US20030196695A1 - Microfluidic flow control devices - Google Patents

Microfluidic flow control devices Download PDF

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Publication number
US20030196695A1
US20030196695A1 US09/985,943 US98594301A US2003196695A1 US 20030196695 A1 US20030196695 A1 US 20030196695A1 US 98594301 A US98594301 A US 98594301A US 2003196695 A1 US2003196695 A1 US 2003196695A1
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United States
Prior art keywords
microfluidic
channel
membrane
layer
flow control
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Abandoned
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US09/985,943
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English (en)
Inventor
Stephen O'Connor
Christoph Karp
Eugene Dantsker
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Nanostream Inc
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Nanostream Inc
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Priority to US09/985,943 priority Critical patent/US20030196695A1/en
Priority to US10/127,081 priority patent/US6619311B2/en
Assigned to NANOSTREAM, INC. reassignment NANOSTREAM, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: DANTSKER, EUGENE, KARP, CHRISTOPH D., O'CONNOR, STEPHEN D.
Publication of US20030196695A1 publication Critical patent/US20030196695A1/en
Abandoned legal-status Critical Current

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    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
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    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
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Definitions

  • the present invention relates to microfluidic devices and the control of fluid flow within those devices.
  • microfluidic systems for acquiring chemical and biological information.
  • complicated biochemical reactions may be carried out using very small volumes of liquid.
  • microfluidic systems increase the response time of reactions, minimize sample volume, and lower reagent consumption.
  • performing reactions in microfluidic volumes also enhances safety and reduces disposal quantities.
  • microfluidic systems have been constructed in a planar fashion using techniques borrowed from the silicon fabrication industry. Representative systems are described, for example, in some early work by Manz et al. (Trends in Anal. Chem. (1990) 10(5): 144-149; Advances in Chromatography (1993) 33: 1-66). These publications describe the construction of microfluidic devices using photolithography to define channels on silicon or glass substrates and etching techniques to remove material from the substrate to form the channels. A cover plate is bonded to the top of the device to provide closure.
  • a number of methods have been developed that allow microfluidic devices to be constructed from plastic, silicone or other polymeric materials.
  • a negative mold is first constructed, and then plastic or silicone is poured into or over the mold.
  • the mold can be constructed using a silicon wafer (see, e.g., Duffy et al., Analytical Chemistry (1998) 70: 4974-4984; McCormick et. al., Analytical Chemistry (1997) 69: 2626-2630), or by building a traditional injection molding cavity for plastic devices.
  • Some molding facilities have developed techniques to construct extremely small molds.
  • a microfluidic device with limited (i.e., on-off) flow control capability is provided in U.S. Pat. No. 5,932,799 to Moles (“the Moles ′799 patent”).
  • polyimide layers enhanced with tin are surface micromachined (e.g., etched) to form recessed channel structures, stacked together, and then thermally bonded without the use of adhesives.
  • a thin, flexible valve member actuated by selective application of positively or negatively pressurized fluid selectively enables or disables communication between an inlet and an outlet channel.
  • the valve structure disclosed in the Moles ′799 patent suffers from numerous drawbacks that limit its utility, however.
  • the valve is limited to simple on-off operation requiring a constant actuation signal, and is incapable of regulating a constant flow.
  • the valve is normally closed in its unactuated state. It is often desirable in microfluidic systems to provide normally open valve structures subject to closure upon actuation.
  • the Moles ′799 patent teaches the fabrication of channels using time-consuming surface micromachining techniques, specifically photolithography coupled with etching techniques. Such time-consuming methods not only require high setup costs but also limit the ability to generate, modify, and optimize new designs.
  • the Moles ′799 patent teaches only fabrication of devices using tin-enhanced polyimide materials, which limits their utility in several desirable applications.
  • polyimides are susceptible to hydrolysis when subjected to alkaline solvents, which are advantageously used in applications such as chemical synthesis.
  • the inclusion of tin in the device layers may present other fluid compatibility problems.
  • polyimides are generally opaque to many useful light spectra, which impedes their use with common detection technologies, and further limits experimental use and quality control verification.
  • microfluidic valve structure having limited utility is disclosed in WIPO International Publication Number WO 99/60397 to Holl, et al.
  • a microfluidic channel is bounded from above by a thick, deformable elastic seal having a depressed region that protrudes through an opening above the channel.
  • An actuated external valve pin presses against the elastic seal, which is extruded through the opening into the channel in an attempt to close the channel.
  • This valve suffers from defects that limit its utility. To begin with, it is difficult to fabricate an elastic seal having a depressed region to precisely fit through the opening above the channel without leakage.
  • valve provides limited sealing utility because it is difficult to ensure that the extruded seal completely fills the adjacent channel, particularly in the lower corners of the channel. Further, the contact region between the external valve pin and the elastic seal is subject to frictional wear, thus limiting the precision and operating life of the valve.
  • a fluid switching device or system would be simple and robust with a minimum number of parts subject to wear.
  • a microfluidic regulating device in a first separate aspect of the invention, includes a first and a second channel segment defined in different layers of a microfluidic device and in fluid communication with one another.
  • a membrane separates the channel segments at a regulatory region. In the presence of a pressure differential between the two channel segments, the membrane is deformed toward and into the channel segment having a lower internal pressure, thus reducing fluid flow capability through the first or the second channel segment.
  • a normally open microfluidic flow control device includes a first and a second microfluidic channel each defined in different stencil layers. Fluid communication may be established between the first and the second channel through an aperture defined in a valve seating surface. A deformable membrane centrally disposed above or below the aperture is capable of being deformed to seal against the valve seating surface, thus preventing fluid flow through the aperture.
  • a microfluidic flow control device in another separate aspect of the invention, includes a microfluidic channel bounded by a lower surface, by lateral channel walls, and by a deformable membrane capable of being deformed by actuation means into the channel and against the lower surface. At least one of the lower surface and the first membrane has an adhesive surface capable of maintaining contact between the lower surface and the first membrane after disactivation of the actuation means.
  • a microfluidic flow control device in another separate aspect of the invention, includes a first control layer and a second control layer each defining multiple channel segments.
  • a channel layer which defining a microfluidic channel network in fluid communication with multiple fluid inlet ports and fluid outlet ports, is disposed between the first and the second control layer.
  • a flexible membrane separates the first control layer and the channel layer, and a flexible membrane separates the second control layer and the channel layer. Fluid flow paths between one or more specific inlet ports and one or more specific outlet ports may be selectively established by manipulating pressure within individual control channels, thus causing deformation of the first and/or the second membrane into the channel network at one or more valve regions.
  • a microfluidic flow control device in another separate aspect of the invention, includes a first and a second microfluidic channel capable of being in fluid communication, and a deformable membrane capable of affecting fluid flow between the two channels.
  • a magnetic element is associated with the deformable membrane.
  • Application of a magnetic field deforms the deformable membrane.
  • a configurable microfluidic device in another separate aspect of the invention, includes a network of interconnected fluid channels and multiple first and second control channels.
  • the first and second control channels are separated from the network of interconnected microfluidic channels by at least one deformable membrane at one or more regulatory regions.
  • FIGS. 1 A- 1 C are cross-sectional views of at least a portion of microfluidic device constructed from 5 layers of material, the device having a deformable membrane separating equally-sized upper channel region and a lower channel region.
  • FIG. 1A illustrates the membrane in a neutral position.
  • FIG. 1B illustrates the membrane being deflected toward and into the lower channel region.
  • FIG. 1C illustrates the membrane being deflected toward and into the upper channel region.
  • FIGS. 2 A- 2 B are cross-sectional views of at least a portion of a 5-layer microfluidic device having a larger upper channel region and a smaller lower channel region.
  • FIG. 2A illustrates the membrane being deformed toward and into the smaller, lower channel region.
  • FIG. 2B illustrates the membrane being deformed toward and into the larger, upper channel region.
  • FIGS. 3 A- 3 E are cross-sectional views of at least a portion of a microfluidic device having three separate channel regions (an upper, a central, and a lower channel region) divided by two deformable membranes (an upper and a lower membrane).
  • FIG. 3A illustrates both membranes in neutral positions.
  • FIG. 3B illustrates the upper deformable membrane being deflected toward and into the central channel region.
  • FIG. 3C illustrates both the upper and the lower deformable membrane being deflected toward and into the central channel region.
  • FIG. 3D illustrates the lower deformable membrane being deflected toward and into the central channel region.
  • FIG. 3A illustrates both membranes in neutral positions.
  • FIG. 3B illustrates the upper deformable membrane being deflected toward and into the central channel region.
  • FIG. 3C illustrates both the upper and the lower deformable membrane being deflected toward and into the central channel region.
  • FIG. 3D illustrates the lower deformable membrane being de
  • 3E illustrates both the upper and lower deformable membrane being deflected away from the central channel region, namely, the upper deformable membrane being deflected toward and into the upper channel region, and the lower deformable membrane being deflected toward and into the lower channel region.
  • FIG. 4A is an exploded perspective view of a five-layer microfluidic device having a pressure-activated regulating valve that controls fluid flow within the device.
  • FIG. 4B is a top view of the assembled device of FIG. 4A.
  • FIG. 5A is a top view of a portion of one layer of at least a portion of a microfluidic device, the layer having a network of interconnected channels.
  • FIG. 5B is a top view of portions of two additional, superimposed layers of the same device shown in FIG. 5A, the two additional layers defining control channels for directing fluid flow within the channel network illustrated in FIG. 5A.
  • FIG. 5C is a top view of a membrane that may be used in the device illustrated in FIGS. 5 A- 5 B, the membrane composed of different membrane materials in four regions.
  • FIG. 5D is a top view of a membrane similar to the membrane illustrated in FIG. 5C, but composed of different membrane materials in sixteen regions.
  • FIG. 5A is a top view of a portion of one layer of at least a portion of a microfluidic device, the layer having a network of interconnected channels.
  • FIG. 5B is a top view of portions of two additional, superimposed layers of the same device shown in FIG. 5A, the two
  • FIG. 5E is a top view of the superimposed layer portions of FIGS. 5 A- 5 B and two membranes assembled into a microfluidic device, with schematic illustration of the device being operated to define one possible fluid flow path.
  • FIG. 5F is a schematic illustration of a microfluidic flow control system including the microfluidic device of FIG. 5E coupled to at least one pressure source and a controller, among other components.
  • FIG. 6A is an exploded perspective view of a five-layer microfluidic device capable of delivering a relatively constant flow rate of fluid over a large range of pressures.
  • FIG. 6B is a top view of the assembled device of FIG. 6A.
  • FIG. 6C is a cross-sectional view of a portion of the microfluidic device of FIGS. 6 A- 6 B along section lines “A-A” shown in FIG. 6B, with the regulatory region in the open position.
  • FIG. 6D provides the same cross-sectional view as FIG. 6C, but with the regulatory region in the closed position.
  • FIG. 6E is a chart showing the flow rates achieved at the unregulated and regulated outlets of the device shown in FIGS. 6 A- 6 D over a range of input pressures, with each outlet tested separately while the other outlet was sealed.
