KR20130124484A - Micro devices for biomedical applications and uses of the same - Google Patents

Abstract

The present invention provides microdevices for biological applications and methods of using the same, each microdevice comprising an outer membrane and properties and having a size ranging from about 1 angstrom to within a few millimeters.

Description

MICRO DEVICES FOR BIOMEDICAL APPLICATIONS AND USES OF THE SAME

The present invention generally utilizes a wide range of new features achieved through functional integration at the microscopic level, and uses advanced state of the art microdevice fabrication techniques such as integrated circuit fabrication techniques to perform disease prevention, diagnosis, or treatment at the microscopic level. To a new micro device and its use.

In the last ten to twenty years, well-known progress has been made in medicine and biology, especially in genomics, but existing approaches to modern medicine, including the prevention, diagnosis and treatment of diseases such as cancer, are fundamentally the same and still The focus is mainly on macroscopic methodologies. For example, current diagnosis of disease technology uses macroscopic data and information such as body temperature, blood pressure, scanned images, measured chemical composition levels, and the like. Even the effectiveness of emerging DNA tests in the diagnosis of a wide range of diseases has not yet been established in a real-time, reliable, accurate, rapid and cost-effective manner. It is very difficult to accurately and early diagnose many diseases with high morbidity and mortality, including cancer and heart disease. In addition, most of the existing diagnostic techniques are invasive.

With regard to disease treatment, the situation is even worse. To date, many surgeries are still very invasive, costly, have a high risk of complications, and require long recovery times. Some treatments destroy healthy cells or tissues. One such example may be cancer treatment using radiation that kills not only cancer cells but also normal healthy cells. Another example may be the treatment of blood-related diseases that are often bothersome, dangerous (eg, heart open surgery), costly, and in many cases the patient cannot return to normal and active life after surgery.

In addition to the general guidelines for healthy eating and regular exercise, in terms of preventing problems, the causes of many diseases such as cancer are still unknown at this time. This lack of knowledge related to the cause of the disease leads to a lack of direct preventive drug development.

Most of the above mentioned problems of prevention, diagnosis, and treatment in modern medicine include, for example, a lack of understanding of pathology at the microscopic level (cell biology level), lack of effective drug delivery and effective response mechanisms, preventive mechanisms and Not only the approach but also the lack of non-invasive monitoring at the microscopic level and the lack of non-invasive, effective, target disease treatments and techniques.

Recently, some efforts have been made in the field of using nanotechnology for biological applications, which are mostly used in vitro. This extra work is actually leading to moderate development. Pantel et al. Have described the use of micro electromechanical (MEMS) sensors to detect cancer cells in the blood and bone marrow in vitro. See Klaus Pantel et al., Nature Review (2008, 8, 329). Wozniak and Chen used laser tweezers and microneedles to measure the force produced by the sample cells. M.A. See Wozniak et al., Nature Review (2008, 8, 329). Kubena et al. Disclosed the deployment of MEMS for detecting biological factors in US Pat. No. 6,922,118, while Weissman et al. Described the use of MEMS sensors for detecting biological substances in US Pat. No. 6,330,885. Started.

Due to the above limitations, many basic problems faced by modern medicine, including detection at the microscopic level, targeted treatment in the body, cancer prevention, early detection, and non-invasive treatment with minimal damage to normal tissues and organs, are fundamental. Is not resolved. However, to date, most disclosures have been limited to cases for in vitro sensing using systems with relatively simple configurations, large size and often limited functionality. There are no reports of highly integrated, multifunctional, microdevices (less than 5 millimeters), especially for in vivo applications and for microscopic, progressive biomedical applications.

Summary of the Invention

The present invention generally utilizes a wide range of new features achieved through functional integration at the microscopic level, and uses advanced state of the art microdevice fabrication techniques such as integrated circuit fabrication techniques to perform disease prevention, diagnosis, or treatment at the microscopic level. To a new micro device and its use. Other fabrication techniques that may be suitable include, but are not limited to, mechanical, chemical, chemical mechanical, electrochemical mechanical, electrobiochemical mechanical, biochemical, biochemical mechanical, optical, photoelectric, photoelectric mechanical, thermal chemical, thermal Mechanical, thermal, chemical, mechanical, and integrated circuit and semiconductor fabrication techniques and processes.

In one class of applications, the microdevice comprises a plurality of components, each component being of an ultra-small size, which is generally approximately the size of a lower biological cell to a general total biological cell (or from 1 micron to several hundred microns). . Multiple components of various functions may be integrated into one micro device to perform various functions, including, for example, the detection, treatment, and purification of diseases, generally at the microscopic level.

Depending on the intended application, the microdevices of the present invention or used in the present invention may have a size ranging from 1 angstrom to 5 millimeters. The functions of the microdevices may include sensing, detecting, measuring, diagnosing, monitoring, analyzing, drug delivery, selective absorption, selective adsorption, performing preventive measures and surgical operations, or any combination thereof.

In one aspect, the present invention provides a micro device for medical application or application in a biological biological system.

In some embodiments, each device comprises an outer membrane and micromechanical, microchemical, microchemical mechanical, microoptical, microacoustic, microbiological, microbiochemical, microbiochemical mechanical, microelectrobiochemical mechanical, Microelectrochemical mechanical, microelectrobiochemical mechanical, microelectromechanical, microelectromagnetic mechanical, microacoustic mechanical, and micro superconducting mechanical properties, wherein the micro device comprises from about 1 Angstrom to about It has a size up to 5 millimeters. For example, microdevices with micromechanical properties may also be called mechanical devices and generally mean that the microdevices perform their intended functions due to these mechanical properties. In some examples of such embodiments, the micro device may be micromechanical, microchemical, microchemical mechanical, microoptical, microacoustic, microbiological, microelectromechanical, microelectromagnetic mechanical, microacoustic mechanical, and microsuperconducting mechanical. Includes two characteristics selected from the group of characteristics. In some other examples, the micro device may further comprise a property selected from the group consisting of charged surfaces, chemical potentials, geometric matching, electromagnetic and electrochemical potential related attractive forces. One or more additional properties may be considered for adsorbing the micro device to the surface of the biological organ or cell structure that it targets.

In some embodiments, the micro device can distinguish cancer cells from normal cells. Microdevices perform this function, for example, by measuring the microscopic properties of cells, including, but not limited to, biochemical, physical, electrical, electromagnetic, biochemical, mechanical, acoustical, thermal, and optical properties. can do.

