R molecular biological analysis and diagnostics" and 6,051,380 "Methods and procedures for molecular biological analysis and diagnostics" (Revelation). On these electronic wafers, the charged DNA (or other) molecules are either directly electrophoresed or attracted to an electrode of opposite polarity, and the corresponding probe molecules have been fixed on this electrode. Although the above It is an example of processing DNA molecules. The use of biochips to process other molecules or molecular complexes or biological particles (such as cells, bacteria, viral 'proteins, nucleic acid molecules, etc.) can also be divided into two types: active wafers or passive wafers. In addition to the above-mentioned molecular hybridization, the biochemical reaction or process on the wafer also includes many other steps, such as molecular / particle transport, molecular / particle separation, molecular / particle identification, molecular-molecular interaction, and Molecular-particle interaction Etc. For example, separating cancer cells from normal cells on a dielectrophoresis wafer is a biochemical process using active wafers. Compared with passive wafers, active wafers have the advantage of rapid response and potential Higher detection sensitivity 'can analyze or test low concentrations of molecules or microparticles or biological microparticles' has the potential to have a higher discrimination rate for different types of molecules or different types of microparticles / biological microparticles. To achieve a specific purpose The use of composite forces has been reported. For example, 'Yasuda et al. Reported the micro-wave in standing wave and DC electric field. • 5 -__ __ This paper size is applicable to China National Standard (CNS) A4 specification (21〇X 297 mm) 593683 A7 B7 V. Description of the invention (3) Particles apply competitive electrostatic force or sound field radiation force, so as to separate polystyrene particles and inscription beads with different sizes and charges in the morning of the fluid pool (Yasuda et al., J. Acoust. Soc. Am, 99 (4): 1965-1970 (1996); Yasuda et al., Jpn. J. Appl. Phys., 35 (1): 3295-3299, (1996)) ° in this example Four platinum wires are used to generate a uniform DC electric field to apply electrostatic force to the charged particles. Two piezoelectric transducers are placed a certain distance apart to generate standing waves. Because only standing waves and uniform DC current are involved Field, the application of such a system is limited to particle manipulation and separation, and can only be applied to a limited number of particle types. The methods and procedures are not very flexible. This system can only handle particles in a limited way. Such systems cannot be used for multi-purpose particle manipulation and processing, such as separating particles to obtain '· purified' components. In other reports, the radiative force of a light field is used to locate particles in a rotating electric field (De Gasperis et al., Meas · Sci. Technol., 9: 518-529 (1998)). In this example, "optical tweezers" consisting of a light source and an optical circuit (including lenses and other components) are specifically used in Locate particles or cells in a rotating electric field. The electric rotating electric field generated on an electro-rotating wafer is used to induce the rotation of particles. The application range of such a system is limited. In this system, the rotation of particles is used to characterize The nature of the particles is not used to manipulate the particles or cells. The light field force is used to specifically control the position of the particles. This system can only be used to characterize the dielectric properties of the particles. In order to be reliable by electrorotation Particle property parameters, the particles should be fixed at a certain position of the rotating electric field and thus subject to a fixed spin_-6- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 593683 A7 B7 V. Description of the invention (4) Transition force. This system cannot be used for other purposes, such as separating particles into different components. Recently, it has been reported that in order to achieve the simultaneous positioning of two particles, Researchers use light field radiating force to control one particle while using a dielectric electrophoresis cage to fix the other particle (G. Fuhr and C. Reichle, in van den Berg et al. (Ed.), Micro Total Analysis Systems, 2000 , 261-264; and T. Schnelle et al ·, Appl. Phys ·, B Lasers and Optics 70: 267-271 (2000)). The radiative force of the light field is transmitted by the light source and the optical circuit (by the lens and other The composition is composed of "optical clamps" to be applied. Dielectrophoretic cages are produced from the three-dimensional structure of microelectrode elements on a dielectrophoresis wafer. The use of such a system is limited. It cannot be used for other purposes Operations such as transporting particles on a wafer. The present invention takes into account the limitations of previously designed wafers or biochips. One of the objects of the present invention is to provide a new type of wafer and use such wafers for Biochemical, biological or chemical reaction, method of operation, assay and synthesis. Another object of the present invention is to provide an active wafer, especially an active biochip that can be universally applied to various wafer application fields, and the corresponding biology , Chemical, biochemical reactions and processes can be achieved through microfluidic processing and manipulation of molecules and particles in microfluidic devices and systems. Another object of the present invention is to provide a universally applicable active wafer that can uniquely Applied to so-called microchip laboratory systems (integrating many individual biochemical, biological and chemical functions on a single wafer or multi-wafer complex). DISCLOSURE OF THE INVENTION The paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 593683 A7 B7 5. Description of the invention (5) This invention relates to the field of performing physical molecules or molecular operations on wafers. In one aspect, this invention provides a wafer capable of generating a physical field, the wafer comprising: a) a substrate; b) at least two different structures built on the substrate, any of which can be integrated with the built-in structure External energy is combined to produce a type of physics. In a specific embodiment, the built-in structure on the wafer is capable of generating at least two different types of physics. The chip can contain several structurally connected substrates, or it can contain two, three, four or more different types of built-in structures, which can produce two, three, four or more different types of physical fields. In a specific embodiment, the built-in structure on the wafer exists as a single unit. Such a single unit may occupy a part or all of the wafer. In a specific embodiment, the structure built on the wafer is composed of a set of micro-units. Some or all of these microcells can be controlled individually. Some or all of these microcells on the chip are interconnected. The wafer further includes a device capable of selectively applying energy to any one of these microcells. In a specific embodiment, the structure built on the wafer should be able to generate at least two different types of physics fields. These two types of physics fields can be arbitrarily selected from electric, magnetic, acoustic, light, and velocity fields. In a specific embodiment, the built-in structure on the wafer should be able to generate at least two different types of physics fields. These two types of physics fields can be arbitrarily selected from magnetic fields, sound fields, light fields, and velocity fields. In a specific embodiment, the built-in structure on the wafer should be able to generate at least two different types of physics fields. These two types of physics fields can be from electric field, sound field, light field and __- 8 ^ ___ This paper scale is applicable to China National Standard (CNS) A4 Specification (210 X 297 mm) 593683 A7 B7 V. Description of Invention (6)

Arbitrary selection in the speed field. In a specific embodiment, the built-in structure on the wafer should be able to generate at least two different types of physics fields. These two types of physics fields can be arbitrarily selected from electric, magnetic, light and velocity fields. In a specific embodiment, the built-in structure on the wafer should be able to generate at least two different types of physics fields. These two types of physics fields can be selected from electric, magnetic, acoustic and velocity fields. In a specific embodiment, the built-in structure on the wafer should be able to generate at least two different types of physical fields, and these two types of physical fields can be arbitrarily selected from electric, magnetic, acoustic, and optical fields. In another specific embodiment, the built-in structure on the wafer should be able to generate at least two different types of physical fields (excluding the combination of optical radiation fields and uneven AC electric fields). In another specific embodiment, the built-in structural unit on the wafer should be able to generate at least two different types of physical fields (excluding the combination of standing wave fields and 'uniform electrostatic fields'). In another embodiment, the built-in structure on the wafer should be able to generate a physical field (excluding the combination of electric and velocity fields).

In a specific embodiment, at least one of the built-in structures on the wafer can generate an electric field, such as a uniform or non-uniform DC electric field, an uneven field strength distribution, or a non-uniform AC with at least one field component having an uneven phase distribution. electric field. In one example, the built-in structure on the wafer that generates an electric field contains at least one microcell. In another embodiment, at least one structure built into the wafer can generate a magnetic field. In one example, the built-in structure on the wafer that generates a magnetic field contains a ferromagnetic material. In another example, a magnetic field built-in structure on a wafer contains a micro-electromagnetic unit. _-9- This paper size applies to China National Standard (CNS) A4 (210X297 mm) 593683

In another embodiment, at least one structure built into the wafer can generate a sound field. In one example, the built-in structure on the wafer that generates a sound field contains a piezoelectric material. In another embodiment, at least one structure built into the wafer can generate a velocity field. In one example, the built-in structure on the wafer that generates the velocity field contains at least one micromachined tip / capillary. In one example, the built-in structure on the wafer that generates a velocity field contains an array of heating and / or cooling cells. An array of heating and / or cooling units can create a thermal gradient in a medium located near the array. In another embodiment, at least one structure built into the wafer can generate a light field. In one example, the built-in structure on the wafer that generates the light field contains a micromachined array of optical lenses. In another example, a built-in structure on a wafer that generates a light field contains a micromachined electro-light source array. In another example, the built-in structure on the wafer that generates a light field includes a laser clamp. The structure built on the wafer may be a micro structure. The characteristic dimensions of the basic structural elements in the microstructure are between 0 · i microns and 20 mm. The substrate of a wafer can contain many types of surfaces, such as silicon, silicon dioxide, silicon nitride, plastic, glass, ceramic, rubber, and polymer surfaces. For different application needs, the wafer substrate can be either hydrophobic or hydrophilic. On the other hand, this invention provides a wafer which can generate a physical field. The main components of the chip are: a) a substrate; b) at least two different built-in structures built on the substrate, any of which can be combined with external energy to generate a type of physics. ____- 10- This paper size applies to China National Standard (CNS) A4 (210X297 mm) binding

B7 V. Description of the invention (8) On the other hand, this invention provides a wafer that can generate a physical field. The main components of the chip are: a) a base; b) at least two kinds of constructions: different built-in structures on the base, any of which can be combined with external energy to generate a type Physics. ° In yet another aspect, this invention relates to a combination in which the knot contains: a) at least two types of wafers include a substrate and at least two different built-in structures built on the substrate, any of which Both built-in structures can be combined with external energy to generate a type of physics; 的 a method of transporting manipulated physical molecules between the wafers. ^ In one aspect, the invention relates to a device, wherein the device includes a printed sheet, the chip includes a substrate and at least two different built-in structures built on the substrate, any of which can be combined with External energy is combined to produce a certain type of physics. In another aspect, this invention provides a device for operating entity molecules. The device includes a base for receiving or supporting the entity molecules to be operated, b) at least two types of structures inside the device, each of which $ Can be combined with external and external energy sources to generate a type of physical force on the home-only knife. The internal structure of the tritium device should be able to generate at least two different physical forces on the physical molecules to be manipulated. The device may include two, four, four or more types of internal structures, and may generate one, two, four or more types of physical forces on the physical knife to be manipulated. In a specific embodiment, the internal structure is a built-in structure built on the substrate. In another embodiment, the internal structure is not located on the substrate. The device may include multiple structurally interconnected substrates. ^ The paper size applies the Chinese National Standard (CNS) M specification (2 × 0χ tear public love) 1-5. Description of the invention (in a specific embodiment, 'the internal structure of the device is a single .... Exist. A single unit can occupy the chip of the chip. In another concrete example, the internal structure of the device includes two ΓΓΓ: Shaofen or f. All such microunits can be single, " a part of the day or all of them The micro-units are the components that are connected to the energy source. "The micro-units are applied to a specific embodiment. The structure of the device should be: the same as: physical forces. These physical forces can be derived from electric field forces, Magnetic force::, mechanical force, and light field radiation force are optional: for example: this: the internal structure of the device should be able to produce at least two types of not:: In another specific embodiment of the shore, the internal force of the device is 1 There are at least two different types of physical forces. These physical forces can be arbitrarily selected from electric: two: field two mechanical forces and light field light shooting forces. In the other-= thing = her example, the internal structure of the device should be able to generate at least two types Unlike the * force, these physical forces can vary from the electric field Force 'magnetic field force, machine; ^ force buckle: field light shooting force to choose arbitrarily. In another specific embodiment machine = to: two structure: can produce at least two different types of physical forces' these physical forces can be $ # Force, magnetic% force, sound field force, and light field #radio force are arbitrarily selected. ^: In a specific embodiment, the internal structure of the device should be able to generate the same physical force. These physical forces can be determined from electric field force, magnetic field force, Any choice in the sound two. In another specific embodiment, the internal structure & generates at least two different types of physical forces (excluding light field light shot on the paper scale suitable financial standards sg family standard public love) -12 -593683 A7 _______ B7 V. Invention \ --- 10; combination of force and traditional dielectrophoretic force). In another specific embodiment, the internal structure of the child should be able to generate at least two different types of physical forces (excluding A combination of sound field force and electrostatic force). In another specific embodiment, the internal structure can generate at least two different types of physical forces (excluding the combination of mechanical force and electric power). In a specific embodiment, at least The internal structure on a device can produce a Force. In one example, at least one internal structure can generate electrostatic force on W 黾 particles. In another example, at least one internal structure can generate traditional dielectrophoretic force. In another example, at least one internal structure A traveling wave dielectric electrophoretic force can be generated. The internal structure of the device capable of generating an electric field contains at least one microelectrode element. In another specific embodiment, at least one of the internal structures of the device can generate a magnetic field force. In one example, the device can The internal lexicon that generates the magnetic field contains a ferromagnetic material. In another example, the internal structure that generates the magnetic field includes a micro-electromagnetic unit. In another specific embodiment, the internal structure of at least one device can generate a sound field force In one example, the internal structure of the device that produces a sound field contains a piezoelectric material. In another embodiment, the internal structure of at least one device can generate mechanical force. In one example, the internal structure of the device capable of generating mechanical force contains at least one micro-machined fine tip / capillary. In another example, the internal structure of the ' device that generates mechanical force includes an array of heating and / or cooling units. The heating and / or cooling unit array is capable of generating a thermal gradient

___________- 13: This paper size is in accordance with Chinese National Standard (CNS) A4 (21 × 297 mm) 11593683 A7 B7 V. Description of the invention (Speed in the body 0 Internal structure may generate light field In another example micro-machining The velocity field is generated inside the light field of the laser beam and in the medium located at the side of the train. The medium field can apply mechanical force to the physical molecules located in the medium. In another specific embodiment, there is at least one device. In order to generate the light field II shooting force. In one example, the internal structure on the device includes a micro-machined optical lens array. The internal structure on the device that generates the light field includes a private-light source array. In another example, the device can generate a structure that includes a laser clamp. The internal structure of the device can be a microstructure. The basic structure in the microstructure has a characteristic size as early as 7C between G1 microns and 2Gmm. In the device The substrate can contain many types of surfaces, such as broken, silicon dioxide [silicon nitride plastic, glass, ceramic, rubber, and polymer surfaces. For different application needs, the substrate surface can be hydrophobic, but also It can be hydrophilic. The device further includes a containing-block substrate and a fluid pool for holding or supporting or containing a holding molecule to be manipulated. The internal ... structure on the device can be applied to the operating molecule At least two types of physical forces, such as internal structures, may or may not be located on the substrate. The fluid pool may be a closed cavity structure containing at least one inlet port and up to one outlet port. In the specific embodiment, “the device does not include a surveillance or device. In another aspect, the present invention provides a device that can be used to operate entity molecules” The device king includes: a) _ block for containing or supporting the entity to be manipulated Molecular basis; b) at least two types of internal structures, each of which is based on the Chinese paper standard (CNS) A4 specifications (210X297 public attack ·) on this paper. -14- 12 V. Description of the invention (can be combined with additional signals Source combination to generate a type of physical force on the physical molecule. In another aspect, it provides an invention that can be used to operate the physical sub-device. The device king includes: - block or support for receiving a substrate to be handled consistently month beans molecule; b) at least two types of internal structures, each internal structure and the external source # * combination, a physical force on the i type Si can be in the molecule. 'In another aspect, this invention relates to a form of combination in which at least two types of devices include a substrate to contain or support a solid molecule to be operated and at least two substrates built on the substrate Any of these internal structures can be combined with external signal sources to generate a type of physical force on the physical molecule; ㈧ a method of transporting the manipulated physical molecule between devices. On the other hand, this invention relates to a method for manipulating physical molecules, which method includes: a) introducing a to-be-operated entity on a wafer (including a substrate and a built-in structure at least on the substrate) Molecules, where each of these built-in structures can be combined with an external signal source to generate a type of physics field; b) these built-in structures of the wafer are combined with a virtual external signal source to apply on a solid molecule At least two different types of physical forces to achieve the manipulation of solid molecules. On the other hand, this invention relates to a method for manipulating a solid molecule, the method: including: a) on the device (including-a block containing and supporting the to-be-manipulated (base and at least two different types of structures located inside the device) ) Introduce the entity molecule to be manipulated, and its material-like _ structure. This paper is very standard. It is a standard (CNS) A4 specification (21 () χNuo Gongai 1 15- 593683 A7 B7. V. Description of the invention ( 13) Combine with an external signal source to generate a type of physics field; b) Combine these internal structures of the device with an external signal source to apply at least two different types of physical forces on the entity molecule to achieve physical effect on the entity Operation of molecules. In a specific embodiment, the method of operating a physical molecule utilizes at least two different types of physical forces applied to it. In another embodiment, the method of operating a physical molecule utilizes at least Two different types of physical forces applied simultaneously. In some specific embodiments, multiple physical molecules can be operated simultaneously through the above-mentioned operation method. For example, By applying more than one physical force to the physical molecules, at least two different physical molecules are operated by different types of physical forces, so as to achieve the simultaneous operation of multiple physical molecules. In some other specific embodiments, multiple entities The molecules are operated one after the other. For example, by applying more than one physical force to the physical molecules, at least two different physical molecules are operated by different types of physical forces, so as to achieve the operation of multiple physical molecules in succession. In other specific implementations In the example, the entity molecules to be operated are in a mixed system. Using the above-mentioned operation method, the entity molecules can be selectively operated. In some other specific embodiments, the entity molecules to be operated form a mixed system, and the entire mixed system All existing methods are applicable to any type of solid molecules, such as cells, organelles, viruses, molecules and complexes of these substances. Among them, cells can be animal cells, plant cells, fungal cells, bacterial cells, recombinant Cells or cultured cells. Cells Can be nucleus, mitochondria _- 16-_ This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) 593683 A7 B7 V. Description of the invention (14) Body, chloroplast, ribosome, endoplasmic reticulum, Golgi Body, solution, protein body, secretory vesicle, vacuole, or microsome. The molecule can be an inorganic molecule, an organic molecule, or a complex of an inorganic molecule and an organic molecule. The inorganic molecule can be an ion such as an ion, a 4-methyl ion, a thallium ion, # 5 ion, chloride ion, iron ion, copper ion, zinc ion, Ion ion, palladium ion, Qi ion, ions ion, information ion, nickel ion, complex ion, gas ion, fragment ion, rubidium ion, boron ion, or It is a hafnium ion, etc. The organic molecule can be an amino acid, a peptide, a protein, a nuclear fen, a nuclear acid, an oligonucleotide, a nucleic acid, a vitamin, a monosaccharide, an oligosaccharide, a carbohydrate, a lipid, or a complex thereof. This manipulation method can be used to transport, aggregate, enrich, enrich, concentrate, capture, repel, float, separate, fractionate, isolate, or guide solid molecules to perform linear or other directed motion. In another aspect, the present invention leads to a method for manipulating a solid molecule, the method comprising applying at least two types of physical forces to a solid molecule such that the solid molecule is operated by the physical force. Brief Description of the Drawings Figure 1 is a schematic diagram of a multi-force operation wafer or a device designed by the present invention, showing that the wafer (or device) can generate an electric field, a magnetic field, a sound field, and a velocity field. Fig. 2 is a TF view of a multi-force operation wafer according to the present invention. The TF shows that the wafer contains a plurality of micro-units, each of which can generate an electric field, a magnetic field, or a sound field. Each unit may further include biological components. Fig. 3 is a schematic diagram of a two-force operation wafer according to the present invention. The wafer can generate a sound field force and a conventional dielectric electrophoresis force. A) Interdigitated microelectrodes capable of generating conventional dielectrophoretic forces are made _-17-_ This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 15 V. Description of the invention (for use on substrates) The base is made of piezoelectric material and can generate sound. B) The plane electrode electrical material covering both surfaces of the piezoelectric transducer (piezoelectric material substrate) applies a voltage to generate a sound field. A circular microelectrode for generating a conventional dielectric ice force is constructed on a solid substrate (second substrate), and a swimming substrate (ie, the second substrate) is combined with a piezoelectric material substrate to form a two-force operation wafer. c) The sound source array used to generate the sound field is constructed on a solid (first) substrate. The electrode arrays, which are X-crossed to generate conventional dielectrophoretic forces, are built on another solid (second) substrate. The second substrate (generating the electrophoretic force) is combined with the first substrate to form a schematic diagram of a two-force operation wafer / fluid pool. Figure 4 shows the wafer can generate sound. Figure 4 shows the multi-force operating crystal at the bottom of the cavity. Figure 5 shows the% 'force and magnetic field force of the two-force operating wafer of the present invention. A) A micro-electromagnetic unit or an array of electromagnetic units capable of generating a magnetic field force is built on a substrate. The substrate is made of a piezoelectric material and can produce a sound field. B) The sound source array that generates the sound field is built on a solid, piezoelectric substrate. The micro-electromagnetic unit array is constructed on the other (second) = bottom-the base (for generating magnetic field force) and the first base (for generating sound field force) made of piezoelectric material combine to form a two operation Wafer. Knife C) Micro-electromagnetic unit (or electromagnetic unit) array and acoustic transducer array are built on a solid substrate. ^ Ask

This paper is suitable for National Standard (CNS) A4 specifications (210X297 male I) 593683

• Figure 6: Schematic diagram of the two-force operation wafer of the present invention. The wafer can generate a dielectrophoretic force (such as a conventional dielectrophoretic force and / or a traveling wave dielectrophoretic force) and a magnetic field. A) A micro-electromagnetic unit capable of generating a magnetic field force. Or the array of electromagnetic units is first built on the substrate. Then, the electromagnetic unit is covered with a smooth dielectric cladding layer and an interdigitated electrode array is formed on the surface of the dielectric layer. ) This micro-electromagnetic unit or array of electromagnetic units that generate magnetic% force is first built on the substrate, and then the electromagnetic unit array is covered with a layer of smooth = private layer. A four-phase, linear, traveling-wave dielectric electrophoretic electrode array for generating traveling waves is then fabricated on the surface of the dielectric layer. ) 叱 A micro-electromagnetic unit or an array of electromagnetic units that generates a magnetic field force is first built on the substrate. The electromagnetic unit array is then covered with a smooth force layer. A diamond-shaped electrode array is then formed on the surface of the dielectric layer to generate a conventional dielectric electrophoretic force. Hanging Regulations D) Micro-electricity arrays that can generate magnetic field forces. The electromagnetic unit array is then covered with a smooth: dielectric layer. Then, a spiral electrode array is produced on the surface of the dielectric layer to produce the electrophoretic force and the conventional dielectric electrophoretic force. /: π Invented the ice force and magnetic field force of the two-force operation wafer. It is said that the electricity is generated by the day A) The micro-electricity that generates the magnetic field force is constructed on the array that produces U early or early 7 ^. Then cover the electromagnetic unit array-layer smooth B sheet scale binding 2 19- x 297 male ¥ 7 593683 A7

593683

Built on the first base. An optical wafer composed of an optical lens array is fabricated on a corresponding substrate (second substrate). The second force wafer and the light ovum are combined through a viewing base. There is a channel in the middle of the substrate. In addition, an optical port has an inlet port and an outlet port. Acoustic image η 11 疋 Schematic diagram of the three-force operating device of the present invention. The device can generate acoustic% force, magnetic field force, and traveling wave dielectrophoretic force and / or conventional dielectrophoresis A). Material substrate) The planar electrodes on both surfaces apply voltage to the material to generate a sound field. An array of particles or electromagnetic units capable of generating a magnetic field force is first built on the substrate (second best) and then the electromagnetic unit is covered with a smooth dielectric layer. A $ is then made on the dielectric layer I surface to generate a traveling wave dielectrophoretic force = four-phase, parallel, traveling wave dielectrophoretic electrode array. Technical assistance: The second substrate and the piezoelectric substrate of the magnetic early 7L array and the traveling wave dielectric electrophoresis array are combined to form a three-force operation wafer. ) A substrate made of compacted material is used to generate a sound field. Planar electrodes are used to cover both sides of the piezoelectric substrate. The surface of the I electrical substrate is covered with a polished smooth dielectric layer (first dielectric layer). A group of micro-electromagnetic units or an electromagnetic unit array L is fabricated on this dielectric layer (Angle-dielectric layer); and: a polished dielectric layer (first dielectric layer) is covered on the magnetic-encapsulated unit ). The dielectric layer (second dielectric layer) polished on this surface is used to produce a set of concentric circular electrode arrays to generate the conventional dielectric electrophoretic force and traveling wave dielectric electrophoretic force. The sound source array that generates the sound field is constructed on a solid substrate (first -21-: 297 mm)

Hold

Line 19 V. Description of Invention (: Exhibition). The micro-electromagnetic unit or magnetic array used to generate the magnetic field, and the traveling electrode array element array used to generate the traveling wave are produced on the substrate (the second substrate). The second substrate and the first substrate interface supporting the electromagnetic single electrode and the transport electrode array form a three-force operation wafer. The invention of the hibiscus i This invention designed a device called a multi-force operation chip (multi-force chip). This device includes multiple types of devices. These built-in early devices can generate different types of physical fields. (Such as biochips) to apply different types of physical forces to the corresponding operations, control and processing of b. On the one hand, with existing biochips, such as electronic chips that can generate dielectric electrophoretic forces, Compared with electronic wafers that generate electrophoretic forces, magnetic field wafers that generate carbon field forces, etc., the structure of multi-force operation wafers is more complex and requires more complex manufacturing processes. On the other hand, multi-force operation wafers provide a new Approaches for processing biological samples and performing chemical / biological / biochemical reactions. (1) Typical biological wafers can now handle or process one type of particles and molecules. For example, electrophoresis-based wafers can handle charged molecules or particles; electromagnetic The wafer can only handle magnetic particles. However, a single multi-force operation wafer can process or manipulate many different types of particles or molecules. Such as magnetic particles, charged or uncharged particles or molecules, dielectricized particles or molecules. This adds new flexibility to the design and development of bio-analytical technology based on biochips. This paper scale applies Chinese national standards ( CNS) A4 size (210 X 297 mm) -22- 593683 A7

Many of the limitations and side effects of working wafers can be overcome. For example, a typical electrophoretic wafer can only be a liquid solution with a very low conductivity of 2%. It is therefore difficult to integrate multi-step reactions on a single electroprinted plate, if it is not impossible, simply because a considerable amount of biochemical reaction buffer requires a highly conductive solution. A multi-force operation wafer can well meet the need for such integration, because the multi-force operation wafer can not only use electrophoretic force to operate biological reactions including solutions with low conductivity, but also use other types of forces, such as Electromagnetic or acoustic field forces that can operate on biological reactions involving high conductivity / valley fluids. (3) Multiple force operation The wafer can apply multiple physical forces to the particles or molecules in the suspension in sequence or simultaneously. The combined effect of these forces in the three-dimensional space can improve the resolution of the multi-force operation wafer in selective operation, identification and separation of dry particles. Solid molecules (such as molecules and particles) that can be manipulated by multi-force manipulation wafers can include solids (such as glass beads, latex particles, magnetic beads), liquids (such as droplets), or gas particles (such as bubbles) Dissolved particles (such as molecules, proteins, antibodies, antigens, oils, DNA, RN A, molecular complexes), suspended particles (such as glass beads, latex particles, polystyrene beads) 'particle molecular complexes (such as : DNA molecule magnetic bead complex formed by fixing DNA molecules on the surface of magnetic beads, or protein molecule-polystyrene acetate bead complex formed by covering polyphenylene oxide beads with protein molecules). Microparticles can be organic (eg mammalian cells or other cells, bacteria, viruses or other microorganisms) or inorganic (eg metal micro-23) This paper is in accordance with China National Standard (CNS) A4 (210 X 297 mm)