  • FIG. 6F is a chart showing the flow rates at both the unregulated and regulated outlets of the device shown in FIGS. 6 A- 6 D over a range of input pressures, measured with both outlets open.
  • FIG. 7A is a cross-sectional view of a portion of a microfluidic device having three channel segments that meet at a regulatory region and that are separated by a single deformable membrane.
  • FIG. 7B provides the same cross-sectional view as FIG. 7A, but with the membrane deflected toward and into the upper channel segment.
  • FIG. 8A is a cross-sectional view of a deformable membrane having a magnetic element affixed to the membrane.
  • FIG. 8B is a cross-sectional view of a deformable membrane formed with two membrane layers laminated around a magnetic element.
  • FIG. 8C is a cross-sectional view of a deformable membrane formed with a central magnetic element, two outer membrane layers and a central stencil layer.
  • FIG. 9A is a cross-sectional view of a magnetic field generating element microfluidic flow control device and at least a portion of a microfluidic flow control device having a magnetic element laminated within a membrane layer, the membrane being in a relaxed state.
  • FIG. 9B provides the same cross-sectional view as FIG. 9A, but with the membrane in a deformed state to prevent flow between two microfluidic channels within the flow control device.
  • FIG. 10 is a perspective view of a magnetic field generator array disposed above a microfluidic flow control device having multiple fluid inlets and outlets and multiple magnetic elements associated with flexible membranes to provide flow control utility.
  • FIG. 11 is a schematic illustration of a microfluidic flow control system showing interconnections between a microfluidic flow control device, a magnetic field generator array, and a controller, among other components.
  • FIG. 12A is a cross-sectional view of at least a portion of a microfluidic device having a deformable membrane disposed above an aperture permitting fluid communication between two channels.
  • FIG. 12B provides the same cross-sectional view as FIG. 12A, but with the membrane deformed to seal the aperture and prevent fluid communication between the two channels.
  • channel as used herein is to be interpreted in a broad sense. Thus, it is not intended to be restricted to elongated configurations where the transverse or longitudinal dimension greatly exceeds the diameter or cross-sectional dimension. Rather, the terms are meant to include cavities, tunnels, or chambers of any desired shape or configuration through which liquids may be directed. Such a fluid cavity may, for example, comprise a flow-through cell where fluid is to be continually passed or, alternatively, a chamber for holding a specified, discrete amount of fluid for a specified amount of time. “Channels” may be filled or may contain internal structures comprising valves or equivalent components.
  • channel segment refers to a region of a channel.
  • a “change in channel segment shape and geometry” indicates any change in the dimensions of a channel segment. For instance, the channel segment can become smaller, larger, change shape, be completely closed, be partially closed, be permanently restricted, etc.
  • microfluidic as used herein is to be understood, without any restriction thereto, to refer to structures or devices through which fluid(s) are capable of being passed or directed, wherein one or more of the dimensions is less than 500 microns.
  • stencil refers to a material layer that is preferably substantially planar, through which one or more variously shaped and oriented portions has been cut or otherwise removed through the entire thickness of the layer, and that permits substantial fluid movement within the layer (e.g., in the form of channels or chambers, as opposed to simple through-holes for transmitting fluid through one layer to another layer).
  • the outlines of the cut or otherwise removed portions form the lateral boundaries of microstructures that are formed upon sandwiching a stencil between substrates and/or other stencils.
  • Microfluidic devices providing flow control utility may be fabricated in various ways using a wide variety of materials.
  • microfluidic devices according to the present invention are constructed using stencil layers to define channels and/or chambers.
  • a stencil layer is preferably substantially planar and has microstructure cut through the layer.
  • a computer-controlled plotter modified to accept a cutting blade may be used to cut various patterns through a material layer.
  • a computer-controlled laser cutter may be used.
  • stencil layers may be formed using conventional stamping, cutting, and/or molding technologies.
  • materials that may be used to fabricate microfluidic devices using sandwiched stencil layers include polymeric, metallic, and/or composite materials, to name a few.
  • use of stencil-based fabrication methods enables a particular device design to be rapidly “tuned” or optimized for particular operating parameters, since different material types and thicknesses may be readily used and/or substituted for individual layers within a device.
  • the ability to prototype devices quickly with stencil fabrication methods permits many different variants of a particular design to be tested and evaluated concurrently.
  • the top and bottom surfaces of stencil layers may mate with one or more adjacent stencil or substrate layers to form a substantially enclosed device, typically having one or more inlet ports and one or more outlet ports.
  • one or more layers of a device are comprised of single- or double-sided adhesive tape, although other methods of adhering stencil layers may be used.
  • a portion of the tape (of the desired shape and dimensions) can be cut and removed to form channels, chambers, and/or apertures.
  • a tape stencil can then be placed on a supporting substrate, between layers of tape, or between layers of other materials.
  • stencil layers can be stacked on each other.
  • the thickness or height of the channels can be varied by varying the thickness of the stencil (e.g., the tape carrier and the adhesive material thereon) or by using multiple substantially identical stencil layers stacked on top of one another.
  • Suitable tape carrier materials include but are not limited to polyesters, polycarbonates, polytetrafluoroethlyenes, polypropylenes, and polyimides. Such tapes may have various methods of curing, including curing by pressure, temperature, or chemical or optical interaction. The thicknesses of these carrier materials and adhesives may be varied.
  • microfluidic devices according to the present invention are fabricated from materials such as glass, silicon, silicon nitride, quartz, or similar materials.
  • materials such as glass, silicon, silicon nitride, quartz, or similar materials.
  • Various conventional machining or micromachining techniques such as those known in the semiconductor industry may be used to fashion channels, vias, and/or chambers in these materials. For example, techniques including wet or dry etching and laser ablation may be used. Using such techniques, channels, chambers, and/or apertures may be made into one or more surfaces of a material or penetrate through a material.
  • Still further embodiments may be fabricated from various materials using well-known techniques such as embossing, stamping, molding, and soft lithography.
  • attachment techniques including thermal, chemical, or light-activated bonding; mechanical attachment (such as using clamps or screws to apply pressure to the layers); or other equivalent coupling methods may be used.
  • a microfluidic device includes a first microfluidic channel segment and a second microfluidic channel segment that are separated by a deformable membrane at a regulatory region.
  • the channels may be defined in horizontal layers of a device, with the deformable membrane forming a separate horizontal layer separating the channel layers.
  • the channels can overlap at any suitable angle.
  • the channels may be orthogonal, thus limiting the area of the overlap region, or they may be substantially parallel.
  • the first and second channels also can be in fluid communication. Where the channels are in fluid communication, the use of the terms first channel segment and second channel segment refer to regions forming a channel disposed on different layers of the device.
  • a change in relative pressure between the first and second channels results in deformation of the membrane separating the channels.
  • the membrane is deformed towards the channel segment with lower relative pressure.
  • the membrane can partially block flow of the fluid through the channel segment with lower relative pressure or can substantially block flow of the fluid through the channel segment with lower relative pressure.
  • the degree of deformation of the deformable membrane is related to the differential pressure between the first and second channels. Generally, the greater the differential pressure, then the greater the observed deformation of the deformable membrane.
  • FIGS. 1 A- 1 C illustrate at least a portion of a microfluidic device 90 having a deformable membrane 102 that is responsive to changes in pressure between two channel segments 105 , 106 .
  • the channel segments 105 , 106 may be defined in stencil layers 101 , 103 disposed between outer layers 100 , 104 .
  • the deformable membrane 102 separates the first channel segment 105 defined in layer 101 from the second channel segment 106 defined in layer 103 .
  • the deformable membrane 102 adopts a neutral position, as shown in FIG. 1A.
  • the deformable membrane 102 will deform towards channel segment 106 , as shown in FIG. 1B.
  • the deformable membrane 102 (specifically the lower surface 107 of the membrane 102 ) may contact the upper surface 108 of the outer layer 104 .
  • the deformable membrane 102 may deform into the channel segment 105 , as shown in FIG. 1C.
  • the deformable membrane 102 (specifically, the upper surface 109 ) will contact the lower surface 110 of substrate layer 100 .
  • the channel segment-containing portion of the device 90 can be constructed using any suitable materials, by any suitable technique.
  • a microfluidic device is constructed with sandwiched stencil layers.
  • the layers of the device containing channel segments may also be constructed from etched silicon, molded polymers, or using other materials or fabrication methods known to one skilled in the art of making microfluidic devices.
  • the channel segment 105 could be surface etched into a single integral substrate substituted for separate layers 100 and 101 .
  • channel segment 106 could be etched into a single integral substrate substituted for separate layers 103 and 104 .
  • Microfluidic devices described herein may be constructed using still further techniques.
  • channels are constructed in materials using etching, embossing, or molding techniques. Two or more different elements may be constructed. Then, the multiple elements may be assembled face-to-face with a deformable membrane disposed between them. The channels in the two etched or embossed devices may overlap in certain areas of the completed device with the deformable intermediary layer between the channel segments. Additionally, one or more apertures may be defined in the intermediate layer to serve as vias connecting the channels in the upper and lower devices. More complicated systems can be constructed.
  • Control of the properties of the microfluidic device can be achieved by varying the deformable membrane material.
  • the material can be elastically deformable or can be inelastically deformable.
  • Suitable membrane materials include papers, foils and polymers.
  • the membrane is a polymer including, for example, polyesters, polycarbonates, polytetrafluoroethylenes, polypropylenes, polyimides (e.g., KAPTON®) and polyesters (e.g., MYLAR®), silanes (e.g., PDMS) and polymethylmethacrylate (PMMA).
  • a more rigid material will deflect less readily due to a change in pressure, while a more malleable material will deflect more easily.
  • a membrane material also can be chosen based on its ability to perform repeated deformation cycles.
  • the sensitivity of microfluidic device to changes in differential pressure may also be controlled by varying the thickness of the deformable membrane.
  • a thinner membrane material will be more easily deformed and will respond more easily to changes in differential pressure.
  • a thicker membrane will generally be less easily deformed and will be less sensitive to changes in relative pressure.
  • the thickness or height of the channel segment into which the deformable channel segment moves also will impact the fluid control performance of the system.
  • Adjacent microfluidic channels or chambers separated by a deformable membrane may be fashioned in a wide variety of sizes, shapes, and geometries. Channel or chamber segments can overlap in a perpendicular format, at an angle or along a length of channel segment that is parallel. Channels within a regulator region may be formed with constant widths or variable widths.
  • FIGS. 6 A- 6 B One example of a regulatory region is provided in FIGS. 6 A- 6 B, in which the regulatory region 207 is circular.
  • FIGS. 2 A- 2 B show at least a portion of a microfluidic device 299 having, at the valve location, a relatively large channel segment 305 and a smaller channel segment 306 separated by deformable membrane 302 .
  • the membrane 302 in the valve region deforms toward and into the smaller channel segment 306 , as shown in FIG. 2A.
  • channel segment 306 The small relative size of channel segment 306 means that the deformable membrane 302 only reduces the available cross section of channel segment 306 to about half its original size. However, when the relative pressure in channel segment 306 is higher than the pressure in channel segment 305 , then the membrane 302 deforms toward and into the larger channel segment 305 , as shown in FIG. 2B. Because of the relatively large area of the channel 305 bounded by the deformable portion of the membrane 302 , the membrane 302 is able to move more easily into channel segment 305 , thereby significantly changing the cross section of the channel segment 305 .