In some embodiments, the micro device measures microscopic properties of organ and cell structure (eg, by having a detection probe), diagnoses organ and cell structure at the microscopic level, and diagnoses the organ and cell structure at the microscopic level. It is possible to deliver the desired chemical (by having a micro syringe or micro container with delivery function), deliver the desired drug at the microscopic level to the organ and cellular structure, and manipulate the selected organ and cellular structure at the microscopic level. The micro device may perform the intended function in a non-invasive manner or in real time.

In some embodiments, the micro device has a surface charge, resting potential, electrochemical potential, electrical potential, surface wettability, contact angle, adhesion, temperature, density, friction, hardness, surface tension, microchemistry At least one property selected from the group consisting of substance concentration, hydrophobicity level, hydrophilicity level, pH, liquid flow rate, pressure, optical properties, absorption, adsorption, and composition can be measured.

The microdevice of the present invention may include a GPS, a signal transmitter, a signal receiver, a micro motorizer, a micro propeller, or a radio frequency (RF) communication chip. As such, the micro device may be capable of local positioning, positioning, location information communication, and location positioning.

In some other embodiments, the micro device may include a chemical delivery function, a controlled chemical delivery function, a mechanical action, a controlled mechanical action, selective absorption, selective adsorption, microscopic level detection, an electromechanical action that operates after a period of time, Controlled electromechanical action, controlled electrochemical mechanical action, controlled electrobiological action, controlled electrochemical biological action, controlled electrochemical biological action, controlled electrochemical biomechanical action, action triggered by a detected signal, and The method may further include a function selected from a group consisting of an action triggered according to an external indication. Such functionality may be a result of the micro device or a characteristic held by a particular subunit of the micro device.

In some other embodiments, the micro device may have a pre-programmed trigger function for the action selected from the group consisting of chemical delivery, mechanical action, charge injection, luminescence, voltage application, cooling and heating of the organic structure. This function can be programmed into an on-device chip with memory and logic functions, for example, triggered when a sensed signal or response reaches a preset value, triggering one action or A series of actions can be initiated and performed. In some cases, trigger functions include charge, stop potential, electrical potential, electrochemical potential, surface current, bulk current, surface wettability, adhesion properties, hydrophobicity levels, hydrophilicity levels, flow properties, electric fields, magnetic fields, acoustic fields field), temperature, light wavelength and / or intensity, frictional force and coefficient, hardness, pressure, and an external signal detected by the device.

In some embodiments, the micro device may have a dissolution capacity in the target pH range between 30 seconds and 3 days. This means that the microdevice can be dissolved at this target pH within this time limit.

In some embodiments, the micro device comprises a material selected from the group consisting of polymers, organic materials, and inorganic materials that are relatively compatible with organic systems. The term "comparatively compatible" means that the material is generally biocompatible with the mammal's body and does not cause infections, disorders, discomforts, and other negative effects (eg, immune response effects). The microdevices may be manufactured using biomaterials in combination with biomaterials or other materials, or may be connected or coated with biomaterials. Biocompatible materials may include naturally occurring materials, synthetic materials, or complexes of naturally occurring materials (including autografts, allografts, or xenografts) with synthetic materials. have. Examples of such materials are, but are not limited to, silicon and silicon dioxide, polysilicon, silicon nitride, silicon oxynitride, carbon oxides, and carbon nitrides, polymers used in packaging IC devices (expected to be compatible due to their inactivity) ), Lipids, peptides, hydroxyapatite (HA), calcium phosphate, calcium carbonate, magnesium phosphate, ammonium phosphate, silicates, and nautilus shells.

In some embodiments, the microdevice comprises approximately 1 angstrom to approximately 100 millimeters (eg, for cell structure, DNA, or bacterial related applications, for human cell testing and analysis), approximately 1 angstrom to approximately 100 microns ( For example, for selective attachment applications), from about 10 microns to about 2 millimeters, or from about 100 microns to about 1.5 millimeters.

In some embodiments, the micro device comprises one material having a plurality of sub devices integrated into one device having one or more functions. Examples of suitable materials include, but are not limited to, organic polymers, organic materials, biological materials, biochemical materials, inorganic conductors, inorganic semiconductors, inorganic insulators, and ceramics. Examples of suitable biological materials include, but are not limited to, artificial biological materials, natural biological materials, cultured biological materials, and combinations of natural and artificial biological materials.

In some embodiments, the micro device comprises an integrated micro device comprising at least one function selected from the group consisting of sensing, detection, measurement, calculation, analysis, diagnosis, logic processing (decision making), transmission, and surgical functions. to be.

In some other embodiments, the micro device includes a voltage comparator, a four point probe, a calculator, a logic circuit, a memory device, a micro cutter, a micro hammer, a micro shield, a micro dye, a micro Pin, micro knife, micro needle, micro thread holder, micro tweezers micro light absorber, micro mirror, micro shield, micro wheeler, micro filter, micro chopper, micro Shredder, Micro Pump, Micro Absorber, Micro Signal Detector, Micro Driller, Micro Sucker, Micro Tester, Micro Vessel, Micro Puller, Signal Transmitter, Signal Generator, Friction Sensor, Charge Sensor , Temperature sensors, hardness detectors, sound wave generators, light wave generators, heat generators, micro refrigerators, and charge feet Hardware selected from the group consisting further includes. These terms are well known in the art and their general definitions apply to the present invention. For example, the filter may be a micro device (or sub-micro device) capable of separating various components by size, and the vacuum cleaner may be a micro device capable of cleaning, polishing, rubbing and brushing the intended surface. The shredder can be a micro device with sharp edges and blades that can make large articles into smaller pieces. In some yet other embodiments, the micro device comprises a cleaner, filter, shredder, syringe, and pump; Cleaners, filters, shredders, and syringes; A polishing apparatus having a polishing pad; Or a sensor, a micro tip for sample collection, a micro array for testing the collected sample, a data analysis device, and a signal transmitter.

In some embodiments, the micro device can be a micro tester for continuous scanning and analysis of living biological systems for early disease detection and prevention.

Alternatively, the microdevice may be for in vitro application outside of a biological system, and may be enveloped and micromechanical, microchemical, microchemical mechanical, microoptical, microacoustic, microbiological, microelectromechanical, microelectromagnetic mechanical. And one or more properties selected from the group consisting of micro-acoustic mechanical, and micro-superconducting mechanical properties, and have a size ranging from about 1 angstrom to about 5 millimeters.

The microdevices can also be used for medical applications such as arterial clearance and early cancer detection and prevention in the body.