B7 Description of the invention Particles can have different shapes (for example: spherical, ellipsoidal, cuboid, discus, needle) and different sizes (for example: nano-scale gold spheres, micro-scale cells, micrometer-scale aggregates of particles Thing). Microparticles include, but are not limited to, biological molecules (such as DNA, RNA, chromosomes), protein molecules (such as antibodies), cells, colloidal microparticles (such as polystyrene beads, magnetic beads), and molecular microparticle polymers (such as proteins The molecule is attached to an antibody-coated magnetic bead). For a multi-force operation wafer, the most important point is that it has the ability to operate different types of particles simultaneously or sequentially. For example, if a multi-force operation chip is added with a magnetic field force generating element and an electrophoretic force generating element, it can simultaneously operate biomolecule-coated magnetic beads and charged cells or molecules. The detailed description of the present invention is divided into the following parts, the purpose of which is to explain the idea of the present invention more clearly, and does not mean that the present invention includes only the following parts. The meaning of the word is sufficient, and the meanings of all the technical terms and scientific terms used here are consistent with the meanings commonly understood in the technology of the field to which the present invention belongs. All patents, applications, publications referenced by the present invention: Applications and other publications have been incorporated into the text of this patent by reference. 'If the definitions in this section are incorporated into this patent by reference, All patents, applications, published applications, and other publications in this document have inconsistent definitions, so the definitions in this section will supersede the definitions in the references. One refers to "at least one or more or more" ________- 24 · The national standard (CNS) of this paper is suitable for standardization (CNS) U Seek (2— 茇 ------ 593683 A7 B7 22 V. Description of the invention ( "Wafer {refers to a solid substrate with a one-dimensional, three-dimensional, or three-dimensional microstructure on which physical, chemical, biological, biophysical, or biochemical processing can be performed. Microstructures on a wafer, such as slots and holes , Electrode element, electromagnetic element H are integrated, directly fabricated or affixed to the substrate to enable physical, biophysical, biological, biochemical, chemical reactions or processing on the wafer. The wafer can have Various shapes of flakes, such as rectangular, circular, oval, or other irregular shapes. The size of the main surface of the wafer in the present invention is very wide, for example, it can be from about 1 mm2 to about 0.25 m2. More suitably, the size of the wafer is from about 4 mm2 to about 25 cm2, and its characteristic size is from about 1 mm to about 5 cm. The surface of the wafer may or may not be flat. A wafer with a truly non-flat surface may include Channels or holes made on its surface. Physics, other terms also include "physical fields within a certain spatial range or physical fields generated within a certain spatial range" refers to a spatial range with the following characteristics. When a Physical molecules of appropriate properties are placed in these two rooms (that is, into the physical field). As a result of the interaction between the physical molecules and the field fork, the physical molecules are subjected to forces. The physical molecules penetrate the field in the field. The force exerted on it is manipulated. Typical fields include electric, magnetic, acoustic, light, and velocity fields. In the present invention, the physical field always exists in a medium within a certain spatial range, and these are manipulated Permeant molecules are usually suspended, dissolved, or more generally placed in a medium. A typical medium is a liquid such as water or a non-aqueous liquid, or a gas. Depending on the structure of the field, an electric field can be applied to charged entities. Electrophoresis ____- 25- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 593683, A7 B7 V. Description of the invention (23) Neutral solid molecules apply conventional dielectrophoretic forces and / or traveling wave dielectrophoretic forces. Magnetic fields can exert magnetic field forces on magnetic solid molecules; sound fields can exert sound field radiation forces on solid molecules; light fields can apply light to solid molecules Field radiation force. The velocity field in a medium within a certain spatial range refers to the velocity distribution of the medium's movement within this spatial range. Various different mechanisms can cause the movement of the medium and the medium at different positions exhibits different speeds. Therefore, a velocity field is generated. The velocity field can exert mechanical force on the solid molecules. "Medium" refers to a carrier fluid, for example, a liquid or gas, in which the solid molecules to be manipulated are dissolved, suspended, or contained therein. "Microfluidic Applications" Refers to the use of tiny devices for fluid control, especially for the control of some biological, biochemical, or chemical reactions and processes. The characteristic dimensions of basic structural elements range from less than 1 micron to 1 cm. These areas of application include, but are not limited to, biochips (wafers used for biologically related reactions and processes), chemical wafers (wafers used for chemical reactions), or a combination of the two. “Built-in structures on a substrate” means that the structures are embedded on the substrate or that the structures are on the substrate and connected to the substrate. In a specific embodiment, such a built-in structure is fabricated directly on the substrate. For example, as described in "Dielectrophoretic manipulation of cells using spiral electrodes by Wang et al., Biophys. J., 72: 1887-1899 (1997)", spiral electrodes are fabricated on a glass substrate. Here, the spiral electrode is a "built-in" structure on a glass substrate. In another specific embodiment, this built-in structure can be manufactured on a substrate first, but -26- this paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 593683 A7 —— ___ B7 V. Description of the invention (24) After the substrate containing the built-in structure can be connected to another substrate. In this way, the structure is built on both substrates. In yet another embodiment, such a built-in structure can be directly connected to the substrate. For example, a thin electrical wire can be used as an electrode to generate an electric field. These electrical leads can be connected directly to a glass substrate. In this example, the electrical lead is a built-in structure on a glass substrate. Throughout the text, the built-in structure described on the wafer or substrate that has the ability to generate physical forces and / or fields can interact with external signal sources or The combination of external energy sources. The internal structure of a device means that the structure is part of the device integrated and connected to other parts, or these structures are inseparable or inseparable parts of the device. For example, such The internal structure can be micro-machined or combined on a substrate or other structural elements. As long as the device contains a substrate, any of the above-mentioned "built-in structures on a substrate are" the internal structure of the device, as long as the device contains Wafer, any built-in structure on the wafer is the internal structure of the device. Throughout the text, the internal structure described on the wafer or substrate that is capable of generating physical forces and or physical fields can be used with external signal sources Connections. Microstructures "feature sizes ranging from 1 micron to 20 millimeters. The internal structure of the device used to generate the required physical force. Inch should be coordinated with the requirements of the microfluidic applications. Through-molecules; I: Any substance that can be manipulated on a wafer. Generally speaking, the characteristic size of these substances should not exceed i cm. For example, if a suitable substance is spherical or nearly spherical, its characteristic size refers to the diameter of a sphere or approximately spherical shape. If these substances are cubes or approximate cubes, this paper scale applies the Chinese national standard-593683 A7 _ B7 V. Description of the invention (25) Then its characteristic size refers to the side length of the cube or approximate cube. If these materials have irregular shapes, their characteristic dimensions are the average of their maximum and minimum axis lengths. Physical molecules can be, but are not limited to, cells, organelles, viruses, microparticles, molecules (such as proteins, DNA and RNA), or their polymers or complexes. The solid molecules that can be manipulated include a variety of particles-solid (for example: glass beads, latex particles, magnetic beads), liquid (for example: droplets) or gas particles (for example: bubbles), and dissolved particles (for example: molecules, proteins , Antibodies, antigens, oils, DN A, RN A, molecular complexes), suspended particles (for example: glass beads, latex particles, polystyrene beads). The particles can be organic (for example, mammalian or other cells, bacteria, viruses, or other microorganisms) or inorganic (for example, metal particles). Particles can have different shapes (for example: spherical, ellipsoidal, cubic, discus, needle) and different sizes (for example: nano-scale gold balls, micro-scale cells, millimeter-scale particulate polymers). Examples of particles include, but are not limited to, biological molecules (such as DNA, RNA, chromosomes), protein molecules (such as antibodies), cells, colloidal particles (such as polystyrene beads, magnetic beads), and any biological molecules (such as Enzymes, antigens, hormones, etc.). A special type of particle is a complex formed by solid molecules and their linkers, and is called "METHODS FOR MANIPULATING MOIETIES IN MICROFLUIDIC SYSTEMS" (by Wang et al., Filed on August 10, 2000) ) As described in the US patent. Examples of such complexes include microparticle-microparticle complexes, microparticle-molecular complexes (eg, cell-magnetic bead complexes are antigen or protein molecules that permeate the cell surface and are fixed at ______- 28-_ This paper standard applies Chinese National Standard (CNS) M specification (⑽X297 public love) 593683 A7 B7 V. Description of the invention (26) Interaction between antibody molecules on the surface of magnetic beads is formed by cells connected to antibody-covered magnetic beads; DNA The molecule-magnetic bead complex is formed by fixing DNA molecules on the surface of magnetic beads, or the protein molecule-polystyrene beads complex is formed by covering protein molecules on the surface of polystyrene beads. U.S. Patent Application " METHODS FOR MANIPULATING MOIETIES IN MICROFLUIDIC SYSTEM, (under U.S. Patent Application No. 09 / 636,104, filed by Wang et al. On August 10, 2000) can be used to manipulate the device of the invention Solid molecule and / or linker-solid molecular complex. The pending U.S. patent application (U.S. Patent Application No. 09/63 6, 1 04) filed under the name of "METHODS FOR MANIPULATING MOIETIES IN MICROFLUIOIC SYSTEM" by Wang et al. On August 10, 2000 The mode of reference is incorporated in the present invention. Here, "plant" refers to any eukaryotic multicellular organism in the genus Plant that can perform photosynthesis, and is characterized in that it can produce embryos, contain chloroplasts, and have cell walls with cellulose components and cannot move. Here, "animal" refers to any multicellular organism in the genus Fauna, which is characterized by its ability to move, has no photosynthesis mechanism, has a pronounced response to stimuli, has a limited degree of development, and has a generally fixed body structure. . Examples of animals include, but are not limited to, birds (such as chickens), vertebrates (such as fish and mammals, such as rats, mice, rabbits, cats, dogs, pigs, cows, bulls, sheep, goats, horses, Monkeys and other apes) and other "bacteria" refer to small eukaryotes (characteristic size is about 1 micron left _ _-29 -__ This paper size applies to China National Standard (CNS) A4 (210X297 mm) 593683

) The ribosomes and closed-loop DNA with a sedimentation coefficient of about 70 s are synthesized in different ways from eukaryotes. Many antibiotics inhibit the synthesis of bacilli, but do not affect the infected host. "True bacteria" refers to another major subgroup of bacteria other than archaea. Most Gram-positive bacteria, cyanobacteria, mycoplasma, intestinal bacteria, pseudomonas, and chloroplasts are all true bacteria. True bacteria The cytoplasmic membrane contains ester-linked lipids' if there is a cell wall, it contains peptidoglycans; no endogen is found in the genome of a true bacterium. 'Archabacteria' refers to another major subgroup of bacteria besides true bacteria. Wang wants to have three major groups of archaeal bacteria: halophiles, methanogens, and an extremely thermophilic fungus that depends on sulfur for survival. Archaea are distinguished from true bacteria mainly by differences in ribosomal structure and cell membrane composition, and (in some cases) archaeal genomes have internal elements. A "virus" is an organism that lives within a host cell. It does not have the structural characteristics of a cell and has a coat of DNA or RNA and protein. The size of the virus ranges from about 20 to about 300 nanometers. The first type of virus (Baltimore Classification) The genome is double-stranded dNA; the genome of the second type of virus is single-stranded DNA; the genome of the third type of virus is double-stranded RN a; the genome of the fourth type of virus is single-stranded positive-stranded RN A, and the genome itself acts as Viral mRNA; the genome of the fifth type of virus is a single-stranded anti-strand RNA, and the genome is a template for synthesizing mRNA; the genome of the sixth type of virus is a single-stranded positive-strand RNA, but DNA is used for replication and mRNA synthesis. As a medium. Most viruses are identified by the diseases they cause on plants, animals and prokaryotes. Prokaryotic viruses are called -30- This paper is scaled to the Chinese National Standard (CNS) A4 (210 X 297) (Mm)

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For phage. ~ The species of eukaryotes in the eukaryotes, they grow in irregular clusters, and have no tricks, such as γ, γ, Α, or Jujube, and lack of chlorophyll or other capable of light mouth function. Delirious pigment. The female true halide (flat body) is a single cell with a dizziness, stubborn and branched hyphae. The # cell wall (containing glucosamine and chitin, or both) is wrapped and contains the true nucleus. . . Η⑯ refers to any substance that can be related to the entity molecule with affinity and special, objective, and can be manipulated through the desired physical force :. The linker can be, but is not limited to, cells, organelles, pathogens, microparticles, aggregates, human contact V, and k-mouth, or molecular aggregates or complexes. The particles are of any shape, any composition, and have any composite structure. The particles can be manipulated in a microfluidic device by a desired physical force. An example of a particle is magnetic beads that are operated with magnetic field forces. Another example of particles is the particles used in the fine method of operation such as traveling wave-medicine ^ ο inverse; 丨 privately-packed ice force temple electric field force, the size can be from about 0.01 microns to about 10 cm . Even more interesting, the size of the particles is small in this method, from about 0 · 0 1 micron ^ 丨 丨 from Ao 1, wood to about several thousand microns. Examples of microparticles include, but are not limited to, 'plastic microparticles, polystyrene beads, glass beads, magnetic beads, hollow glass spheres, composite component particles, micro-addition microstructures, etc. "Other particles include fine particles ^ A ^ G 祜, Qiu cells, organelles, large biological molecules such as DNA, RNA and proteins. "Operation" refers to the movement and processing of these physical molecules, resulting in real # molecules on the wafer (including on a single wafer or on or between multiple wafers, in ^

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This paper size applies to China National Standard (CNS) A4 specifications (210X297 Public Love T -31-593683 A7 B7 V. Description of the invention (29) on the bottom or between multiple substrates in the device) for one-dimensional, two-dimensional or Movement in three dimensions. The manipulation of these solid molecules can also be performed in a liquid container. "Operation" includes, but is not limited to, transport, focusing, enrichment, enrichment, aggregation, capture, repulsion, floatation, separation, fractionation, isolation, linear, or movement of solid molecules in other directions. In order to achieve effective operation, the entity molecule to be operated and the physical force applied to it should be coordinated. For example, a magnetic entity molecule may apply a magnetic field force. Similarly, charged solid molecules can be subjected to electrostatic forces (ie, electrophoretic forces). In the case of operating linker-entity molecular complexes, the properties of these physical molecules or corresponding linkers and the physical forces used for the operation must be coordinated. For example, a solid molecule or its linker has certain dielectric properties, can be dielectrically polarized, and can use a dielectrophoretic force. “Non-manipulable solid molecules” means that under the action of specific physical forces, when these solid molecules are not connected to their linkers, no visible movement is observed. "Physical force" refers to a force used to move an entity molecule or its attachment, and it does not chemically or biologically react with the entity molecule or its attachment, does not affect or hardly affect The biological and chemical properties of a solid molecule or its linker. The term "force" or "physical force" always refers to the "force" or "physical force" acting on these physical molecules. The "force" or "physical force" is generated through the action of a field and is derived from the nature of the physical molecule Decide. Therefore, when a field or physical field is given, in order to generate physical forces on the solid molecules, these solid molecules must have certain properties. Some types of fields can be used in a variety of solid molecules with different properties -32- This paper size applies to China National Standard (CNS) A4 specifications (210X 297 mm)

All of them have a force effect, a limited type of entity VIII: certain types of fields may only work on some of the physical entity molecules 22-her afterburner effect. For example, magnetic fields can only generate forces or magnetic fields on magnetic molecules that are not suitable for magnetic entities, such as other types of particles, such as polystyrene beads. On the other hand, the electric field applied by A 5 can be used to add physical force to many different types of entities, such as $ cylinder blades and so on. And Fen Yongfeng vinyl beads' cells, as well as magnetic micro-second, does not require the physical field to be used on different types of solid molecules, but the physical field must be able to generate force on at least one solid molecule and one solid molecule. … Sub-field force ”1 The force exerted by an electric field on a solid molecule. Magnetic field force is the force exerted by a magnetic field on a solid molecule. Sound field force (radiation force of a sound field) refers to the light field force exerted by a sound field on a solid molecule. (Light radiation force) "is the force exerted by a light field on a solid molecule. Mechanical force is the force exerted by a velocity field on a solid molecule. The full binding of the entity molecule to be operated to the surface of the linker means a full percentage. It is best that most of the entity molecules to be operated are bound to the surface of the linker and can be realized by operating the linker with appropriate physical forces. Operations on solid molecules. Usually, at least 0.5% of the actual molecules to be manipulated are bound to the surface of the linker. More suitable is at least i%, 2%, 3%, 4%, 5%, 100/0, 20/0, 30/0, 40/0, 5000/0, 60%, 70%, 80%, or 90% of the solid molecules are bound to the surface of the linker. The percentage of binding entity molecules includes binding to the surface of a particular linker or to multiple linkers. When using a variety of connectors -33- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)

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When, on. These substances can be simultaneously or sequentially bound to the surfaces of multiple linkers. The entity molecules to be manipulated are completely bound to the surface of the linker. At least the entity molecules to be manipulated are bound to the surface of the linker. What is more, at least 91%, 92%, 93%, 94% 95%, 96% 97% 98% '99% or just% of the entity molecules to be operated are bound to the surface of the linker. The percentage of bound entity molecules includes binding to the surface of a particular linker or to multiple linkers. When multiple linkers are used, the streptococcal molecules can be simultaneously or sequentially bound to the surface of multiple linkers. The "intracellular solid molecule part" is a solid molecule located in the cell, that is, located in the cytoplasm or organelle substrate, attached to On any cell inner membrane, on the plasma membrane (if present), or on the cell surface, that is, on the outer surface of the plasma membrane or cell wall (if present). Wafers and devices In one aspect, the invention provides a wafer for generating a field, the wafer comprising: a) a substrate; b) at least two built-in structures built on the substrate, any one of which Both built-in structures can be combined with external signal sources to produce a type of physics. Here, the generation of the physical field is achieved by a combination of an external signal source ("external" is relative to the crystal in the present invention) and a built-in structure on the substrate or wafer. The external signal source is connected to the built-in structure on the chip and provides signals to it, so that the built-in structure generates a corresponding physical field, such as an electric field, magnetic field, sound field, light field, or velocity field. An external signal source can provide an appropriate form of signal (for example: electrical signal, or optical signal, or optical radiation). These are from external letters -34- This paper size applies to China National Standard (CNS) A4 specifications (210X297 mm) A7

The signal generated by the signal source is loaded to generate the corresponding physical field degree field. The built-in structure located on the substrate or wafer, such as electric field, magnetic field, sound field, light field, or speed. The wafer of the present invention may include only four basic structures, or may include multiple structures that are interconnected. Base. For example, ^〗 For example, an electrode array can be fabricated on -2 :, and a micro-electromagnetic unit can be fabricated on a second substrate. ^ 4 唬 / original connection, can generate DC or AC 1… The magnetic unit array can generate a field by connecting with an external electrical signal source. The two bases can be fixed together to form an electrode base, and the lower part is a private magnetic base. These two substrates are structurally related substrates, and the steps of re-de # # I draw similar steps can form a wafer containing more than two structurally related substrates. #In another example, two wafers can be connected together in turn, and then tied to a third wafer. Such two substrates are structurally connected. Any suitable solid substrate can be used in today's wafers. For example, the substrate material can be silicon (with a silicon dioxide or silicon nitride surface layer or other thin dielectric layer surface), plastic, glass, ceramics, rubber, or polymer. The base material may be porous or non-porous. It is true that there are at least two different types of structures in the wafer of the present invention that can generate a single or multiple types of fields, but the wafer is designed with built-in structures on it to generate at least two different types of physics. It is not necessary to match the number of types of built-in structures with the number of types of physics generated through these structures. However, it is best to match the numbers. For example, a wafer can contain two different types of built-in structures to produce two different types. _______- 35- This paper size applies to China National Standard (CNS) A4 size (210X297 mm) binding

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34593683 V. Description of the invention (Electricity = At least two physical fields other than this combination. In another specific implementation ^ m structure w is selected to generate at least two other than the combination of sonic standing wave field and uniform sentence electrostatic field Two types of physics. In another ip embodiment, the built-in structure can selectively generate at least two types of physics in addition to the combination of electric field and velocity ^. &Amp;: The field can pass through the substrate or the wafer. The electrode structure is generated, and its energy comes from an external electrical signal source. The built-in structure is an electrode element and an electrode array that are added to the wafer. When an appropriately designed electrode element and electrode array are applied by an external electrical signal source When an electrical signal is generated, an electric field is generated in the space 7 around the wafer. According to whether the electric field is reduced-a fixed direction or the direction of the field = changes over time, the electric field can be divided into a DC electric field and an AC electric field. Electric field and non-uniform electric field. Here, the "uniform hook", or "non-uniform," of the electric field is divided according to the spatial distribution of the electric field. Pair = non-uniform first-order harmonic parent mud electric field (for example, The frequency of the field is transformed into a sine wave with time, and its frequency ranges from 10000 Hz to several hundred, such as fGHz. The amplitude and phase of the electric field have a non-uniform distribution. The AC electric field can have 3 multiple frequency components. The amplitude and frequency of the field should be able to wither. In addition to the sinusoidal change of the field over time, it can also be a function relationship. The electrode structure or electrode element used to generate the electric field includes: but is not limited to, as follows As shown, a planar electrode covering the entire surface of the substrate or most of the substrate ("Most," means that if the generated field = is used to manipulate a solid molecule, the electrode size in one direction is less than ten Times the size of the entity molecule being operated), as well as staggered electrodes, parallel electrodes, spiral electrodes, and comb electrodes that are intertwined to form a domain-shaped electrode. [Tear the public seal] 593683 A7 B7 V. Description of the invention (35) The term electrode can be individually gated electrode array where each electrode element can be round, square, or other regular or irregular The following article provides many examples of electrode structures that can be used to generate electric fields: Gale et al.? IEEE Trans. Biomedical Engineering 45: 1459-1469 (1998); Wang, et al. 5 Biochim. Biophys. Acta. 1243: 185D194 (1995); Wang, et al ·, IEEE Trans · Ind · Appl · 33: 6600669 (1997); Wang, et al ·, Biophys · J 72: 1887-1899 (1997); Wang, et al ·, Biophys. J. 74: 2689-2701 (1998), Huang, etal ·, Biophys · J. 73: 1118-1129 (1997) and Yang, et al. 5 Anal. Chem. 71 (5): 911 D918 (1999); Gascoyne, et al ·, IEEE Trans. Ind · Apps. 33 (3): 670CI678 (1997), Becker, et al ·, Proc. Natl. Acad · Sci. USA 92: 8600864 (1995) and Becker , et al. 5 J. Phys. D: Appl. Phys. 27: 2659D2662 (1994); Huang, et al., J. Phys. D: Appl. Phys. 26: 152801535 (1993); Wang, et al. , J. Phys. D: Appl. Phys. 26: 127801285 (1993); Hawkes, etal., Microbios 73:81, 86 (1993); and Cheng, et al.? Nat. Biotech. 16: 5470546 (1998 )); Stephens, et al. 5 Bone Marrow Transplantation 18: 777D782 (1996)); Washizu, e t al. 3 IEEE Trans. Ind. Appl. 30: 835 □ 843 (1994); Green and Morgan, J. Phys. D: Appl. Phys. 30: L41DL44 (1997); Hughes, et al.? Biochim. Biophys Acta. 1425: 1190126 (1998); and Morgan, etal., Biophys J. 77: 516, mouth 525 (1999)); Fuhr, etal., Biochim. Biophys. Acta. 1108: 2150233 (1992)); Washizu, etal ·, IEEE Trans · Ind · Appl · 26: 3520358 (1990); Fiedler, et al ·, Anal · Chem · 70: 1909D 1915 (1998); and Miiller, et al. 5 Biosensors and ___- 38-_ 本Paper size applies Chinese National Standard (CNS) A4 (210 X 297 mm) 593683 A7 B7 V. Description of the invention (36)

Bioelectronics 14: 247D256 (1999)); Schnelle, et al., Biochim. Biophys. Acta. 1157: 127D140 (1993); Fiedler, et al. (1995); Fuhr5 et al. (1995a); Fiedler, et al. (1998); Miiller, et al. (1999)); Hagedorn, et al ·, Electrophoresis 13: 49054 (1992); Fuhr, et al ·, Sensors and Actuators A: 41: 2300239 (1994); Morgan, et al ·, J. Micromech. Microeng. 7: 65D70 (1997);. Schnelle T.5 et al.? In Biochim · Biophys. Acta. 1157: 127-140, 1993, pages; Miiller, T ·, et al.? in Biosensors and Bioelectronics, 14: 247-256, (1999); Fuhr, G., et al ·, in Cellular Engineering. Autumn: 47-57, (1995); Fiedler S. et al ·, in. Microsystem Technologies. 2: 1-7, 1995; Fiedler, S., et al., Anal. Chem. 70: 1909-1915, (1998) o Electrode elements, electrode structures, and electrode arrays can be processed on the substrate by many different processing methods These methods are common techniques in the field of micro-etching and micro-machining (see Rai-Choudhury P. (Editor), Handbook of Microlithography, Micromachining and Microfabrication, Volume 2: Micromachining and microfabricationSPIE Optical

Engineering Press, Bellingham, Washington, USA (1997)). In many cases, standard micromachining and micromachining methods and operating procedures can be used. A typical processing method is photolithography using a single or multiple reticle. The microfabrication process includes many basic steps, such as photomask formation, metal deposition, insulator deposition, photoresist deposition, and photolithography with a mask and developer on a photoresist layer, metal layer, or dielectric layer Pattern or structure. The electrode can be made of metal materials, such as Ming, gold, silver, tin, copper, graphite, graphite, and semiconductor materials such as porous doped particles or _____- 39- _ This paper size applies to Chinese National Standards (CNS) A4 specification (210X297 mm) 593683 A7 B7 V. Description of the invention (37) Other materials with sufficiently high conductivity. The base material used to make the electrodes can be silicon, plastic, glass, ceramic, or other solid materials. The solid material can be porous or non-porous. Those familiar with the fields of microfabrication and microfabrication can select or decide the machining procedures and materials used for the fabrication of specific electrode structures. The magnetic field can be generated by different methods. For example, a U.S. patent application (application serial number 09/3 99,299, with application date of September 16, 1999) in the process of reviewing an electromagnetic chip is being designed. Generally, such an electromagnetic chip with a single-selectable micro-electromagnetic unit is composed of the following parts: a substrate; there are multiple micro-electromagnetic units on the substrate, and each unit can generate a magnetic field after applying a current; A method of applying an electrical signal to a single unit to generate a magnetic field. Preferably, the surface of the electromagnetic wafer has a functional layer that can be used to fix a certain type of solid molecule or molecule. In this example, the micro electromagnetic unit is a built-in structure located on a wafer or a substrate, and the current source connected to the micro electromagnetic unit is an external current source. When an external current source applies a certain current to the micro electromagnetic unit, a magnetic field will be generated in the space around the electromagnetic unit. Other geometries and geometries can be used. Examples of such electromagnetic units include, but are not limited to the following, as shown below: Ahn, C., et al., J. Microelectromechanical Systems, Volume 5: 151-158 (1996); Ahn, C., et. al ·, IEEE Trans. Magnetics · Volume 30: 73-79 (1994); Liakopoulos et al., in Transducers 97, pages 485-488, presented in 1997 International Conference on Silid-State Sensors and Actuators, Chicago, June 16- 19, 1997; US Patent No. 5,883,760 by Naoshi a / ... the above ___- 40-_ This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 38 38593683 5. Description of the invention (public Research work and U.S. patent application in the process of application examination (application serial number is 09/3 99,299, application date is 9999 2)-further provides materials and methods that can be used to process electromagnetic structures on wafers And operating procedures .: The sound field can be generated by a variety of methods. For example, the voltage I converter used to generate the sound field can be added to or made on a substrate. An example is a Z ceramic disc as a substrate, which is more Metal on both sides Membrane electrode cover. Another example is the use of Enden ceramics wafers as substrates, and electrode arrays of different geometries are deposited on the surface of ceramics materials. Another example is a substrate using a non-piezoelectric conversion material. The surface surname is engraved with an array consisting of the grooves of the person 1 and 1. Then electrode materials and pressure materials are deposited in the grooves to form a piezoelectric converter of the Meiji structure: electrode / piezoelectric material / electrode. The other one An example is the use of a piezoelectric transducer phase array described by Qeftering, R. in U.S. Patent 6,029,5 1 8. In all of these examples, a piezoelectric transducer composed of a piezoelectric material and an electrode is a substrate or a wafer Built-in structure on the surface. When an electrical signal from an external signal source is applied to the electrode, the piezoelectric transducer generates a mechanical displacement, so that sound can be generated in a medium that is closely connected to the substrate. According to the structure of the substrate and the substrate Different structures made on it can generate different types of sound fields. A standing wave sound field can be in a sound wave reflecting plate containing a piezoelectric material substrate and separated by a suitable distance. (E ^ Xinyang Ru K Yitu ^ Acoust. Soc. Am. Vol. 10 (l), p642-645, July, 1997; Yasuda K. and Kamakura T. Appl. Phys. Lett, V 71 (13), pl771-1773, Sep. 1997). In another example, a traveling wave sound field can be used. Again at -41 A7