  • a membrane having a deformable portion 5 mm in diameter will deflect across a 3-mil (75 microns) channel segment more readily than a 2 mm diameter deformable membrane portion, because there is less of a percentage of deformation of the larger membrane.
  • a channel subject to fluidic control defines an aperture opposite and substantially aligned with the center of a deformable membrane.
  • a fluid flow path is provided in a direction parallel to the direction of travel of the deformable membrane.
  • FIG. 6C shows at least a portion of a microfluidic device having a channel segment 207 in fluid communication with an aperture 210 aligned substantially centrally below the deformable membrane 202 . Deformation of the membrane 202 towards channel segment 207 results in substantially complete blockage of fluid flow between channel segments 210 and 207 .
  • While similar devices can be constructed with the aperture disposed in various positions relative to the path of the deformable membrane, it is highly preferable to position the aperture near to the center of travel of the deformable a membrane to promote substantial blockage of the fluid flow path by the membrane.
  • the size of the aperture will also affect the amount of pressure required to provide substantially leak-free sealing.
  • a system can be constructed in which deformation of the material results in either partial blockage or substantially complete blockage of fluid flow through a channel segment.
  • An elastic material may be used where reversible control of fluid flow is desired. Lowering the pressure in the higher relative pressure channel segment allows the deformable membrane to resume its neutral state, allowing unrestricted fluid flow.
  • an inelastic material Upon increase in pressure in one channel segment, an inelastic material will be plastically deformed towards the channel segment with lower pressure. The material will remain substantially in the deformed position. Such results may be obtained with semi-malleable materials including suitable metal foils.
  • a deformable membrane also can be made of materials with surface properties that alter its behavior.
  • a membrane can be tacky or have an adhesive coating. Such properties or coatings can be applied to one or both sides of the deformable membrane.
  • the deformable membrane can operate as a variable switch. At low relative pressures, the membrane can act elastically. At high pressures, or for systems designed for the deformable membrane to physically contact the opposing wall of the adjacent channel segment, the deformation can result in permanent or semi-permanent closure of the adjacent channel segment.
  • the membrane used can be non-adhesive, but the surface against which it seals can be constructed with a tacky or adhesive surface. For example, in FIG.
  • the lower surface 107 of the deformable membrane 101 can be coated with an adhesive, or can be constructed from an adhesive tape, such that upon deformation sufficient to provided contact between the membrane 102 and the lower layer 104 , the deformable membrane 102 can be affixed to the upper surface 108 of the lower layer 104 .
  • the degree of permanence of the closure depends on factors including elasticity of the membrane and the strength of the adhesive material used. Similar results can be achieved by coating the upper surface 108 with adhesive or both surfaces 107 and 108 with adhesive, or by forming one or more of these surfaces from single- or double-sided self-adhesive tape materials. Referring to FIG.
  • the bottom surface of the membrane 107 or the upper surface 108 of the bottom layer 104 may include permanent or semi-permanent adhesives.
  • the membrane 102 When the membrane 102 is deformed, such as by an elevated pressure within the upper chamber 105 , then the membrane 102 may be deformed to contact the lower layer 104 to permit the adhesive to bind the surfaces together and permanently or semi-permanently obstruct the lower channel segment 106 .
  • the membrane 102 may be deformed and adhered to the lower surface in a semi-permanent manner that may be reversed by further manipulation. For example, when pressure is applied to 105 , the membrane 102 is deformed so as to the contact the lower layer 104 , where the membrane 102 and the upper surface 108 of the lower layer 104 are adhesively bound. Alternatively, the membrane 102 may be plastically deformed into the lower channel 106 . When the pressure is re-equalized between the upper and lower chambers 105 , 106 , the membrane 102 will remain affixed to the lower layer 104 until sufficient pressure is applied to channel segment 106 to overcome the adhesive bond or plastic deformation of the membrane 102 . In many cases, the pressure required to reposition (i.e., re-deform) the membrane 102 may be greater than the pressure to originally deform it.
  • a microfluidic valve may include two microfluidic channels separated by a seating surface defining an aperture for mating with a deformable membrane to provide flow control utility.
  • FIGS. 12 A- 12 B illustrate a microfluidic device 197 fabricated from seven layers 200 - 204 , 220 , 221 and having a control channel 205 bounded in part by a deformable membrane 202 . With the deformable membrane in a relaxed, neutral state, fluid flow may be established between a first channel 207 and a second channel 222 defined in different layers 203 , 220 of the device 197 and separated by a seating layer 204 defining an aperture 210 .
  • the deformable membrane 202 is disposed substantially centrally above the aperture 210 to promote tight sealing of the aperture when the control channel 205 is pressurized to deform the membrane 202 to contact the seating layer 204 , as shown in FIG. 12B.
  • the valve seating layer 210 adjacent to the aperture 210 may be considered a valve seating surface.
  • the device 197 thus serves as a normally open valve that permits flow through the aperture when the deformable membrane is in an undeformed state. Selective pressurization of the control channel 205 permits closure of the valve.
  • Either or both of the membrane 202 and the seating layer 204 may be provided with an adhesive surface to provide latching valve utility.
  • more complex fluid control structures utilizing multiple membranes may be formed.
  • more than two channels can meet at a valve region separated by one or more membranes.
  • more than one pressure regulator may be stacked in a given vertical position of a microfluidic device.
  • three channels overlap at a single valve region, with two deformable membranes separating the various channels.
  • FIGS. 3 A- 3 E show five cross-sectional views of such an overlap.
  • FIG. 3A shows a cross-section of at least a portion of a microfluidic device 119 formed using sandwiched stencils, the device having seven layers 120 - 126 and forming three channel segment/chamber regions 127 - 129 .
  • the central stencil layer 123 has a greater height than the other layers, and the layers 122 and 124 are flexible or deformable membranes. Fluid flow through the central channel segment 128 is affected by both the upper chamber region 127 and the lower chamber region 129 .
  • FIG. 3B shows the central channel segment 128 being partially blocked following a pressure increase within the upper chamber 127 , causing deflection of the upper membrane 122 toward and into the central channel 128 .
  • FIG. 3C shows the channel segment 128 being substantially (almost completely) blocked following pressure increases in both the upper and lower chamber 127 , 129 , which cause both membranes 122 , 124 to deform toward and into the central channel 128 .
  • FIG. 3B shows the central channel segment 128 being partially blocked following a pressure increase within the upper chamber 127 , causing deflection of the upper membrane 122 toward and into the central channel 128 .
  • FIG. 3C shows the channel segment 128 being substantially (almost completely) blocked following pressure increases in both the upper and lower chamber
  • 3D shows another operating state wherein the channel segment 128 is partially blocked following a pressure increase in the lower chamber region 129 .
  • the central channel segment 128 is enlarged in response to a reduced pressure in both the upper and lower chambers 127 , 129 .
  • a differential pressure can be generated between a first and a second channel segment either by increasing the pressure in one channel segment, or through a relative decrease in pressure in one channel segment.
  • the pressure of a fluid (encompassing both liquids and gases) can be increased by a pump such as, for example, a syringe or other mechanically operated pump.
  • Reduced pressure can be achieved in the channel segment by applying a vacuum to a channel segment, for example using a vacuum pump.
  • a channel segment is pressurized to greater than atmospheric pressure and a pressure reduction is desired, then the pressure can be reduced by venting the channel segment to the atmosphere or to a lower-pressure reservoir. Pressure can also be controlled by changing the temperature within one channel segment of the device.
  • the fluid within the channel segment undergoes a large volume change with changing temperature.
  • the fluid is a gas.
  • the pressure can be increased by raising the temperature of the gas within the channel segment and can be decreased by lowering the temperature within the channel segment.
  • the pressure within a channel segment also can be changed by processes such as vaporization or electrolysis (a process in which an electric current is used to break a liquid within a channel segment into gaseous components). For example, water may be electrolyzed into hydrogen gas and oxygen gas.
  • Microfluidic membrane valves may be actuated with means other than pressure.
  • a membrane can be moved within a device manually or with a mechanical actuator.
  • Mechanical actuators include, for example, a piston, a solenoid, and a lever.
  • the flexible membrane also can be coupled to a material that alters shape in response to a stimulus, for example, heat or an electric current. Titanium-Nickel composites are known that undergo large conformational changes in response to changes in temperature. Such a composite can be incorporated into the deformable membrane. When heated, as by passing an electric current through the composite, the composite will change shape and deflect the deformable membrane.
  • the membrane also can be constructed of a magnetic material, or provided with a magnetic coating. As will be discussed further hereinafter, deformation of such a membrane can be achieved using an external magnet, including an electromagnet or an electric field generator.
  • Microfluidic membrane valves may be combined into more complex devices.
  • the embodiments shown in FIGS. 3 A- 3 E and others form the basics of microfluidic logic elements.
  • the embodiment shown forms a microfluidic AND/OR element.
  • the flow through the channel 128 may be considered to be 1 unit, in FIG. 3B about ⁇ fraction (1/2) ⁇ of one unit, in FIG. 3C about 0 units, in FIG. 3D about 1 ⁇ 2 of one unit, and in FIG. 3E about 2 units.
  • the flow control elements shown in FIGS. 3 A- 3 E can be combined in a network in order to make a two dimensional fluid control system.
  • a network of channels 150 are defined in the center layer of a three dimensional device.
  • the channel network has multiple inlet ports 151 and outlet ports 152 . Any given inlet port is in fluidic connection with all of the outlet ports in the unaltered layer.
  • the channels 150 depicted in FIG. 5A will be disposed between control channels and flexible membranes, such as the channel segment 128 shown in FIGS. 3 A- 3 E.
  • control layers are also made within the device, one disposed above and one disposed below the channel network 150 .
  • the upper control layer of the three-dimensional device includes four vertical control channels 160 - 163
  • the lower control layer of the device has four horizontal control channels 156 - 159 .
  • These control channels 160 - 163 and 156 - 159 overlap in specific regions 155 .
  • the cross-section of each of these overlap regions 155 are the same as those shown in FIGS. 3 A- 3 E.
  • control channels 160 - 163 are represented in cross section by the channel segment 127 in FIGS. 3 A- 3 E and the control channels 156 - 159 are represented in cross section by the channel segment 129 of FIGS. 3 A- 3 E.
  • Two flexible membranes one disposed on either side of the channel network 150 , separate the channel network 150 from the upper and lower control layers. These membranes may be homogeneous membrane layers, or they may be heterogeneous layers to permit the valving or flow control characteristics at any particular region to be “tuned.” Examples of heterogeneous membrane layers are provided in FIGS. 5 C- 5 D.
  • a first heterogeneous membrane layer 175 is composed of four membrane regions 175 A- 175 D, any of which may be formed of different materials to provide desired response characteristics for each quadrant of four nodes or intersections of control channels.
  • a second heterogeneous membrane layer 176 is composed of sixteen membrane regions 176 A- 176 P to permit the response characteristics for each individual overlap region 155 to be separately tuned if desired.