Accordingly, the present invention also provides methods of using the microdevices of the present invention for cleaning biological materials. Each method includes contacting a micro device with a biological material, the micro device comprising an outer membrane and a micro mechanical, micro chemical, micro chemical mechanical, micro optical, micro acoustic, micro biological, micro biochemical, micro biochemical Mechanical, microelectrochemical, microelectrochemical, microelectrochemical, microelectromechanical, microelectromechanical, microacoustic, and microsuperconducting. The micro device has a size ranging from approximately 1 angstrom to approximately 5 millimeters. Examples of biological materials to be cleared include, but are not limited to, veins or arteries in mammals. Cleaning may include, for example, mechanical polishing, mechanical rubbing, chemical mechanical polishing, chemical dissolution, chemical passivation, chemical treatment, biological treatment, polishing through chemical dissolution, laser ablation , Or a combination thereof.

In some embodiments, the method of claim 38 comprises delivering a micro device to a general area of biological material; Selectively selecting a local temperature, a local pressure, a local friction force, a local surface charge, a local stop potential, a local electrical potential, a local surface property, a local composition, or a local fluid flow rate; Selectively triggering a cleaning function; Performing a cleaning; Selectively collecting cleaning debris with a microcollector and moving the debris away; And selectively collecting debris with a micro filter and moving the debris away.

In some embodiments, the method comprises delivering a micro device to a vein; Selectively sensing and analyzing data collected, such as, for example, local pressure; Selectively triggering a clearing function when a target vein position is reached; Cleaning the plaques and deposits on the vein wall in the triggered position; Selectively injecting the desired chemical into the blockage to be cleaned to soften the plaque to be cleaned, to prevent the generation of large debris from breakage of the plaque, and to minimize possible damage to the vein; Selectively dissolving the micro device after completion of cleaning or filtration through blood filtration; Selectively filtering the micro device and debris during the cleaning and after the cleaning is completed through blood filtration; And optionally performing a post-cleaning process by the micro device.

Another aspect of the invention provides methods for delivering multiple doses of a drug to a target location in the body, each comprising transporting a micro device to the target location; Delivering the first drug to the target location; And delivering a second dose of drug to the target location within a desired time interval from the delivery time of the initial delivery, wherein the micro device comprises an outer membrane and a micromechanical, microchemical, microchemical mechanical, microoptical, microacoustic Microbiological, microbiochemical, microbiochemical mechanical, microelectrobiochemical mechanical, microelectrochemical mechanical, microelectrobiochemical mechanical, microelectromechanical, microelectromagnetic mechanical, microacoustic mechanical, and microsuperconducting mechanical properties. The micro device has a size ranging from approximately 1 angstrom to approximately 5 millimeters.

In some embodiments, each dosage delivers a different drug than another dosage. In some other embodiments, the drugs are different chemicals and the delivery of the first drug enhances attachment selectivity for the second drug.

Alternatively, the present invention also provides methods of using a micro device for medical purposes, the micro device comprising an outer membrane and a micro mechanical, micro chemical, micro chemical mechanical, micro optical, micro acoustic, micro biological, micro biochemical Microbiological, mechanical, microelectrochemical, microelectrochemical, microelectrochemical, microelectromechanical, microelectromechanical, microacoustic, and microsuperconducting mechanical properties. Wherein the micro device has a size ranging from approximately 1 angstrom to approximately 5 millimeters, the medical purpose being drug delivery, cleavage, ablation, polishing, transport, conjugation, diagnosis, sensing, selective protection, target ablation, measurement, Or blood-related treatment of disease, and the target area (up to about 500 microns in size) are selected from the group consisting of a secondary medical treatment function on the cellular structure or a micro-organ level within.

In some embodiments, the method is for treating cancer and optionally attaching a micro device with drug delivery function to cancer cells; Triggering an injection function in the micro device; And injecting the drug into cancer cells. Alternatively, the method includes selectively attaching a micro device with high optical reflectivity to healthy cells; Performing laser treatment to destroy unhealthy cells; And removing unhealthy cells from the treatment due to laser exposure.

In some embodiments, the micro device used for such a method may include a characteristic selected from the group consisting of a signal sensing device, a memory device, a logic processing device, a signal transmitter, and a microsurgery, wherein the micro device may comprise diagnostics, Performing a sensing or measuring function, the method comprising: delivering a micro device to a target measurement location; Performing a measurement at the target location; Writing data to the memory device; Selectively triggering a task using a logic processing function; Selectively performing a surgery using a micro device; Recovering the micro device; And analyzing the recorded data.

In some other embodiments, the micro device can perform the function of diagnosing, sensing, or measuring a target position, wherein the micro device can be a signal sensing device, a memory device, a signal transmitter, a logic device for field decision making, and a micro Wherein the method comprises delivering the micro device to a target location and performing a diagnostic, sensing, or measuring function at the target location; Writing data to the memory device; Analyzing the data by the micro device; Determining the procedure and type of microsurgery based on data analysis by the microdevice and pre-programmed logic determination; And performing microsurgery at the target location.

In some yet other embodiments, the micro device includes an electrical property measurement apparatus and can detect cancer cells at the target location, the method comprising delivering the micro device to the target location; And measuring at least one property selected from the group consisting of surface charge, charge density, stop potential, electrical potential, electrochemical potential, surface current, bulk current, and current density at the target location. The micro device may further comprise a voltage comparator, for example having a voltage measurement sensitivity of better than 1 mV.

In some other embodiments, the methods can be used for cancer cell detection at a target location, delivering the micro device to the target location; And surface charge, stop potential, electrochemical potential, electrical potential, surface current, bulk current, surface wettability, contact angle, adhesion properties, temperature, density, friction, hardness, surface tension, trace chemical concentration, pH, liquid at the target location. Measuring one or more properties selected from the group consisting of flow rate, pressure, optical properties, absorption, adsorption, and composition.

The microdevices of the present invention are known in the art, for example, integrated circuit fabrication, semiconductor fabrication, mechanical fabrication, chemical treatment, synthesis, electrochemical treatment, biological treatment, biochemical treatment. It can be produced by one or more methods selected from the group consisting of methods, mechanical manufacturing methods, and laser processing methods.

Accordingly, another aspect of the present invention provides data and information in real time at the cellular structure level in a non-invasive manner, such as using micro voltage comparators, four-point probes and other circuit designs for measuring cell surface charge. It is the use of a micro device for obtaining. Identification of cell surface charge can be an important factor in determining the healthy or unhealthy condition of a cell and, if necessary, its proper treatment. One example may be the use of such a device to measure surface and / or bulk electrical properties, including stationary potential and surface charge to distinguish between normal and cancer cells.