In another example, the sound field may have both standing and traveling wave components. Force: Two: Ten thousand! A light field can be generated. In one example, the built-in structure is an optical element and array added to a substrate or wafer, and an external signal source (e.g., a laser source). When the optical signal source produces: light, 'optical elements and arrays built on the wafer or substrate, a light field is generated around the wafer'. The distribution of the light field depends on the built-in optical elements and arrays. Geometry, size and composition. In another example, the built-in structure is an optical-electrical component and array added to the chip, and the external signal source is an electric source (such as a DC power source or an AC power source). When an electrical signal from an external electrical signal source is applied to the built-in optical-electrical components and arrays, these components and arrays can generate light, and a light field is generated in the area around the wafer. The velocity field in the medium in a certain area of space refers to the velocity distribution of the medium moving in this area. There are several ways to cause the medium to move to produce a velocity field. In one example, the surface of the substrate is treated to cause the surface to have a suitable charge or a suitable charge distribution. The substrate can be combined with other structures (such as cover plates, substrates) to form a fluid pool with multiple input / output ports. When the liquid medium is introduced into this fluid pool, the external pen # 5 source can generate a voltage in a certain direction of the fluid pool. Voltage: The electric field generated can interact with the surface charge on the substrate (and / or the surface charge on other surfaces of the fluid pool) to cause the flow of the liquid medium. In this way, the velocity distribution produced at this position in the fluid pool is a velocity field. In another example, the velocity field can be transmitted through the thermal gradient in the medium. -42- This paper size applies the Chinese National Standard (CNS) A4 (210X297 mm) 593683 A7

Or temperature gradients. One or more heating or cooling elements can be made on the substrate. The heating element can be a thin film resistor or a thin wire resistor (such as a metal film or metal wire). The cooling element can be a Peltier effect junction or a Peltier element. These heating and cooling elements all receive signals from external electrical signal sources. The current from an external electrical signal source can be applied to a metal film or metal wire to generate "heat", thereby forming a heating element. Current from an external signal source can be applied to the Peltier element to raise or lower the temperature. Such heating and / or cooling processes will create a temperature gradient in the medium directly or indirectly connected to the heating and / or cooling elements. Temperature gradients cause movement of the medium, which produces a velocity field. In another example, the velocity field can be generated by using an electromechanical element / device integrated on a wafer. The external signal source can be an electrical signal source (eg a DC power supply). The electromechanical device can be a micromachined pump (such as an electromagnetic pump) that generates pressure to pump fluid. The electromechanical device can also be a micromachined valve, which can cause the flow of liquid by opening and closing. The electromechanical element / device may be a micro-machined thin end / capillary tube. These capillaries and thin ends are covered with corresponding functional materials, such as temperature-sensitive materials, surface memory alloys. These capillaries and thin ends can be further connected to an external electrical signal source or coupled with external physical forces, so that the capillary or thin ends can be moved after an appropriate signal is provided. When a certain electrical signal is applied to the electromechanical components / devices that are carefully designed and manufactured on the wafer, these components / devices, or the components in these components / devices, will undergo some form of movement, resulting in direct or indirect interaction with them The connected media is in motion. In this way, the velocity generated in the medium is 593683 A7 ____B7 5. The invention description (41) ~ is a velocity field. Other types of physics can be generated through built-in structures on the substrate or wafer. All of these physical fields have the following properties: When physical molecules, microparticles, or solid molecule-conjugate complexes with appropriate properties are placed in the physical field, they will be subject to corresponding physical forces. The size of the built-in structure that produces the required physics must meet the needs of microfluidic applications. For example, the built-in structure should be a microstructure. In general, the basic structural elements of microstructures have a characteristic size of about 0.1 μm to about 20 μm. It is preferably between about 1 micrometer and about 1 millimeter. Current wafers are widely used in chemistry, biochemistry, biological reactions, processing, and processes. These reactions, processes, and procedures can be used in biomedical research, clinical diagnosis, and drug development. The wafer in the present invention can be used in many processes, such as manipulating physical molecules, promoting chemical / biochemical / biological reactions, controlling chemical / biochemical / biological processes, such as controlling temperature in a reaction chamber to control fluids. Take control and more. The built-in structure or built-in components on the wafer can be designed according to specific needs. Various wafers with different built-in structures can be processed or manufactured into different devices according to different application needs. In addition to the built-in structures and / or components that generate physics as described above, the wafer may include structural elements suitable for other special purposes, or the wafer may be used with other elements. For example, if a wafer is used for the manipulation of physical molecules, the wafer can be used with other structural units such as cover plates, substrates, and input / output 珲 to support and retain the physical molecules to be operated. Going one step further, the wafer may include a functional layer to immobilize a solid molecule. This paper is suitable for size @ S 家 鲜 (CNS) A4 size (210 X 297 public director) 593683 A7 B7

Another aspect of this invention relates to a form of bonding, where the bonding includes: a) at least two wafers, each wafer containing a substrate, and at least two different built-in structures built on the substrate, any of which Such a built-in structure can be combined with an external signal source to generate a certain type of physics; and b) a method for transporting manipulated physical molecules between wafers. In these examples, each wafer may contain at least two different types of the above-mentioned, 'a structure, when an external signal is applied to the structure, a physical field' such as an electric field, magnetic field, sound field, light field and velocity field, Some other fields 0 In another aspect, this invention relates to a device, wherein the device includes a block to support and retain the substrate of the entity molecule to be operated, and at least two different internal structures built on the above substrate, any of which One such structure can obtain signals from external signal sources to generate a certain type of post-physics. These internal structures that can generate physical fields and physical forces can be placed on the substrate, and the internal structure can also be built outside the wafer, but the structure is still a complete part of the device. Because the physical field of the present invention can cause a solid molecule with appropriate properties to be subjected to a force during the physical field, as described above, the wafer in the present invention is an example of the device of the present invention. Therefore, the device may include any one of the wafers that can be produced, and the composition of the wafer is: a) a substrate = at least two different structures located on the substrate d = any such structure can be Obtain a signal from an external signal source; Generate a chirped type of physics. As long as the internal structure in the device can be applied to the molecules of the entity to be operated, the paper standard (CNS) A4 specification (21〇X 297 ^ jy)

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€ -45- 593683 A7 B7 V. Description of the invention (43) Different types of physical forces, the device can contain only a base. These devices may also include multiple structurally connected substrates. For example, an electrode array can be processed on one substrate, and a micro-electromagnetic unit can be processed on another substrate. After the electrode array is connected to the electrical signal source, a DC or AC electric field can be generated, and an electric field force (such as a DC electric field force, and / or a conventional dielectric electrophoretic force) can be applied to uncharged or charged solid molecules, and / or Traveling Wave Dielectric Force). After the electromagnetic unit array and the electric signal source are connected, a magnetic field can be generated and a magnetic field force can be exerted on a solid magnetic molecule. Two substrates can be combined to form a composite substrate, where the top is the electrode substrate and the bottom is the electromagnetic substrate. The two substrates are structurally connected. This step can be repeated to build a composite substrate with more than two structurally connected substrates. In another example, two substrates can be connected together in sequence and combined with a third substrate. These two are structurally connected bases. This step can be repeated to form a composite substrate containing more than two structurally connected substrates. An electrode array can be processed on one substrate, and a micro-electromagnetic unit can be processed on another substrate. After the electrode array is connected to the electrical signal source, a DC or AC electric field can be generated, and an electric field force (such as a DC electric field force, and / or a conventional dielectric electrophoretic force) can be applied to uncharged or charged solid molecules, and / or Traveling Wave Dielectric Force). After the electromagnetic unit array and the electric signal source are connected, a magnetic field can be generated and a magnetic field force can be exerted on a solid magnetic molecule. Two substrates can be combined to form a device, such as: a fluid pool, an electrode substrate as the bottom plate of the cavity, an electromagnetic substrate as the top plate, and a substrate to separate the two substrates. -46- This paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) 593683 A7 B7 V. Description of the invention (44)

These two substrates are structurally connected in the device. This device (such as a fluid cell) should further include input and output ports to allow component introduction = out of the fluid cell. In yet another example, an electrode array can be processed on a substrate. After the electrode array is connected to the electrical signal source, a DC or AC field can be generated and an electric field can be applied to the uncharged or charged solid molecules: (eg, DC electric field force, and / or conventional dielectric electrophoretic force, and / Or traveling wave dielectric electrophoretic force). A micro-machined lens array or filter or other light element can be processed onto another substrate. The processed optical element array 2 is connected with an external optical signal source to generate an optical radiation field, and thereby exerts a light radiation force on the physical molecules. These two substrates can be used together to form: a device, such as a fluid pool, consisting of a substrate containing an electrode array as a bottom plate, a substrate containing an optical array as a top plate, and a substrate for separation. These two substrates are structurally connected in the device. This device (such as a fluid cell) should further include input and output ports to allow physical molecules to be introduced into or removed from the fluid cell. Any suitable solid substrate can be used in the present invention. For example, the base material can be silicon (surface with silicon dioxide or silicon nitride or other thin surface of insulation), plastic, glass, ceramic, rubber, or polymer. The base material can be porous or dense. Although there are at least two different types of internal structures in the wafer of the present invention that can generate a single or multiple types of fields, the internal structure of a wafer designed thereon can generate at least two different types of physical fields. It is not necessary to make the number of types of internal structures and the types of physical fields generated by these structures ______- 47- This paper size applies the Chinese National Standard (CNS) A4 specification (21 × 297 mm) 593683 A7 B7 V. Description of the invention (45 corresponds to the number. However, it is better to make the two] correspond to 1. For example, a print can contain two different types of physics, or it can include 3 kinds of structures to produce two different types. I have already described a different type of internal structure to generate three different types of physics, or include four different types of internal structures to generate four different types of physics, or include more than four different types of internal structures to Generate more than four different types of physical fields. Multiple types of forces can act on one entity molecule or one type of entity molecule. In addition, multiple types of physical forces can act on multiple entity molecules. In this way, when a device contains two (Three, four, or more than four) Different types can produce two (three, four, or more than four) different types of physical forces When it comes to the type of internal structure, it does not mean that there are two (three, four, or more than four) different types of physical forces acting on the same entity molecule or the same type of entity molecule. There are several points in this entire application. Note. These structures are different when referring to the "internal," structures, or "built-in," on a wafer, of structures that generate physical forces and / or physical fields, or when these structures generate physical forces and / or physical fields. An external signal source is connected. Here, the term "force," or "physical force" always refers to the "force," or "physical force," or "physical force," which acts on these physical molecules through the action of a field The generation is determined by the nature of the entity molecule. Therefore, when a field or physical field is given, in order to generate physical forces on the entity molecule, these entity molecules must have certain properties. Certain types of fields can have multiple properties. The physical molecules of different properties generate forces, and some types of fields may only apply forces to a limited number of solid molecules. For example, magnetic fields L__ -48- This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 297 mm) 46 in the specific embodiment of the force, female 7 electric field force in the specific embodiment of the force, such as the electric field force in the specific embodiment, the description of the invention (Second, force or magnetic force is generated on magnetic penetrating molecules or solid molecules with certain magnetic properties. It is not suitable for other types of particles, such as polystyrene beads.: = 10,000 faces, a non-uniform electric field can Apply physical force on many different types of male molecules, such as polystyrene beads, cells, magnetic beads, etc. In fact, it is not necessary to require physical fields to exert force on different types of physical knives. However, the physical field must be able to generate forces on at least one solid molecule and one solid molecule. These internal structures can be integrated on the wafer in any suitable form. For example, the 'internal structure may be a single unitary material, which may be located on the wafer / section 77 or the entire wafer. Or, this king structure can contain one microcell. Such microcells can be partially or completely single-gated or = When a group of microcells is applied to a wafer, the present invention also provides a method for selective application of signals as early as 7L. The device of the month can be specifically designed to generate the required physical force, preferably at least two types of physical force. In a particular embodiment, the structure can selectively generate at least two kinds of physical forces, such as electric field two = force / sound field force, mechanical force, and light field light shooting force. In the other one, the internal structure can selectively generate at least two kinds of physics such as chirp force, magnetic field force, sound field force, and light field light force. In another inner Shao structure, at least two kinds of physical magnetic field force, light field radiation force and mechanical force can be selectively generated. In another: the structure can selectively generate at least two physical acoustic force, light field light force, and mechanical force. In another internal structure can selectively produce at least two physical

593683 A7 ---, B7 V. Description of the Invention (μ) The internal structure that generates the electric field force can be located outside the base, which is the internal force of the device ^ # Support and retain the role of the entity molecules to be operated. These examples include, but are not limited to, electrode elements made of thin wires (e.g., a diameter of! 0 microns to 2000 microns). These electrical leads can be wrapped in a base material or located in a special location next to the base. The wires are structurally identical to the device containing the substrate, and are the internal structure of the device. When electrical signals are applied to these wires, an electric field is generated in the surrounding areas of the wires, including on or near the substrate. Therefore, when physical molecules with appropriate properties are introduced, electric field forces act on these physical molecules. Electric field forces can be divided into DC electric field forces, conventional dielectric electrophoretic forces, and traveling wave dielectric electrophoretic forces. These forces will be described in detail later. The magnetic field force can be generated by any internal structure in the device, as long as the structure can generate the corresponding magnetic field force when connected to an external signal source. The internal structure that generates the magnetic field force can be located on the substrate, which is part of the device and supports and retains the molecules of the entity to be operated. As long as the device includes a substrate as described above, the internal structure on the substrate used to generate the magnetic field force includes all "built-in" I-structures on the substrate. Examples of those "built-in," structures include, but are not limited to, an array of electromagnetic cells. This array can be found in the pending U.S. patent application (application serial number 09/3 99,299, the application date is (September 16, 1999). The internal structure that generates the magnetic field force can be located outside the substrate, which is part of the device and supports and retains the molecules of the entity to be operated. These examples include, but are not limited to, electrical wires ( Such as the diameter of 10 microns to 2 000 microns) wrapped magnetic core (such as made of ferromagnetic materials) composed of electromagnetic -51-This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 593683

Everything. These electromagnetic units are located in a special position next to the substrate. The electromagnetic unit is structurally connected to the device containing the substrate, and is the internal structure of the device. When an electrical signal is applied to these electromagnetic units, a magnetic field is generated in the surrounding area of the wire, including on or near the substrate. Therefore, when entity molecules with appropriate properties are introduced, magnetic field forces act on each of the molecules. These magnetic field forces will be described in detail later. The sound field force can be generated by any internal structure in the device, as long as the structure is connected to an external signal source, the sound field force can be generated. The internal structure that generates the sound field force can be located on the substrate, which is the part of the device that supports and retains the molecules of the entity to be operated. As long as the device includes the above-mentioned substrates, the internal structure on that chirped substrate to generate sound field forces includes the "built-in" structures on all substrates. Examples of those built-in structures include, but are not limited to, using pressed ceramic discs as substrates, and ceramics on the surface are deposited with electrode arrays of different geometries. The internal structure that generates the sound field force may be located outside the substrate, which is part of the device and plays a role of supporting and retaining the molecules of the entity to be operated. Such examples include, but are not limited to, acoustic wave sources formed from piezoelectric materials or other means. The sound wave source can be located in a special position close to the substrate. The acoustic source is structurally connected to the substrate of the device containing the substrate. The sound source is the internal structure of the device. When an external signal (such as a voltage signal from a power source) is applied to a sound wave source, the sound field is generated in the surrounding area of the sound wave source, including on or near the substrate. Therefore, when solid molecules with certain properties are introduced, the sound field force acts on these solid molecules. These sound field forces will be described in detail later. -— ____- 52-This paper size applies to China National Standard (CNS) A4 (210X297 public love)

50 V. Description of the invention (The light field force can be generated by any internal structure in the device, as long as the structure can generate the light field force when it is connected to an external signal source. The internal structure that generates the light field force can be on the substrate, which is the device One part plays the role of supporting and retaining the solid molecules to be operated. As long as the device includes the above-mentioned substrate, the internal structure on the substrate for generating the light field force includes the built-in structures on all the substrates. Examples of those built-in structures include But it is not limited to optical and optical-electrical elements or arrays that can be integrated on the substrate. The internal structure that generates the light field force can be located outside the substrate. The substrate is part of the device and supports and retains the molecules of the entity to be operated. Examples include, but are not limited to, optical devices made of an array of optical elements such as filters and lenses on an optical substrate. Optical devices can be positioned in a special position close to the substrate. Optical devices are structurally identical to The base of Jichen's device is connected. The optical equipment is the internal structure of the device. When an optical signal is applied to an optical device, a light field is generated in the surrounding region of the optical device, including on or near the substrate. Therefore, when a solid molecule with certain properties is introduced, the light field force acts on these On solid molecules. These light field forces will be described in detail later. 'Mechanical forces can be generated by any internal structure in the device, as long as the structure is connected to an external signal source, mechanical forces can be generated. The internal, structure that generates the mechanical force can It is located on the substrate. The substrate is a part of the device that supports and retains the molecules of the entity to be operated. As long as the device includes the above substrate, the internal structure on the substrate to generate mechanical forces includes all built-in structures on the substrate. Examples of those built-in structures include, but are not limited to, different types of electromechanical components integrated on the substrate, integrated on the substrate L -______- 53- This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297) %) 593683

Heating and / or cooling elements and special surface configurations on the substrate. The internal structure that generates the mechanical force can be located outside the substrate, which is part of the device that plays the role of supporting and retaining the solid molecules to be operated. Such examples include, but are not limited to, electrical equipment such as valves, pumps, and the like. The electromechanical device can be positioned in a special position with respect to the substrate and structurally connected to the substrate of the device containing the substrate. Mechanical equipment is the internal structure of the device. When an external electrical signal is applied to an electromechanical device, the electromechanical device or a part of the electromechanical device will move, resulting in the movement of a medium directly or indirectly connected to the electromechanical device. The motion of the medium creates a velocity field. Therefore, when mollusc molecules with certain properties are introduced, the mechanical force acts on these solid molecules. These mechanical forces will be described in detail later. Other types of physical forces can be generated by any internal structure in the device, as long as the structure is connected to an external signal source. According to the nature of these forces and the structure of the device, the internal structure that generates these physical forces can be located on a substrate, which is part of the device that supports and retains the molecules of the entity to be manipulated. The size of the built-in structure that produces the required physics must meet the needs of microfluidic applications. For example, the built-in structure should be miniaturized. In general, the characteristic dimensions of the basic structural elements of a microstructure are from about 0.1 μm to about 20 mm. It is preferably between 1 micrometer and 1 millimeter. Current wafers are widely used in chemistry, biochemistry, biological reactions, processing, and processes. These reactions, processes, and procedures can be used in biomedical research, clinical diagnosis, and drug development. _______- 54 in the present invention-This paper size applies to China National Standard (CNS) A4 (210X 297 mm) binding

Line-593683 A7 B7 V. Description of the invention (52 The Japanese film can be used for #multiple processes, such as manipulating physical molecules, promoting chemical / biochemical / biological reactions, controlling chemical / biochemical / biological processes, = Control the temperature during the reaction to control the fluid, etc. You can design the built-in structure on the wafer or the built-in Yuanniu according to the needs of the special requirements. Various wafers with different built-in structures can be processed or processed according to different application needs. Manufactured into different devices. In addition to the built-in, 'sigma structure and / or components' that produce the physics as described above, the wafer may also include structural elements suitable for other special purposes, or the wafer may be used with other elements. For example If chip j is used for the operation of physical molecules, the chip can be used with other structural units such as cover plates, substrates, and input and output ports to support and retain the physical molecules to be operated. Furthermore, The chip can include a functional layer that can be used to build solid molecules. C. Operation method for setting the line · When the solid molecules participate in a certain object on the wafer Physical, chemical, biological, biophysical or biochemical processes, the wafers and devices designed by the present invention can be used to operate them. The entity molecules to be operated on can be cells, organelles, viruses, molecules or their aggregates. The entity molecule that is manipulated can be pure or present in a mixture, where the target entity molecule is only one substance in the mixture. For example, == cells from leukemia patients 22 and cells from solid tissues of patients with solid tumors Cancer cells can all be solid molecules to be manipulated. Similarly, various blood cells in the blood such as red blood cells and white blood cells can also be solid molecules to be manipulated. In one aspect, the present invention relates to a method for operating a solid molecule, and the method includes : A) Introduce a kind of entity molecule-one containing a substrate and the paper size applicable Chinese National Standard (CNS) A4 specification (210 X 297 mm) -55- 53 ^ 3683 5. Description of the invention (at least two different types of The internal structure of the device is operated, and the structure: each can be connected to an external signal source to generate permission The internal structure of the device is the same as that of the external part, so that at least two different physical forces are applied to the entity molecules, and the two child molecules are operated by the physical forces. Make & at least two different types of Physical forces can be applied sequentially or on body molecules. "At least two different types of physical forces: ▼ to ::: are applied to a single entity molecule at a time. For example, an electrophoretic device can simultaneously apply this Two types = two; death: such as cells or granules, the device can also turn on the sound field force generating element according to the following process, so that the real ## ^^ cell 'particles) receive the sound field force within a specific time; No. = Generating element 'turn on conventional dielectrophoresis force == (such as cells, particles) subject to conventional dielectrophoresis force 0 knife to many' = type Γ type of physical force "can also be applied sequentially or simultaneously. For example, one can generate a sound field force and a conventional media device can simultaneously apply two different types of force to two discriminating cells such as cells and beads. Therefore, a device that generates both force and traveling wave dielectrophoretic force for two kinds of entity molecules can work simultaneously: points :: such as magnetic beads and certain types of biological cells) Application phase: "k-like, magnetic beads are only subjected to magnetic fields The effect of force is only applied to biological cells by wave electrophoretic force. Another example of a device for% force and travelling wave electrophoretic force can be operated according to the following procedure. 593683 A7 B7 V. Description of the invention (^) 54 1. Turn on The magnetic field force generating element causes the magnetic beads to be subjected to the magnetic field force within a specific time; second, the magnetic field force generating element is turned off, and the traveling wave dielectrophoretic force generating element is turned on, so that biological cells are subjected to the action of the traveling wave dielectric electrophoresis force. Although this method can also be used to operate one entity molecule at a time, this method is best used to operate multiple entity molecules at the same time. In some applications, the entity molecules to be operated can be selectively operated from a mixture. Selective operation means that the operation process of the entity molecule to be operated is selective, either by receiving a different operation force from other entity molecules or experiencing other entity molecules. In the same operation process, the entity molecules to be operated can be separated from the mixture. In other applications, the entity molecules to be operated constitute a mixture, and the entire mixture is operated. The entity molecules to be operated include two types: directly Physical molecules operated by various physical forces; physical molecules that cannot be operated directly by physical forces, but can be operated by operating physical molecule-conjugate complexes. In specific embodiments, the manipulated physical molecules may be cells , Organelles, viruses, molecules or their aggregates or complexes. Existing methods can be used for various types of operations. Examples of operations include, but are not limited to, transport, focusing, enrichment, and concentration of solid molecules , Aggregation, capture, repulsion, suspension, separation, separation, separation, and movement of solid molecules in linear or other directions. The device using this method must internally contain two or more different types of structures, each The structure can be connected to an external signal source, so that a certain type of Physical force. Any _-57-_ can be used in this method. This paper size is applicable to China National Standard (CNS) A4 (210 X 297 mm) 593683 A7 B7. 5. Description of the invention (A physical force. In a specific specific In an embodiment, the internal structure of the device can be applied to the entity molecules to be operated with electric field force (such as DC electric field force, conventional dielectric electrophoretic force and traveling wave dielectric. Electrophoretic force), magnetic field force, sound field force, light field force, and mechanical At least two physical forces in the force. In a specific embodiment, the internal structure of the device can be applied to the physical molecules to be operated with an electric field force (such as a DC electric field force, a conventional dielectric electrophoretic force, and a traveling wave dielectric electrophoresis). Force), magnetic field force, sound field force, light field force. At least two physical forces. In a specific embodiment, the internal structure of the device may apply an electric field force (such as a DC electric field force) to the entity molecules to be operated. , Conventional dielectrophoretic force and traveling wave dielectrophoretic force), magnetic field force, sound field force and mechanical force of at least two physical forces. In a specific embodiment, the internal structure of the device can be applied to the entity molecules to be operated with electric field force (such as DC electric field force, conventional dielectric electrophoretic force and traveling wave dielectric electrophoretic force), magnetic field force, and light field force. And mechanical forces of at least two physical forces. In a specific embodiment, the internal structure of the device can be applied to the entity molecules to be operated with electric field force (such as DC electric field force, conventional dielectrophoretic force and traveling wave dielectrophoretic force), sound field force, and light field. At least two physical forces of force and mechanical force. In a specific embodiment, the internal structure of the device may apply at least two physical forces of a magnetic field force, a sound field force, a light field force, and a mechanical force to the entity molecule to be operated. In another specific embodiment, the internal structure of the device can apply at least two physical forces to the entity molecules to be manipulated, excluding the combination of light field forces and dielectric electrophoretic forces. In another specific embodiment, the internal structure of the device can be applied to the entity molecules to be operated to exclude binding by _-58- This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm)