  • the various layers of the flow control device 180 may be assembled in the following order: a lower substrate, a lower control channel layer, a lower flexible membrane layer, a central channel network layer, an upper flexible membrane layer, an upper control channel layer, and finally an upper substrate or cover.
  • any given inlet port 151 can be connected to any given outlet port 152 by simply controlling the pressures of the control channels 160 - 163 and 156 - 159 . This may be accomplished with a fluid control system 320 such as illustrated in FIG. 5F.
  • control valves 326 A- 326 D and 328 A- 328 D which are preferably three-way valves or the equivalent to permit excess air to be released if necessary.
  • Each valve 326 A- 326 D and 328 A-D is controlled by a controller 313 .
  • the controller 313 is preferably electronic, and more preferably microprocessor-based.
  • the controller 313 may be programmed to execute complex, sequential or repetitive fluid functions on the device 180 .
  • One or more sensors 329 may be in sensory communication with the microfluidic flow control device 180 and coupled to the controller 313 to provide feedback and/or sensory data to be stored in or otherwise used by the controller.
  • An input device 331 and display 332 may be coupled to the controller 313 to aid with programming and processing sensory data, among other functions.
  • FIG. 5E An example showing operation of the microfluidic device 180 is shown in FIG. 5E.
  • a pressure of 20 psi (138 kPa) is applied to control channel segment 157
  • negative 10 psi (69 kPa) is applied to control channel segment 160
  • positive 10 psi (69 kPa) is applied to control channel segment 159 .
  • All of the other control channels are left at atmospheric pressure.
  • All of the fluid channels under control channel segment 157 are blocked, because 10 psi (69 kPa) is sufficient to substantially block the channels.
  • the valve regions of interest are 170 , 171 , and 172 .
  • the upper control chamber has 20 psi (69 kPa), and the bottom control chamber has ⁇ 10 psi (69 kPa) for a net of +10 psi (69 kPa), which is sufficient to locally block the fluid channel in network 150 .
  • the bottom has negative 10 psi and the channel segment is opened more.
  • the +10 psi (69 kPa) applied to the top control channel equals the ⁇ 10 psi (69 kPa) applied to the bottom control channel, and the central channel segment remains open.
  • the fluid supplied to the central channel layer 150 through the input ports 151 can only take the pathway shown by the arrow.
  • any outlet port 152 can be reached by varying the pressure combinations to the control channels 156 - 159 and 160 - 163 .
  • a flow control device can have more than one channel segment on a given layer at a regulatory region.
  • a microfluidic device 699 includes two channel segments 706 and 707 defined in layer 703 and separated by a deformable membrane 702 from a channel segment 705 defined in an upper layer 701 .
  • the deformable membrane 701 is not adhered a seating region 703 A defined in the layer 703 .
  • the pressure in the channel segment 705 is high relative to both channels 706 and 707 , then fluid communication between the channels 706 and 707 within the regulatory region is prevented by the membrane 702 pressed into contact with the seating region 703 A, such as shown in FIG. 7A.
  • both channels 706 and 707 are higher than that in the channel 705 , such as shown in FIG. 7B, then the membrane 702 will deform toward and into the channel segment 705 , thus allowing fluidic passage between the channels 706 and 707 .
  • Factors affecting whether an increased pressure in channel segments 706 or 707 is sufficient to open a flow path between the channels indude the size of the seating region, the thickness and composition of the flexible membrane 702 , and the size of the regulatory region (which affects the size of the membrane subject to deformation).
  • pressure-sensitive regions may be integrated into a microfluidic device to provide internal feedback, such that a change in pressure or flow rate within one region of a channel segment will affect another region.
  • a feedback loop is used to create a pressure regulation device.
  • a microfluidic device is constructed where a first channel segment located in one layer of a three-dimensional device is in fluid communication with a second channel segment in another layer of the device.
  • the two channels in distinct layers may be connected through a via or through-hole between layers.
  • one channel segment is positioned so that it passes back over the other channel segment in a lower layer. This upper section can pass over the lower region one or more times and can pass over the channel segment in parallel along its axis or cross the channel segment at an angle.
  • a deformable membrane separates the two channel segments at a regulatory region.
  • a pressure increase in the upstream part of the channel segment will cause the first channel segment to expand, thus compressing the overlapping downstream part of the channel segment. This will deform the membrane towards the second channel segment, altering the shape or geometry of the second channel segment.
  • the flow through the second segment also can decrease, and will vary depending on the design of the regulatory region and with the pressure applied.
  • the membrane can provide a partial blockage or a substantially complete blockage to fluid flow through one channel segment.
  • a subsequent decrease in the pressure within the channel segment will result in said channel segment attaining its previously unrestricted or “relaxed” neutral state.
  • a pressure-activated valve can regulate flow between two channel segments in a single microfluidic channel because of the pressure-drop that occurs “downstream” in microfluidic channels.
  • the pressure within a microfluidic channel decreases with distance from the inlet port. At low input pressures, there is a minimal pressure drop in a long channel segment. As the input pressure increases, it becomes more difficult for the internal pressures to equalize, and the pressure differential from one end of a channel segment to the other is much larger. The higher the operating pressure of the microfluidic device, the greater the pressure differential generated over the length of a channel.
  • shut-off pressures can be designed or “programmed” into the device.
  • a relatively long channel segment connects the one side of the shut-off valve membrane and the other; a long channel segment length is preferably provided to create the pressure differential.
  • FIGS. 4 A- 4 B A microfluidic device with a built in pressure regulation system is shown in FIGS. 4 A- 4 B.
  • a microfluidic device 130 was constructed using a sandwiched stencil fabrication method from five layers 131 - 135 .
  • the first layer 131 defines one inlet port 136 and two outlet ports 137 , 138 .
  • the second layer 132 defines two vias 140 and a channel segment 139 having a nominal width of 40 mils (1000 microns).
  • the third layer 133 defines a central via 141 and two lateral vias 142 .
  • the fourth layer 134 defines a channel 143 also having a nominal width of 40 mils (1000 microns). All of the vias are 70 mils in diameter.
  • the layers 131 - 134 stencil layers are all constructed from 3 mil (75 microns) thickness single-sided tape comprising a polypropylene carrier with a water-based adhesive.
  • the bottom stencil 100 is a 0.25 inch (6.3 mm) thick block of acrylic.
  • fluid is injected at inlet port 136 at a low backpressure.
  • the fluid passes through channel segment 139 until it reaches junction point 144 .
  • the fluid then splits evenly down the two parts of channel segment 143 until it reaches the outlet ports 137 and 138 .
  • the fluid splits evenly at the junction point 144 and is divided evenly.
  • the pressure within the channel segment increased, as did the flow rate.
  • the pressure in the upper channel segment 139 pushes on the polymeric membrane 133 that separates the two channels.
  • the polymer material 133 is locally deformed and partially blocks the lower channel segment 143 , thus partially restricting the flow in that channel segment.
  • the size of the exit channels are adjusted such that the flow out of the device 130 remains constant no matter what backpressure is applied.
  • This device 130 may be used in various applications, including but not limited to constant delivery of materials such as in drug delivery applications.
  • inlet port 136 is connected to a pressurized container of fluid (not shown) that contains a drug of interest.
  • the outlet ports 137 , 138 are connected to a delivery mechanism to a body. When the pressurized container is full, the backpressure is high and the outlet 137 is closed and 138 is open. Although the pressure remains high, the resistance in the channels is even higher since there is only one outlet.
  • a microfluidic device was constructed to regulate flow rate over a large range of input pressures.
  • a microfluidic flow regulation device 199 was constructed using a stencil fabrication method from five layers 200 - 204 . Starting from the bottom, the first layer 204 defined one inlet port 209 and two outlet ports 210 , 211 . The second layer 203 defined a via 214 and a channel 206 terminating at a chamber 207 . The third layer 202 defined two vias 208 , 208 A. The fourth layer 201 defined a channel 205 and connected chamber 215 . The fifth layer 200 served as a cover for the fourth layer 201 . The assembled device is shown in FIG.
  • FIGS. 6 C- 6 D The overlap region 212 is shown in cross section in FIGS. 6 C- 6 D with the valve in open and closed positions, respectively.
  • fluid is injected into the inlet port 209 .
  • the fluid travels through the vias 214 , 208 , through channel segment 205 , down through the via 208 A and the channel 206 and is split towards the two exit ports 210 and 211 .
  • the inlet pressure is relatively low, the flexible membrane 202 is not substantially deformed (see FIG. 6C) and the fluid passes evenly out of the two exit ports 210 , 211 .
  • the pressure at the inlet is increased, the pressure in the channel 205 and chamber 215 increases, thus deforming the membrane 202 (see FIG. 6D) and partially blocking the outlet port 210 .
  • FIGS. 12 A- 12 B A structure substantially similar to that illustrated in FIGS. 6 C- 6 D is provided in FIGS. 12 A- 12 B, with the primary difference being the addition of outlet channels 222 defined by stencil layer 220 and a substrate 221 to continue flow within the device 197 .
  • a flow control device such as a valve is magnetically actuated.
  • magnetic actuation requires a field generator and a magnetic (i.e,, paramagnetic or ferromagnetic) element.
  • the magnetic element moves in response to application of a magnetic field, with the direction of motion of the magnetic element depending on the direction of the applied magnetic field.
  • Opening or closing force of a magnetically actuated valve may be adjusted by varying the magnitude of the applied magnetic field, or selecting a magnetic element with appropriate response characteristics (e.g., magnetization). For example, if strong magnetization is desirable, then magnetic elements formed from rare earth magnetic materials may be used.
  • At least one magnetic element is integrated into a microfluidic flow control device and used in conjunction with a deformable membrane.
  • a deformable membrane includes one or more discrete magnetic elements.
  • a discrete magnetic element may be attached to a deformable membrane using various means including adhesives and mechanical retention.
  • FIG. 8A illustrates a magnetic element 400 affixed to a deformable membrane 401 using an adhesive.
  • a discrete magnetic element 402 is sandwiched between multiple deformable membrane layers 403 , 404 .
  • a central membrane layer 407 may be a stencil layer defining an aperture into which a magnetic element 405 may be inserted.
  • Multiple membrane layers 406 - 408 may be laminated together using conventional bonding methods such as, for example, adhesive or thermal bonding.
  • at least one membrane layer containing the discrete magnetic element comprises a self-adhesive tape material.
  • Adhesiveless films of deformable materials such as latex, polypropylene, polyethylene, and polytetrafluoroethylene are readily available in thicknesses of approximately 0.5 mil (13 microns) or less. If supplied as self-adhesive tape, such materials are readily available with a total (carrier plus adhesive) thickness between approximately 1.5 and 2.0 mils (38 to 50 microns).
  • An embodiment such as shown in FIG. 8B may thus be provided with a combined membrane thickness of approximately 2.0 to 2.5 mils (50 to 63 microns).
  • the central layer 407 may be a stencil layer formed of contact adhesive, so as to form a laminated membrane of approximately the same total thickness as before (approximately 2.0 to 2.5 mils, or 50 to 63 microns).