Another aspect of the invention is the use of a micro device to deliver a drug to a target location in the human body and to distinguish between healthy and unhealthy (eg cancer) cells. This can be achieved through selective absorption or adsorption of microdevices into healthy and unhealthy cells (eg cancer cells), eg, to remove some of the unhealthy organs with laser surgery. Micro devices with high light reflectivity can be used to selectively absorb healthy cells, thus protecting good cells from being removed through laser treatment.

The term "or" as used herein is meant to include both "and" and "or".

As used herein, the term "one" and the term including one noun includes the meaning of a plurality of nouns.

As used herein, a “micro device” can be any of a wide variety of materials, properties, shapes, complexity and degrees of integration, or any suitable combination thereof. The term has a general meaning for applications from one material to very complex devices that include a number of subunits and a number of functions with many functions. The complexity expected in the present invention ranges from a very small particle having a series of desired properties to a fairly complex, integrated device with various functional devices contained therein. For example, a simple micro device may be one spherical article made of a small diameter, such as 100 angstroms, with a desired hardness, a desired surface charge, or a desired organic chemical absorbed on the surface. More complex microdevices may be one millimeter devices that include sensors, simple calculators, memory devices, logic devices, and cutters, all of which are integrated into the device. In the former case, particles can be formed through a fumed or colloidal precipitation process, while devices with various integrated components can be manufactured using various integrated circuit fabrication processes.

The microdevices of the present invention or used herein can range in size (eg, diameter) from about 1 angstrom to about 5 millimeters. For example, microdevices ranging in size from approximately 10 Angstroms to approximately 100 microns can be used in the present invention to target small sized biological molecules, entities or components such as cell structures, DNA, and bacteria. Alternatively, microdevices ranging in size from approximately 1 micron to approximately 5 millimeters can be used in the present invention to target relatively large biological materials such as parts of human organs. For example, a simple micro device, as defined in this application, has a diameter of 100 angstroms or less, having desired surface properties (eg, with surface charge or chemical coating) for preferential absorption or adsorption to cells of a target type. It may be a simple particle.

The word "absorption" generally means a physical bond between a surface and a substance attached to the surface (in this case, adsorbed). On the other hand, the word "adsorption" usually means a stronger chemical bond between the two. These properties can be effectively used for attachment by the desired micro device for (a) measurement at the microscopic level, (b) target removal of unhealthy cells, and (c) protection of healthy cells during treatments such as laser surgery. Because of this, it is very important in the present invention.

As used herein, the term "chemical" generally refers to a compound that is capable of reacting with a chemical in a particular activity (eg, a large or small compound) or a substance in a targeted delivery region.

With new microdevices, new combinations and integrations of these, and integrated operational process flows, many problems in today's medicine can be solved. In particular, according to the present invention, microdevices can be used to "clean" biological organs, for example to clean veins to prevent heart attacks, strokes and blood clogs due to plaque and fat deposits in the veins.

1 is a perspective view of a micro device that can serve as a micro syringe, showing the micro device before and after the injection process is completed.
2 is a perspective view of a micro device that may serve as a micro polisher.
3 is a perspective view of a micro device that may serve as a micro polisher, a micro filter, a micro syringe, a micro sensor and a micro shredder.
4 is a perspective view of a micro device that may serve as a micro knife.
5 is a perspective view of a micro device that may serve as a micro filter.
6 is a perspective view of a micro device that may serve as a micro shredder.
7 is a perspective view of the microdevice in the blood vessel when approaching plaque in the vessel wall.
8 is a perspective view of a micro device in a blood vessel that senses a change in pressure around the plaque and triggers a cleaning function of the micro device.
9 is a perspective view of the micro device in the vessel after the device cleans the plaque from the vessel wall.
10 is a detailed perspective view of a group of healthy cells and a group of unhealthy cancer cells.
11 is a detailed perspective view of a group of healthy cells and a group of unhealthy cancer cells and microdevices that serve as voltage comparators in these cells.
12 is a detailed perspective view of a group of healthy cells and a group of unhealthy cancer cells.
FIG. 13 is a detailed perspective view of microdevices absorbed or adsorbed into a group of healthy cells and a group of unhealthy cancer cells and healthy cells.
14 is a detailed perspective view of an integrated micro device with various subunits that are a micro cutter, a micro needle, a memory device, a device for analysis and logic processing, a micro sensor, and a signal transmitter.
15 is a detailed perspective view of a micro device with a sensing device, a logic device and a micro syringe.

The present invention provides new microdevices for biological applications that are expected to solve many important problems in modern approaches to medicine. Such problems include, for example, a lack of understanding of the pathology and prevention for many fatal diseases; Lack of non-invasive, microscopic, and effective diagnosis of various disease states; And lack of effective and targeted drug delivery systems and treatments for fatal diseases such as cancer.

The microdevices of the present invention may range in size from approximately 1 angstrom to approximately 5 millimeters (eg, approximately 1 angstrom to approximately 100 microns or approximately 100 microns to 5 millimeters). For detection, measurement, and diagnostic purposes at the cellular structural level or at the molecular (eg DNA, RNA, or protein) level, smaller microdevices (eg, approximately 1 Angstrom to approximately 100), particularly for obtaining information and data While microns) can be used, larger microdevices (eg, from about 100 microns to about 5 millimeters) can be used in mechanical or surgical operations of human organs or tissues, with the exception of manipulation at the cellular structure level. .

As used herein, the general term “micro device” may refer to a wide variety of materials, properties, shapes, complexity and degrees of integration, or mixtures thereof. The complexity expected in the present invention ranges from very small, one particle to a variety of functional subunits, with a very complex, integrated device having a series of desired properties. For example, a simple micro device may be one spherical article made of a small diameter, such as 100 angstroms, with a desired hardness, a desired surface charge, or a desired organic chemical absorbed on the surface. More complex microdevices may be one millimeter devices that include sensors, simple calculators, memory devices, logic devices, and cutters, all of which are integrated into the device. In the former case, the particles can be formed, for example, through a fume or colloidal precipitation process, while devices with various integrated components can be manufactured using various integrated circuit fabrication processes.

The microdevices of the present invention may have a wide range of designs, structures, and functions. These include, for example, voltage comparators, 4-point probes, calculators, logic circuits, memory devices, micro cutters, micro hammers, micro shields, micro dyes, micro pins, micro knives, micro needles, micro thread holders, micro tweezers, Micro light absorber, micro mirror, micro wheeler, micro filter, micro chopper, micro shredder, micro pump, micro absorber, micro signal detector, micro driller, micro circus, micro tester, micro vessel, signal transmitter, signal generator, friction sensor, Charge sensors, temperature sensors, hardness detectors, sound wave generators, light wave generators, heat generators, micro refrigerators, and charge generators.