Green 593683

At least two physical forces including a sound field force generated by a standing wave sound field and a DC electric field force generated by a uniform electric field. In another specific embodiment, the internal structure of the device may be applied to the physical molecules to be operated without at least two physical forces including a combination of electric and mechanical forces. In another aspect, the present invention relates to a method for operating a solid molecule. The method includes: a) introducing a solid molecule to be operated into a wafer. The wafer is composed of a substrate and at least two different types of built-in structures on the substrate. Each of these structures can be connected to an external signal source to generate a certain type of physics; # b) connect the built-in structure of the chip to an external signal source & Applying at least two types of physical forces causes the aforementioned physical molecules to be manipulated by physical forces. / Operable cells include, but are not limited to, animal cells, plant cells, fungal cells, bacterial cells, recombinant cells, or cultured cells. The animal cells, plant cells, fungal cells, and bacterial cells to be operated on originate from one genus or subspecies of the animal kingdom, plant kingdom, fungal kingdom, and bacterial kingdom, respectively. Cells belonging to ciliates, bacillus, flagella, and microspores can also be manipulated. Cells derived from birds such as chickens, vertebrates such as fish and mammals such as rats, rabbits, cats, dogs, pigs, cows, bulls, sheep, goats, monkeys and other apes and humans can be used with this chip and device And method operations. For animal cells, cells derived from a particular tissue or organ can be manipulated. For example, cells such as connective tissue, epithelial tissue, muscle tissue, or neural tissue. Similarly, cells in various organs can also be manipulated, such as ocular accessory organs, annular spiral organs (anniU〇Spiral 〇rgan), ear organs

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593683 A7 B7 V. Description of the invention (57) Officer, Chevitz organ, periventricular organ, Corti, key organ, enamel, peripheral organ, female external reproductive organ, male external reproductive organ, floating organ, flower-spray organ of Ruffini, reproductive organ, Golgi's tendon, taste organ, auditory organ, female internal reproductive organ, male internal reproductive organ, insertion organ, Jacobson's organ, nerve blood organ, tendon spindle, olfactory organ, otolith , Ptotic organ, Rosenmuller, sensory organ, olfactory organ, spiral organ, lower commissure, subfornix organ, supernumerary organ, touch organ, stem organ, taste organ, tactile organ, urinary organ, vascular organ of lamina terminalis , Vestibular organs, vestibular organs, degenerate organs, visual organs, pear nose organs, migratory organs, Weber organs and para-aortic bodies. From animal internal organs such as brain, lung, liver, spleen, bone marrow, thymus, heart, lymph, blood, bone, cartilage, pancreas, kidney, gallbladder, stomach, intestine, testis, egg nest, uterus, rectum, nervous system, The cells of the glands, blood vessels in the body, etc. are easier to handle. Furthermore, any plant, fungus (such as yeast), or bacteria (such as Eubacteria or Archaea) can be manipulated. Recombinant cells from any eukaryotic or prokaryotic organism, such as animals, plants, fungi or bacteria, can be manipulated. Body fluids from various parts of the body, such as blood, urine, saliva, bone marrow, semen or other ascites cells, and their components such as serum and blood aggregates can also be manipulated. Operable organelles include nuclei, mitochondria, chloroplasts, ribosomes, endoplasmic reticulum, Golgi apparatus, lysosomes, proteasomes, vesicles, vacuoles or microsomes. Operable virus (whether it is a complete virus or any virus structure) can come from, for example, the first type virus, the second type in its life cycle _-60-_ This paper standard applies to China National Standard (CNS) A4 specification (210X 297 mm) 593683 A7 B7 V. Description of the invention (Virus, third virus, fourth virus, fifth virus or sixth virus 0 Manipulable intracellular molecules refer to solid molecules located in the cell , That is, located in the cytoplasm or organelle base, attached to any cell inner membrane, on the plasma membrane (if present), or on the cell surface, that is, attached to the outer surface of the cell plasma membrane or cell wall (if present). Any The required intracellular solid molecules can be separated from the target cell. For example, organelles, molecules or their aggregates can be separated. Examples of such organelles include 'but not limited to' the nucleus, mitochondria, Chloroplasts, ribosomes, endoplasmic reticulum, Golgi apparatus, lysosomes, proteasomes, vesicles, vacuoles or microsomes, membrane receptors, antigens in the cytoplasm, enzymes And proteins. Operable molecules can be inorganic molecules such as ions, organic molecules or their complexes. Examples of operable ions include, but are not limited to, nano ions, potassium ions, magnesium ions, calcium ions, chloride ions, Iron ions, copper ions, zinc ions, manganese ions, vanadium ions, nickel ions, chromium ions, fluoride ions, silicon ions, tin ions, boron ions, or arsenic ions. Examples of operable organic molecules include, but are not limited to, Amino acids, peptides, proteins, nuclear acids, nuclear acids, oligonucleotides, nucleic acids, vitamins, monosaccharides, oligosaccharides, carbohydrates, lipids or their complexes. This method can handle any amino acid, such as D—and L-amino acid. In addition, all the building blocks of naturally occurring peptides and proteins, including alanine (A), arginine (R), asparagine (N), aspartic acid ⑺), cysteine (C), glutamine (Q), glutamic acid (E), glycine (G), histamine = (H), isolysine (I), leucine, lysine, methionine Standard Applicable Standards (CNS) A4 Specifications (21 () x297 Public Love)

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Le-61-593683 A7 B7 V. Description of the Invention (59) (M), Phenylalanine (F), Proline (P), Serine (S), Threonine (T), Tryptophan (W ), Tyrosine (Υ) and valine (V) can be manipulated. This method can work with any protein and peptide. For example, membrane proteins (such as receptor proteins) on cell membranes, enzymes, transport proteins (such as ion channels and ion pumps), nutrition or storage proteins, contraction or movement proteins (such as actin and myosin), structural proteins Defense proteins or regulatory proteins (such as antibodies, hormones, and auxins). Protein or peptide antigens can also be manipulated. This method can handle any nucleic acid, including single-, double-, and triple-stranded nucleic acids. Examples of such nucleic acids include DNA (such as A-, B-, Z-type DNA) and RNA (such as mRNA, tRNA, and rRNA). This method can operate on any nuclear poverty. Examples of such nuclear fens include adenine nucleus, guanosine nucleus, cytosine nucleus, thymus 17 dense bite nucleus, and urine urinary nucleus. This method can also handle any nucleic acid. Examples of such nucleic acids include AMP, GMP, CMP, UMP, ADP, GDP, CDP, UDP, ATP, GTP, CTP, UTP, dAMP, dGMP, dCMP, dTMP, dADP, dGDP, dCDP, dTDP, dATP, dGTP, dCTP and dTTP. This method can handle any vitamin. For example, water-soluble vitamins such as vitamin B !, vitamin B2, nicotinic acid, vitamin B3, vitamin B6, vitamin IX, folic acid, vitamin B12, and vitamin C can be manipulated. Similarly, fat-soluble vitamins such as vitamin A, vitamin D, vitamin E, and vitamin K can also be manipulated. This method can handle any monosaccharide (whether it is D- or L-monosaccharide, and regardless of age: sugar or g with sugar). Examples of monosaccharides include trisaccharides (such as glyceric acid), -62-_. This paper size applies the Chinese National Standard (CNS) A4 specification (21 × 297 mm).

Line * 593683 A7 B7 V. Description of the invention (60 Tetrasaccharides (such as erythrose and threose), pentoses (such as ribose, arabinose, xylose, lyxose and ribose), hexoses (such as Allo Sugar, altose, glucose, mannose, gulose, idose, galactose, talose, and fructose) and heptose (such as sedoheptulose). This method can handle any lipid. Lipids Examples include triacylglycerols (such as glyceryl stearate, glyceryl palmitate, and glyceryl oleate), paraffin, and glycerol vinegar (such as phosphatidylethanolamine, lecithin, phosphatidylserine, phosphatidylinositol, and Phosphatidyl glycerol), sphingosides (such as sphingomyelin, cerebrolipids, and gangliosides), sterols (such as cholesterol and stigmasterol), and sterol fatty acids. Fatty acids can be saturated fatty acids (such as ten Dialkanoic acid, myristic acid, palmitic acid, stearic acid, arachidic acid, and arachidonic acid, and also unsaturated fatty acids (such as palmitoleic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid) ). For solid molecules that cannot be manipulated directly using physical forces, if A conjugate that can be directly manipulated by a suitable physical force can bind to a solid molecule. The operation of such a type of solid molecule can be achieved by operating a conjugate-solid molecular complex. Any can bind to a solid molecule with a certain affinity and specificity And conjugates that can be manipulated by appropriate physical forces can be used in this method. The conjugates can be cells such as animals, plants, fungi or bacterial cells; organelles such as nuclei, mitochondria 'chloroplasts, ribosomes, endoplasmic reticulum , Golgi, lysosomes, proteasomes, vesicles, vacuoles or microsomes; viruses, microparticles or their polymers or complexes. Cells, organelles and viruses described in section c can also be used as conjugates. The size of the microparticles used in this method is about 0.01 micrometers to 10 centimeters. Paper size Chinese National Standard (CNS) A4 size (210 X 297 public love) 63-

593683 A7 B7 V. Description of the invention () 61. Preferably, the particle size used in this method is between about 0.0 micrometers and several thousand micrometers. The particles used may be, but are not limited to, plastic particles, polystyrene particles, glass beads, magnetic beads, hollow glass spheres, metal particles, or particles with complex components or microstructures produced by various micromachining. Wait. The manipulated entity molecule can be bound to the surface of the conjugate by any known method. For example, a solid molecule can bind to the surface of a conjugate directly or through a linker arm (preferably a cleavable linker arm). Solid molecules can also be bound to the surface of the conjugate through a covalent or non-covalent bond. Alternatively, a solid molecule can be bound to the surface of the conjugate through specific or non-specific binding. Preferably, the linker between the solid molecule and the conjugate is a cleavable linker. For example, the linker can be cut by chemical, physical or enzymatic treatment. Similarly, a method for coupling and decoupling solid molecules and conjugates in a US patent entitled "METHODS FOR MANIPULATING MOIETIES IN MICROFLUIDIC SYSTEMS" (by Wang et al., Filed on August 10, 2000) can be used. The entity molecules that are best manipulated are essentially bound to the surface of the conjugate. Even better, the manipulated entity molecules are completely bound to the surface of the conjugate. Preferably, a method of manipulating a physical molecule by using a conjugate in a U.S. patent named "METHODS FOR MANIPULATING MOIETIES IN MICROFLUIDIC SYSTEMS" (by Wang et al., Filed on August 10, 2000) can be used without direct use The manipulation of physical molecules by physical forces. The method described above can also be used to operate the physical separation on non-wafer carriers. ______- 64-_ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) binding

Line, 593683 A7 B7 V. Description of the invention (π) 62 The same method can be used without using the above device to achieve the purpose of operating solid molecules. Accordingly, in another aspect, the present invention leads to a method for operating a physical molecule, the method comprising applying at least two types of Yangli force to the physical molecule, so that the physical molecule is operated by the physical force. The physical force can be a magnetic field force, a dielectrophoretic force, a sound field force, a light field force, and a mechanical force. For example, a combination of magnetic and dielectrophoretic forces can be used to manipulate solid molecules. In another example, a magnetic force and a sound field force are combined to operate a solid molecule. The manipulated entity molecule can be liquid or gaseous, or it can be in a liquid or gaseous medium, or a combination of the two. Preferably, the solid molecules are manipulated in a liquid medium. The liquid medium can be a suspension, a solution, or a combination of the two. Liquid media can be placed in any liquid container, and manipulation of solid molecules can also be achieved in these containers. Liquid containers include fluid cells, flasks, beakers, Erlenmeyer flasks, tubes (such as test tubes, Eppendorf tubes, centrifuge tubes, collection tubes, etc.), petri dishes, or multi-well plates (such as 96-well plates, 384-well plates, 480-well plates, 960 well plate, etc.). The structure for generating a physical force acting on a solid molecule may be separated from the liquid container, or may be connected or attached to the liquid container. The structure for generating a magnetic field force can be an electromagnetic coil structure, and a magnetic field can be generated by applying a current. The solenoid can be separated from the liquid container. In operation, the electromagnetic coil can be placed in the vicinity of the liquid container so that the magnetic field generated by exciting the electromagnetic coil can be coupled to the liquid container and manipulate the magnetic particles in the liquid container. Of course, the electromagnetic coil can also be connected to each other in the liquid container. In addition, the method used to generate the magnetic field _-65 -__ This paper size applies the Chinese National Standard (CNS) A4 specification (21 × 297 mm) 593683 A7 B7 V. Description of the invention („) The 63 method also includes the use of permanent magnets. This force permanent magnet can also be connected to the liquid container or separated from the liquid container. Other methods that can generate a sufficient magnetic field in the liquid container can also be used. The structure used to generate the dielectric electrophoretic force includes electrical wires and / Or other electrical conductors. These electrical wires or conductors have a specific geometric relationship with each other. The wires and / or other conductors may be independent of the liquid container. In operation, these wires and / or other conductors are placed in the vicinity of the liquid container In this way, the AC electric field generated by exciting the electric wires and / or other conductors can be coupled to the liquid container and manipulate the solid molecules in the liquid container. Of course, the electric wires and / or other conductors can also be connected to the liquid container. Other methods can be used to generate a sufficient electric field in the liquid container. The structure used to generate the sound field includes a defined source of sound waves or ultrasound. This Acoustic and ultrasonic sources can contain piezoelectric elements. Such piezoelectric elements can generate acoustic and ultrasonic waves when excited by an electric field. The acoustic source can be independent of the liquid container. In operation, the acoustic or ultrasonic source can be placed in the vicinity of the liquid container In this way, the sound waves or ultrasonic waves generated by the sound source (or excitation) can be coupled to the liquid container and manipulate the magnetic particles in the liquid container. Of course, the sound wave or ultrasonic source can also be connected to each other in the liquid container. The structure for generating a light field includes a defined light source and a light focusing device / apparatus. This type of light focusing device / apparatus may contain optical lenses, filters, and other optical elements. When a liquid container is placed in conjunction with this type of light focusing device In the special structure related to the device, the light focusing device / device can generate a light field in the liquid container and operate the magnetic particles in the liquid container. _- 66 -___ This paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) Staple

593683 A7 B7 V. Description of the invention () 64 The device for generating mechanical force includes a fluid pump and a valve. These pumps and valves can cause liquid flow in the liquid container, and the mechanical force generated by the liquid flow can act on and operate the solid molecules in the liquid container. In a specific embodiment, the method for manipulating a physical molecule employs at least two different types of physical forces that act sequentially on the physical molecule. In another entity molecule, the method used to manipulate the entity molecule uses at least two different types of physical forces. These forces act on the entity molecule simultaneously. In a specific embodiment, a plurality of entity molecules are simultaneously operated by using the operation method described above. For example, by using more than one type of physical force to operate multiple physical molecules simultaneously, at least two different physical molecules are operated by different types of physical forces. In other specific embodiments, multiple entity molecules are operated sequentially. For example, by using more than one type of physical force to sequentially operate multiple physical molecules, at least two different physical molecules are operated by different types of physical forces. In other specific embodiments, the manipulated entity molecules are in a mixture and the entity molecules are selectively manipulated by using the methods described above. In another specific embodiment, the manipulated entity molecules constitute a mixture and are operated as a mixture. The procedures described herein can be used to manipulate any type of solid molecule such as a cell, organelle, virus, molecule, or their aggregates or complexes. Cells can be animal cells, plant cells, fungal cells, bacterial cells, recombinant cells and cultured cells. Organelles can be nucleus and mitochondria _-67 -___ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm)

Body, chloroplast, ribozyme, vesicle ml Golgi, lysosome, protein :: capsule and microsome. Molecules can be inorganic molecules and their complexes. Helmet shock $ 钱 刀 4 Private worker " The archetype molecule is an ion, which can be a proton ion, a potassium ion, a magnesium ion, a calcium ion, a mouse ion, an iron ion, a copper turtle zinc ion, a manganese ion, Isahaya &, j ion ,, cobalt ion, iodine ion, molybdenum ion, syllium, ion dichromium ion, fluoride ion, silicon ion, tin ion, boron ionite temple. Organic molecules can be amino acids, peptides, proteins, lauric acid, oligonucleotides, nucleic acids, vitamins, monosaccharides, oligosaccharides, lipids, and the like. The operation method described here can transport, aggregate, enrich, concentrate, concentrate, capture, repel, suspend, separate, 'separate, divide, or make solid molecules linear or other Forms of movement. D. Physics and Forces Typical physics and forces, and the typical structure that produces these fields, are described in the following subsections. (I) Acoustic field force Acoustic field force refers to the force generated on a solid molecule such as a particle and / or a molecule through a sound wave field. It can also refer to the sound field radiation force. Sound field forces can be used to manipulate, for example, capture, move, and guide 'process particles in a liquid. The sound field force used for particle manipulation in ultrasonic standing waves can be used to enrich red blood cells (Yasuda et al, J. ". Yoshiho, 102 (1). ^ 4, 645 (1 997)), enriched at the micron level Polystyrene beads (0.3 μm to 10 μm, Yasuda and Kamakura, ie / · ρ / ζγ · 11X111: 1 77 1-1 773 (1 997)), enriched with DNA molecules (Yasuda paper size Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) 593683 A7 B7 66 V. Description of the invention (et a 15 J. Acoust. S oc · Am ,, 9 9 f 2): 1 7 4 R-ι 9 ^ (1 996)), and Shen Jiang cells (pui et al, II; 146-152 (1995)). Through the competition of static electricity and sound field radiation force, the separation of polystyrene beads of different sizes and charges has been Reported (Yasuda et al? J. Acoust. Soc. Am., £ ^ Χ_ 9 · 1 9 6 5_ 1 970 (1 996); and Yasuda et al., Jpn ^ j Appl installed P hy s., 3_5 (1 ): 3295-3299 (1996)). Further, the sound field force is used to manipulate mammalian cells as characterized by ion leakage (for red blood cells Yasuda et al? J. Acoust. Soc. Am. ^ 102 (1): 6 4 2-645 (1 99 7)) 'or antigen Little or no damage and damaging effects (for hybridoma cells, Pui et al, 1 52 (1 99 5)) A sound wave can be generated by a sound wave sensor such as piezoelectric ceramics such as pZT materials. Manufactured using piezoelectric materials Piezoelectric ceramic sensors generate an electromagnetic field when they change shape under the application of a mechanical force (piezoelectric or energy effect). Conversely, when an applied electric field creates a mechanical stress (electrostrictive or Motor effect). They convert energy from mechanical energy to electrical energy and vice versa. When an AC voltage is applied to the piezo sensor, vibrations are generated on the sensor and the vibrations are passed into the cavity containing the piezo sensor. Liquid in the body. For a multi-force operation wafer (multi-force operation wafer) contains an acoustic wave sensor, a cavity can be constructed so that the wafer forms the main surface of the cavity. When an AC signal of an appropriate frequency is applied to the sound field sensing On the electrode of the transformer, the alternating mechanical stress is generated in the piezoelectric material and transferred to the liquid in the cavity 593683 A7

In solution. Considering the position of the cavity structure, a standing wave is generated in the direction of sound wave propagation and reflection (such as the Z-axis). In a liquid, the change of the standing wave in space along the z axis can be expressed by the following formula:

Ap (z) = p0 sin (kz) c〇s (cot) where Δρ is the sound pressure at position z, A is the sound pressure amplitude, k is the number of sound waves (仏 / 乂, where λ is the wavelength), and z is the pressure The distance between nodes, ω is the angular frequency, and t is the time. In one example, the generation of a standing wave sound field can be formed by the superposition of a sound wave generated by an acoustic wave sensor forming the main surface of a cavity and a reflected wave of the main surface of another cavity. According to the theory developed by Yosakaka and KaWasima (Ac〇ustic RadiaUon presswe 〇na Compressible Sphere by Yosioka K. and Kawasima Y. in Acustica, Volume 5? Pages 167- 1 73, 1 9 5 5), The sound field force acting on a spherical surface in a static standing wave field is given by: 4ττ

Acoustic = —-yrzk Eacoustic A sin (2Az) where r is the radius of the particle, is the average sound field energy density, and A is a constant given by: 2Pp + Pm rm where An and the density of the particle and the medium, 4 and 6 are the compressibility coefficients of the particles and the medium, respectively. The compressibility factor of a substance is the product of the density of the material and the speed of sound waves in the material. Compressibility is sometimes called sonic damping. A is the acoustic wave polarization coefficient. When A > 0, the particles move to the pressure node (2 = 0) of the standing wave. _____-70-This paper size applies to China National Standard (CNS) A4 (210X297 mm)

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Line 593683 A7 B7 V. Description of the invention () 68 When A < 0, the particles leave the pressure node. More clearly, the radiating force of sound waves acting on particles depends on the distribution of the sound field energy density and the density and compressibility of the particles. When located in the same standing wave sound field, particles of different densities and compressibility will be subjected to different sound wave radiating forces. The radiating force of sound waves acting on particles with a diameter of 10 microns varies between < 0.01 and > 1 000 pN, depending on the dense skin distribution of the established sound field energy. The above analysis considers the radiating force of a sound wave on a particle in a standing wave of the sound field. Further analysis can be extended to the example of the sound field radiating force exerted on a particle in a traveling wave. In such an example, the particles in the cavity are subjected to a sound field radiation force different from the above formula. The following article will provide a detailed analysis of the sound field light force exerted on particles in traveling and standing waves: "Acoustic Radiation Pressure on a Compressible Sphere" by Yosioka K. and Kawasima Y. in Acustica, Volume 5, pages 167-173, 1955; and "Acoustic-Radiation force on a solid elastic sphere" by Hasegawa T. and Yosioka K. in Journal of Acoustic Society of America. The radiating force acting on particles can also pass through the sound waves of different examples produce. For example, “Acoustic radiation force on a small compressible sphere in a focused beam” by Wu and Du, J. Acoust · Soc. Am ·, 87: 997-1003 (1990)), or through Acoustic towns ("Acoustic tweezers" by Wu J. Acoust. Soc. Am ·, 89: 2140-2143 (1991)). The acoustic wave field established on a liquid can also introduce a time-independent liquid _____- 71 -___ This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 593683 A7 B7 V. Description of the invention (^) 69 Flow, which is called sonic flow. For example, such a sonic stream can be used in biochip applications or microfluidics applications that transport or pump liquids. Furthermore, such sonic liquid flow can also be used to manipulate molecules or particles in the liquid. Acoustic current depends on the distribution of the sound field and the properties of the liquid ("Nonlinear phenomena ', by Rooney JA in" Methods of Experimental Physics: Ultrasonics, Editor: PD Edmonds ", Chapter 6.4, pages 319-327, Academic Press, 1981; "Acoustic Streaming" by Nyborg WLM in "Physical Acoustics, Vol. II-Part B, Properties of Polymers and Nonlinear Acoustics, Chapter 11, pages 265-330). Typical example of a 'sound field force generating unit in a multi-force operation wafer Including, but not limited to: (1) A multi-force operation wafer using a piezoelectric material substrate. The electrodes are located on the two main surfaces of the piezoelectric material substrate, and sound waves can be generated by the multi-force operation wafer substrate. (2) one Multi-force operation wafer using piezoelectric material substrate. Electrode arrays are located on the two main surfaces of the piezoelectric material substrate, and multiple acoustic waves are generated by specific electrode arrays located on the multi-force operation wafer substrate. The electrode array may include a single optional Electrode unit or all connected electrode units. Acoustic waves described in US Patent No. 6,029,5 1 8 The column can be used for such purposes. (3) A multi-force operation wafer without using a piezoelectric material substrate. Although a piezoelectric film can be deposited on the substrate surface. Such a thin film can cover the entire substrate and serve as a source of sound waves. Alternatively, the film can be patterned so that a single optional sound wave can be formed. ____ -72 -__ This paper size applies to China National Standard (CNS) A4 specification (21〇 × 297 mm) binding

Line 593683 A7 B7 V. Description of the invention () 70 source or sound source connected together. The piezo film can be deposited on a part of the multi-force wafer or the entire surface of the multi-force wafer. (4) A multi-force operation wafer partially using a piezoelectric material substrate. Electrodes can be deposited on a portion of the substrate to generate a source of acoustic waves. (5) Active wafers or biochips made of non-piezoelectric materials that can produce specific types of main power on molecules or particles. However, a piezoelectric sensor (a single sonic source or an array of sonic sources) can be bound to an active biochip to form a multi-force operation wafer. In all the examples above, further changes to the sound wave generating unit may be included so that the focused sound beam can be used. For example, acoustic prisms can be used to focus acoustic waves (eg ·, "Nozzleless droplet formation with focused acoustic beams by Elrod et al, J. Applied Physics, 65 .; 3441-3447 (1989)) ° (II) electric field force electric field force Refers to the force applied to physical molecules (such as particles, cells, etc.) through an electric field. Electric field forces are sometimes also called electric and electric forces. Depending on the structure of the field and the nature of the physical molecules in the field, different types of electric field forces can be applied On solid molecules. One type of electric field force is a DC electric field force, which refers to the force generated on charged physical molecules (such as molecules, cells, particles) through a DC electric field or a low-frequency AC electric field (less than 1 kHz). DC electric field forces are It is called electrophoretic force. Another type of electric field force is dielectric electrophoretic force, which refers to the force generated on charged or neutral entity molecules through a non-uniform electric field. Electric field _-73-_ This paper size applies to Chinese national standards (CNS ) A4 * grid (210 X 297 mm)

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593683 A7 B7 V. Description of the invention (7l) Must be non-uniformly distributed in the amplitude or phase of the electric field, and the solid molecules must have different dielectric properties from the surrounding medium so that the solid molecules can be electroded in the electric field, so that Generate non-zero dielectrophoretic forces on solid molecules. There are two types of dielectrophoretic forces, the first type is a conventional dielectrophoretic force, and the second type is a traveling wave dielectrophoretic force. A detailed description of these forces will be provided later. 11 · A DC electric field force A DC electric field force refers to the force generated on a charged entity molecule (such as a molecule, a cell, or a particle) through a DC electric field or a low-frequency AC electric field (less than 1 k Η z). DC electric field forces are caused by the interaction of an electric field with the electrostatic charge on a solid molecule, such as a particle, molecule, or cell. The DC electric field force acting on a particle in the applied electric field foot is given by Fe = QpEzaz where ... is the effective charge on the particle. The direction of the DC electric field force on the charged particles depends on the polarity of the particle charge and the direction of the applied electric field. The DC electric field for operating a solid molecule such as a molecule or a particle in a multi-force manipulation wafer-based cavity or a multi-force manipulation wafer-based device can be transmitted through the manufacturing and multi-force manipulation wafer (multi-force wafer) or integrated and The cavity or the electrode or micro-electrode unit of the multi-force operating wafer-based device is generated by applying a direct current signal. Typical examples of electrodes or microelectrodes fabricated on a multi-force operation wafer include, but are not limited to, the following examples: (1) A single selectable microelectrode array can be used. Each unit can be _-74-_ This paper size applies to China National Standard (CNS) A4 (210X297mm) binding