  • a discrete magnetic element to be integrated with a membrane layer may be provided in any size or shape sufficient to promote the desired flow control characteristics. If the flow control device utilizes a valve seat of a particular geometry, then the desired shape and size of the magnetic element is preferably selected to interface with the valve seat geometry. Particular shapes of magnetic elements that may be used include cylindrical, spherical, or annular shapes.
  • a valve seat may include an aperture that may be selectively sealed to control fluid flow. Preferably, the membrane may be deformed by magnetic force to seal the aperture, thus preventing fluid flow.
  • an annular magnetic element may be disposed adjacent to an aperture defined in a membrane, so that under certain conditions fluid is permitted to flow through both the membrane aperture and the annular magnetic element. This fluid flow path may be selectively blocked or re-established through application of a magnetic field that deforms the membrane against a valve seating surface.
  • a flexible membrane comprising a diffuse magnetic layer may be provided. If a diffuse magnetic layer is used, then it is preferably coupled to a deformable membrane selected for desirable material properties such as chemical compatibility or sealing characteristics.
  • the magnetic field generator preferably comprises a coil of current-carrying wire, preferably insulated wire.
  • Current may selectively applied to the coil, such as by using an external current source, to generate a magnetic field.
  • the strength of the magnetic field may be adjusted by varying the magnitude of the current and the number of turns of wire.
  • the direction of the resulting magnetic field is parallel to the central axis of the coil.
  • a field-concentrating element such as a ferromagnetic core, is provided along the central axis of the coil.
  • a magnetic field generator 425 having a field-concentrating element 427 and a coil of insulated wire 426 is shown in FIGS. 9 A- 9 B.
  • the field-concentrating element 427 is preferably substantially cylindrical in shape, and if a highly focused field is desired then the cylinder should be of a small diameter.
  • the current-carrying wire 426 may be directly wrapped around the field-concentrating element 427 .
  • a magnetically actuated membrane valve is operated by selectively applying current to the coil 426 .
  • current in one direction is applied to the coil 426 .
  • current is applied in the opposite direction.
  • FIG. 9A shows the membrane 411 in a relaxed position, with the field generator 425 substantially centered above the magnetic element 417 , which in turn is substantially centered over an aperture 420 permitting fluid communication between a first channel segment 418 and a second channel segment 419 within a microfluidic flow control device 410 .
  • the flow control device 410 is formed from a three-layer composite membrane 411 and four other device layers 413 - 416 .
  • FIG. 9B shows the membrane 411 in a deformed position and contacting the seating layer 414 adjacent to the aperture 420 to prevent fluid flow between the first channel segment 418 and the second channel segment 419 .
  • a microfluidic flow control device 430 includes at least one flexible membrane and multiple discrete magnetic elements 431 .
  • the device 430 may be used to manipulate fluid between multiple fluidic inlet ports 432 and multiple outlet ports 433 .
  • a magnetic field generator array 435 having multiple coils and field concentrating elements 436 may be positioned in relatively close proximity to the microfluidic flow control device 430 to manipulate fluid within the device 430 .
  • the field generator array 435 preferably does not contact the microfluidic device 430 .
  • one coil and field focusing element 436 is provided and paired with each magnetic element 431 .
  • One advantage of using field focusing elements in such a device is to minimize unwanted interference between unpaired coils and magnetic elements.
  • High density arrays of field generators may thus be used to provide precise control over fluid flowing in a small area. Complex operation of a fluidic system can thus be provided without requiring any external to ever physically contact the device 430 .
  • utility similar to that described in connection with FIGS. 5 A- 5 F may be provided.
  • a controller 442 is provided to selectively apply currents to the various field generator coils 436 , such as may be contained in a field generator array 435 .
  • the controller 442 is preferably electronic, and more preferably is microprocessor-based, and receives power from a power source 444 .
  • the controller 442 is programmable to permit execution of complex, repetitive and/or sequential functions with minimal user interaction.
  • one or more sensors 440 are included in sensory communication with the microfluidic device 430 to provide feedback and/or useful data to the controller 442 .
  • Suitable sensors may include, for example, pressure sensors, flow sensors, optical sensors, and displacement sensors. If the provided sensors are capable of inferring fluid flow, then the system may be used to provide flow regulation utility. More specifically, feedback from a flow sensor may be provided to the controller 442 , which in turn may provide an analog signal to one or more field generators to regulate flow. Alternatively, pressure regulation utility may be provided in a similar fashion.
  • An input device 446 and display 448 are preferably coupled to the controller 442 to aid in programming and/or analyzing data generated by the system 450 .

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  • Chemical & Material Sciences (AREA)
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  • Engineering & Computer Science (AREA)
  • Dispersion Chemistry (AREA)
  • Mechanical Engineering (AREA)
  • Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Micromachines (AREA)
  • Flow Control (AREA)
  • Reciprocating Pumps (AREA)
  • Magnetically Actuated Valves (AREA)
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Cited By (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030138829A1 (en) * 2001-11-30 2003-07-24 Fluidigm Corp. Microfluidic device and methods of using same
US20040115838A1 (en) * 2000-11-16 2004-06-17 Quake Stephen R. Apparatus and methods for conducting assays and high throughput screening
US20050196321A1 (en) * 2004-03-03 2005-09-08 Zhili Huang Fluidic programmable array devices and methods
US6960437B2 (en) 2001-04-06 2005-11-01 California Institute Of Technology Nucleic acid amplification utilizing microfluidic devices
US20060076068A1 (en) * 2004-10-13 2006-04-13 Kionix Corporation Microfluidic pump and valve structures and fabrication methods
US20080057274A1 (en) * 2006-05-22 2008-03-06 Aida Engineering, Ltd. Micro-channel chip and a process for producing the same
US20080182757A1 (en) * 2007-01-26 2008-07-31 Illumina, Inc. Image data efficient genetic sequencing method and system
US20080271799A1 (en) * 2005-09-20 2008-11-06 Koninklijke Philips Electronics, N.V. Microfluidic Regulating Device
US7452726B2 (en) 2002-04-01 2008-11-18 Fluidigm Corporation Microfluidic particle-analysis systems
WO2008073691A3 (en) * 2006-12-08 2008-11-20 Siemens Healthcare Diagnostics Sample preparation device
US20090093085A1 (en) * 2004-08-30 2009-04-09 Masanori Onodera Carrier Structure for stacked-type semiconductor device, method of producing the same, and method of fabricating stacked-type semiconductor device
US20090269248A1 (en) * 2008-04-23 2009-10-29 Bioscale, Inc. Method and apparatus for analyte processing
KR100931302B1 (ko) 2008-02-05 2009-12-11 한국과학기술원 서로 다른 임계압력을 가지는 밸브를 이용한 마이크로유체분배기
US20090320930A1 (en) * 2008-06-30 2009-12-31 Canon U.S. Life Sciences, Inc. System and method for microfluidic flow control
US20100116343A1 (en) * 2005-01-31 2010-05-13 President And Fellows Of Harvard College Valves and reservoirs for microfluidic systems
US20100137166A1 (en) * 2007-01-26 2010-06-03 Illumina, Inc. Independently removable nucleic acid sequencing system and method
US20100166609A1 (en) * 2008-12-26 2010-07-01 Aida Engineering, Ltd. Microchannel chip
US7815868B1 (en) 2006-02-28 2010-10-19 Fluidigm Corporation Microfluidic reaction apparatus for high throughput screening
US7867194B2 (en) 2004-01-29 2011-01-11 The Charles Stark Draper Laboratory, Inc. Drug delivery apparatus
US7867193B2 (en) 2004-01-29 2011-01-11 The Charles Stark Draper Laboratory, Inc. Drug delivery apparatus
US8127794B2 (en) 2006-09-19 2012-03-06 Agency For Science, Technology And Research Dispenser arrangement for fluidic dispensing control in microfluidic system
CN102449368A (zh) * 2009-05-29 2012-05-09 西门子公司 片上实验室系统中的阀，阀的操纵和制造方法
US8658418B2 (en) 2002-04-01 2014-02-25 Fluidigm Corporation Microfluidic particle-analysis systems
US8871446B2 (en) 2002-10-02 2014-10-28 California Institute Of Technology Microfluidic nucleic acid analysis
US8876795B2 (en) 2011-02-02 2014-11-04 The Charles Stark Draper Laboratory, Inc. Drug delivery apparatus
ITTO20130447A1 (it) * 2013-05-31 2014-12-01 St Microelectronics Srl Valvola microfluidica a membrana e procedimento per fabbricare una valvola microfluidica a membrana
US8965076B2 (en) 2010-01-13 2015-02-24 Illumina, Inc. Data processing system and methods
US9046192B2 (en) 2007-01-31 2015-06-02 The Charles Stark Draper Laboratory, Inc. Membrane-based fluid control in microfluidic devices
WO2014039844A3 (en) * 2012-09-06 2015-07-23 The Board Of Trustees Of The Leland Stanford Junior University Punch card programmable microfluidics
US9267618B2 (en) 2010-05-18 2016-02-23 Samsung Electronics Co., Ltd. Microvalve device and method of manufacturing the same
US9498914B2 (en) 2011-02-15 2016-11-22 National Research Council Of Canada 3D microfluidic devices based on open-through thermoplastic elastomer membranes
US9714443B2 (en) 2002-09-25 2017-07-25 California Institute Of Technology Microfabricated structure having parallel and orthogonal flow channels controlled by row and column multiplexors
EP3248681A1 (de) * 2016-05-23 2017-11-29 ETH Zurich Mikrofluidische vorrichtung zur definition einer anordnung von probenkammern
US10131934B2 (en) 2003-04-03 2018-11-20 Fluidigm Corporation Thermal reaction device and method for using the same
WO2019040088A1 (en) * 2017-08-23 2019-02-28 Facebook Technologies, Llc FLUIDIC SWITCHING DEVICES
US10240622B1 (en) 2017-01-30 2019-03-26 Facebook Technologies, Llc Switchable fluidic device
US10286395B2 (en) 2014-03-20 2019-05-14 Nec Corporation Microchip, microchip controlling method and microchip controlling apparatus