As disclosed herein, the range of functions and applications of using microdevices can be made very effective due to their various characteristics, high level of adaptability, and ability to integrate and miniaturize.

It should also be noted that advances in manufacturing technology have made it possible to manufacture a wide range of microdevices and to integrate various functions into the microdevices, which are now very feasible and cost-effective. Typical human cell size is approximately 10 microns. Using state-of-the-art integrated circuit fabrication techniques, the minimum functional size formed in a micro device can be as small as 0.1 micron. Thus, the microdevices of the present invention are ideal for biological applications.

In terms of materials for microdevices, the general principle is the compatibility of materials with biological materials. The microdevices of the present invention may be different because the time of contact with a biological material (e.g., a biological molecule such as DNA, RNA, or protein; cell, group of cells; tissue; or organ) may vary depending on its application. Various materials can be selected to make any subunit thereof. In some cases, a substance may be dissolved at a given pH in a controlled manner and thus selected as a suitable substance. Other considerations include cost, simplicity, ease of use, and feasibility. Significant advances in microfabrication techniques, such as integrated circuit fabrication techniques, currently allow highly integrated devices with small minimum functional sizes, such as 0.1 micron, to be cost effective and commercially manufactured. One example is the design and manufacture of micro electromechanical devices (MEMS), which are used in a wide range of applications in the integrated circuit industry.

The following section contains some examples of the use of various types of microdevices of the present invention that can be used for new biological applications.

Detection, measurement, and diagnostics

Prior to the present invention, it is believed that no probes, in real time, measure microscopic properties at the cellular level in vivo (in vivo). New microdevices provided by the present invention can measure cellular characteristics in living organs. It is anticipated that the information from the measurements may be retrieved for use as a diagnostic tool.

For example, the microdevices of the present invention can be utilized to detect cancer cells in living organs in a non-invasive manner. FIG. 10 shows a region in the human body with a number of healthy (or normal) cells “a” 39 and a number of unhealthy (or abnormal) cells “b” 40. Electrical properties such as charge and stop potential of healthy cell “a” 39 differ from those of unhealthy cell “b” 40. First, a microdevice with a voltage comparator is adjusted by measuring surface charge (or voltage) in known healthy cells. Then, as shown in FIG. 11, for an area comprising both healthy cells 39 and unhealthy cells 40, a micro device 41 with a voltage comparator 42 is used to define the area. Check it. By comparing the voltage at the cell surface (difference in charge or potential), unhealthy cells 40 can be easily distinguished from healthy cells 39. This micro device 41 incorporates a voltage comparator, a logic circuit device, and a microsyringe (needle) capable of delivering a cancer removal material specifically to cancer cells, for example, to identify, measure and treat cancer cells. It can be easily extended to perform functions.

Drug delivery

To date, although laboratory tests on mice have been successful, many cancer therapeutic drugs have not shown their expected promising results in human experiments. It is believed that there may be a major problem with successful and effective drug delivery to target cancer cells. Since these drugs are often administered in the form of tablets or by injection into the human body, there may be serious problems with the drug reaching the target cancer site. Even if a drug can reach its target position, its strength (concentration) and chemical composition may change, which makes it partially or wholly ineffective. Increasing the amount of drug delivered in this manner will increase side effects and may lead to increased mortality.

In the present invention, a new, effective and targeted drug delivery system hopes to solve the above problem. As shown in FIG. 15, a micro device 64 having a sensing device 62, a logic device 63, and a micro syringe 61 is used. The micro device 64 is designed to preferentially absorb (or adsorb) only unhealthy cells. Alternatively, sensor 62 may detect unhealthy cells attached to detected unhealthy cells and through measurement of the desired physical, chemical, electrical and biological properties of the cell under test. Once the micro device 64 is attached to unhealthy cells, one or more cancer removal materials will be injected into the cancer cells through the micro syringe 61. To prevent injection into healthy cells due to errors in the attachment process, logic device 63 may be used to make accurate decisions based on sensor data received from sensing device 62. Since this approach is a targeted approach using cancer elimination drugs that are delivered to unhealthy cells, very improved effects are expected for standard therapies traditionally used for current cancer treatments.

cleaning

Another major area of focus for the present invention is a new type of microdevice for biological "cleaning" purposes, especially for "cleaning" of human arteries and veins. FIG. 7 shows blood vessel wall 30, microdevice 32 moving in one direction 33, thrombus 36, hypotension P1 34 and hypotension P2 35. In this type of application, the invention is a micro device 32 with at least one attached cleaner. A more complete micro device may consist of at least one sensor, one cleaner, one micro filter, one syringe, one shredder and one pump.

As shown in FIG. 8, a micro device 32 with integrated functions of sensing (for local pressure measurement) and cleaning 37 can be used for arterial and vein cleaning. In this case, the local pressure is higher at the plaque 36 located at P2 35 in the vessel wall 30. The device 32 senses this increase in local pressure as it approaches the plaque, triggering the cleaning function 37 to be deployed.

FIG. 9 shows the vessel wall 30 after the micro device 32 with the cleaning function 37 has finished cleaning the plaque in the region 38 in the vessel wall 30. This is just one of many examples in which the microdevices disclosed herein can be used as "smart" devices for biological applications in a non-invasive and real-time manner.

In FIG. 3, a more refined micro device 17, consisting of a cleaner arm 8 and a cleaner 9, a sensor 15, micro filters 13 and 14, a micro shredder 11, and a micro syringe 16. Is disclosed. This design is intended to facilitate the cleaning process and ensure that the cleaning debris is reduced to smaller pieces, which are completely removed and do not cause blood clots in other areas of the human body. Vacuum cleaners generally have the ability to polish or rub, while filters are used to filter cleaning debris to prevent them from moving to other parts of the human body causing clogging problems.