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Applying a suitable DC signal allows the field distribution to be used for molecular and micro :, and to adjust the DC current ^ ^ ^ two important electrostatic operations. Different pole sizes / shapes or dimensions of the electrode array can be used (2) All units or some units can be connected. An array of microelectrode units can be removed for use. Different electrical rescue sizes / shapes are available early. Dimensions of the shape or pole array can be μ. ™, called “叩”, “multi”. To apply a DC electric field with uniform or uneven sentences. 11 · Β Dielectrophoretic Force (Dielectrophoresis) The force generated by the uniform electric field on the band. It + 4 3 + A + or the neutral penetrating molecule produces an electric field to interact with the polarized charge caused by the two fields and the non-uniform two: generated by the two houses. The polarized charge is caused on the solid molecule. This is due to the difference in dielectric properties between the Ca% and the medium in which the particles and the particles are suspended. ^ 1 and 1 are all wave electric field attacks. In the time domain, it can be expressed as ^ (0 = Υ ^ Εα ^ ο ^ {2τφ + φα) αα " The unit vector of (α ~ χ, y, ζ) 笛 in a Cartesian coordinate system, where 0 and% are the amplitude and phase in three field coordinates. When a cell is in such a non-uniform electric field (&Amp;. and / or% varies with position), a net dielectrophoretic force acting on the cell due to field and field-induced dipole electrical interactions. By Wang et al in article "An unified theory of dielectrophoresis" and travelling-wave dielectrophoresis by Wang et al., J. D., 27: 1571-1574 (1 The formula of the dielectrophoretic force given by 994) is: F = 2nsmrz (Re (/ CA / + Im (/ CM) (^ 2〇V φχ + + £; 0 V φζ)) CNS) A4 specification (210X297 mm) 593683 A7 B7 5. Description of the invention (Number radius '~ is the dielectric constant of the particles suspended in the medium', "RMS amplitude. The coefficient" Seven 乂 "/ («) is the dielectric number (Also called: la ius_Mossotti coefficient.) The complex dielectric Γ / d dielectric polarization coefficient is determined by the frequency of the applied field 1p) and the conductivity of its suspension medium (~). Sections, #

Swimming force and traveling wave dielectrophoresis force. Synchronization of conventional dielectrics $ ,, σ, and J is related to synchronization (by pre 4 :) 2: The force is related to the gradient of the polarized field strength caused by the field (▽ (). The coefficient,) has' = 2 , Dielectrophoretic force and field-induced Yanghua's heterophasic part (by M / cm) member response), the imaginary part of the mesh number y · complex is related to the field phase gradient (%, ▽%, ▽%). The term Im (/ cM) is sometimes called the traveling wave dielectric electrophoresis factor. : Order (" //. 5. / j Conventional Dielectrophoretic Force

The reed gauge pen force refers to the force on the component caused by the non-uniform distribution of the AC electric field strength. In the literature, conventional dielectrophoretic forces are sometimes referred to simply as dielectrophoretic forces. This simplification as a term should be avoided for clarity. For example, An unified theory of dielectrophoresis and travelling-wave dielectrophoresis by An unified theory of dielectrophoresis and travelling-wave dielectrophoresis by Wang et al. J. P / zys. Z). But 〆. Phys. 27: 1571-1574, ( (1994)) and "Non-uniform spatial distributions of both the magnitude and phase of AC electric fields determine dielectrophoretic forces by Wang et al.? Biochim ___- 76- This paper size applies the Chinese National Standard (CNS) A4 specification (210 x 297 (Mm) 593683 A7 B7 V. Description of the invention (5 / 〇 户 / 2: ^ ”Price 7, 1243: 185-194 (1995),“ Dielectrophoretic force ”as a general term includes conventional dielectrophoresis and traveling waves Dielectric electrophoresis. Conventional dielectric electrophoretic force refers to the force generated on a component by the non-uniform distribution of the field strength of an alternating electric field. Phase non-uniform distribution). A conventional dielectrophoretic force acting on a particle of radius r is determined by the electric field of the non-uniform field strength given by Is the field strength's RM S value, and is the dielectric constant of the medium. The equation of this conventional dielectric electrophoretic force is the same as the general calculation formula of the dielectric electrophoretic force. The factor is the particle polarization factor, which is given by Out,

Xdep ~ ε — ε "RE" refers to the real part of a complex number. The symbol < = heart- is the composite dielectric constant (particle X = p, medium X = m). parameter. . with. . These are the effective dielectric constant and the particle conductivity. These parameters can often be interdependent. For example, a typical biological cell will consist of frequency dependence, effective conductivity and dielectric constant, at least because of the polarization of the plasma membrane of the cell. The above equation of conventional electrophoretic force can also be written as P′ΟΕΡ = 2πεηιΓ3χΟΕΡΥ2 (νιρ) where P (X, y, ζ) is a square field distribution excited by a unit voltage on the electrode, and V is the voltage used. Particles such as biological cells have different dielectric properties (such as the above-mentioned dielectric constant and conductivity) and will be subjected to different dielectric electrophoretic forces (conventional and traveling-wave dielectric electrophoresis. This paper applies Chinese National Standard (CNS) A4 specifications (210X 297 mm) -77- 593683 A7 ___ B7 V. Description of the invention () 75 force). For the electrophoretic operation of a particle, a conventional force acts on a particle with a diameter of 10 micrometers, which can vary between 〇 · 〇1 and 100 〇〇〇ρρΝ. A non-uniform electric field can be established based on a multi-force In the wafer handling chamber, an AC signal AC is applied to the micro-electrodes integrated in the structure of the wafer for multi-force manipulation (multi-force wafer). A variety of electrode component arrays and electrode arrays can be used. A large number of dielectric electrophoretic electrodes reported in the literature can be used 'including mutual offset castle electrodes, multiple electrodes, spiral electrodes 0 1243: 185-194 (1995),'; "Electrode design for negative dielectrophoresis, by Huang and Pethig, Meas. Sci. TechnoL, 2_: 1142-1146 (1991) ";" Positive and negative dielectrophoretic collection of colloidal particles using interdigitated castellated microelectrodes by Pethig et al.? J. Phys. D: Appl Phys., 25: 881-888 (1992) ''; “Three-dimensional electric field traps for manipulation of cells-calculation and experimental verification by Schnelle et al. 5 Biochim. Biophys. Acta., 1157: 127-140 (1993)”, “A 3-D microelectrode system for handling and caging single cells and particles, by Mliller, et al.? Biosensors and Bioelectronics, M: 247-256 (1999) ,; "Dielectrophoretic field cages: technique for cell, virus and marcromolecule handling, by Fuhr et al.5 Cellular Engineering., Autumn, pages 47-57 (1995) ^; "Electrocasting-formation and structuring of suspended microbodies using AC generated field cages, by Fiedler S. et al. 5 ____- 78 -__ This paper size applies to China National Standard (CNS) A4 (210X297 mm) 593683 A7 B7 V. Description of the invention () 76

Microsystem Technologies., 2: 1-7, (1995) ''; “Dielectrophoretic sorting of particles and cells in a microsystem, by Fiedler et al.? Anal · Chem., 70: 1909-1915 (1998), can be With a single-gated microelectrode array, each element can apply an AC signal to create a non-uniformly distributed electric field, and can be adjusted for dielectric manipulation of molecules and particles. Electrodes of various sizes and geometries or various sizes All electrode arrays may be used. In microelectrode element arrays, all or some of them are connected to each other, and various electrode geometries, various electrode sizes, and various electrode array sizes may be used. Electrode elements can cover (II.B.2) Traveling wave dielectrophoresis force Traveling wave dielectrophoresis force refers to the force that a solid molecule (particle or molecule) is subjected to in a traveling wave electric field. The characteristic of the wave electric field is that the phase values of its AC electric field components are unevenly distributed. Here, we analyze the traveling wave dielectric electric field of an ideal traveling wave electric field Dielectric electrophoretic force F acting on particles of radius r in a traveling wave electric field £ = jEe ° St2; r (/ iz / A ())> x (for example, when an electric field in the X direction runs in the z direction) F2-

^ Human A a, —— IX L. rt ^ DEP-: r hTWD11 'az ,,, JF tw The dielectric electric ice can be given by the formula ^, where E is the field strength, is the dielectric constant of the medium, < _ Is the polarization factor of the particle

/ ♦ * N 广 _ £ P ~ £ m btwDEP ~~ i number, Ctto is given by the following formula (~ + ~ ”, where I m refers to the imaginary part of the complex number, and the symbol ~ = 心 n / 2 # 是 （ Particle χ ^ ρ and medium _-79 -__ This paper size is applicable to China National Standard (CNS) A4 specification (210 X297 mm) 593683 A7 B7 77 V. Description of the invention (x = m) Composite permittivity, parameters, Now I and P are the effective dielectric constant and the electrical conductivity of the particles. These parameters are based on the frequency. For example, biological cells and other particles with different dielectric properties (as defined by the dielectric constant and electrical conductivity) will show Diverse electrophoretic forces of <U. Traveling wave dielectric electrophoresis of particles (including biological cells) is also described at first. Travelling wave dielectrics loaded on a particle with a diameter of 10 microns (+ ,, 丄 J) 丨 The electric ice force can be changed between 〇 · 〇i-ΙΟΟρΝ. The traveling wave dielectric electric field can be applied to the micro-electrodes connected to the multi-force operation chip structure by passing an appropriate AC signal. Built in a reactor or instrument based on multi-force operation of the wafer. ^ In order to generate a traveling wave field, it is necessary to At least three types of electrical signals with different phase values are used. One method is to apply four linear, parallel signals (0, 90, 180, and 270 degrees) to four linear, parallel electrodes on the wafer surface. In this way, the four electrodes form a basic, repetitive unit. In most cases, at least two such units need to be close together. 'They can generate a traveling wave electric field on or around them. Another method is like As described in the document Dielectrophoretic manipulation of cells using spiral electrodes by Wang et al.3 Biophys. J.3 72: 1887-1899 (1997) ", four orthogonal signals are applied to four parallel spiral electrode elements by applying To generate a traveling wave electric field. As long as the electrode elements are arranged in a certain spatial sequence, a continuous phase signal can be applied to generate a traveling wave electric field around the electrode. Specific traveling wave dielectric electrophoretic electrodes include four parallel linear spiral electrodes, respectively. 'Parallel linear electrodes, spiral electrodes. See the literature for details (^ Dielectrophoretic manipulation of cells using spiral electrodes) National Standard (CNS) A4 specification (210X297 mm) -80- 593683 A7 B7 V. Description of invention (%) by Wang et al ·, Biophys. J., 72: 1887-1899 (1997) ,; "Dielectrophoretic Manipulation of Particles by Wang et al, IEEE Transaction on Industry Applications, 33 (3): 660-669 (1997) "," Electrokinetic behavior of colloidal particles in traveling electric fields: studies using yeast cells by Huang et al, J. Phys D: Appl. Phys "26: 1528-1535", "Positioning and manipulation of cells and microparticles using miniaturized electric field traps and traveling waves. By Fuhr et al., Sensors and Materials" 7: 131-146 "," Non -uniform spatial distributions of both the magnitude and phase of AC electric fields determine dielectrophoretic forces by Wang et al.? Biochim Biophys Acta., 1243: 185-194 (1995) "Compared with other types of physical forces, traveling wave dielectrics Electrophoretic force has a unique property, that is, it can be in a one-dimensional or two-dimensional space (along a certain orbit line on a straight or flat surface). Transmitting particles. For example, a multi-force operation wafer can include multiple units (or reaction centers), and traveling wave dielectrophoretic forces can be used to transport substances (such as particles or molecular-particle complexes) between these units.

Traveling-wave dielectrophoretic forces can also be used to control, switch, and guide particles through particle switches or particle switches, like the one called "METHODS FOR MANIPULATING MOIETIES IN MICROFLUIDIC SYSTEMS," (by Wang et al., Filed on August 10, 2000) The same is described in the U.S. patent. The various electrode structures in the patent can be used in multi-force manipulation wafers and used to operate and control particles and substances with traveling wave dielectric electrophoretic force. For example, in a specific particle switch, it At least including the ability to produce separately ....- _- 81-This paper size applies to China National Standard (CNS) A4 (210X297 mm) binding

A7

φ ab ^ Three sets of electrodes that carry the traveling wave dielectric electrophoretic force of the particles. This private pole has independent power from each other, and these tracks can communicate with each other at a common junction to make the traveling wave dielectric. Electrophoretic forces can transport particles from one orbit to another. (111) Magnetic field force Magnetic field force refers to the force that is exerted on solid molecules such as particles due to the existence of an electric field. Generally speaking, if there is sufficient magnetic field force to manipulate particles, the particles must be sufficiently magnetized or polarized. Let's consider an example of a typical magnetic particle composed of a paramagnetic substance. When this particle is placed in a magnetic field _ ^ piXp-Xn) —, the particle will produce a magnetic dipole only, where 6 is the particle The volume, the center, and the Xn fraction are the magnetic susceptibility of the particle and the surrounding medium, the magnetic permeability of the medium, and the magnetic field strength. The magnetic pre-force applied to the particle can be obtained through $, indirect magnetic dipoles, and magnetic field gradients, where the symbols “·,” and, respectively, refer to the results of the dot product and the gradient. It is obvious whether there is a magnetic field force added to the The particle depends on the magnetic susceptibility between the particle and its surrounding medium. Generally, particles are suspended in a non-magnetic liquid medium (its magnetic susceptibility is close to zero), so magnetic particles must be used (its magnetic susceptibility is much greater than 0). When the magnetic field force and particle attachment force reach equilibrium, the particle velocity vparticle can be given by ^ magnetic particle — ^ π% where r is the radius of the particle 'η m makes the surrounding medium dry. Therefore,' to get enough For large magnetic operating forces, the following factors must be considered: (1) the magnetizability of particles should be optimized, (2) the magnetic field strength should be maximized, ____- 89-This paper size applies Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 593683 A7 B7 V. Description of the invention () 80 (3) The field strength gradient of the magnetic field should be optimized. A magnetic field can be generated by applying a current to a micro-electromagnetic element in a reactor based on a multi-force operation wafer. each A micro-electromagnetic component can generate a corresponding magnetic field according to the DC or AC current passed. An electromagnetic component can be a ring wound by a wire or a coil wound around a magnetic core. Many types of electromagnetic components are already in The patent No. 09/3 99299 filed on September 16, 1999 is described in the patent, which can be integrated by referring to all its references. Examples of other electromagnetic components for multi-force operation of wafers Including but not limited to the following: Ahn, C., et al., J. Microelectromechanical Systems. Volume 5: 151-158 (1996); Ahn? C.? Et al. 5 IEEE Trans. Magnetics. Volume 30: 73 -79 (1994); Liakopoulos et al.? In Transducers 97, pages 485-488, presented in 1997 International Conference on Silid-State Sensors and Actuators, Chicago, June 16-19, 1997; US patent No. 5,883,760 by Naoshi et al .. As a specific example, a multi-force operation chip can be composed of an array of single-point selectable electromagnetic components. These components are arranged or arranged in a certain order. So that when one, some or all of the components are applied with voltage (or magnetization), it can generate the ideal magnetic field distribution and generate magnetic field force for operating magnetic particles. However, the multi-force operation wafer may also be composed of a plurality of interconnected electromagnetic components so that these components can be turned on or off in synchronization. Of course, the multi-force operation chip may also include only one electromagnetic element capable of generating a magnetic field after being energized. Operations on magnetic particles include linear motion, focusing motion, and defamatory motion ____ This paper size applies Chinese National Standard (CNS) A4 specifications (210X 297 mm) 593683 A7 B7 V. Description of the invention () 〇1 and so on. The movement of magnetic particles in the field again is called "magnetophoresis". Theories and examples of magnetophoresis for cell separation and other uses can be found in many literatures. (Such as: Magnetic Microspheres in Cell Separation, by Kronick, PL in Methods of Cell Separation, Volume 3, edited by N. Catsimpoolas, 1980, pages 115-139; Use of magnetic techniques for the isolation of cells, by Safarik I. And Safarikova M.? In J. of Chromatography, 1999, Volume 722 (B), pages 33-53; A fully integrated micromachined magnetic particle separator, by Ahn CH et al., In J. of Microelectromechanical systems, 1996, Volume 5, pages 151-157) (IV) Light field force Light field force refers to the force that is exerted on solid molecules such as particles or cells due to the existence of a light intensity gradient. It is also sometimes called light light force. When a particle is placed in a non-uniform light intensity field, the radiation force is applied to the particle. The magnitude of this radiation force depends on the particle size, light intensity distribution, particle refractive index, and surrounding media. Many literatures describe this force in detail ("Laser trapping in cell biology, by Wright et al., In IEEE J. of Quantum Electronics, 1990, Volume 26, pages 2148-2157"; "Laser manipulation of atoms and particles, by Chu S. in Science, 1991, Volume 253, pages 861-866 "). When a material with a refractive index different from that of the surrounding medium (such as particles) is placed in the gradient light field, the light field force is called the gradient force. When light passes through a polarizable material, it creates an instantaneous dipole. These dipoles interact with the gradient of the electromagnetic field. When the refractive index of these materials is greater than the surrounding medium, a ___ &gt;-84 ~ _. This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 593683 A7 __ B7 V. Description of the invention () 82 Force directed at the bright area of light. Conversely, when the refractive index of a substance is smaller than that of the surrounding medium, it will be subjected to a force that pulls it toward the darker areas of light. Light field forces or radiative forces have been used in optical clamps to aggregate, capture, float, and manipulate particles. Optical clamps are generally single-beam gradient laser tubes. Theories and examples of various biological applications of optical forceps have been described in detail in many literatures (eg "Making light work with optical tweezers, by Block S · M ·, in Nature, 1992, Volume 360, pages 493-496 "; Forces of a single-beam gradient laser trap on a dielectric sphere in the ray optics regime, by Ashkin, A., in Biophys. J., 1992, Volume 61, pages 569-582"; "Laser trapping in cell biology, by Wright et al., in IEEE J. of Quantum Electronics, 1990, Volume 26, pages 2148-2157 ";" Laser manipulation of atoms and particles, by Chu S. in Science, 1991, Volume 253, pages 861- 866 "). In order to generate light field light in a reactor or instrument based on a multi-force operation wafer, a light field and / or an intensity field need to be generated, such as built-in optical elements and arrays and external devices that can operate the wafer through multi-force operation Light source or built-in photoelectric element and array through multi-force operation chip and electric signal source of external structure. In the former case, when the light generated by the optical signal source passes through the built-in optical elements and arrays, the light is processed by these elements / arrays through reflection, focusing, interference, etc., and the light field is generated in the area around the multi-force operation wafer. In the latter case, when the electrical signals generated by the external electrical signal source are absorbed by the built-in photoelectric elements and arrays, they will generate light, and a light field is generated around the multi-operated wafer. Other methods can also be used to make the multi-manipulation wafer produce light ----- 85-_ This paper size is applicable to China National Standard (CNS) A4 (21〇 X 297 mm)

83 field ’, which produces a light field force. Optical errors can be used to apply light field forces to the instrument of the present invention. Various structures can be used to operate the wafer or the instrument with multiple forces to facilitate the introduction of single or multiple elements into the instrument or multi-force operated wafer-based reactor. Optical forceps. Single optical forceps can be used at specific locations on the instrument to manipulate, attract, or repel particles, molecules, or molecular complexes. Multi-optic clamps, on the other hand, can be used in many locations on the instrument. Light field force or light light force can be used to locate, control, and operate particles or molecules. For example, particles can be captured by a light intensity field determined by an optical clamp 'or light-guided or converted by a light field generated by an optical clamp array. (V) · Mechanical force Mechanical force refers to the force on a solid molecule due to the existence of a velocity field in a certain medium, in which the solid molecule can be suspended, dissolved or positioned. We consider the case when a spherical particle with a diameter of% and a density of 6 is placed in the velocity field. The velocity of a particle can be given by P _ \ ^, *: ^ r (w%) + Λ Particle relaxation time r = _4 ^ _, which is defined by the formula: Re〃 where is the viscosity of the medium and C is the resistance D. JU- ~ Up \ DpPm

Rp ------ coefficient, P is the Reynolds constant of the particle, which is defined by the following formula ^ where A is the density of the medium, and the first term on the right side of the above equation is a summary of the S t o k e s resistance acting on the particle. As is known to all, the Stokes force applied to spherical particles can be calculated by the following formula: heart --- ~ = 3milk heart-\) ~, St () kes force is the force added to the particles due to the relative velocity between the media. Because ___- 86- This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) 84593683 A7 B7 Five invention description (this, when a particle (or various other types of Moiety) is placed in the velocity field, A mechanism (Stokes resistance) will be applied to the particles to move them at the same speed as the speed of the medium in which they are located. Such a mechanical force can affect the position, velocity, and other dynamic behavior of the particles, and can be used The velocity field of the medium refers to the velocity distribution of the moving medium. The velocity of the medium can be given by the following equation: (dum ^ \ Γ η Ρ〇 [^ Γ + = + Pof +-P〇g βτ (Τ -T0) + ^ Cncn L n Eight is the density of the medium at temperature r, t is the speed of the medium, p is the pressure inside the medium, 7 is the weight on the medium, f is the acceleration vector of gravity, and the outside is the temperature The volume expansion coefficient related to the change, I is the volume expansion coefficient related to the type of medium. In the above parameters, except for and-, all are functions related to their position in the medium. According to the above equation, several different methods can be used. To change the velocity field of the medium. (1) change the pressure in the medium, (2) apply volumetric force to the medium, (3) change the temperature or temperature gradient of the medium, and (4) change the concentration of various media. Here we analyze several Several methods that can generate a velocity field and thus a mechanical force acting on real fa molecules in the medium. (V · 1) The mechanical force generated by thermal convection establishes a temperature gradient in the medium. According to the above equation, such a The temperature gradient will cause the medium to flow, thus forming a velocity field in the medium. The flow of this medium is partly caused by thermal diffusion that tends to reach the thermal equilibrium of the medium. In addition, for aqueous solutions, the temperature distribution of the solution tends to correspond to the corresponding The density distribution is consistent, and such a density distribution is also the same as the paper size. The Chinese national standard (CNS) A4 specification (210 X 297 public love &quot; ------- ^ 593683 A7 B7) V. Description of the invention () 85 It can cause the flow of the medium to reach equilibrium. The flow of the medium caused by the temperature gradient is sometimes called thermal convection. Thermal convection can occur on a relatively large scale. In the medium, it can be used to promote the mixing of liquids, and it can also be used as a force to bring molecules from a remote place to a specific reaction position. In the present invention, by installing heating and / or cooling in a multi-force operation wafer structure The element can also build a temperature gradient profile in a multi-force manipulation wafer-based reactor or instrument. This heating element can be a simple Joule heating resistor that can be processed into a multi-force manipulation wafer Instead of thin conductive films such as those with a limited length and installed in a specific location. Similarly, heating resistors can also replace those miniature wires (with a certain length and installed in a specific location) wound with insulators. These heaters must have a special impedance. Taking a heater with an impedance of 10 ohms as an example, a current of 0.2A will produce 0.4W joules of thermal energy. If this coil is installed in an area less than 500 square microns Then it will effectively raise the local temperature and generate a temperature gradient in the medium. Similarly, the cooling element may be a semiconductor Peltier element that can cause a drop in ambient temperature when an electric current is applied. In a specific example, the multi-force operation wafer can be provided with an array of optional heating elements. These elements must be placed in a certain order or structurally designed so that when each, some or all of the elements are A temperature gradient can be established at startup to produce ideal thermal convection, and thus a velocity field can be established in a medium introduced into an instrument composed of a multi-force operating wafer. For example, when a heating element is activated or energized, the temperature rise of the adjacent medium around this element will generate a local temperature gradient, resulting in _-88-_ This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm)

Thermal convection. In another example, the multi-force operation chip may include a plurality of interconnected Canadian military switches 々 门 祥 ..., so as to enable these units to be opened simultaneously in two instances of 'multi-force operation' The chip may contain only one 'when the current is applied, it can raise the local temperature, and produce in the medium. Similarly, a multi-force operation wafer may contain an array of individually selectable cooling elements, or a single cooling element. (V.2.) Mechanical forces due to changes in medium pressure can produce pressure gradients in the medium. According to the equation of the velocity in the medium, ', the pressure gradient or pressure change in the medium will cause the medium to flow and generate a velocity field. The physical molecules f-body molecules in the velocity field will be affected by physical or mechanical forces. The force manipulation wafer 5? Is made into various structures so that various ideal pressure gradients or pressure changes can be obtained. For example, the multi-power operation chip has a built-in micro pump, which can generate a pressure gradient in the medium when the pump is operating. Therefore, this kind of pressure gradient can cause the flow of the medium (for example, J shell is transported a certain distance in an instrument), and the solid molecules in the medium will receive mechanical force and be operated by this force. Another example might be an array of micromachined valves / capillaries integrated on a multi-force operation wafer. These valves / capillaries can be moved or controlled by physical devices on the periphery. For example, 'these capillaries or valves are covered with functional materials such as temperature-sensitive materials, surface storage alloys, etc., and they can be further connected to the external source 4 or coupled with external physical forces, they can cause Capillary officer or valve movement. When one or more of these valves or capillaries in the medium move, a pressure change or pressure gradient can occur. This paper is suitable for financial standards (CNS) A4 size (X 297 mm)-593683 A7 ______ _______ B7 V. Description of the invention () 87 pressure gradients can cause movement of the medium near these valves or capillaries' Due to the generation of the velocity field in the matter, the solid molecules in the medium are subjected to mechanical forces. In the present invention, various internal structures can be adopted. For example, an electron tube (or microelectron tube) or pump (or micropump) can be connected to the reaction chamber of an active wafer ', which will generate one or more physical fields and apply one or more physical forces to the physical molecules. These tubes or pumps can be operated to produce a pressure gradient or pressure change in the reaction chamber medium and cause the medium to flow. Therefore, these internal structures of the instrument (including these structural elements and reaction chambers) can be used to generate velocity fields and act on mechanical forces of solid molecules. (V · 3 ·) Mechanical force due to volume force acting on the medium The velocity field in the medium * can be generated by the volume force applied in the medium. For example, the surface of a substrate of a Xi Li operation wafer is processed to have a special surface charge or surface charge distribution. This substrate can be used with other structures (such as coverslips, rings, spacers) to form a mud pool with various input and output ports. When a liquid medium is input into such a fluid pool, an external electric h source can apply an electrical signal in a certain direction, and the electric field generated by this voltage can be related to the substrate (and / or other surfaces of the fluid pool). (Charge) The interaction of surface charges creates a fluid motion in the medium. The velocity distribution generated in the fluid pool is a velocity field. This velocity field can then be used to generate forces that operate on solid molecules. The multi-force operation wafer and instrument in the present invention may include other internal structures capable of generating a velocity field and applying a mechanical force to a solid molecule. &amp; Zhang Jiu Shi Shi Cai § Seasonal Material Millimeter p 593683: 91- Description of the invention ((VI) Physical molecules manipulate other physical forces of physical molecules In the present invention, a wafer or a device based on such a wafer, The instrument can also apply various physical forces not mentioned above. The inventor of this patent 2 envisages applying a variety of physics in a multi-force operation wafer structure. These forces can be used for external control and use of external energy sources, and can be used to see molecules in the body. E. Examples of wafers and instruments