WO2019103236A1 (ko) * 2017-11-24 2019-05-31 (주)비비비 시료의 흐름을 조절할 수 있는 미세유체분석칩
US10422362B2 (en) 2017-09-05 2019-09-24 Facebook Technologies, Llc Fluidic pump and latch gate
US10502327B1 (en) * 2016-09-23 2019-12-10 Facebook Technologies, Llc Co-casted fluidic devices
US10514111B2 (en) 2017-01-23 2019-12-24 Facebook Technologies, Llc Fluidic switching devices
US10591933B1 (en) 2017-11-10 2020-03-17 Facebook Technologies, Llc Composable PFET fluidic device
WO2018213282A3 (en) * 2017-05-15 2020-03-26 The University Of Chicago Universal microfluidic culture system to analyze and control cell dynamics
DE112011106142B3 (de) * 2011-02-15 2020-12-17 National Research Council Of Canada Durchbrochene thermoplastische Elastomer-Membran, ihre Verwendung und Verfahren zu ihrer Herstellung
US11098737B1 (en) 2019-06-27 2021-08-24 Facebook Technologies, Llc Analog fluidic devices and systems
US11231055B1 (en) 2019-06-05 2022-01-25 Facebook Technologies, Llc Apparatus and methods for fluidic amplification
US11371619B2 (en) 2019-07-19 2022-06-28 Facebook Technologies, Llc Membraneless fluid-controlled valve
US12421546B2 (en) 2007-01-26 2025-09-23 Illumina, Inc. Nucleic acid sequencing system
EP4466105A4 (de) * 2022-01-23 2025-10-01 Emerging Viral Diagnostics Hk Ltd Mikrofluidisches ventil

Families Citing this family (106)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3949056B2 (ja) * 2001-04-03 2007-07-25 マイクロニクス， インコーポレイテッド スプリット集中サイトメーター
US7318912B2 (en) * 2001-06-07 2008-01-15 Nanostream, Inc. Microfluidic systems and methods for combining discrete fluid volumes
US7465382B2 (en) * 2001-06-13 2008-12-16 Eksigent Technologies Llc Precision flow control system
US20020189947A1 (en) * 2001-06-13 2002-12-19 Eksigent Technologies Llp Electroosmotic flow controller
US20040109793A1 (en) * 2002-02-07 2004-06-10 Mcneely Michael R Three-dimensional microfluidics incorporating passive fluid control structures
US6976590B2 (en) 2002-06-24 2005-12-20 Cytonome, Inc. Method and apparatus for sorting particles
US6877528B2 (en) * 2002-04-17 2005-04-12 Cytonome, Inc. Microfluidic system including a bubble valve for regulating fluid flow through a microchannel
US6808075B2 (en) 2002-04-17 2004-10-26 Cytonome, Inc. Method and apparatus for sorting particles
US9943847B2 (en) 2002-04-17 2018-04-17 Cytonome/St, Llc Microfluidic system including a bubble valve for regulating fluid flow through a microchannel
US20030210799A1 (en) * 2002-05-10 2003-11-13 Gabriel Kaigham J. Multiple membrane structure and method of manufacture
US6805809B2 (en) * 2002-08-28 2004-10-19 Board Of Trustees Of University Of Illinois Decal transfer microfabrication
US8220494B2 (en) * 2002-09-25 2012-07-17 California Institute Of Technology Microfluidic large scale integration
DE10254312B4 (de) * 2002-11-21 2005-04-21 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Variabler Flußwiderstand
JP2006512092A (ja) * 2002-12-30 2006-04-13 ザ・リージェンツ・オブ・ジ・ユニバーシティ・オブ・カリフォルニア 病原体の検出および分析のための方法および装置
GB0303920D0 (en) * 2003-02-21 2003-03-26 Sophion Bioscience As Capillary stop
CA2522410A1 (en) * 2003-05-19 2004-11-25 Japan Science And Technology Agency Micro chamber for cell culture
AU2004304787A1 (en) * 2003-08-11 2005-07-07 California Institute Of Technology Microfluidic large scale integration
WO2005043112A2 (en) * 2003-09-30 2005-05-12 West Virginia University Research Corporation Apparatus and method for edman degradation on a microfluidic device utilizing an electroosmotic flow pump
DK1722670T3 (da) 2004-03-06 2014-01-06 Hoffmann La Roche Kropsfluidum-prøveudtagningsapparat
US7819822B2 (en) 2004-03-06 2010-10-26 Roche Diagnostics Operations, Inc. Body fluid sampling device
US20070095393A1 (en) * 2004-03-30 2007-05-03 Piero Zucchelli Devices and methods for programmable microscale manipulation of fluids
US7694694B2 (en) * 2004-05-10 2010-04-13 The Aerospace Corporation Phase-change valve apparatuses
US8642353B2 (en) * 2004-05-10 2014-02-04 The Aerospace Corporation Microfluidic device for inducing separations by freezing and associated method
US7721762B2 (en) * 2004-06-24 2010-05-25 The Aerospace Corporation Fast acting valve apparatuses
US7686040B2 (en) * 2004-06-24 2010-03-30 The Aerospace Corporation Electro-hydraulic devices
US7650910B2 (en) * 2004-06-24 2010-01-26 The Aerospace Corporation Electro-hydraulic valve apparatuses
US7608160B2 (en) * 2004-10-13 2009-10-27 Rheonix, Inc. Laminated microfluidic structures and method for making
US7837821B2 (en) 2004-10-13 2010-11-23 Rheonix, Inc. Laminated microfluidic structures and method for making
US7662545B2 (en) * 2004-10-14 2010-02-16 The Board Of Trustees Of The University Of Illinois Decal transfer lithography
WO2006042365A1 (en) * 2004-10-18 2006-04-27 Varian Australia Pty Ltd Liquid chromatography apparatus
US9260693B2 (en) 2004-12-03 2016-02-16 Cytonome/St, Llc Actuation of parallel microfluidic arrays
US7540469B1 (en) 2005-01-25 2009-06-02 Sandia Corporation Microelectromechanical flow control apparatus
AU2005330177C1 (en) * 2005-04-04 2011-08-04 Avantium International B.V. System and method for performing a chemical experiment
CA2620285C (en) * 2005-08-23 2016-08-16 University Of Virginia Patent Foundation Passive components for micro-fluidic flow profile shaping and related method thereof
AU2012200887B2 (en) * 2005-08-23 2015-02-12 University Of Virginia Patent Foundation Passive components for micro-fluidic flow profile shaping and related method thereof
JP2009507193A (ja) * 2005-09-02 2009-02-19 カリフォルニア インスティチュート オブ テクノロジー 流体装置におけるバルブの機械的作動に対する方法及び装置
CA2624243C (en) 2005-09-29 2013-12-31 Siemens Medical Solutions Usa, Inc. Microfluidic chip for synthesizing radioactively labeled molecules suitable for human imaging with positron emission tomography
EP1790861A1 (de) * 2005-11-25 2007-05-30 Bonsens AB Mikrofluidisches System
US7976795B2 (en) * 2006-01-19 2011-07-12 Rheonix, Inc. Microfluidic systems
US7862000B2 (en) * 2006-02-03 2011-01-04 California Institute Of Technology Microfluidic method and structure with an elastomeric gas-permeable gasket
EP1981636A4 (de) * 2006-02-03 2010-06-09 California Inst Of Techn Mikrofluidisches verfahren und struktur mit gasdurchlässiger elastomerdichtung
WO2007094254A1 (ja) * 2006-02-15 2007-08-23 Aida Engineering, Ltd. マイクロ流路チップ及びその製造方法
US7766033B2 (en) * 2006-03-22 2010-08-03 The Regents Of The University Of California Multiplexed latching valves for microfluidic devices and processors
CN101501792A (zh) * 2006-08-15 2009-08-05 皇家飞利浦电子股份有限公司 磁场产生装置
WO2008036997A1 (en) * 2006-09-28 2008-04-03 Fluidyx Pty. Limited A system and method for controlling fluids within a microfluidic device
WO2008039875A1 (en) * 2006-09-28 2008-04-03 California Institute Of Technology System and method for interfacing with a microfluidic chip
CA2664758C (en) * 2006-10-18 2015-06-16 The New Zealand Institute For Plant And Food Research Limited Fluid release valve using flexible fluid permeable membrane
WO2008052138A2 (en) 2006-10-25 2008-05-02 The Regents Of The University Of California Inline-injection microdevice and microfabricated integrated dna analysis system using same
WO2008089769A2 (en) * 2007-01-26 2008-07-31 Diramo A/S Pressurized reservoir for an analysis system
EP1970122A1 (de) * 2007-03-12 2008-09-17 Koninklijke Philips Electronics N.V. Mikrofluidisches System auf der Basis von magnetischen Aktuatorelementen
US8133629B2 (en) 2007-03-21 2012-03-13 SOCIéTé BIC Fluidic distribution system and related methods
US8679694B2 (en) * 2007-03-21 2014-03-25 Societe Bic Fluidic control system and method of manufacture
KR101522418B1 (ko) * 2007-03-21 2015-05-21 소시에떼 비아이씨 유체 다기관 및 그 방법
WO2008124781A1 (en) * 2007-04-09 2008-10-16 Auburn University A microfluidic array system for biological, chemical, and biochemical assessments
US8071035B2 (en) 2007-04-12 2011-12-06 Siemens Medical Solutions Usa, Inc. Microfluidic radiosynthesis system for positron emission tomography biomarkers
WO2008137997A1 (en) * 2007-05-08 2008-11-13 The Regents Of The University Of California Microfluidic device having regulated fluid transfer between elements located therein
US8016260B2 (en) * 2007-07-19 2011-09-13 Formulatrix, Inc. Metering assembly and method of dispensing fluid
US8206025B2 (en) 2007-08-07 2012-06-26 International Business Machines Corporation Microfluid mixer, methods of use and methods of manufacture thereof
WO2009039378A2 (en) 2007-09-19 2009-03-26 The Charles Stark Draper Laboratory, Inc. Microfluidic structures for biomedical applications
WO2009049268A1 (en) 2007-10-12 2009-04-16 Rheonix, Inc. Integrated microfluidic device and methods
KR100969667B1 (ko) 2008-03-24 2010-07-14 디지탈 지노믹스(주) 생리활성물질을 전기적으로 검출하는 방법 및 이를 위한바이오칩
WO2009126826A1 (en) * 2008-04-11 2009-10-15 Fluidigm Corporation Multilevel microfluidic systems and methods
ES2352581T3 (es) * 2008-06-02 2011-02-21 Boehringer Ingelheim Microparts Gmbh Estructura de lámina microfluídica para dosificar líquidos.
US9017946B2 (en) * 2008-06-23 2015-04-28 Canon U.S. Life Sciences, Inc. Systems and methods for monitoring the amplification of DNA
DE102009041325A1 (de) 2008-09-19 2010-05-12 GeSIM Gesellschaft für Silizium-Mikrosysteme mbH Mikroventil zum Schalten von Kanälen in Mikroflusssystemen
US20100102261A1 (en) * 2008-10-28 2010-04-29 Microfluidic Systems, Inc. Microfluidic valve mechanism
TWI383146B (zh) * 2008-11-19 2013-01-21 Univ Nat Cheng Kung Can be accurate micro sampling and sample of microfluidic chip
US8058630B2 (en) * 2009-01-16 2011-11-15 Fluidigm Corporation Microfluidic devices and methods
US8100293B2 (en) 2009-01-23 2012-01-24 Formulatrix, Inc. Microfluidic dispensing assembly
US20110082563A1 (en) * 2009-10-05 2011-04-07 The Charles Stark Draper Laboratory, Inc. Microscale multiple-fluid-stream bioreactor for cell culture
DE102010001412A1 (de) * 2010-02-01 2011-08-04 Robert Bosch GmbH, 70469 Mikrofluidisches Bauelement zur Handhabung eines Fluids und mikrofluidischer Chip
JP5218443B2 (ja) * 2010-02-10 2013-06-26 ソニー株式会社 マイクロチップ及びマイクロチップの製造方法
CA2788314C (en) * 2010-02-12 2018-04-10 Dan Angelescu Passive micro-vessel and sensor
US9869613B2 (en) 2010-02-12 2018-01-16 Fluidion Sas Passive micro-vessel and sensor
US9772261B2 (en) 2010-02-12 2017-09-26 Fluidion Sas Passive micro-vessel and sensor
US9389158B2 (en) 2010-02-12 2016-07-12 Dan Angelescu Passive micro-vessel and sensor
US10408040B2 (en) 2010-02-12 2019-09-10 Fluidion Sas Passive micro-vessel and sensor
DE102011015184B4 (de) 2010-06-02 2013-11-21 Thinxxs Microtechnology Ag Vorrichtung für den Transport kleiner Volumina eines Fluids, insbesondere Mikropumpe oder Mikroventil
CN103003702B (zh) * 2010-06-30 2015-04-15 美特宝思科润株式会社 微型化学芯片、其制造方法及其使用方法
WO2012004423A1 (es) * 2010-07-07 2012-01-12 Ikerlan, S.Coop Método de fabricación de dispositivos microfluidicos.