The syringe is used to provide a dissolving agent for dissolving debris from the cleaner portion of the micro device, and can also deliver a substance to facilitate the "cleaning" (polishing) process. The micro shredder 11 can be used to chop (if necessary) relatively large debris from the cleaning activity. More particularly, the cleaning device may be a polishing pad 9 formed of polymer material (s) having a desired roughness for polishing or rubbing. A polishing solution may be applied to the micropolishing site through the use of a syringe 16 to reduce mechanical force and prevent breakage into large pieces of plaque. In a preferred method, plaque is removed in a layer-by-layer (several single layer thickness of about 10 angstroms) process, with controlled removal rate. A balanced chemical mechanical polishing process, in which both surface chemical reactions and mechanical wear are present, is preferred, where the mechanical wear is controlled to a low level that will not cause breakage of the plaque. On the other hand, the micro filters 13 and 14 are used to prevent large debris from leaving the cleaning area and damaging other parts of the human body. For patients who tend to have precipitates formed in the veins, cleaning should be performed using the disclosed methods to reduce the risk of heart attack and stroke and to reduce the difficulty of subsequent cleaning procedures.

Since the diameter of the aorta is generally a few millimeters (diameter of about 2 mm to 4 mm), the size of the microdevices for this type of cleaning (aortic cleaning) is about 10 microns to 2 millimeters or less, for example, about 100 microns to It can reach approximately 1.5 millimeters.

Targeted therapy

The microdevices disclosed herein are ideally suited for targeted medical treatment to remove or destroy unhealthy cell or organ sites while minimizing damage to healthy cell or organ sites. This can be done with a high level of selectivity, can be non-invasive, and can be done in a microscopic manner.

12 shows a region in the human body with a number of healthy cells 39 and a number of unhealthy cells 40. FIG. 13 shows that for use in laser surgery using an optical ablation process, healthy cells 39 are first covered with a micro device 43 (called a micro shield) with high light reflectivity. Next, unhealthy cells 40, such as cancer cells, are removed through optical removal, while healthy cells 39 are protected by the micro shield 43. This selective attachment of the micro shield 43 to healthy cells is possible through surface adsorption (or absorption) between the micro device and healthy cells through desired micro device characteristics such as micro device sensing processes and / or charge attraction. For example, the microdevices can be designed and programmed to attach only to healthy cells through surface charge measurements and subsequent logic decisions and actions as specified in FIG. 11 above.

Another embodiment of the present invention for targeted therapy is the use of an integrated micro device with sensing, logic processing, and infusion functions. The micro device first uses the winding function to find its target. The micro device then attaches itself to the target. Finally, the micro device injects the cancer removal material (s) into the cancer cells.

Micro surgery

As disclosed herein, a variety of microdevices capable of performing a wide range of surgical functions may be used to achieve certain goals. Some examples of microdevices capable of performing microsurgery are shown in FIGS.

1 shows a micro device 6 before being triggered and a micro device 7 after being triggered. The device 6 consists of an envelope 1, a sensing device 2, a floor 3, and an area 4 in which a variety of materials can be accommodated prior to the trigger. The triggered device 7 has an area 5 which is empty when the floor 3 is left vertically to discharge the contents of the area 4. 2 shows a micro device 10 with a polisher / scrubber function 9 attached to an extension arm 8 outside of the envelope 1. 4 shows a micro device 20 with a vertical attachment 19 with an envelope 1 and a cutting knife end 18. FIG. 5 shows a micro device 25 having a top surface 24, an envelope 21, and a series of openings 22 in the top surface 24, the openings 22 being completely micro devices 25. Through passage 23 to bottom surface 26. 6 shows a micro device 29 having a body 27 and a reflector 28 attached to the top of the body 27.

For practical surgical applications, it should be emphasized that integrated micro devices with multiple functional components and functions may be the preferred choice, which will be the most effective and versatile tool for surgery. A clear advantage of these "smart" devices disclosed herein is that they can perform surgery at the microscopic level with high precision, high selectivity, in a minimally invasive manner and with minimal damage to healthy cells and organs.

One example of an integrated micro device is at least one sensor, one memory device, one logic processing unit, one signal transmitter, one signal receiver, at least one micro syringe, multiple micro knives, multiple micro needles At least one micro tweezers, and at least one micro thread holder. This integrated micro device will be able to perform some basic surgical operations. One example of such an integrated micro device is shown in FIG. 14. FIG. 14 shows an integrated micro device 43 with a sensing device 47 attached to a sensing arm 48 connected to the memory device 50 via an envelope 44, a path 49, and said Memory device 50 is connected via path 51 to analysis / logic device 52 attached to signal transmitter 45 via path 46, and device 52 extends beyond envelope 44. Is attached via a path 53 to a microneedle device 55 reaching outside through the needle 54, which device 52 has a micro-cutter device with an extension arm 58 having a cutting end 59. Attached to path 57 via path 56.

Accordingly, in accordance with the invention disclosed herein, there is provided a microdevice for biological application, in particular at microscopic level, for disease detection, treatment, and prevention in a biological system, which fully meets the needs and advantages set forth herein. It is obvious. While specific embodiments have been disclosed herein, it will be understood by those skilled in the art that all modifications and variations can be made without departing from the spirit of the invention. Accordingly, the invention is not limited by the disclosure herein. All combinations of microdevices disclosed herein and all specific extensions of microdevices for biological applications will be included in the present invention. In addition, all incorporation of the disclosed microdevices for therapies, including disease detection, prophylaxis, and surgical operations in the living human body, will be included in the invention disclosed herein. Accordingly, the present invention includes all arrangements calculated to achieve the same purpose, and all such modifications and changes are included in the appended claims.

The reader's surroundings are directed to all articles and documents submitted simultaneously with this specification and published for publication together with this specification, the contents of which are incorporated herein by reference. All features disclosed in this specification (including the appended claims, abstracts and drawings) may be replaced by alternative functions serving the same, equivalent or similar purpose unless explicitly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example of a generic series of equivalent or similar features.

All elements in a claim that do not explicitly state "means" for performing a particular function or "steps" for performing a particular function or "steps" for performing a particular function are described in U.S.C. As indicated at 112 (6), it is not to be interpreted as "means" or "steps".

All disclosures mentioned above are incorporated herein by reference in their entirety.