The instrument or chip in the Ming (such as a multi-force operation chip, MFC) can be similar to a force-generating element or structure, such as an electromagnetic element that generates a DC electric field force and an electrode field force. The combined form of the two forces includes, but is not limited to, a sound field force plus an electric field force (the electric field force may be a DC electrophoretic force of a DC hybrid I and a traveling wave dielectric electrophoretic force% θ S hanging field force plus a light field force; Sound field force plus mechanical: ° Magnetic% force 'Sound force plus mechanical force; Electric field force plus light field force · Two force envelopes plus first% force; Light field radiation force plus mechanical force. Force force, magnetic field force, sound field Force, mechanical force, Qian Liru, pen field force, the total number of private forces is 2 ". If we divide the electric field force into three types," field force, conventional dielectrophoretic force, traveling wave Jitai two soil straight / Guadian Medium type of force: sound field force, magnetic field skin 2 :: Force force ': There will be the following seven forces, traveling wave dielectrophoresis force, mechanical force 1, and hanging gauge dielectrophoresis first% force, a combination of these forces There are 2 * 1 types. The instrument or chip in the present invention (for example, includes three types of force-generating components or structures, such as production and film, paper). ^ .A4 binding 89895683 5. Description of the invention (Part or structure, electromagnetic component that generates traveling wave dielectrophoretic force Combination of three forces, generating magnetic term force / conventional dielectrophoretic force / magnetic field force ;: two, but not limited to 'sound field force; sound field force / traveling wave dielectrophoretic force / mechanical: force / DC electric field force / Magnetic field force / light field force; sound field force / mechanical force / magnetic field force ^ force / conventional dielectric electric field force; sound field force / DC electric field force / optical field force, mechanical field force / magneto-mechanical force, · He Lita group. Opposite. Sound field force / DC electric field force / 夂 八 刀, and 口. For the five types of two forces, sound field force 'mechanical force, light field Λ force, magnetic field c5 ^ 1! 113 = 10 You Yeli, the total number of joint forces is ... 3 "1. If we divide the electric field force into three types, such as mu, cloud two: force, conventional dielectric electrophoretic force, and traveling wave medium: seven types of Force ·· Sound field force and magnetic field have the following forces, traveling wave dielectric electrophoresis force, mechanical force, light = force electrophoresis, 3-7 * 6 * 5 ^ You Yeli, the combination of these forces is e7 = F ^ r-5 · kinds: instruments or wafers in the invention (such as: multi-force operation wafer package: four types of force-generating elements or structures, such as generating dimensional forces ... Electrode element, = electromagnetic element, heating element that generates mechanical force. Four; The formula includes: sound field force / traveling wave electrophoretic force / magnetic field force / light field force, in various possible combinations, for five kinds of forces such as ·· Electric field force, ^ field force, acoustic field force, mechanical force, light field force, the total number of joint forces is g :: We divide the electric field force into three types, such as DC electric field force, conventional: electrophoretic force, traveling wave Dielectric electrophoretic force, there will be the following seven types of force ^ Sound field force, magnetic field force, electric field force, conventional dielectric electrophoretic force, traveling wave dielectric This paper standard is applicable to the national standard T4 (CNS) A4 (redundant) _Χ297 公 爱 -92- V. Description of the invention () 90 7 • Mechanical force, light beep force, the combination of these forces is 7 Τ *? Ϊ 2 ^ 7 = 35 2 the instrument or chip in the Ming Dynasty (such as: Force operation of the wafer, mfc) can also depend on the 711 pieces or structures that generate forces at four betas. The number of combined forces depends on Li !, the number of! N and the number of forces N used in the instrument or chip. In this case, 'different types of forces may be generated / caused by the same kind of generating force; Therefore, the structure or structure that generates different kinds of forces can be a whole, for example, the same electrode element or junction ::: is excited to generate a DC electric field force and a conventional dielectrophoretic force to act on the manipulated molecules and particles. In the design, unless otherwise specified, the internal structure of the force-generating element or structure of the instrument, or in the present invention they are always built-in or built on a substrate that is a wafer and an instrument-part. The type of force can be used in the required order and conditions: Xishao signal source material uses some force-generating components or structures. For example, the order of the forces generated by a sound field force, a conventional dielectrophoretic force, and a magnetic field force element or a junction 'for a multi-force operation chip' may be: first, a household element or structure is maintained to maintain a specific length Time so that all the particles can be manipulated 'Second, the magnetic element or structure is activated—determining :: as magnetic particles', and finally the dielectric element or junction is activated: 疋 The dielectric characteristics of the particles. Make the special paper size applicable and the house standard specifications (2 breasts 97 cm -93- 593683 A7 B7 V. Description of the invention (91) Because there are many different types of multi-force operation wafers or devices, instruments based on multi-force operation wafers, Specific examples of the system, we describe some specific examples of multi-force operation wafers below. These descriptions may naturally extend to the device or instrument based on multi-force operation wafers in the present invention. (A) Multi-force operation wafers include multiple structural units A multi-force operation wafer contains multiple structural units that form an array of cells. Each unit contains various structural elements that can generate different types of physical forces. For example, a microelectromagnetic element or structure, a microelectrode structure or element A micro-electromagnetic element or structure and a piezoelectric element or structure can be integrated to form a basic unit. The micro-electromagnetic element or structure can be activated to generate the required magnetic field, and the micro-electrode element can generate a suitable non-uniform electric field after being energized. , A piezoelectric element or structure can generate a sound field when energized. In another example, a micro An electromagnetic element or structure, a microelectrode element or structure, a piezoelectric element or structure, and a heating element can be integrated to form a basic unit. When a multi-force operation wafer contains multiple units and these units form a cell array, each unit It can be basically the same between them. These units can be integrated on a chip in an orderly or disorderly manner. These units can be gated one by one so that each type of component in each different unit can be selectively identified, Therefore, any productive element in any unit can be selectively found at any time, and all types of productive elements can also be selectively determined in any given unit at the same time. In addition, some or all of these elements It can also be connected together so that some of the productive elements in these units can be activated or powered at the same time. _-94-_ This paper size applies to China National Standard (CNS) A4 (210X 297 mm)

According to different applications, the multi-force operation is different from the overall array of daily films. It can be different, so different units will have different physical thrusts. ? For example, the first sub-array may include an electromagnetic unit to generate a magnetic field. The second sub-array may include a microelectrode unit and an acoustic power unit. The object of the present invention is to develop a variety of physical forces for the manipulation, control and processing of molecules and particles. Therefore, a multi-force operation wafer can contain any number of early: each unit can contain any number of productivity elements. Different spoon units can be distinguished by their structural elements or contain different structural elements. For a multi-force operation chip like a driver, different units can be connected using a specific mechanism. One possibility is as follows: different units can be connected through a liquid flow channel that allows liquid beans to be transported in it. These units can also be connected by a path through which microparticle and molecular particle complexes are transmitted. For example, a traveling-wave dielectric electrophoresis electrode can be used to fit or connect different cells. (β) The multi-force operation wafer includes all structures that generate physical forces. Another force-manipulating wafer device may contain all the different physical forces. For example, a multi-force manipulating wafer may include an array to generate traveling wave chirp / permanent force, and an array of micro-electromagnetic units may be used to Magnetic% force; a piezoelectric unit is used to generate sound waves. The difference between a full structure and a single unit_ structure-array is that when the full structure is energized, the corresponding physical force will be generated at the location of the fluid pool based on the multi-force operation wafer or the instrument based on the multi-force operation wafer, and the unit -Structure-Array method allows the internal unit to be activated, and the corresponding physical force is only in the corresponding area of the fluid pool or instrument

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Domain generation. (c) The force-operating chip includes a full structure and an array of structural elements that generate a specific type of physical driving force to generate other types of force. Another device for the multi-force operating chip includes generating a specific type of physical driving force. . Configurations and arrays of structural elements are used to generate other types of forces. For example, the Xili operation wafer may include a full-electrode structure, and when a signal is applied, the Risi ’dagger will generate a non-uniform electric field at any position in the groove or instrument based on the multi-force operation wafer. At the same time, the multi-manipulation wafer can also contain a unique array of micro-electromagnetic units with a certain position. It can generate a magnetic field only in the immediate area of the unit where energy has been input / activated. For ten thousand; an array containing structural element units, different units can be connected through a 1 疋 mechanism. In one case, the different units can be connected through the fluid f, so that liquid can be transported inside these units. For such a power-operated wafer, different units can be connected using a specific mechanism. One possibility is as follows: Different units can be connected through a fluid channel that allows liquid f to be transported therein. These units can also be connected through pathways that allow microparticle and molecular particle complexes to be transported in them. For example: Traveling-wave dielectric electrophoresis electrodes can be used to match or connect different XTtTs. Variations in the structure of Xi Li's operating wafers can further include biological / biochemical elements in different units. Here, the biological / biochemical element can include a variety of molecules fixed on the surface of the multi-manipulator wafer, such as protein molecular nucleic acids, antibodies, or various biological particles, such as cells, bacteria, or viruses. These biological / biochemical elements can be uniformly covered on the multi-force operation X 297 mm) 593683 V. Description of the invention (94 as a wafer surface or selectively coated on the surface of the multi-force operation wafer. F · Examples below Examples illustrate the structure of a multi-force manipulation wafer and how it can be used for physical molecular manipulations and for biological, biochemical, and chemical processing. For example, · separating target cells and molecules from a mixture, transporting target cells and molecules, and analyzing targets Cells and molecules, detection and analysis results, etc. Figure 丨 shows a schematic diagram that can generate four physical fields and therefore force. The instrument includes a substrate 10., and four: = 100 micro-machined Structure, the first structure includes a micro-electrode unit 1 1 5, which can generate an electric field EU20 through an externally applied electrical signal (not shown in Figure 丨). The 1S6 entity molecules of the introduced or inserted electric field will be subjected to an electric field force of 128 (for example, a DC electric field force, a conventional dielectrophoretic force, or a traveling wave dielectrophoretic force). The second structure includes a piezoelectric unit 135, which can generate mechanical vibrations. Such vibrations can be integrated into a medium that is in direct or direct contact with the substrate, and eventually cause an acoustic wave field a (i4〇) in the medium. 146 solid molecules placed or introduced into field 140 will experience a sound field force of 148. The third structure contains an electromagnetic unit 155, which can generate a magnetic field M (160). Part 166 has specific magnetic properties. When it is put into the magnetic field 160, it will experience a magnetic field force 168. The fourth structure includes a heating element 175, which can generate a temperature gradient on the dielectric that is in direct or indirect contact with the heating element 175, resulting in a velocity field of 8q. When invisible 186 is placed in the velocity field 18o, it will withstand mechanical force 88. The four structures in FIG. 1 are fabricated on a substrate 100. In an alternative way, these four structures can take different forms and can be attached to ------- 97- This paper size applies the Chinese National Standard (CNS) A4 specification (210X2 ^ 97 public love) I ~ 593683 V. Description of the invention (A7

Or it can be combined with the base. Fig. 1 shows the two two multi-force crystals that can generate four kinds of forces. Fig. 2 depicts a package that is still catchy. On the 9th spoon of filth, the mouth of Duoyou and Yuanyuan 2 10 array of Duoli said μ 200. Each 21 ° unit is composed of an electrical component / structure 220, which is used to produce ^ pieces; 1 piece / structure 26 ° to generate a magnetic field, 2 cores, and 1 magnetism. Ms. Liu's Guer Prefabrication / Structure 2 4 0 &gt;, Generate sound field. Each 210 units can be further: 270 biological elements can be attached or fixed ^ 1 child ^ molecular molecules, biological units can be used for 3 Z molecules or 4, the specific peak library on the surface of the Japanese film = Chemistry y for example: if you want to ㈣㈣: then the biological element can be a single-bladed knife fixed on the surface of the wafer. When the target DNA molecule is operated on the surface of the wafer, it can make all kinds of forces generated by the second part. Under the action of electric field force, each = when acting or acoustically acting ', if the target molecule and the probe molecule are complementary, they can hybridize or bind under appropriate conditions. The hybridization reaction can be detected by a suitable method. All the cells in the wafer in FIG. 2 are the same, although, this is not necessary. In other examples, different units on a multi-force chip can be composed of the same structural elements ... Each unit can be a magnetic element /: an acoustic element; another unit can include an electrical element :. The four units shown in Figure 2 are in different locations, although they are not necessary. In other examples, the same structural elements are re-registered or occupy the same location on the wafer. For example, the electrical component can be co-located with the acoustic component. -98- 297 mm)

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Yuan · 593683 A7 B7 V. Description of the invention (Figure 3 A, 3 B, 3 C shows three different parts of the two-force wafer of the present invention, which can generate sound field forces and conventional dielectrophoretic forces. In Figure 3 In A, the substrate 3 0 0 is made of a piezoelectric material (such as piezoelectric ceramic pz T). Any type of piezoelectric material can be used as long as it can generate sufficient mechanical vibration when an electrical signal is applied to it. It can be used Many commercially available piezoelectric wafers and substrates. Piezoelectric substrates of appropriate thickness should be used to generate the acoustic wave field at the required frequency. Examples of piezoelectric materials can be found in many literatures, including Yasuda K. et al, J. Acoust. Soc. Am. Vol. 102 (1), p642-645? July, 1997; Yasuda K. and Kamakura T. Appl. Phys. Lett, Vol. 71 (13), pl771-1773, Sep. 1997; Pui et al, Biotechnol. Prog., 11: 146-152 (1995); Yasuda et al5 J. Acoust. Soc. Am., 99 (4): 1965-1970 (1996); and Yasuda et al., Jpn. J Appl. Phys ·, 35 (1): 3295-3299 (1996). As shown in Fig. 3A, one main surface of the substrate 3 00 3 20 conductive layer (for example, thin gold Film), which can be used as an electrode connected to external signals to provide energy to the piezoelectric substrate. In FIG. 3A, an offset electrode array 3 4 0 is fabricated on the other main surface of the substrate 300. The electrode array contains two Group of linear electrode elements, the electrode elements in each group are connected together. Therefore, there are two electrical connection pads 3 42 and 346 connected to these two groups of electrodes. The electrode array 340 can use a simple photomask to micro Photolithography on substrate 300, or other microlithography and microstructuring methods, like the smart methods of microlithography and microstructuring as we know (eg See, for example, Rai-Choudhury P. (Editor), Handbook of Microlithography, Micromachining and Microfabrication, Volume 2: _____- 99- This paper size applies to China National Standard (CNS) A4 (210X297 mm)

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Micromachining and microfabrication. SPIE Optical Engineering Press, Bellingham, Washington, USA (1997)). Microstructuring methods can include many basic steps, for example: photolithography mask making, metal layer fabrication, dielectric layer fabrication, photoresist layer fabrication, photoresist layer photolithography using a reticle and developing solution, metal layer And dielectric layer processing. The electrode can be made of metal materials: aluminum, gold, silver, tin, copper, platinum, palladium, and carbon. Semiconductor materials are phosphorous-doped, and any other material with high conductivity. Those who are proficient in microstructure and micromachining can easily decide what methods and materials to use for the fabrication of such electrodes. The electrodes shown in Figure 3A are mutually offset electrodes, although there are many other electrode structures available. For example: the electrodes can be offset electrodes, spiral electrodes, multiple electrodes, etc. In the fabrication of electrodes of different geometries, many steps are the same. The difference is that different shapes of reticle are used, which correspond to the required electrode array. The piezoelectric substrate 300 in FIG. 3A can be supplied with energy through an external signal source 3 60 through the connection between the surface 3 2 0 of the substrate 300 and the pads 3 4 6 on the substrate 300. When an AC signal of a suitable waveform (a typical sinusoidal signal of a suitable wavelength) generated from the signal source 3 60 is applied to the substrate. The substrate 300 will generate mechanical vibration. This vibration can be integrated into the medium directly or indirectly connected to the substrate 300 (not shown in Figure 3A), and a sound field is generated in the medium. The solid molecules in the medium will Experience the sound field force from the sound field. For such a two-acting wafer, vibration occurs only in a specific area of the piezoelectric substrate. These areas correspond to the electrodes connected to the connection block 346. The electrode array 3 4 0 on the substrate 3 0 in Figure A can pass through the pad _-100-_ This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 593683 A7 _____B7 V. Invention Note () and 4 6 use an external ^ number source 3 8 0 to provide energy and generate a non-uniform electric field in the medium directly or indirectly connected to the electrode array. The frequency of the signal provided by the signal source 380 may be less than 1HZ or greater than 1GHZ. The physical molecules in the medium are subjected to electric field forces (for example, conventional dielectrophoretic forces). The surface of the substrate 300 with the electrode array 34 may be further coated or coated with a thin layer of functional substance. In this case, when a medium is introduced into an instrument with a substrate 300, the medium is not in direct contact with the substrate. This indirect contact is through the functional substance layer (and through some areas of the electrode array) 340). The functional substance layer can be used to immobilize specific biomolecules on the surface of the substrate. Examples of functional layers include, but are not limited to, molecular monolayers, membranes, glues, porous or non-porous material layers. Functional layer An additional layer that can adhere to the surface of a substrate. Another possibility is that the functional layer can be formed by direct chemical modification on the substrate surface. Ideally, there should be minimal or no non-specific binding between the 疋 ′ functional layer and molecules other than the molecule to be immobilized, and effective binding or attachment of the target molecule should be ensured. Specific molecules that are integrated into the functional layer to bind the target molecule to the substrate surface are called functional groups. Examples of functional groups include, but are not limited to, acetaldehyde, carbodiimide, succinimide ester, antibody '5: body and exogenous lectin. Functional groups also include chemical groups and sites formed by chemically modifying molecules on the surface of the wafer. The functional group can be selected from the following, which can form a group of hydrophilic molecular monolayers, a hydrophilic molecular monolayer with functional groups, a hydrophobic molecular monolayer, a hydrophobic molecular monolayer with functional groups, a hydrophilic membrane, and functional groups Hydrophilic membrane, hydrophilic glue, hydrophilic glue with functional groups, hydrophobic glue, hydrophobic glue with functional groups, porous -------- 101 -_____ This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 mm) 593683 A7 B7 99 V. Description of the invention (πλ) Materials, porous materials with functional groups, non-porous and non-corrosive materials ^ Feixi porous materials 枓, functional groups, non-polycrystalline materials . In Fig. 3B, the two acting forces are &amp; ~~ 3 and the substrate 3 55. The substrate 3⑽ is made of a piezoelectric material (for example, piezoelectric ceramics PZT). Any of the materials described in Figure 3A can be used. As shown in FIG. 3B, the main surface of the substrate 3⑽ is both covered with a conductive layer (for example, a thin metal sheet), and the conductive layer is used as an electrode for the piezoelectric material. The two conductive surfaces can be connected to an external signal source 36o. On the surface of the second substrate 355, a ring electrode element array, 37 °, was fabricated. The electrodes in each group are interconnected. Therefore, there are two electrical connection pads 3 72 # 3 76 connected to these two sets of electrodes. The substrate 3 55 on which the electrode array 37G has been formed on the surface is attached, bonded or connected to the piezoelectric substrate 300. A careful combination between the piezoelectric substrate 3G () # 3 5 5 is necessary, so that the acoustic wave field generated from the substrate 3⑽ can pass through the substrate 355 and directly or indirectly contact the medium with the substrate 355 (not shown in FIG. 3B). (Shown) integration. The two substrates should be fully bonded to ensure that there is no gap between them ... One way to bond the substrates is to glue them together. The piezoelectric substrate 300 in FIG. 3B can supply energy through an external signal source 36 for connecting the surfaces 32 and 3500 of the substrate 300. When an A 匸 signal from a suitable waveform (a typical sinusoidal signal of a suitable frequency) from the signal source 360 is applied to the substrate, the mechanical vibration generated by the substrate 300 can be integrated into the medium through the substrate 355 (not shown in FIG. 3B) ) To produce a sound wave field in the medium. The solid molecules in the medium will experience the effects of sound field forces originating from the sound field. The electrode array 3 7 0 on the substrate 3 5 5 in FIG. 3B passes through an external signal source 3 8 0

-102- A7 B7 100 V. Description of the invention (Provides energy and generates a non-uniform electric field on the medium in direct or indirect contact with the electrode array. The frequency of the signal provided by the signal source 3 8 〇 may be less than 1HZ or greater than igHZ. The electric field in the medium can exert a force on the solid molecules placed therein (for example, the conventional dielectrophoretic force). The surface of the substrate 355 in FIG. 3B also has an electrode array 37, which can be further coated Or cover a thin layer of functional substance. In this case, when the medium is introduced into an instrument with a substrate 355 (and substrate 300), the medium is not in direct contact with the substrate. The medium and the substrate 3 5 5 is Indirect contact through the functional substance layer (and through certain areas of the micropolar array 3 70). The functional material layer can be used to immobilize specific biomolecules on the surface of the substrate 3 5 5. Some examples of functional layers are shown in the figure 3 A has been given in the text. In Figure 3 C, the two-force wafer contains the substrates 3 9 0 and 3 5 5. The substrate 3 9 0 can be made of any solid material, such as: silicon, glass, Plastic, etc. As long as they can be microstructured or micromachined into channels and cells. The substrate 390 is preferably not made of piezoelectric materials. A piezoelectric element array 3 9 5 is fabricated on the substrate 3 9 0 (for example: a sound source array ). The manufacturing process is as follows: a ring-shaped array cell is formed by etching a predetermined depth at a certain position on the substrate 390. Each cell has a predetermined circle diameter (50 μηι to mm) and a cell depth (5 μηι to 1〇111111). The etching step may include the use of photolithography or other micro-machining methods. The etched pools are connected through channels with the same depth as the pools. A conductive material (such as · · Gold, titanium) thin layer (for example: between 50nm * μιη) to cover the etched pool and via. Therefore, the thin conductive layer in the etched pool and the bottom of the channel is continuous electrical communication __- 103- This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 101 5. Description of the invention (). Then, a thin layer of piezoelectric material is made on the surface of the substrate, and the thickness of the thin layer is the best Less than the depth of the pool. The metal layer and piezoelectric layer on the surface of the substrate other than the pool and channel etched can be removed with a specific processing step. A thin conductive layer is added to the substrate to cover All pools and channels. The conductive layer is of sufficient thickness so that it is in electrical communication with the entire surface of the substrate. Therefore, we have two conductive layers; one in the etched pool and channel At the bottom, another on the surface of the substrate, there is an array of annular discs (such as * discs) made of piezoelectric material between the two conductive layers. So on the substrate 39 of Figure 3C, we made a transmission The electrodes are sandwiched by a piezo disc and a 3 9 5 array of piezo elements connected in parallel. The conductive layer can be connected to the external signal source 36 through the disks 3 92 and 3 98. The above process of fabricating a 3 95 array of piezoelectric elements on a non-piezoelectric substrate is merely an example. Any microfabrication method and micromachining method suitable for making a thin layer of piezoelectric material on a substrate can be used. Those who are proficient in making acoustic arrays can easily choose suitable methods, processes, solutions and materials to make acoustic wave sources (or piezoelectric element arrays) on wafers. Piezoelectric elements of other structures can also be used. By way of example, the etched pool can be of any shape, such as, for example, square &quot; diamond &quot; It can be of any size suitable for producing the required sound waves. The fabricated piezoelectric element arrays do not need to be buried in the substrate: in fact they can be formed on the surface of the substrate. All manufactured 7C pieces need not be connected together. For example: some elements may be connected together, in other examples, individual elements may be selectively gated. An offset electrode array 34G is fabricated on the first substrate 355 in 0 3C. This electrode array is misaligned with each other as shown in Figure 3A. The paper size is based on the Chinese National Standard (ϋ) A4 (210 X 297 mm) 593683 A7 B7 102 5. Description of the invention (The electrode has a similar structure, including two Set of linear electrode elements. The 黾 electrode elements in each group are connected to each other. Therefore, there are two electrical connections 塾 3 4 2 and 3 4 6 connected to these two groups of electrodes. The substrate on the surface has an electrode array 34〇 3 5 5 is attached, bonded, or connected to the substrate 3 90. Careful bonding between the substrate 39 and the substrate 3 5 is necessary so that the acoustic wave field can pass directly or indirectly from the substrate 390 through the substrate 355 (Figure 3B). (Not shown in the figure). The two substrates are taken to be completely combined so that there is no S air gap between them. One way to combine the substrates 355 and 390 can be to glue them together, or other methods, such as · Anode bonding. The piezoelectric element 395 on the substrate 390 in FIG. 3C can be supplied with energy from an external signal source 36 through the connection of the connection pads 392 and 398. When an appropriate waveform (suitable frequency) will be emitted from the signal source Typical sine letter When the A c signal is applied to the piezoelectric elements 3 9 5, mechanical vibrations are generated from these elements. This vibration can be transmitted through 3 5 5 and the medium directly or indirectly in contact with the substrate 3 5 5 (Figure 3C). (Not shown in the figure) integration to generate a sound wave field in the medium. In this way, each piezoelectric element 395 is a sound wave source. The solid molecules in the medium will experience the sound field forces produced by the sound wave field. Figure The electrode array on the substrate 3 3 5 in 3 B 3 4 0 can be supplied with energy from an external signal source 3 8 0 to generate a magnetic field in the medium. The electric field in the medium will exert an electrical force on the physical molecules placed therein (such as conventional Dielectrophoretic force). The surface of the substrate 3 5 5 with the electrode array 340 in FIG. 3C may be further coated or covered with a thin layer of functional groups. In this case, when the medium is introduced into the substrate 355 And 390 instruments, the medium and the substrate are indirect contact. This indirect contact between the medium and the substrate is through the function _____ -105- This paper size applies to China National Standard (CNS) A4 specifications (210X 297 public %) 593683 V. Description of Invention A7 B7 103 ib, and through the electrode array 34 o) in the special area. Functional materials can be used to immobilize specific biomolecules on the surface of the substrate 3 5 5. Some have been provided in the text of Figure A. An example of a functional layer. ^ The multi-power chip of this month (such as shown in 1,2,3 A-3 C) to use Erjong :: Wan to perform operations on the molecules, you need to build a fluid ^ ' Fast. An example of such a fluid pool is shown in Figure 4. At the bottom of the fluid pool there is a multi-force wafer ㈣, which passes through the middle digging cymbal 5200 to the thickness of the moon pool. The top plate has a fluid inlet 560 and an outlet 58. These three parts are combined to form a fluid for easy explanation. These three parts are not drawn together. Multi-force chips have built-in structures on the surface or substrate. For the sake of clarity, in Figure 4 the structure of the taxi and the head is not thin, and for the sake of explanation, the schematic diagram of the Mingxi force chip in Figure 2f is also used here. The multi-force chip 500 in FIG. 4 includes a 7-7C array ', each of which can generate an electric field, and the magnetic field and sound%' can further contain biological elements. The 7ΓΓ U pool in Θ is for illustration only. Fluid cell and manipulator :: Other arrangements are made instead of as shown in head 4. For example, the gasket 520 may be part of the top cover 550. Therefore, fresh 5 = is made into a structure with a specific channel. The top cover can be a region with a certain thickness on a side of the base of broken matuchen 'glass. The most specific requirements for fluid pools and operating devices are: · The substrate can support the solid molecules to be operated, and its internal structure must be able to exert multiple forces on the solid / knife. The fluid cell contains a cavity that can be combined with the substrate. This cavity can be used to contain the solid molecules to be manipulated. The fluid pool can be based on the Chinese National Standard (CNS) A4 specification (21〇297297) -106- 593683 A7 B7 5. The invention description (1 () 4) is open or closed. It can contain bottom, top and side walls. An example of such a fluid pool is shown in Figure 4. Such a fluid pool can have an art piece or a loop. There is a multi-force wafer at the bottom of the fluid cell. Such a fluid cell should have a wafer that generates physics / force at the bottom and at least one wafer that generates physics / force at the top of the fluid cell. For a closed fluid cell, it is best to have an input port and an output port to input the fluid cell with the sample containing the entity molecule to be manipulated. The output section is used to remove samples from the fluid cell. For an open fluid pool, the outlet and outlet can be integrated. The fluid cell can be open with bottom and side walls. When the sample is added and the top plate is covered, it becomes a closed fluid cell. The fluid cell containing the sample can then be completely sealed for experiments. There are many reports in the literature about fluid pools, integration into wafers and biochips. The structure and layout of the devices reported in the literature can be borrowed from current inventions of fluid cells or multi-force wafer manipulation instruments. Here are some documents describing fluid pools: "Dielectrophoretic manipulation of particles by Wang et al, in IEEE Transaction on Industry Applications, Vol. 33, No. 3, May / June, 1997, pages 660-669"; "Separation of human breast cancer cells from blood by differential dielectric affinity by Becker et al5 in Proc. Natl. Acad. Sci ·, Vol ·, 92, January 1995, pages 860-864 ";" Selective dielectrophoretic confinement of bioparticles in potential energy wells by Wang et al. in J. Phys. D: Appl. Phys.? Volume 26, pages 1278-1285 ";" Ultrasonic manipulation of particles and cells "by Coakley et al. Bioseparation. 1994 · 4: 73-83", "Particle column ____- 107-_ This paper size applies to China National Standard (CNS) A4 (210X297 mm) 593683 A7 B7 V. Description of the invention (105) Formation in a stationary ultrasonic field 55 by Whitworth et al. 5 J. Accost Soc. Am. 1992 · 91: 79-85 "," Electrokinetic behavior of colloidal particles in traveling electric fields: studi es using yeast cells by Huang et al, in J. Phys. D: Appl. Phys., Vol. 26, pages 1528-1535 "," Positioning and manipulation of cells and microparticles using miniaturized electric field traps and traveling waves. By Fuhr et al.? in Sensors and Materials. Vol. 7: pages 131-146 "," Dielectrophoretic manipulation of cells using spiral electrodes by Wang, XB. et al. 5 in Biophys. J. Volume 72, pages 1887-1899, 1997 ";" Preparation and hybridization analysis of DNA / RNA from E. coli on microfabricated bioelectric chip by Cheng, J. et al., In Nature Biotech., Volume, 70: 2321-2326, 1998 ";" Cell separation on microfabricated electrodes using dielectrophoretic / gravitational field-flow-fractionation by Yang, J. et al. in Anal. Chem. 71: 911-918, 1999, '· Figures 5A-5C show the two-force wafer of the present invention. For example, it is possible to generate acoustic and magnetic forces for operating an object. Shown in FIG. 5A is a micro-electromagnetic unit array or a micro-electromagnetic unit fabricated on a substrate 300 to generate a magnetic field force. The substrate 300 is made of a piezoelectric material (such as piezoelectric ceramic PZT), so it can generate a sound field. Any piezoelectric material mentioned in the text of Figure 3A can be used. Both major surfaces of the substrate 300 are covered by a conductive layer (thin metal layer), which are used as electrodes to supply energy to the piezoelectric material. In Fig. 5A, only the conductive layer 320 on the bottom surface is shown for clarity, and the conductive layer on the top layer is not shown. However, at the base 300 ___- 108 -__ This paper size applies Chinese National Standard (CNS) A4 (210X297 mm) binding