CA2808412C (en) 2010-08-18 2021-10-12 Pressure Biosciences Inc. Flow-through high hydrostatic pressure microfluidic sample preparation device and related methods therefor
US8709353B2 (en) * 2011-03-24 2014-04-29 Boehringer Ingelheim Microparts Gmbh Device and method for producing a fluidic connection between cavities
TWI448413B (zh) * 2011-09-07 2014-08-11 Ind Tech Res Inst 氣動式微幫浦
CN103157523A (zh) * 2011-12-15 2013-06-19 三星电子株式会社 微流器件及其制造方法
US9371965B2 (en) 2012-02-21 2016-06-21 Fluidigm Corporation Method and systems for microfluidic logic devices
WO2014003535A1 (en) * 2012-06-25 2014-01-03 Mimos Berhad A microfluidic device
CN110579435B (zh) 2012-10-15 2023-09-26 纳诺赛莱克特生物医药股份有限公司 颗粒分选的系统、设备和方法
WO2014087160A1 (en) * 2012-12-05 2014-06-12 Intelligent Energy Limited Microvalve
US9987576B2 (en) 2012-12-10 2018-06-05 University Of Virginia Patent Foundation Frequency-based filtering of mechanical actuation using fluidic device
US9791068B2 (en) * 2013-01-15 2017-10-17 The Regents Of The University Of California Lifting gate polydimethylsiloxane microvalves and pumps for microfluidic control
US12173263B2 (en) * 2013-12-20 2024-12-24 President And Fellows Of Harvard College Organomimetic devices and methods of use and manufacturing thereof
CN104492510A (zh) * 2014-12-05 2015-04-08 苏州国环环境检测有限公司 一种二维微流控纸芯片及其制作方法
US11071979B2 (en) * 2014-12-15 2021-07-27 Nec Corporation Microchip, liquid transfer method and microchip controlling apparatus
WO2017210494A1 (en) * 2016-06-01 2017-12-07 Carnegie Mellon University Microfluidic-based multiplex cell assay for drug compound testing
WO2018175411A1 (en) 2017-03-20 2018-09-27 Nanocellect Biomedical, Inc. Systems, apparatuses, and methods for cell sorting and flow cytometry
ES2967510T3 (es) 2018-02-16 2024-04-30 Cequr Sa Dispositivos y métodos para la restricción de flujo en un circuito microfluídico para la administración de fármacos
ES2968846T3 (es) 2018-05-02 2024-05-14 Cequr Sa Dispositivos y métodos para proporcionar una dosis en bolo en un circuito microfluídico de una bomba
GB201807489D0 (en) * 2018-05-08 2018-06-20 Sentinel Subsea Ltd Apparatus and method
CN109114250A (zh) * 2018-09-21 2019-01-01 昆明理工大学 一种磁流体换向微阀装置及其使用方法
EP4175568A4 (de) * 2020-07-06 2024-07-10 Cornell University Verfahren und vorrichtungen zur automatisierten mikrofluidischen oozyten-denuierung
US11859734B2 (en) 2020-11-16 2024-01-02 Siemens Healthcare Diagnostics Inc. Valve for microfluidic device
CN113251208B (zh) * 2021-05-13 2022-09-23 哈尔滨工业大学 一种气控两位三通阀
WO2023019447A1 (zh) * 2021-08-17 2023-02-23 京东方科技集团股份有限公司 控制阀结构、其使用方法、微流控芯片及核酸提取装置
EP4430312A4 (de) * 2021-11-13 2025-03-19 Gao, Run Ze Mikrofluidische ventile und kanäle sowie minifluidische ventile und kanäle für weiche robotervorrichtung, kleidung und verfahren
EP4572889A1 (de) * 2022-08-17 2025-06-25 thinXXS Microtechnology GmbH Mikrofluidische flusszelle, herstellungsverfahren, verwendung und analyseeinrichtung
CN116272719B (zh) * 2023-01-05 2025-12-12 汉德精工（厦门）科技有限公司 一种高通量压力控制器及平行反应系统

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4676274A (en) 1985-02-28 1987-06-30 Brown James F Capillary flow control
US5542821A (en) * 1995-06-28 1996-08-06 Basf Corporation Plate-type diaphragm pump and method of use
US5703360A (en) 1996-08-30 1997-12-30 Hewlett-Packard Company Automated calibrant system for use in a liquid separation/mass spectrometry apparatus
US5932799A (en) * 1997-07-21 1999-08-03 Ysi Incorporated Microfluidic analyzer module
US6293012B1 (en) * 1997-07-21 2001-09-25 Ysi Incorporated Method of making a fluid flow module
DE19739722A1 (de) * 1997-09-10 1999-04-01 Lienhard Prof Dr Pagel Zwei- und Dreidimensionale fluidische Mikrosysteme aus Leiterplatten
CA2306126A1 (en) 1997-10-15 1999-04-22 Aclara Biosciences, Inc. Laminate microstructure device and method for making same
US6074725A (en) 1997-12-10 2000-06-13 Caliper Technologies Corp. Fabrication of microfluidic circuits by printing techniques
CA2320296A1 (en) 1998-05-18 1999-11-25 University Of Washington Liquid analysis cartridge
US6146103A (en) * 1998-10-09 2000-11-14 The Regents Of The University Of California Micromachined magnetohydrodynamic actuators and sensors
EP1194693B1 (de) * 1999-06-28 2006-10-25 California Institute Of Technology Mikromechanische pump- und ventilsysteme
US6431212B1 (en) * 2000-05-24 2002-08-13 Jon W. Hayenga Valve for use in microfluidic structures

Cited By (116)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9926521B2 (en) 2000-06-27 2018-03-27 Fluidigm Corporation Microfluidic particle-analysis systems
US10509018B2 (en) 2000-11-16 2019-12-17 California Institute Of Technology Apparatus and methods for conducting assays and high throughput screening
US20040115838A1 (en) * 2000-11-16 2004-06-17 Quake Stephen R. Apparatus and methods for conducting assays and high throughput screening
US8455258B2 (en) 2000-11-16 2013-06-04 California Insitute Of Technology Apparatus and methods for conducting assays and high throughput screening
US9176137B2 (en) 2000-11-16 2015-11-03 California Institute Of Technology Apparatus and methods for conducting assays and high throughput screening
US7887753B2 (en) 2000-11-16 2011-02-15 California Institute Of Technology Apparatus and methods for conducting assays and high throughput screening
US8673645B2 (en) 2000-11-16 2014-03-18 California Institute Of Technology Apparatus and methods for conducting assays and high throughput screening
US7378280B2 (en) 2000-11-16 2008-05-27 California Institute Of Technology Apparatus and methods for conducting assays and high throughput screening
US8273574B2 (en) 2000-11-16 2012-09-25 California Institute Of Technology Apparatus and methods for conducting assays and high throughput screening
US7833708B2 (en) 2001-04-06 2010-11-16 California Institute Of Technology Nucleic acid amplification using microfluidic devices
US8936764B2 (en) 2001-04-06 2015-01-20 California Institute Of Technology Nucleic acid amplification using microfluidic devices
US6960437B2 (en) 2001-04-06 2005-11-01 California Institute Of Technology Nucleic acid amplification utilizing microfluidic devices
US8486636B2 (en) 2001-04-06 2013-07-16 California Institute Of Technology Nucleic acid amplification using microfluidic devices
US8163492B2 (en) 2001-11-30 2012-04-24 Fluidign Corporation Microfluidic device and methods of using same
US7118910B2 (en) * 2001-11-30 2006-10-10 Fluidigm Corporation Microfluidic device and methods of using same
US20030138829A1 (en) * 2001-11-30 2003-07-24 Fluidigm Corp. Microfluidic device and methods of using same
US7820427B2 (en) 2001-11-30 2010-10-26 Fluidigm Corporation Microfluidic device and methods of using same
US9643178B2 (en) 2001-11-30 2017-05-09 Fluidigm Corporation Microfluidic device with reaction sites configured for blind filling
US7452726B2 (en) 2002-04-01 2008-11-18 Fluidigm Corporation Microfluidic particle-analysis systems
US8658418B2 (en) 2002-04-01 2014-02-25 Fluidigm Corporation Microfluidic particle-analysis systems
US9714443B2 (en) 2002-09-25 2017-07-25 California Institute Of Technology Microfabricated structure having parallel and orthogonal flow channels controlled by row and column multiplexors
US9579650B2 (en) 2002-10-02 2017-02-28 California Institute Of Technology Microfluidic nucleic acid analysis
US10940473B2 (en) 2002-10-02 2021-03-09 California Institute Of Technology Microfluidic nucleic acid analysis
US8871446B2 (en) 2002-10-02 2014-10-28 California Institute Of Technology Microfluidic nucleic acid analysis
US10328428B2 (en) 2002-10-02 2019-06-25 California Institute Of Technology Apparatus for preparing cDNA libraries from single cells
US10131934B2 (en) 2003-04-03 2018-11-20 Fluidigm Corporation Thermal reaction device and method for using the same
US7867194B2 (en) 2004-01-29 2011-01-11 The Charles Stark Draper Laboratory, Inc. Drug delivery apparatus
US7867193B2 (en) 2004-01-29 2011-01-11 The Charles Stark Draper Laboratory, Inc. Drug delivery apparatus
US9180054B2 (en) 2004-01-29 2015-11-10 The Charles Stark Draper Laboratory, Inc. Drug delivery apparatus
US20050196321A1 (en) * 2004-03-03 2005-09-08 Zhili Huang Fluidic programmable array devices and methods
US9142440B2 (en) * 2004-08-30 2015-09-22 Cypess Semiconductor Corporation Carrier structure for stacked-type semiconductor device, method of producing the same, and method of fabricating stacked-type semiconductor device
US20090093085A1 (en) * 2004-08-30 2009-04-09 Masanori Onodera Carrier Structure for stacked-type semiconductor device, method of producing the same, and method of fabricating stacked-type semiconductor device
US7832429B2 (en) 2004-10-13 2010-11-16 Rheonix, Inc. Microfluidic pump and valve structures and fabrication methods
US20060076068A1 (en) * 2004-10-13 2006-04-13 Kionix Corporation Microfluidic pump and valve structures and fabrication methods
US20100116343A1 (en) * 2005-01-31 2010-05-13 President And Fellows Of Harvard College Valves and reservoirs for microfluidic systems
US8985547B2 (en) 2005-01-31 2015-03-24 President And Fellows Of Harvard College Valves and reservoirs for microfluidic systems