Claims (53)

In a micro device for application in a biological system, the micro device is an outer membrane and micromechanical, microchemical, microchemical mechanical, microoptical, microacoustic, microbiological, microbiochemical, microbiochemical Mechanical, microelectrochemical, microelectrochemical, microelectrochemical, microelectromechanical, microelectromechanical, microacoustic, microthermal, microthermal, microthermal, electrothermal, and microsuperconducting A feature selected from the group consisting of features, wherein the micro device has a size ranging from approximately 1 angstrom to approximately 5 millimeters. The method of claim 1,
Micro Mechanical, Micro Chemical, Micro Chemical Mechanical, Micro Optical, Micro Acoustic, Micro Biological, Micro Electromechanical, Micro Electromagnetic Mechanical, Micro Acoustic Mechanical, Micro Thermo Mechanical, Micro Thermo Chemical Mechanical, Micro Thermo Electrical, Micro Thermo Electrical A micro device comprising two properties selected from the group consisting of mechanical and micro superconducting mechanical properties. The method of claim 1,
Characterized in that it further comprises a property selected from the group consisting of charged surface, electrical potential, chemical potential, geometric matching, electromagnetic, ion gradient, temperature gradient, surface tension, mechanical force, electrochemical potential, and physical force related attraction. Microdevices. The method of claim 1,
The micro device is capable of distinguishing cancer cells from normal cells. The method of claim 1,
The microdevice measures microscopic properties of organ and cellular structures, diagnoses organ and cellular structures at the microscopic level, delivers desired chemicals to organ and cellular structures at the microscopic level, and desired organs and cellular structures at the microscopic level. A micro device, which delivers a drug and is capable of manipulating selected organ and cell structures at the microscopic level. The method of claim 5, wherein
And the micro device performs a function in a non-invasive manner. The method of claim 5, wherein
And the micro device performs a function in real time. The method of claim 5, wherein
The microdevice has surface charge, resting potential, electrochemical potential, electrical potential, surface wettability, contact angle, adhesion, temperature, density, friction, hardness, surface tension, trace chemical concentration, hydrophobicity level. And at least one property selected from the group consisting of hydrophilicity level, pH, liquid flow rate, pressure, optical properties, absorption, adsorption, and composition. The method of claim 1,
Further comprising a geolocation system (GPS), signal transmitter, signal receiver, micro motorizer, micro propeller, or radio frequency (RF) communication chip, logic circuit, and memory circuit Microdevices. The method of claim 1,
Chemical delivery function, controlled chemical delivery function, mechanical action, controlled mechanical action, selective absorption, selective adsorption, microscopic detection, electromechanical action after a certain time, controlled electromechanical action, controlled electrochemical Group consisting of mechanical action, controlled electrobiological action, controlled electrochemical biological action, controlled electrochemical biological action, controlled electrochemical biomechanical action, action triggered by detected signal, and action triggered by external indication The micro device further comprises a function selected from. The method of claim 1,
The micro device has a pre-programmed trigger function for the action selected from the group consisting of chemical delivery, mechanical action, charge injection, luminescence, voltage application, cooling and heating of the organic structure. The method of claim 11,
The trigger functions include charge, stop potential, electrical potential, electrochemical potential, surface current, bulk current, surface wettability, adhesion properties, hydrophobicity level, hydrophilicity level, flow characteristic, electric field, magnetic field, acoustic field And by using a group of parameters selected from the group consisting of temperature, light wavelength and / or strength, friction and coefficients, hardness, pressure, and external signals detected by the device. The method of claim 1,
The micro device has a dissolution capacity in the target pH range between 30 seconds and 3 days. The method of claim 1,
The micro device comprises a material selected from the group consisting of polymers, organic materials, and inorganic materials that are relatively compatible with organic systems. The method of claim 1,
And wherein said micro device has a size ranging from approximately 1 angstrom to approximately 100 millimeters. The method of claim 1,
And wherein the micro device has a size ranging from approximately 1 angstrom to approximately 100 microns. The method of claim 1,
And the micro device comprises one material having a plurality of sub-devices integrated into one device having at least one function. The method of claim 1,
And a material selected from the group consisting of polymers, organic materials, biological materials, biochemical materials, inorganic conductors, inorganic semiconductors, inorganic insulators and ceramics. The method of claim 18,
And wherein the biological material is selected from the group consisting of artificial biological materials, natural biological materials, cultured biological materials, and combinations of natural and artificial biological materials. The method of claim 17,
And the micro device has a size ranging from approximately 0.01 micron to approximately 5 millimeters. The method of claim 1,
The micro device is an integrated micro device comprising one function selected from the group consisting of sensing, detection, measurement, calculation, analysis, diagnosis, logic processing (decision making), transmission, and surgical functions. device. The method of claim 1,
Voltage comparator, four point probe, calculator, logic circuit, memory device, micro cutter, micro hammer, micro shield, micro dye, micro pin, micro knife, micro needle , Micro thread holder, micro tweezers micro light absorber, micro mirror, micro shield, micro wheeler, micro filter, micro chopper, micro shredder, micro pump, micro absorber , Micro signal detectors, micro drillers, micro sucker, micro testers, micro containers, micro pullers, signal transmitters, signal generators, friction sensors, charge sensors, temperature sensors, hardness detectors, sound wave generators, Light wave generator, thermomechanical device, thermochemical mechanical device, thermoelectromechanical device, heat generator, micro cold And, a micro device according to claim 1, further including a hardware selected from the group consisting of micro-signal transmitter, a micro-signal receiver, and a charge generator. The method of claim 1,
The micro device is a group consisting of an integrated circuit manufacturing method, a semiconductor manufacturing method, a mechanical manufacturing method, a chemical processing method, a synthesis method, an electrochemical processing method, a biological processing method, a biochemical processing method, a mechanical manufacturing method, and a laser processing method. Manufactured by the method selected. The method of claim 1,
A micro device further comprising a cleaner, filter, shredder, syringe, or pump. The method of claim 1,
A micro device further comprising a cleaner, filter, shredder, or syringe. The method of claim 1,
And a polishing apparatus having a polishing pad. The method of claim 1,
And wherein said micro device has a size ranging from approximately 10 microns to approximately two millimeters. The method of claim 1,
And wherein said micro device has a size ranging from approximately 100 microns to approximately 1.5 millimeters. The method of claim 1,
Wherein said micro device is a micro tester for continuous scanning and analysis of living biological systems for early disease detection and prevention. The method of claim 1,
A micro device further comprising a sensor, a micro tip for sample collection, a micro array for testing the collected sample, a data analysis device, or a signal transmitter. The method of claim 1,
And the micro device has a size ranging from approximately 1 micron to approximately 100 microns. The method of claim 1,
And wherein said micro device has a size ranging from approximately 10 microns to approximately 5 millimeters. The method of claim 1,
And wherein the micro device has a size ranging from approximately 2 angstroms to approximately 500 microns. The method of claim 1,