Edge 593683 A7 B7 V. Description of the invention (The top surface of the display shows a connection 塾 4 3 5. Therefore, the electrical signal generated from the signal source 3 6 0 will be connected to the electrodes 4 3 5 and 3 2 0 to give the piezoelectric The substrate provides energy. An insulating dielectric layer (not shown in Figure 5) is added to the conductive layer on the surface of the substrate 300. The dielectric layer can be made of a variety of materials, such as crushed dioxide, nitrogen Dream or other dielectric film. The thickness of the dielectric layer can be from 1 micron to 200 microns. The thickness of the dielectric layer is preferably between 3 microns and 50 microns. Then a micro-electromagnetic layer is fabricated on the dielectric layer. Cell array 4 1 5. In order to make an electromagnetic unit, the dielectric layer should be properly treated, for example: the dielectric layer should have a smooth surface or be appropriately polished. As long as it can generate current when the electromagnetic unit is applied with current, Magnetic field, it can be arranged in any shape and structure. Each unit can have different geometries, for example, in. 〇- 卩 € 11 (111 ^ 118 卩 61 ^ 30 卩 1bi 31: 1〇11561 ^ 1] ^ 〇: 09 / 399,299, filed on September 16, 1999. Examples of electromagnetic units that can be integrated into a wafer shown in Figure 5 include, but are not limited to, the structures described in the following articles or publications: Ahn, C., et al., J. Microelectromechanical Systems. Volume 5: 151-158 (1996); Ahn, C., et al., IEEE Trans. Magnetics. Volume 30: 73-79 (1994); Liakopoulos et al., In Transducers 97, pages 485-488, presented in 1997 International Conference on Silid-State Sensors and Actuators, Chicago, June 16-19, 1997; US patent No. 5,883,760 by Naoshi et al. Different microstructuring schemes and methods, as mentioned in literature and publications Can be used to make these electromagnetic units. In "Handbook of Microlithography, Micromachining -109- This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) binding"

Line · 593683 A7 B7 V. Invention Description (107) and Microfabrication, by Rai-Choudhury P. (Editor), Volume 2: Micromachining and microfabrication. SPIE Optical Engineering Press, Bellingham, Washington, USA (1997) Many examples and principles of microlithography and microstructures. Based on the special geometry and other requirements of the electromagnetic unit (for example, the necessary magnetic field force), those who are proficient in microstructures and thin layer processing on the substrate can choose Suitable materials and methods to construct the electromagnetic unit. The electromagnetic units 4 1 5 in the array shown in Figure 5 A can be individually gated. Alternatively, some or all of the units can be connected together in parallel. Different The method of selectively exciting a single cell in an array, such as that described in co-pending US patent application serial No: 09 / 399,299, filed on September 16, 1999, can be used. Figure 5A shows electromagnetic and electromagnetic fields. Units 4 and 15 are made together with pads_440. For clarity, we only show some electrical connections between the connection pads and some electromagnetic units 415, although In the case where all the units can be individually gated, all units have corresponding pads. Through these pads 4 4 0, the current (AC or DC) applied from an external current source 4 50 can be connected to the electromagnetic Unit 415, so that unit 415 can be supplied with energy to generate a magnetic field. The piezoelectric substrate 3 0 0 shown in FIG. 5A can be transmitted through an external signal source 3 6 0 through the connection pad 4 3 5 and the conductive surface 3 2 0 Supply energy. When an AC signal of a suitable waveform (typical sinusoidal signal of a specific wavelength) is applied from a signal source 3 60, the mechanical vibration generated from the substrate can be integrated into a medium that is in direct or indirect contact with the substrate 3 00, Thereby, a sound wave field is generated in the medium. The solid molecules in the medium will experience the sound field force originating from the sound field. The electricity in Figure 5 A _____ -110 -___ This paper size applies the Chinese National Standard (CNS) A4 specification (210X 297 mm) 593683 A7 B7 108 V. Description of the invention (The magnetic unit 4 1 5 can generate a magnetic field in the medium through an external current source 4 5 0. This magnetic field will generate a magnetic force on objects with magnetic properties. Figure 5 With an array of electromagnetic cells 3〇〇 surface of the substrate may be further coated or covered with a functional substance. In this case, when the medium is introduced into the instrument 300 with the substrate, the substrate in contact with the medium 3 billion billion non-direct. This indirect contact is achieved through the functional layer (and through the electromagnetic unit in some areas). The functional layer can be used to immobilize specific biomolecules on the surface of the substrate 300. Examples of functional layers are described in the text of Figure 3A. An acoustic wave source array formed on the surface of a piezoelectric substrate 300 for generating acoustic waves is shown in FIG. 5B. An array of micro-electromagnetic units is formed on the second substrate 355. The second substrate is then combined with the first acoustic substrate to produce a multi-force wafer that can simultaneously generate both sound field and magnetic field forces. The acoustic wave source array is formed by making an electrode array 46 on the surface of the piezoelectric substrate 30 () (the upper surface in FIG. 5B). The electrode array 460 in FIG. 5B is a ring-shaped electrode array, and they are connected together through the electrode wires 468. Electrodes of other geometries can also be used if the required sound source can be met. Although the electrodes in FIG. 5A are connected together, the electrodes in the array may be individually addressed, or some electrodes in the array may be connected together. The other surface 32 (the bottom surface in Fig. 5B) may be covered with a thin layer of conductive material. When the AC number from the external signal source 3 60 is applied to the electrode surface 32o and the pole array 460 through the connection pad 462, the area of the substrate 300 sandwiched between the surface 320 and the electrode array 460 will be Subject to AC current and produce mechanical vibration. The method of making an electrode array on a piezoelectric base and the method of making a mutual offset type with 3A ^ Zhang scale is applicable _ home standard _ A4 specifications (21〇: -111-: 297 mm) 593683

The polar array approach is similar. The electromagnetic unit array 415 is fabricated on the second layer substrate 3 5 5, as shown in FIG. 5β. The geometry and structure of the electromagnetic unit 415, the layout of the array and the method of making the electromagnetic single S array are similar to the electromagnetic unit array described in Fig. 5A. The substrate 3 5 5 containing the electromagnetic unit array 415 is adhered to the pressing substrate 3 00. The coupling between the substrate 3 00 and the substrate 3 55 needs to be carefully manipulated to ensure that sound waves can pass from the substrate 300 to the medium through the substrate 3 5 5 (not marked in Figure 5B). The method of bonding these two substrates is similar to the method of bonding the acoustic substrate and the substrate containing the dielectric electrode shown in FIG. The piezoelectric substrate 300 shown in FIG. 5B can be activated by an external signal source 36 by passing through the wiring and the conductive surface 3 2 0 on the pad 462. When using an AC signal with a suitable waveform (such as a typical sinusoidal signal, suitable frequency) from the signal source 3 60, the piezoelectric sensor array generates mechanical vibrations and can pass through the substrate 355 into the medium (not labeled in Figure 5B) A sound field is generated in the medium. Due to the sound field, part of the medium will experience the sound field force. The electromagnetic unit array 415 shown in FIG. 5B can be activated by an external current signal source 450, which generates a magnetic field in the medium. The magnetic field in the medium will exert a magnetic field force on the part with the appropriate magnetic characteristics. The substrate 3 5 5 which has already contained the array of electromagnetic cells is coated with a thin layer of functional material. In this way, when the medium is introduced into the device including the substrate 355 and the substrate 300, the medium is indirectly connected to the substrate 3 5 5. The indirect connection between the medium and the substrate 3 5 5 is established through the functional material layer and the electromagnetic unit in some areas. The functional material layer may fix the biomolecules on the substrate 355. Some examples of functional material layers are provided in the description of Figure 3A. ._________- 112- This paper size applies to Chinese National Standard (CNS) A4 specification (210X 297 mm) 593683 V. Description of invention A7 B7

FIG. 5C illustrates a micro-electromagnetic unit array 415, which is fabricated on a fixed base 390 to make a piezoelectric disk element 395. The method of processing the piezoelectric element 395 is similar to the method of manufacturing a piezoelectric element described in FIG. 3C. The method of making electromagnetic = elements is similar to the method of making electromagnetic units described in Figs. 5A and 5B. These methods can be used in combination. Professionals in microfabrication and magnetic film processing can easily decide and use appropriate processing techniques to process piezoelectric elements and electromagnetic foundations 415 on a substrate. The piezoelectric element shown in FIG. 5C is disc-shaped, but it can be processed into other shapes according to the needs of the sound field. Similarly, the shape and structure of the electromagnetic unit 415 are also various. Figure 5a provides several styles. The piezoelectric element 3 95 shown in FIG. 5C can be activated by the external signal source 3 60 through the pads 3 92 and 398. When using an alternating current signal with a suitable waveform from a signal source 36 (such as a typical sinusoidal signal at a suitable frequency), the piezoelectric inductive sensor array generates mechanical vibrations and can be introduced into the medium from the piezoelectric element 3 9 (Not shown in Figure 5B), a sound field is generated in the medium. Part of the medium will experience the sound field force from the sound field. The electromagnetic unit array 415 shown in FIG. 5C can be activated by an external current signal source 45 to generate a magnetic field in the medium. The magnetic field in the medium will exert a magnetic field force on the part with the appropriate magnetic characteristics. The surface of the substrate 3 90 which has already received the electromagnetic unit array 415 and the piezoelectric element 3 9 5 is coated with a thin layer of functional material. Thus, when the medium is introduced into a device including the substrate 390, the medium is indirectly connected to the substrate 390. The indirect connection between the medium and the substrate 3 5 5 is established through layers of functional materials and electromagnetic units or piezoelectric elements in certain areas. The functional material layer can hold the biomolecules on the substrate 390. Functional material layer is provided in the description of FIG. 3A

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Some examples. 6A-6D are schematic diagrams of an example of a double-liquid film in the present invention, ^ ^ ^ ^ Α and ri-ri film, productivity (conventional dielectrophoresis or traveling wave dielectrophoresis force) and magnetic field force. The micro electromagnetic unit 415 array shown on the substrate 3 5 5 The shape and structure of the magnetic single 71415, the layout of the array, and the method of making the electric + 415 are similar to the electromagnetic unit array described in FIG. 5A. Layer = ::: array :? After the operation is completed, the substrate 355 is coated with a thin layer: the material of the g layer can be dioxygen cut, nitric acid dream, or other materials; electrical materials. The thickness of the thin layer h ° is known to be less than 1 μm to 200 μm. The thickness of the interlayer = layer is ^ 1G microns. The explanation is very clear, the dielectric: and, the bottom 355 are separated. The surface of the dielectric layer 46 is polished, so that the electrode array 34 () at an angle to each other can be processed on the dielectric layer 46. The structure of the electrode 340, the layout of the array, and the method of making the same are described in FIG. 3C. The method is similar. After the fabrication of the electrode array, it is necessary to ensure that the disk 44 () of the electromagnetic unit 415 on the substrate 355 is compatible with the external circuit. This can be achieved by protecting the pad state during the production process or using a suitable lithography process. The electromagnetic unit 415 in FIG. 6A may be activated by a direct current or an alternating current generated by an external signal source 乂 0 connected to the pad state. In the vicinity of the electromagnetic unit, each magnetic% of the generated magnetic field can be transmitted through the dielectric layer 460 to the dielectric f directly or indirectly connected to the dielectric layer 46 (not shown in FIG. 6A). The magnetic field in the medium will exert a magnetic field force on the material with specific magnetic properties. The electrode 34 shown in FIG. 16a can be activated by the electrical signal (AC, [Hertz] to greater than 1G Hertz) generated by the source 386. Balance the electric field. Unbalanced electric field 593683 A7 B7 V. Description of the invention (

Conventional dielectrics will be applied to parts that are different from the dielectric properties of the dielectric; As shown in FIG. 6A, the surface of the dielectric layer 460 has been processed to support the electrode array 340, and a thin layer of functional material may be coated. Thus, when a medium is introduced into a device including a substrate 3 5 and a dielectric layer 460, the medium is indirectly connected to the dielectric layer. The dielectric may be indirectly connected to the dielectric layer 460 through the functional material layer (and the electrode array 340 in some regions). The functional material layer may be used to immobilize certain biomolecules on the surface of the dielectric layer 460. Examples of functional layers are provided in the description of Figure 3A. The multiple force wafers shown in Figs. 6B, 6C, and 6D are similar to those shown in Fig. 6A, except that the electrode structure on the dielectric layer 460 is different. In FIG. 6B, a four-phase, linear, traveling-wave dielectric electrode array 4800 is fabricated on 460. The layout and structure of the array 480 is similar to the description in the literature. Such as Positioning and manipulation of cells and microparticles using miniaturized electric field traps and travelling waves95, G. Fuhr et al.5 Sensors and Materials, vol. 7, pages 131-146, 1995 or Large-area traveling-wave dielectrophoretic particle separator ", Morgan et al.? J. Micromech. Microeng. Volume 7? Pages 65-70, 1997. Although not shown in Figure 6B, the electrode array 4 80 has a multilayer structure. Lithography for processing these electrodes requires multiple masks. Micromachining Professionals can easily select the appropriate processing technology to make such an electrode array 4 8 0. The electrode array 4 8 0 can pass through the pad 4 8 6 and the four-phase signal (0, 9 0 generated by the signal source 4 9 0). Sine or near-sinusoidal waveform at 180 and 270 degrees) is activated to produce a non-uniform traveling wave electric field. This field can apply conventional or traveling wave dielectric electrophoretic force to the part introduced into this field. ______ -115- This paper size is applicable to China National Standard (CNS) A4 (2i × 297mm)

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In FIG. 6C, an array of diamond electrodes 610 is formed on the dielectric layer 460. As shown in FIG. 6C, all electrodes are divided into two groups, and each group of electrodes is connected to the private electrode. The method of making mutual angle electrodes shown in FIG. 3A (such as lithography using a suitable mask) can be used. method). The diamond-shaped electrode array 610 can be activated by the electric signal (usually an alternating current of 1 Hz to i GHz) generated by the signal generator 38 through the circuit boards 612 and 618, and generate uneven hooking%. This electric field can apply a conventional dielectrophoretic force to the portion introduced into the field. A 'a spiral electrode array 63 0 is formed on the dielectric layer 460 in FIG. 6D. The spiral array has four parallel linear spiral electrode sections. The electrode can be fabricated by the method of making mutually angled electrodes as shown in Figure 3A (such as lithography using a suitable mask). The spiral electrode array 63 can be activated by the four-phase signals (sine or near-sinusoidal waveforms of 0, 90, 180, and 270 degrees) generated by the signal generator 490 through the circuit board 6 36 to generate an uneven traveling wave electric field. This field can apply a conventional or traveling-wave dielectrophoretic force to the part introduced into this field. The geometry and principle of spiral electrodes and the manipulation of cells with spiral electrodes are described in the document Dielectrophoretic manipulation of cells with spiral electrodes, XB · Wang et al., Biophysical J ·, ν〇ι · 72, pages 1887-1899, Introduced in 1997. The multi-force wafers shown in Figs. 6A, 6B, 6C, and 6D can all generate magnetic fields (such magnetic field forces can act on parts with a certain magnetic characteristic) and a large number of scattered non-uniform electric fields (conventional dielectrophoretic forces). The wafers shown in Figures 6B and 6D can also generate a traveling wave electric field (traveling wave electrophoretic force). Figures 7A and 7B are the intentions of the two-force wafer in the present invention. The wafer can be ______-116- This paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm)

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Fate 593683

Generates DC electric and magnetic force. FIG. 7A shows a micro-electromagnetic unit array 415 formed on the substrate 3. What is the electromagnetic unit array 4 ?, the layout of the array and the manufacturing method are similar to ... description = single array. After the electromagnetic unit array M 415 has been fabricated, it must be coated.-Thin layer dielectric. 46Ge dielectric material is available-hard, nitrate or other dielectric materials. The thickness of the thin layer can be less than 200 microns The suitable thickness of the electrical layer is ^. Micron = 460 is separated from the base 355. The surface of the dielectric layer 46 is polished to make the single-gated electrode array "60 processable" On the dielectric layer 460. The electrodes here are rectangular (dimensions in several micrometers, such as $ micrometers in length and 1 micrometer in width to several millimeters, such as 13 mm in width and 1 mm in width). Each electrode can be activated by an electric signal transmitted from the pad 662 shown in FIG. 7A. In Figure 7A, we only show some of the wiring between electrodes and pads. The method of making a pole array is similar to the method described in FIGS. 3A and 3C. It should be noted that after making the electrode array, it is necessary to confirm that the pad 44 is in communication with the external circuit. This can be achieved by protecting the pad 44 during the fabrication process or by using a suitable lithography process. 'In FIG. 7A, the electromagnetic unit 415 can be activated by a direct current or an alternating current generated by an external signal source 450 connected through a pad 440. A magnetic field is generated near the electromagnetic unit. The magnetic field can be transmitted through the dielectric layer 4 60 to a medium that is directly or indirectly connected to the dielectric layer 4 6 0 (not shown in Figure 7A). The magnetic field in the medium will exert a magnetic field force on the part with specific magnetic characteristics. The electrode array 660 shown in FIG. 7A can be activated by the electrical signal (usually mud power or low-frequency DC power '1 Hz to several kilohertz) generated by the signal source 680 through the pad 662. Applicable to China National Standard (CNS) A4 (210X297 mm)