US20080271799A1 (en) * 2005-09-20 2008-11-06 Koninklijke Philips Electronics, N.V. Microfluidic Regulating Device
US8420017B2 (en) 2006-02-28 2013-04-16 Fluidigm Corporation Microfluidic reaction apparatus for high throughput screening
US7815868B1 (en) 2006-02-28 2010-10-19 Fluidigm Corporation Microfluidic reaction apparatus for high throughput screening
US20080057274A1 (en) * 2006-05-22 2008-03-06 Aida Engineering, Ltd. Micro-channel chip and a process for producing the same
US8127794B2 (en) 2006-09-19 2012-03-06 Agency For Science, Technology And Research Dispenser arrangement for fluidic dispensing control in microfluidic system
WO2008073691A3 (en) * 2006-12-08 2008-11-20 Siemens Healthcare Diagnostics Sample preparation device
US9121063B2 (en) 2007-01-26 2015-09-01 Illumina, Inc. Independently removable nucleic acid sequencing system and method
US11499191B2 (en) 2007-01-26 2022-11-15 Illumina, Inc. Independently removable nucleic acid sequencing system and method
US8315817B2 (en) 2007-01-26 2012-11-20 Illumina, Inc. Independently removable nucleic acid sequencing system and method
US8725425B2 (en) * 2007-01-26 2014-05-13 Illumina, Inc. Image data efficient genetic sequencing method and system
US8244479B2 (en) 2007-01-26 2012-08-14 Illumina, Inc. Nucleic acid sequencing system and method using a subset of sites of a substrate
US20080182757A1 (en) * 2007-01-26 2008-07-31 Illumina, Inc. Image data efficient genetic sequencing method and system
US12421546B2 (en) 2007-01-26 2025-09-23 Illumina, Inc. Nucleic acid sequencing system
US8914241B2 (en) 2007-01-26 2014-12-16 Illumina, Inc. Nucleic acid sequencing system and method
US20080262747A1 (en) * 2007-01-26 2008-10-23 Illumina, Inc. Nucleic acid sequencing system and method
US10053730B2 (en) 2007-01-26 2018-08-21 Illumina, Inc. Independently removable nucleic acid sequencing system and method
US9797012B2 (en) 2007-01-26 2017-10-24 Illumina, Inc. Nucleic acid sequencing system and method
US12435371B2 (en) 2007-01-26 2025-10-07 Illumina, Inc. Nucleic acid sequencing system
US20100138162A1 (en) * 2007-01-26 2010-06-03 Illumina, Inc. Nucleic acid sequencing system and method using a subset of sites of a substrate
US20100137166A1 (en) * 2007-01-26 2010-06-03 Illumina, Inc. Independently removable nucleic acid sequencing system and method
US12497657B2 (en) 2007-01-26 2025-12-16 Illumina, Inc. Nucleic acid sequencing system
US8412467B2 (en) 2007-01-26 2013-04-02 Illumina, Inc. Nucleic acid sequencing system and method
US20110009296A1 (en) * 2007-01-26 2011-01-13 Illumina, Inc. Nucleic acid sequencing system and method
US20110009278A1 (en) * 2007-01-26 2011-01-13 Illumina, Inc. Nucleic acid sequencing system and method
US7835871B2 (en) 2007-01-26 2010-11-16 Illumina, Inc. Nucleic acid sequencing system and method
US12497656B2 (en) 2007-01-26 2025-12-16 Illumina, Inc. Independently removable nucleic acid sequencing system and method
US9046192B2 (en) 2007-01-31 2015-06-02 The Charles Stark Draper Laboratory, Inc. Membrane-based fluid control in microfluidic devices
US9651166B2 (en) 2007-01-31 2017-05-16 The Charles Stark Draper Laboratory, Inc. Membrane-based fluid control in microfluidic devices
KR100931302B1 (ko) 2008-02-05 2009-12-11 한국과학기술원 서로 다른 임계압력을 가지는 밸브를 이용한 마이크로유체분배기
US20090269248A1 (en) * 2008-04-23 2009-10-29 Bioscale, Inc. Method and apparatus for analyte processing
US8961902B2 (en) 2008-04-23 2015-02-24 Bioscale, Inc. Method and apparatus for analyte processing
US9427736B2 (en) 2008-06-30 2016-08-30 Canon U.S. Life Sciences, Inc. System and method for microfluidic flow control
US20090320930A1 (en) * 2008-06-30 2009-12-31 Canon U.S. Life Sciences, Inc. System and method for microfluidic flow control
US8122901B2 (en) 2008-06-30 2012-02-28 Canon U.S. Life Sciences, Inc. System and method for microfluidic flow control
WO2010002797A1 (en) * 2008-06-30 2010-01-07 Canon U.S. Life Sciences, Inc. System and method for microfluidic flow control
US8939171B2 (en) 2008-06-30 2015-01-27 Canon U.S. Life Sciences, Inc. System for microfluidic flow control
US20100166609A1 (en) * 2008-12-26 2010-07-01 Aida Engineering, Ltd. Microchannel chip
CN102449368B (zh) * 2009-05-29 2015-07-29 贝林格尔·英格海姆维特梅迪卡有限公司 片上实验室系统中的阀,阀的操纵和制造方法
CN102449368A (zh) * 2009-05-29 2012-05-09 西门子公司 片上实验室系统中的阀，阀的操纵和制造方法
US12307670B1 (en) 2010-01-13 2025-05-20 Illumina, Inc. Analyzing image data from nucleic acid sequencing
US12380561B2 (en) 2010-01-13 2025-08-05 Illumina, Inc. Creating a template of nucleic acid site locations on a flow cell
US12223651B2 (en) 2010-01-13 2025-02-11 Illumina, Inc. Identifying nucleotides by determining phasing
US9530207B2 (en) 2010-01-13 2016-12-27 Illumina, Inc. Data processing system and methods
US11676275B2 (en) 2010-01-13 2023-06-13 Illumina, Inc. Identifying nucleotides by determining phasing
US8965076B2 (en) 2010-01-13 2015-02-24 Illumina, Inc. Data processing system and methods
US11605165B2 (en) 2010-01-13 2023-03-14 Illumina, Inc. System and methods for identifying nucleotides
US10304189B2 (en) 2010-01-13 2019-05-28 Illumina, Inc. Data processing system and methods
US9267618B2 (en) 2010-05-18 2016-02-23 Samsung Electronics Co., Ltd. Microvalve device and method of manufacturing the same
US8876795B2 (en) 2011-02-02 2014-11-04 The Charles Stark Draper Laboratory, Inc. Drug delivery apparatus
US9764121B2 (en) 2011-02-02 2017-09-19 The Charles Stark Draper Laboratory, Inc. Drug delivery apparatus
US9498914B2 (en) 2011-02-15 2016-11-22 National Research Council Of Canada 3D microfluidic devices based on open-through thermoplastic elastomer membranes
DE112011106142B3 (de) * 2011-02-15 2020-12-17 National Research Council Of Canada Durchbrochene thermoplastische Elastomer-Membran, ihre Verwendung und Verfahren zu ihrer Herstellung
DE112011104891B4 (de) 2011-02-15 2018-01-25 National Research Council Of Canada 3D-Mikrofluid-Vorrichtungen auf der Grundlage von durchbrochenen thermoplastischen Elastomer-Membranen
WO2014039844A3 (en) * 2012-09-06 2015-07-23 The Board Of Trustees Of The Leland Stanford Junior University Punch card programmable microfluidics
US10272427B2 (en) 2012-09-06 2019-04-30 The Board Of Trustees Of The Leland Stanford Junior University Punch card programmable microfluidics
US10197189B2 (en) 2013-05-31 2019-02-05 Stmicroelectronics S.R.L. Membrane microfluidic valve and process for manufacturing a membrane microfluidic valve
ITTO20130447A1 (it) * 2013-05-31 2014-12-01 St Microelectronics Srl Valvola microfluidica a membrana e procedimento per fabbricare una valvola microfluidica a membrana
US10286395B2 (en) 2014-03-20 2019-05-14 Nec Corporation Microchip, microchip controlling method and microchip controlling apparatus
EP3248681A1 (de) * 2016-05-23 2017-11-29 ETH Zurich Mikrofluidische vorrichtung zur definition einer anordnung von probenkammern
WO2017202710A1 (en) * 2016-05-23 2017-11-30 Eth Zurich Microfluidic device defining an array of sample chambers
US10502327B1 (en) * 2016-09-23 2019-12-10 Facebook Technologies, Llc Co-casted fluidic devices
US11519511B1 (en) 2016-09-23 2022-12-06 Meta Platforms Technologies, Llc Fluidic devices and related methods and wearable devices
US11204100B1 (en) 2016-09-23 2021-12-21 Facebook Technologies, Llc Co-casted fluidic devices
US10514111B2 (en) 2017-01-23 2019-12-24 Facebook Technologies, Llc Fluidic switching devices
US10989330B1 (en) 2017-01-23 2021-04-27 Facebook Technologies, Llc Fluidic switching devices
US10240622B1 (en) 2017-01-30 2019-03-26 Facebook Technologies, Llc Switchable fluidic device
WO2018213282A3 (en) * 2017-05-15 2020-03-26 The University Of Chicago Universal microfluidic culture system to analyze and control cell dynamics
US11912970B2 (en) 2017-05-15 2024-02-27 The University Of Chicago Universal microfluidic culture system to analyze and control cell dynamics
WO2019040088A1 (en) * 2017-08-23 2019-02-28 Facebook Technologies, Llc FLUIDIC SWITCHING DEVICES
US11193597B1 (en) 2017-08-23 2021-12-07 Facebook Technologies, Llc Fluidic devices, haptic systems including fluidic devices, and related methods
CN111279108A (zh) * 2017-08-23 2020-06-12 脸谱科技有限责任公司 射流开关器件
US10648573B2 (en) 2017-08-23 2020-05-12 Facebook Technologies, Llc Fluidic switching devices
US10422362B2 (en) 2017-09-05 2019-09-24 Facebook Technologies, Llc Fluidic pump and latch gate
US10989233B2 (en) 2017-09-05 2021-04-27 Facebook Technologies, Llc Fluidic pump and latch gate
US10591933B1 (en) 2017-11-10 2020-03-17 Facebook Technologies, Llc Composable PFET fluidic device
WO2019103236A1 (ko) * 2017-11-24 2019-05-31 (주)비비비 시료의 흐름을 조절할 수 있는 미세유체분석칩
US11231055B1 (en) 2019-06-05 2022-01-25 Facebook Technologies, Llc Apparatus and methods for fluidic amplification
US11098737B1 (en) 2019-06-27 2021-08-24 Facebook Technologies, Llc Analog fluidic devices and systems
US11371619B2 (en) 2019-07-19 2022-06-28 Facebook Technologies, Llc Membraneless fluid-controlled valve
EP4466105A4 (de) * 2022-01-23 2025-10-01 Emerging Viral Diagnostics Hk Ltd Mikrofluidisches ventil

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