And said micro device is used for arterial cleaning. The method of claim 1,
The micro device is used for the early detection and prevention of cancer in the body. A method of using a micro device for cleaning a biological material, the method includes contacting the micro device with a biological material, the micro device comprising an outer membrane and a micro mechanical, micro chemical, micro chemical mechanical, micro optical, Micro Acoustic, Micro Biological, Micro Biochemical, Micro Biochemical Mechanical, Micro Electrobiochemical Mechanical, Micro Electrochemical Mechanical, Micro Electrobiochemical Mechanical, Micro Electromechanical, Micro Electromagnetic Mechanical, Micro Acoustic Mechanical, Micro Thermal Mechanical And micro thermochemical mechanical, micro thermo electrical, micro thermo electromechanical, and micro superconducting mechanical properties. Method characterized in that it has a size of up to about 1 Angstrom to about 5 millimeters. The method of claim 36,
The biological material comprises a mammal's vein or artery. The method of claim 36,
Delivering the micro device to a general area of biological material;
Selectively selecting a local temperature, a local pressure, a local friction force, a local surface charge, a local stop potential, a local electrical potential, a local surface property, a local composition, or a local fluid flow rate;
Selectively triggering a cleaning function;
Performing a cleaning;
Selectively collecting cleaning debris with a microcollector and moving the debris away; And
Selectively collecting debris with a micro filter and moving the debris away. The method of claim 36,
Delivering the micro device into a vein;
Selectively sensing and analyzing data collected, such as, for example, local pressure;
Selectively triggering a clearing function when a target vein position is reached;
Cleaning the plaques and deposits on the vein wall in the triggered position;
Selectively injecting the desired chemical into the blockage to be cleaned to soften the plaque to be cleaned, to prevent the generation of large debris from breakage of the plaque, and to minimize possible damage to the vein;
Selectively dissolving the micro device after completion of cleaning or filtration through blood filtration;
Selectively filtering the micro device and debris during the cleaning and after the cleaning is completed through blood filtration; And
Selectively performing a post-cleaning process by the micro device. The method of claim 36,
The cleaning may include mechanical polishing, mechanical rubbing, chemical mechanical polishing, chemical dissolution, chemical passivation, chemical treatment, biological treatment, polishing through chemical dissolution, laser ablation, or their Method comprising the combination. A method for delivering multiple doses of a drug to a target location in the body, the method comprising:
Transporting the micro device to a target location;
Delivering the first drug to the target location; And
Delivering a second dose of drug to a target location within a desired time interval from the delivery time of the initial delivery,
The microdevices can be used in outer membrane and micromechanical, microchemical, microchemical mechanical, microoptical, microacoustic, microbiological, microbiochemical, microbiochemical mechanical, microelectrobiochemical mechanical, microelectrochemical mechanical, microelectrobiochemical Mechanical, microelectromechanical, micro electromagnetic mechanical, micro acoustic mechanical, micro thermo mechanical, micro thermo chemical mechanical, micro thermo electrical, micro thermo electromechanical, and micro superconducting mechanical properties; And the micro device has a size ranging from approximately 1 angstrom to approximately 5 millimeters. 42. The method of claim 41,
Each dose delivering a drug that is different from another dose. 42. The method of claim 41,
Wherein the drugs are different chemicals and delivery of the first drug enhances attachment selectivity to the second drug. In a method of using a micro device for medical purposes, the micro device may include an outer membrane and micromechanical, microchemical, microchemical mechanical, microoptical, microacoustic, microbiological, microbiochemical, microbiochemical mechanical, and microelectrobiochemistry. Including mechanical, microelectrochemical, microelectrochemical, microelectromechanical, microelectromechanical, microacoustic, and microsuperconducting mechanical properties;
The micro device has a size ranging from about 1 angstrom to about 5 millimeters,
The medical purpose is in a group consisting of drug delivery, cleavage, ablation, polishing, transport, conjugation, diagnosis, detection, selective protection, target ablation, measurement, and assistance of medical therapeutic function at the cellular structure or micro-organ level within the target area. Selected method. 45. The method of claim 44,
The method is for the treatment of cancer,
Selectively attaching the microdevice having the drug delivery function to cancer cells;
Triggering an injection function in the micro device; And
Injecting a drug into the cancer cell. 45. The method of claim 44,
Selectively attaching the micro device with high optical reflectivity to healthy cells;
Performing laser treatment to destroy unhealthy cells; And
Removing unhealthy cells from the treatment due to laser exposure. 45. The method of claim 44,
The micro device may include a characteristic selected from the group consisting of a signal sensing device, a memory device, a logic processing device, a signal transmitter, and a microsurgery,
The micro device performs a diagnostic, sensing or measuring function,
The method comprises:
Delivering the micro device to a target measurement location;
Performing a measurement at the target location;
Writing data to the memory device;
Selectively triggering a task using a logic processing function;
Selectively performing a surgery using a micro device;
Recovering the micro device; And
Analyzing the recorded data. 45. The method of claim 44,
The micro device performs a function of diagnosing, detecting, or measuring a target position,
The micro device includes a signal sensing device, a memory device, a signal transmitter, a logic device for field decision making, and a micro surgery,
The method comprises:
Delivering the micro device to a target location and performing a diagnostic, sensing, or measuring function at the target location;
Writing data to the memory device;
Analyzing the data by the micro device;
Determining a process and type of microsurgery based on data analysis by the microdevice and a pre-programmed logic decision; And
Performing microsurgery at the target location. 45. The method of claim 44,
The micro device includes an electrical property measuring device and can detect cancer cells at a target location,
The method comprises:
Delivering the micro device to a target location; And
Measuring at least one property selected from the group consisting of surface charge, charge density, stop potential, electrical potential, electrochemical potential, surface current, bulk current, and current density at the target location. The method of claim 49,
And the micro device further comprises a voltage comparator. 51. The method of claim 50,
And the voltage comparator has a voltage measurement sensitivity of better than 1 mV. 45. The method of claim 44,
The method is used for cancer cell detection at the target location,
Delivering the micro device to a target location; And
Surface charge, stop potential, electrochemical potential, electrical potential, surface current, bulk current, surface wettability, contact angle, adhesion properties, temperature, density, friction, hardness, compressibility, shear modulus at the target location, Measuring at least one property selected from the group consisting of acoustic properties, surface tension, trace chemical concentration, pH, liquid flow rate, pressure, optical properties, absorption, adsorption, and composition. In microdevices for applications outside biological systems, the microdevices may be enveloped and micromechanical, microchemical, microchemical mechanical, microoptical, microacoustic, microbiological, microelectromechanical, microelectromagnetic mechanical, microacoustic Mechanical, and micro superconducting mechanical properties, including one property selected from the group consisting of,
And wherein said micro device has a size ranging from approximately 1 angstrom to approximately 5 millimeters.

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