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Green 593683 A7 B7 5. Description of the invention (115) An alternating current (or low frequency direct current) electric field is generated in the mass. This electric field will apply a DC electric field force to the charged part of the medium. As shown in FIG. 7A, the surface of the dielectric layer 460 has been processed to support the electrode array 660, and a thin layer of functional material may be coated. Thus, when a medium is introduced into a device including a substrate 355 and a dielectric layer 460, the medium has an indirect relationship with the dielectric layer 460. The dielectric can be indirectly connected to the dielectric layer 460 through the functional material layer (and the electrode array 660 in some areas). The functional material layer may be used to immobilize certain biomolecules on the surface of the dielectric layer 460. Examples of functional layers are provided in the description of Figure 3A. The multi-force wafer shown in FIG. 7B is similar to that shown in FIG. 7A, except that the electrode structure on the dielectric layer 460 is different. In Fig. 7B, a four-phase, linear, traveling-wave dielectric electrode array 480 is fabricated on 460. The layout, structure and manufacturing method of the electrode array 480 are similar to those described in FIG. 6B. The electrode array 4 800 can be activated by a phase-converted signal (usually a pulse) generated by the signal source 700 through the pad 4 8 6 to generate a traveling wave AC electric field in the medium. This field can apply a traveling wave electrophoresis (or traveling wave DC electric field) force to the charged part introduced into this field. The principle of the traveling electrophoretic motion of the charged part can be referred to the copending US Application "METHODS FOR MANIPULATING MOIETIES IN MICROFLUIDIC SYSTEMS" by Wang et al, filed on August 10, 2000. Figure 8 is a schematic diagram of a two-force wafer in the present invention. Electrophoretic forces and mechanical forces caused by thermal convection. Figure 8 shows a single-point strobe array. Electrical heating elements 750 are fabricated on a solid substrate 720. The substrate 720 can be made of a variety of solid materials, such as silicon, glass, plastic, and ceramic. _-118 -__ This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 mm) 593683 A7 _ _ B7 5. Description of the invention (116) The base 720 may or may not have holes. The electric heating element 750 can be made by forming a small electric wire (for example, depositing gold as a wire in a mutually misaligned combination area with a length of 10 micrometers and a width of 5 micrometers). According to special requirements, heating elements with suitable resistors need to use the right materials and geometries. The size of the resistor used depends on the requirements of each heating element and the voltage applied to the resistor. The heating element 750 is manufactured using standard micromachining and micromechanical techniques (such as thin conductive film processing technology). Many examples of micromachining and their principles can be found in Handbook of Microlithography, Micromachining and Microfabrication, by Rai-Choudhury P. (Editor), Volume 2: Micromachining and microfabrication. SPIE Optical Engineering Press, Bellingham, Washington, USA (1997). According to the special geometric structure of electric heating elements, professionals who are familiar with micromachining on substrates and films can easily select the appropriate materials and methods for making heating elements 750. Each individually selectable heating element is connected to a plate 7 80 on a substrate 7 2 0. The plate 780 and the line electrode between the plate and the heating element can also be made in a similar way to the array of heating elements. In Fig. 8A ', although all the components are connected to the pads, we only show the circuits between some heating elements and the pads. The heating elements on the array need not be individually gated. Depending on special requirements, some or all of the heating elements can be connected in parallel or in series so that they can be gated together. The electrical signal generated by the signal source 790 can be applied to the heating element 750 through the pad 750. The local temperature rise is caused by the heat generated by the resistance of the component 750. As shown in FIG. 8, after the heating element is formed on the substrate 720, a thin dielectric layer 460 is coated on the substrate 72. The material of the dielectric layer can be silicon dioxide and nitrate. __119-_ This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) 593683 A7 ------- B7 V. Description of the invention () 117; acid stone or other dielectric materials. The thickness of the thin layer can be from less than 1 micrometer to 200 micrometers: a more suitable thickness of the dielectric layer is i to 10 micrometers. The dielectric layer "0" is separated from the bottom layer j55. The surface of the dielectric layer 46G is polished, so that a single-point gated electrode array 81o can be processed on the dielectric layer. The electrodes here are hexagonal (The size is several micrometers, such as 3 micrometers to a few millimeters, such as 3mm wide.) Each electrode can be gated through the electrical signal transmitted from the circuit board 8 12 shown in Fig. 8. In the figure In 8, we only show the connection relationship between some electrodes and pads. The method of making the electrode array 8 is similar to the method of making the mutually angled electrode array described in Figs. 3A and 3C. Note that the electrode array 8 is finished. 〇 After that, it is necessary to ensure that the pad 7 80 is in communication with the external circuit. This can be achieved by protecting the pad 0 during the production process or using a suitable lithography process. The heating element 7 5 in FIG. 8 can be transmitted through the circuit board 7 8 〇 Excited by an electrical signal (voltage or current, DC or AC) from an external signal source 790. A nearby heating element will cause a local temperature change. This temperature change will be transmitted through the dielectric layer to the dielectric layer 4 6 0 in the base with direct or indirect connections (Not shown in Figure 8). The temperature gradient formed in the medium will cause the medium to move, forming a velocity field in the medium. This velocity field will apply mechanical force to the part placed or suspended in the medium. The electrode array shown in Figure 8 8 1 0 can be activated through 'j: on disk 8 1 2 by the electrical signal generated by the signal source 6 8 0 (usually AC or low-frequency DC, 1 Hz to several kilohertz) to generate AC (or low-frequency DC) in the medium. ) Electric field. This electric field will apply a DC electric field force or an electrophoretic force to the charged part of the medium. As shown in Figure 8, the surface of the dielectric layer 4 6 0 has been processed to support the electrode array. • 120- This paper size applies to Chinese national standards (CNS) A4 specification (210X297 mm) 593683 A7 B7 118 5. Description of the invention (8 1 0, can also be coated with a thin layer of functional material. In this way, when the medium is introduced into the package 2 substrate 720 and the dielectric layer 46 0 device In the medium, the medium has an indirect connection with the dielectric layer 46. The medium can be indirectly connected with the dielectric layer 46 through the functional material layer (and the electrode array 660 in some areas). The functional material layer can be used on the surface of the dielectric layer 460 Fixed on Biomolecules. Some examples of functional layers are provided in the description of Figure 38. Figure 9 is a schematic diagram of an example of a two-force wafer of the present invention, which can generate a dielectrophoretic force and a thermally mediated mechanical force. The Duoli chip is similar to that in FIG. 8 except that the geometry of the electrode array 83 on the substrate 46 is the same. Here, the array 83 is composed of ring electrodes that can be individually gated, and there are several micrometers to several millimeters apart. M diamond-shaped electrode. In Figure 9, the heating element 750 can be excited by an electrical signal (voltage or current, DC or AC) generated by an external signal source 79 〇 through the pad 7 800. The nearby heating element will Cause local temperature changes. This change in temperature will pass through the dielectric layer to the substrate that has a direct or indirect connection with the dielectric layer 460 (not labeled in Figure 8). The temperature gradient formed in the medium will cause the motion of the medium 形 a velocity field in the medium. The 4-knife velocity field will exert mechanical force on the part placed or suspended in the medium. The electrode array 83 shown in Figure 9 is transparent. The 8-8 ridge is activated by an electrical signal (usually alternating current or low-frequency "electricity" i Hertz to several kilohertz) generated by the signal source 3 800. Uniform AC electric field. This electric field will apply a conventional dielectric electrophoretic force to the medium with different dielectric characteristics from the medium. Θ diagram / 疋 This invention-a schematic diagram of a two-force device. The chip can generate magnetic force, wave-dielectric electrophoretic force, and light. Field force. This device is composed of a fluid pool, a second force, a paper mark, and a suitable scale @ 目 家 标准 (CNS "A4 Regulations-121-119593683 V. Description of the invention (=, cymbals, and optical chips. Can generate magnetic field force and traveling wave medium The electric and electronic two-chip wafer is fabricated on the substrate 3 5 5. The structure and layout of the one-chip wafer in β 10 and the manufacturing method map shown by the user — =: The cymbal 850 with a suitable thickness is placed on the two-chip wafer. II. This 852. An optical chip is manufactured on a composite substrate 870 such as glass. Arrays of optical elements such as lenses, inspection programs, etc. The geometric structure and composition of the optical element 880 are specially formulated. The preform wafer also needs to be processed. The input and output ports 872 and the academic chip, the whole chip and the second force chip are combined together to form a single unit. For example, they can be glued together. For the sake of clarity, they are separated in Figure 10. One in * in operation ' The medium with the manipulated component passes through the input port 87 5 through 852 towels. The electrical signal generated by the signal source 45G is applied to the electromagnetic unit to generate a magnetic field, which is introduced into the tube 852 through the dielectric layer 46. The magnetic field can A magnetic field force is applied to the characteristic part. The electrical signal generated by 90 can be applied to the electrode array 48o at: Hook an electric field. This electric field can apply a wave ... ice force to a part in the medium. An optical signal generated by an external light source 900 (Illustration) The optical element m that can be applied to the optical wafer, in the medium 4: light field. This light field can apply a light radiating force to a portion of the medium. The results are shown in Figures 3A-3B ', Figures 5A to 9 Duoli wafers are similar. The surface that already contains a four-phase, linear electrode array electrode array 46〇 also includes: functional materials. In this way, the 'dielectric and dielectric layer 46 ’indirectly strike through the functional material layer (and the electrode array 48 in some areas). 〇) Blood mediation 120 A7 B7 V. Hair Description (46 ° indirect connection. Functional material layers can be used to immobilize certain biomolecules on the surface of the dielectric layer 46 °. Examples of functional layers are provided in the description of Figure 3A. Figures ha, 11B, 11c are the invention An example of a three-force wafer is shown in FIG. 9, which can generate acoustic, magnetic, and traveling-wave dielectrophoretic forces and / or conventional dielectrophoretic forces. The wafer shown in FIG. 11A consists of a piezoelectric substrate 300 and a substrate. 3 5 5 composition. The surfaces 320 and 350 of the substrate 300 are coated with a thin conductive layer as a pensotine pole and the press-dried substrate material is similar to the piezoelectric substrate of FIG. 3B. An array of electric f-units 415 is fabricated on the substrate 355 . The geometric structure of the electromagnetic unit 415, the layout of the array, and the method of manufacturing the electromagnetic unit 415 are similar to the electromagnetic unit array shown in FIG. 6B. When the array of electromagnetic units 45 is fabricated, the substrate 355 is coated with a thin dielectric layer 460. The dielectric layer can be made of silicon oxide or nitric acid or other dielectric materials. The thickness of the thin layer can be from less than 1 micron to 200 microns. The dielectric layer preferably has a thickness of 1 to 10 micrometers. To explain clearly, the dielectric layer 460 is separated from the substrate 355. The surface of the private layer 460 is polished so that the four-phase linear traveling wave electrode array 920 can be processed on the dielectric layer 460. The structure of the electrodes, the layout of the array, and the method of fabricating the electrode array are the same as the fabrication method described in FIG. 6B, except for the 11 electrodes and the 9G I shown in FIG. 6B. It should be noted that after manufacturing the private electrode array 8 1 0, it is necessary to ensure that the pad 7 8 0 is in phase with the external circuit. This can be achieved by protecting the pad 4 4 0 during the production process or using a suitable lithography process. Although the substrate 3 00, the substrate 3 5 5 (and the dielectric layer 460 on the substrate) are in the paper size, the general Chinese National Standard (CNS) A4 specification (210X ^ 97 mm)-593683 A7 B7 V. Invention Note (11A is separate, but in fact they are combined into a wafer, like the two-force wafer shown in 3B. Using the wafer in FIG. 11A, the electrical signal from the signal source 36 is applied to the piezoelectric substrate 3 00 to generate a sound wave. The field is combined with the medium placed or introduced on the surface of the dielectric layer 46. The sound field exerts a sound field force on a portion of the medium. The electrical signal (such as a current) generated by the signal source 450 can be applied to the substrate 3 5 5 The electromagnetic element generates a magnetic field and passes through the dielectric layer 46 to the medium. A psychrophilic field can exert a magnetic field force on a part having a certain magnetic characteristic. The signal source 4 = the electric signal emitted can be applied to the electrode array 9 2 〇, A non-uniform traveling wave electric field is generated in the medium. This electric field can apply conventional and traveling wave dielectrophoretic forces to a portion of the medium. The wafer shown in FIG. 11B contains a piezoelectric substrate 300. Both sides of the piezoelectric substrate are coated A thin conductive layer is used as an electrode. The electrical base material is similar to the piezoelectric substrate shown in Fig. 5A. The electromagnetic unit array 415 is fabricated on the substrate 300. The geometric structure of the electromagnetic unit 415 is the array of your array and the electromagnetic = element, and the method of making the column is as described in head 5A. The method of fabricating an electromagnetic unit array on a piezoelectric substrate is similar. After the electromagnetic unit 415 is fabricated, a layer of dielectric ^ 46 ° needs to be coated on the substrate 355. The material of the dielectric layer can be SiO2, nitrate, or other materials. Dielectric material. The thickness of the dielectric layer can be from less than 20 micrometers to 20G micrometers. The more suitable thickness of the dielectric layer is ii (1) micrometers. For the sake of explanation, the dielectric layer 460 is separated from the substrate 355. The surface of the dielectric layer 4 60 is polished so that the traveling wave dielectric electrophoresis electrode array 9 $ 〇 can be processed on the dielectric ^ 460. The electrode array 9 50 includes a set of concentric circular electrodes' each four rings The electrodes are connected together. This electrode array is made: 297 mm. 122 V. Description of the invention (= 二 &quot;: The production method described is similar. For example, the electrode array needs to be shifted to 95 °. It is necessary to pay attention to the production of the second coffee. Electrical pad 440 is in phase with external circuit :: Ensure that 44 ° or the appropriate lithographic process is used; ^ Used as a protection pad for private use. The electrical signals from 古… 0 in Figure 1 1B and 矣… 0 can be transmitted through the acoustic wave field, and Placed on or introduced Λ20 and applied to the piezoelectric substrate 300 to generate a field to the medium in the medium "force = medium 'layer 460 surface of the medium combination. Acoustic _ Shao Dao She added acoustic field force. The two households generated by the signal source 450 are: magnetic Wide ", generating a magnetic field through the dielectric layer 丄 :: letter 2 ϋ pair has some kind of transition« field force. The electrical signal sent can be applied to the electrode array 9 50 to generate a traveling wave electric field at + chop gauge t. The electric field can be applied to a portion of the medium; the gauge and chirped wave electrophoretic forces. The wafer shown in FIG. Lie includes a base 390 and a base 355 element array 3 95 fabricated on a base 39G. The structure of the piezoelectric element 395 and the layout of the array are similar to the method in the piezoelectric array described in FIG. 3C. Both the electromagnetic unit array 415 and the four-phase linear traveling wave dielectric electrode array 96 are fabricated on the substrate 355. The geometric structure of the electromagnetic unit 415, the layout of the array, and the manufacturing method of the electromagnetic unit array are similar to the method of manufacturing the electromagnetic unit array on the piezoelectric substrate described in FIG. 5A. An electrode array 96 is connected to each electromagnetic unit and includes a multi-conductive layer. The electrode array 96o is used to transport substances along the directions indicated by the electrode array as indicated by arrows 962, 965, and 968 in FIG. The transport force is a traveling wave dielectrophoretic force. -125- This paper size is in accordance with China National Standard (CNS) A4 specification (210X297mm). The material can be controlled at the intersection of the electrode branches (see intersection point 9 6 6 in Figure 11c). Although not specified here, the Chinese patent application entitled "Device for Particle Operation and Particle Guidance and Method of Use, (Wang Xiaobo et al., Filed on September 27, 2000) may be incorporated herein. Professionals who are proficient in micromachining can easily choose the appropriate processing technology and method to make the electromagnetic unit array 415 and the electrode array 96G. After the electromagnetic unit 415 is fabricated, the substrate 355 needs to be coated with a dielectric layer. Dielectric The material of the layer can be dioxygen cutting, nitric acid crushing, or other insulating materials. The thickness of the thin layer can be from less than i microns to 200 microns. The more suitable thickness of the dielectric layer is 1 to 1 () microns. For clarity, the dielectric The layer 460 is separated from the substrate 355. The surface of the dielectric layer 46 is polished so that the traveling wave dielectric electrophoretic electrode array 95 can be processed on: electricity | 460. The electrode array 95 includes a set of concentric Round electrodes are connected to every four ring electrodes. The method of making this electrode p train is similar to that of 0 6 B Thai. For example, electrode arrays require multiple conductive layers. If the lithography technique is used, a multi-layer mask is used to form the electrode array 950. It should be noted that after the electrode array 95 is fabricated, it is necessary to ensure that the plate 440 is in communication with external circuits. This can be achieved by protecting the pads during the manufacturing process ^ or by using a suitable lithography process. Using the chip shown in FIG. 1 ic, the electrical signal from the signal source 36 is applied to the piezoelectric element array 3 95, and an acoustic wave field is generated in the substrate 6 placed on or introduced into the substrate surface. The sound field exerts a sound field force on a portion of the medium. The electric signal generated by the 仏 source 450 can be applied to the electromagnetic elements on the substrate, 415, and a magnetic field is generated in the medium. This magnetic field can exert a magnetic field force on a Shaofen with certain magnetic properties. The electrical signal from the signal source 49 can be applied to the electrical paper size. The national standard (CNS) M specification (Can> <297 public love) 124 5. Description of the invention (Polar array 950 'produces unevenness in the medium Crossing wave electric field. Part of this electric field can be applied with conventional and traveling wave dielectrophoretic forces. Note that the electrode array 960 is used to transport substances (such as cells, particles, etc.) between different electromagnetic units through the traveling wave dielectrophoretic force. ). The substance can be transported in the direction indicated by the electrode array, as shown by the arrows 962, 965, 968 in Figure lie. The substance can be controlled at the intersection of the Thai pole branch (see intersection 966 in Figure 11c). Multi-force wafers are similar. The three-force wafers shown in Figures 11a, 11b, and uc can be coated with a thin layer of functional material. The functional material layer can be used to immobilize certain biomolecules β_3A on the surface of the crystal. Provided in the description Here are some examples of functional layers. In the above example, 'the structural elements used to generate various forces are mostly fabricated on various substrates through various micro-assembly and / or micro-machining methods. However, these structural elements must be able to bind To the substrate. For example, the conductive fine metal wire as an electrode may generate an electric field. These metal wires each permeable

Li :: bottom binding, such as adhesion. In another example, the purpose of the electromagnetic unit _ ^ face_ is to explain the problem ', not to limit the scope of this <1. There are various possible changes mentioned above. Various changes include == sub- 'rather than being limited to these examples, the substrate material used to make the wafer, the electrode structure, the structure of the electromagnetic unit that generates the magnetic field, the production of the acoustic piezo element, and the optical element that generates the light field; gradients Heating or cooling elements and much more. Various modifications and above examples: The purpose is that the invention is limited only by the scope of additional patents. ^

Claims (1)

593683 Patent application scope AB c D-A wafer capable of generating a physical field, the wafer includes: a)-a substrate; and b) the substrate has at least two different types of built-in structures, each of which can be external to An energy combination that produces one type of physics. 2. Multiple wafers as described in the first patent application. 3. If the wafer in the scope of patent application No. 1 generates at least two different types of physics. 4. · If the wafer structure of the patent application item 1 can generate two different types of physics fields 5 · If the wafer structure of the patent application item 1 can generate three different types of physics 6 The structure can generate four different types of physics fields. 7 · For example, the wafer of the first scope of the patent application is more than four different types of physics. 8 · The form of the wafer unit of the i scope of the patent application. 9 · If the wafer of the patent application item 8 is a part of the wafer, or it is full of the whole 10 · If the wafer of the patent application item 1 is a micro unit. 11. If the chip in the scope of application for patent No. 10 contains structurally connected structural products, including two different built-in 0, including three different built-in 0, including four different Built-in 0, including more than four kinds of built-in structures. , Where the built-in structure is a single, where a single unit is located on the chip. 'The built-in structure includes multiple, at least a part of which is a micro-single binding 128- This paper size applies to the Chinese National Standard (CNS) A4 specifications (21〇χ 297 mm) 593683 A8 B8 C8 _________ D8 6. The scope of patent application can be single Gating. 12. As for the wafer in the scope of patent application No. 10, at least a part of the micro units are interconnected. 13. The wafer for which the scope of patent application is item 10, further including a method for selectively applying a signal to any one of a plurality of microcells. 14. For the wafer of the first patent application scope, the built-in structure can generate at least two different types of physical fields selected from the group consisting of electric field, magnetic field, sound field, light field and velocity field. 15. For the wafer of the first patent application scope, the built-in structure can generate at least two different types of physical fields selected from the group consisting of magnetic field, sound field, light field and velocity field. 16. For a wafer in the scope of patent application 1, the built-in structure can generate at least two different types of physical fields selected from the group consisting of electric, acoustic, light, and velocity fields. 17. As for the wafer of the first patent application scope, the built-in structure can generate at least two different types of physical fields selected from the group consisting of electric field, magnetic field, light field and velocity field. 18. As for the wafer of the first patent application scope, the built-in structure can generate at least two different types of physical fields selected from the group consisting of electric field, magnetic field, sound field and velocity field. 19. The wafer as claimed in item 1 of the patent application scope, wherein the built-in structure can generate at least two different types of physical fields selected from the group consisting of an electric field, a magnetic field, a sound field, and an optical field. -129- The standard of this paper is applicable to the national standard of China (CNST ^^ 0 χ297mm): -— AB c D State 683 Application for patent scope 20. For the chip with the scope of patent application item No.], the built-in structure At least two different types of physical fields can be generated that do not include such a combination of a light field and a non-uniform AC electric field. 21. For a wafer in the scope of patent application, the built-in structure can generate at least two different types of physical fields that do not include the combination of a standing wave acoustic field and a uniform DC electric field. 22. For a wafer in the scope of patent application 1, the built-in structure can generate at least two different types of physics that do not include this combination of electric and velocity fields. / i For example, if the wafer in the first patent scope is applied for printing, at least one of the built-in structures can generate an electric field β Θ 24. For the wafer in the patent scope, the built-in structure can generate a uniform electrostatic field. 25. For the wafer with the scope of patent application No. 23, the built-in structure can generate a non-uniform AC electric field with a non-uniform distribution of the field amplitude. 26. The chip of claim 23, wherein the built-in structure can generate a non-uniform AC electric field with at least one field component having a non-uniformly distributed phase value. • A wafer as claimed in item 23 of the patent application, wherein the built-in structure that generates the electric field includes at least one microelectrode element. For example, if the chip of claim 1 is claimed, at least one of the built-in structures can generate a magnetic field. 29. The wafer of claim 28, wherein the built-in structure that generates the magnetic field includes a ferromagnetic substance. -130- Zhang scale is applicable to China National Standard (CNS) A4 specification (21GX297 public love) ^ 3683 A8 B8 C8 D8 Patent application scope 30. As for the patent application scope item 28, the built-in structure that generates a magnetic field includes a micro-electromagnetic unit. 31. As for the chip in the scope of patent application, at least one of the built-in structures can generate a sound field. 32. The wafer as claimed in claim 31, wherein the built-in structure that generates a sound field includes a piezoelectric substance. For example, at least one of the built-in structures of the wafer of the patent application No. 1 can generate a light field. 34. For a wafer with a patent scope of item 33, the built-in structure that generates the light field includes an "optical clamp." 35. For a wafer with a patent scope, the at least one built-in structure can generate speed. 36. For a wafer with a patent scope of 3 $, the speed field can generate mechanical force according to the pressure change in the medium. 37. For a wafer with a scope of patent 36, the built-in structure includes at least one micro Processed thin tip / capillary. &Amp; A wafer as in item 35 of the patent application, where the velocity field can generate mechanical force based on thermal convection. 39. A wafer as in item 38 of the patent application, which is built in The structure includes an array of heating and / or cooling units. 40. For example, the wafer of the scope of patent application No. 1 in which the built-in structure is a miniaturized structure. 41. For the wafer of the scope of patent application No. 40, where the micro The characteristic size of the basic structural elements of the structure is from about 0.1 micrometers to about 20 millimeters. 131-This paper standard (CNS) M size (210X297 mm) ⑽3 ⑽3 A8 B8 C8 D8 Circumference 42. If the wafer in the scope of the patent application is the first item, further includes a functional layer on the substrate. 43. If the wafer in the scope of the patent application is the first item, the substrate includes silicon, glass, ceramics, rubber Or a surface selected from the group consisting of polymer surfaces. 44. For example, if the chip is under the scope of patent application No. 43, the silicon surface is a surface made of silicon dioxide or silicon nitride. The wafer of the range 丨, wherein the substrate includes a hydrophobic or hydrophilic surface. 46 · —A kind of wafer capable of generating a physical field. The main composition of the wafer is: a) a substrate; and b) there are at least two kinds of substrates. Different types of internal structures, each of which can be combined with external energy to generate a type of physics. 47 · A wafer capable of generating physics, the composition of the wafer is: a) a block substrate; and b) a far substrate There are at least two different types of internal structures, each of which can be combined with external energy to generate a type of physics. 48.-A device for operating solid molecules, the device Include: a) a block for holding or supporting a solid molecule; b) at least two different types of internal structures, each of which can be combined with external energy to apply a type of physical force to the solid molecule. -132- This paper size applies to China National Standard (CNS) A4 (210X297mm) Hold 593683 A8 B8 49. The device according to the patent application No. 4.8, wherein the internal structure is a built-in structure on the substrate. 50. The device according to item 48 of the patent application, wherein the internal structure is not located on the substrate. '51. The device according to item 48 of the patent application scope, which device comprises a plurality of structurally connected substrates. 52. The device of claim 48, wherein the internal structure can exert at least two different physical forces on the entity molecule. 53. The device under the scope of patent application No. 48, the device includes two internal structures capable of applying two different types of physical forces to the reader molecules. 54. The device according to item 48 of the scope of patent application, the device includes three internal structures that can apply three different types of physical forces to the entity molecule. 55. The device according to item 48 of the scope of patent application, the device includes four internal structures that can apply four different types of physical forces to the entity molecule. 56. The device according to item 48 of the scope of patent application, which includes more than four internal structures that can apply more than four different types of physical forces to the entity molecule. 57. The device according to item 48 of the patent application, wherein the internal structure is in the form of a single unit, and these units are located on a part of the substrate or cover the entire substrate. 58. The device according to claim 48, wherein the internal structure includes a plurality of micro-units. 59. The device of claim 58 in which at least some of the micro-units can be individually gated. -133- A8 B8 C8 D8 Patent application scope 58 items of devices 60. If the patent application scope number is connected, they are interconnected. At least part of the micro-units 61. Like any one of the units in the scope of the patent application. The device of item 8 further includes a device for selectively applying signals to a plurality of picocells. The device of item 48 of the 2nd patent, wherein the internal structure can be j2 electric field force, magnetic field force, sound field force, mechanical force and light. Field light shot ^, and at least two different types of cage forces selected in the group 0 63 · = Apparatus for scope of patent application No. 48, wherein the internal structure can generate light field radiation force and conventional Dielectrophoretic forces combine up to two different types of physical forces. ° ^ 64. For a device with a scope of 48 patent applications, the internal structure can generate at least two different physical forces that do not include a combination of sound field forces and electrostatic forces. / 65 · If the device under the scope of patent application 48, the internal structure can generate at least two kinds of physical forces excluding the combination of mechanical force and electric power. The device structure under the scope of patent application 48 can generate electric field force. 67. The device according to item 66 of the patent application f% particles apply electrostatic force. For example, the device under the scope of patent application No. 66 generates conventional dielectrophoresis force. At least one of these internal junctions, where the internal structure can produce the internal structure of 〃 中 -134- Installation line 69. For the device under the scope of patent application No. 66, the internal structure can generate traveling wave dielectrophoretic force. 70. The device according to item 66 of the patent application scope, wherein the internal structure capable of generating electric field force includes at least one microelectrode element. 71 The device according to item 48 of the patent application, wherein at least one of the internal structures can generate a magnetic field force. 72. The device according to item 71 of the patent application, wherein the internal structure capable of generating a magnetic field includes a ferromagnetic substance. 73. The device according to item 71 of the patent application, wherein the internal structure capable of generating a magnetic field includes a micro-electromagnetic unit. 74. The device according to item 48 of the patent application, wherein at least one of the internal structures can generate a sound field force. 75. The device 1 as claimed in claim 74, wherein the internal structure capable of generating a sound field force includes a piezoelectric substance. 76. As for the device in the 48th area of the patent application, due to the pressure change in the medium, at least one of the internal structures can generate mechanical force. 77. The device of claim 76, wherein the internal structure generating the mechanical force includes at least one micromachined tip / capillary. 78. As for the device under the scope of patent application No. 48, at least one of the internal structures in # can generate optical light power. ^ 79. As for the device under the scope of patent application No. 78, the internal structure that can generate light force includes a "optical clamp". 80. If the device in the scope of patent application No. 48, due to thermal currents, one less internal structure can generate mechanical force. , -135- A8 B8 I; :: Range 8th. An item of equipment in which a thermal gradient is generated to 82 &quot; an array of heating and / or cooling units. The installation of the 48th item of Li Yu, where the internal structure can be grouped! : At least two different types of physical forces selected by sound field, mechanical, and light field radiation forces. The device of the 48th scope of the utility model, in which the internal structure can produce at least two different types of physical forces consisting of "2% force, sound field force, mechanical force, and cutting force." The device according to Item 48, wherein the internal structure can produce: at least two different types of physical forces composed of field force, magnetic field force, mechanical force, and light field radiation force. •: Patent application scope The device of item 48, wherein the internal structure can produce at least two different types of physical forces selected from the group consisting of electric field force, magnetic field force, sound field force, and light field radiation force. 86 · 如 申 it 利 范围 第The device of 48 items, wherein the internal structure can produce at least two different types of physical forces selected by the group consisting of B% force 'magnetic field force, sound field force, and mechanical force. A. The device, in which the internal structure is a miniaturized structure. For example, the device in the scope of patent application No. 8 ?, wherein the characteristic size of the basic structural elements of the miniaturized structure is from about 0 micron to about 20 mm. 89. Means Lee range 4 8, further comprising one functional layer on the substrate. U π 90 · stomach apparatus 48 as the scope of the patent application, which comprises a substrate made of stone Xi, -136- Pretend C8 D8 Patent Scope A surface selected from the group consisting of plastic, glass, ceramic, rubber, or polymer surfaces. 91. The device according to item 90 of the patent application scope, wherein the surface of Shi Xi is a surface of a silicon dioxide bite or a silicon nitride. 92. The device of claim 48, wherein the substrate comprises a hydrophobic or hydrophilic surface. 93 · = The device under the scope of patent application No. 48, wherein the device includes a flow pond, and the mud pond contains a base and a shell. The fluid pool can contain or support or contain solid molecules to be manipulated. 4. The device according to claim 93 of the patent application, wherein the fluid pool is closed 'and contains at least one inlet port and at least one outlet port. 95. The device under scope 48 of the patent application does not include monitoring or detection devices. 96 · A device for operating a solid molecule, the device is mainly composed of: a) a block for containing or supporting a solid molecule to be manipulated; b) at least two different types of internal structures, each of which can be combined with A combination of external energy sources that applies a type of physical force to the entity molecule. 97 · A device for operating a solid molecule, the device consists of: a) a substrate for containing or supporting the entity molecule to be manipulated; b) at least two different types of internal structures, each of which can be external to the outside A combination of energy sources that applies a type of physical force to the entity molecule. 98. — Combinations, including: -137- This paper size applies to the Chinese National Standard (CNS) A4 specification (210X297 mm) 593683 Application for patent application A8 B8 C8 D8 99. a) At least two 48 items of equipment; and b) a method for transporting entities to be manipulated between the devices. This device includes a wafer such as the first item in the patent application. 100. A method for operating an entity molecule, the method comprising: a) introducing an entity molecule to be operated into a device under the scope of patent application 48; and b) combining external energy on the internal structure of the device to the entity A molecule exerts at least two different types of physical force, and the physical molecule is operated by the physical force. 101. The method of the scope of patent application, wherein the solid molecules are sequentially applied with at least two different types of physical forces. 102. A method as claimed in patent application No. 100, in which a solid molecule is simultaneously applied with at least two different types of physical forces. 103. The method according to the scope of patent application, wherein a plurality of entity molecules are operated simultaneously. 104. For the method of applying for item No. 103 of the patent application, in which a plurality of physical molecules are operated simultaneously by using more than one physical force, so that fewer two physical molecules are operated by different types of physical forces. 105. For example, the method of applying for item No. 100 in the scope of patent application, and the entity molecules in the evening and evening are sequentially operated. Binding 106 · If the method of applying for item No. 105 in the patent scope is applied, and the physical molecules are used in turn to defend the dance by using more than one type of physical force, so that at least two physical molecules are different Type of physical force operation-138- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) 593683 A8 B8 C8 D8 Patent application scope 107. The method according to patent application No. .100, wherein the entity molecules to be operated are in a mixture and are selectively operated. 108. The method of claim 100, wherein the entity molecules to be manipulated constitute a mixture and the entire mixture is manipulated. 109. The method of claim 100, wherein the entity molecule to be manipulated is selected from the group consisting of a cell, an organelle, a virus, a molecule, or an aggregate or a complex thereof. 110. The method of claim 109, wherein the cells are selected from the group consisting of animal cells, plant cells, fungal cells, bacterial cells, recombinant cells, and cultured cells. 111. The method of claim 109, wherein the organelle is composed of a nucleus, a mitochondria, a chloroplast, a ribosome, an endoplasmic reticulum, a Golgi apparatus, a lysosome, a proteasome, a vesicle, a vacuole, and a microsome. Selected in the group. 112. According to the scope of application for patent No. 09, the molecules are selected from the group consisting of inorganic molecules, organic molecules and their complexes. 113. The method of claim 112, wherein the inorganic molecule is an ion, and the ion is sodium ion, potassium ion, magnesium ion, calcium ion, chloride ion, iron ion, copper ion, zinc ion, and manganese ion. , Cobalt ion, Iodine ion, Molybdenum ion, Vanadium ion, Nickel ion, Chromium ion, Gas ion, Broken ion, Tin ion, Shelf ion, Ping ion. Machine 114 · The method of applying item 112 of the patent scope, in which the organic molecule is -139-593683 AB c D 々, the amino acid, peptide, protein, nucleoside, riboflavin, oligoaluminate, nucleic acid , Vitamins, monosaccharides, oligosaccharides, carbohydrates, lipids and their complexes. 115. If the method of the scope of application for patent No. 100, it can transport, focus, enrich, concentrate, aggregate, capture, repel, suspend, separate, fractionate, isolate or straighten the solid molecules. Or other forms of exercise. 116. A method for manipulating a solid molecule, the method comprising applying at least two types of physical forces to a solid molecule such that the solid molecule is manipulated by the physical force. 117. The method according to item 116 of the patent application, wherein the solid molecules are operated in a liquid medium. 118. The method according to item 11 of the scope of patent application, wherein the solid molecules are operated in a liquid container consisting of a beaker, a flask, a graduated cylinder, a test tube, an Enpindorf tube, a centrifuge tube, a petri dish and a multiwell Selected from the group of boards. -140- This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm)