EP2078958A1 - Filtre microfluidique reconfigurable basé sur des champs électriques - Google Patents

Filtre microfluidique reconfigurable basé sur des champs électriques Download PDF

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Publication number
EP2078958A1
EP2078958A1 EP07119287A EP07119287A EP2078958A1 EP 2078958 A1 EP2078958 A1 EP 2078958A1 EP 07119287 A EP07119287 A EP 07119287A EP 07119287 A EP07119287 A EP 07119287A EP 2078958 A1 EP2078958 A1 EP 2078958A1
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Prior art keywords
particles
filter
electrodes
channel
electric field
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EP07119287A
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German (de)
English (en)
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Koninklijke Philips NV
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Koninklijke Philips Electronics NV
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Priority to EP07119287A priority Critical patent/EP2078958A1/fr
Priority to PCT/IB2008/054340 priority patent/WO2009053907A1/fr
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00—Separating dispersed particles from liquids by electrostatic effect
    • B03C5/02—Separators
    • B03C5/022—Non-uniform field separators
    • B03C5/026—Non-uniform field separators using open-gradient differential dielectric separation, i.e. using electrodes of special shapes for non-uniform field creation, e.g. Fluid Integrated Circuit [FIC]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00—Separating dispersed particles from liquids by electrostatic effect
    • B03C5/005—Dielectrophoresis, i.e. dielectric particles migrating towards the region of highest field strength
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C5/00—Separating dispersed particles from liquids by electrostatic effect
    • B03C5/02—Separators
    • B03C5/022—Non-uniform field separators
    • B03C5/028—Non-uniform field separators using travelling electric fields, i.e. travelling wave dielectrophoresis [TWD]

Definitions

  • This invention relates to filters for filtering particles in a fluid, to methods of using such devices for manipulating particles, and to methods of manufacturing and operating such devices.
  • Lab-on-a-chip systems show great promise for a variety of medical, life-science, forensic and environmental applications. Their advantages include ease of use and low fabrication costs (ultimately leading to disposable chips), low fluid volumes and reagents consumption, large integration of functionalities, high-throughput analysis via massive parallelization and increased process control due to the faster response of the system.
  • a key aspect when performing analysis on lab-on-a-chip devices is sample preparation. Ideally, all preparation steps should be done on-chip in order to allow the use of raw, unprocessed samples as input. Essential preparation steps are filtration of the sample prior to processing and concentration of the analyte to increase the sensitivity of the device.
  • a specific target cell population has to be extracted from a heterogeneous cell mixture. Examples are the isolation of hematopoietic stem cells, antigen-specific lymphocytes and circulating tumor cells from peripheral blood or the isolation of fetal cells from maternal blood.
  • purification and concentration of the analyte is critical.
  • the desired species are often extracted from a biological sample with the aid of micrometer-sized beads. Such beads can be designed to bind to specific cells or macromolecules (DNA, RNA, or proteins) and greatly simplifies the recovery of material for further studies.
  • microfluidic filters have included creation of flow restrictions, such as porous membranes, mesh structures or arrays of cylindrical pillars with high aspect ratio.
  • Such structures can be realized, e.g., by deep reactive ion etching in silicon or by lithography in polymeric materials such as SU8 or PDMS. In the following, some applications of these structures are explained.
  • Cells in suspension are usually transported with flow, but can be physically retained in a lab-on-a-chip device by filters or traps.
  • the separation can be made selective by carefully designing the filter.
  • white blood cells have been separated from other components of whole blood via size exclusion using a row of micropillars inside a chamber on a microchip (see N. J. Panaro et al., Biomolecular Engineering 21, 157-162, 2005 ).
  • the authors of this study determined 3.5 ⁇ m to be the optimal sieve size to capture most white blood cells while allowing blood serum, red blood cells and platelets to pass through the sieve.
  • micromesh structures were fabricated using conventional photolithography (see H. Sato et al., Sensors and Actuators A 111, 87-92, 2004 ). In this publication the structures were used to trap 20 ⁇ m beads, while smaller beads could freely pass through the microfilter.
  • Microspheres of 0.8, 0.9, and 1.0 ⁇ m were sorted in 40sec with a resolution of ⁇ 10nm in a device containing nine sections, each of which had a different gap width.
  • Bacterial artificial chromosomes could be separated with the same method in 10min with a resolution of ⁇ 12%.
  • Micropillar cages can in this case be used to confine the beads to a specific location on the device, thereby defining a micro reaction chamber.
  • the mechanical barrier holds the microspheres within the chamber but allows liquid, reagents and smaller particles to flow freely through the chamber.
  • the shape of the microreactor can be designed to be compatible with the used detection system, as for example a square camera pixel.
  • An object of the invention is to provide improved apparatus or methods for filtering particles in a fluid.
  • the invention provides:
  • a filter for filtering particles in a fluid having a channel for the fluid, and electrodes arranged to create an electric field pattern in the fluid in the channel, to repel the particles at locations spaced apart in the channel, so as to selectively block particles of a one size, and allow particles of another size to pass.
  • the electric field pattern generates field-induced obstacles.
  • the device of the present invention does not rely on differences in the dielectric properties of the particles and therefore shares the robustness and reliability of conventional methods based on arrays of solid obstacles, i.e. conventional filters.
  • the electric field pattern is in the form of field-induced obstacles.
  • the field-induced obstacles can be implemented by equipping the device with micropatterned electrodes, which result in a high electric field at specific locations.
  • the device can also include drive circuitry for generating the field pattern.
  • the drive circuitry can be integrated in the device or may be separate from it.
  • An advantage of the present invention is that it can be applied to highly conductive media such as PBS or blood serum.
  • the present invention provides:
  • a reconfigurable filter for filtering particles in a fluid having a channel for the fluid, and electrodes arranged to create a selectable electric field pattern in the fluid in the channel, to repel the particles at locations spaced apart in the channel, so as to selectively block particles of a one size, and allow particles of another size to pass.
  • Embodiments within this aspect of the invention can have any additional features, and some such additional features are set out in dependent claims, and some are set out in the examples in the detailed description.
  • filter being arranged to use dielectrophoresis to repel or attract the particles.
  • dielectrophoresis to repel or attract the particles.
  • electrophoresis can be used.
  • control circuitry arranged to vary the field, e.g. reduce the electric field to allow blocked particles to pass. This can be useful to prevent clogging of the filter, or allow the blocked particles to be further processed for example.
  • the control circuitry can be integrated in the device or separate from it.
  • Another such additional feature is the electric field pattern to be arranged to use negative DEP. This ensures, in some embodiments, that particles are kept within zones of low field strength. In turn such lower field strengths can reduce the risk of damage to the particles, and can help to enable lower power consumption and greater integration for example.
  • drive circuitry being arranged to drive the electrodes with an AC signal, with substantially 180 degree phase difference between opposing electrodes. This can create an area of relatively high electric field to act as an obstacle to the particles.
  • Another such additional feature is the electrodes being arranged on opposing sides of channel for the fluid.
  • Another such additional feature is the channel having at least one branch, arranged so as to provide different exit paths for different sized particles
  • control circuitry arranged to reconfigure the filter by changing the pattern of the electric field in the channel so as to change a size of particles which are blocked or passed. This can enable more sophisticated filtering of selected sizes in sequence, or unclogging of the filter for example.
  • Another such additional feature is the electrodes being arranged in a line across the channel, and the reconfiguring involving altering the relative drive levels of different ones of the electrodes in the line.
  • Electrodes comprising at least one two dimensional array of separately drivable electrodes on at least one side of the channel. This can enable a wide variety of patterns of electric field to be generated.
  • Another such feature is the drive circuitry for the electrodes in the two dimensional array being integrated together with the respective electrodes.
  • Electrodes and drive circuitry being arranged to enable a cage of obstacles to the particles of the given size, for use as a micro reactor.
  • Another such feature is the device being an integrated micro fluidic device having integrated fluid handling components.
  • Another aspect provides a method of using a filter to filter particles in a fluid, the filter having a channel for the fluid, and electrodes, the method having the steps of introducing the particles to the filter, and creating an electric field pattern to repel the particles at locations spaced apart in the channel, so as to selectively block particles of a given size, and allow particles of another size to pass.
  • An additional feature of some embodiments of such a method is using the method for any one or more of the following: isolation of cells from blood or other substance, sorting of cells, or for filtering micro carrier beads loaded with cells.
  • One such additional feature is using dielectrophoresis to repel or attract the particles.
  • One such additional feature is the step of reducing the electric field to allow blocked particles to pass. Another such additional feature is arranging the electric field pattern to use negative DEP. Another such additional feature is driving the electrodes with an AC signal, with substantially 180 degree phase difference between opposing electrodes. Another such additional feature is the channel having at least one branch, and the step of using different exit paths for different sized particles.
  • Another such additional feature is the step of reconfiguring the filter by changing the pattern of the electric field in the channel so as to change a size of particles which are blocked or passed.
  • Another such additional feature is the electrodes being arranged in a line across the channel, and the reconfiguring step involving altering the relative drive levels of different ones of the electrodes in the line.
  • Another such feature is the electrodes comprising at least one two dimensional array of separately drivable electrodes on at least one side of the channel and the reconfiguring step involving altering the relative drive levels of different ones of the electrodes in the array.
  • Another such feature is the step of generating the electric field pattern to form a ring of obstacles to the particles of the given size, for use as a micro reactor.
  • Some of the embodiments are described herein as a method or combination of elements of a method that can be implemented by a processor of a computer system or by other means of carrying out the function.
  • a processor with and memory and the necessary instructions for carrying out such a method or element of a method forms a means for carrying out the method or element of a method.
  • an element described herein of an apparatus embodiment is an example of a means for carrying out the function performed by the element for the purpose of carrying out the invention.
  • Another aspect provides software on a computer readable medium for controlling the driving of different ones of the electrodes to generate the electric field pattern for use in any of the above methods.
  • an element described herein of an apparatus embodiment is an example of a means for carrying out the function performed by the element for the purpose of carrying out the invention.
  • DEP has been applied to manipulate and separate a variety of cells including bacteria, yeast, and mammalian cells in microsystems.
  • DEP has been used to separate cancer cells from blood, isolate CD34+ stem cells from blood, bacteria from blood and to separate various cell sub-populations of blood.
  • US patent 5,814,200 shows separation by DEP forces which are different on different types of particle, such as proteins and chromosomes.
  • a filter device that can be reconfigured, for example, to change the sieve size, vary the distributions of pillars in an array or remove the obstacles completely to release the captured particles or prevent clogging.
  • a filter device that can be reconfigured, for example, to change the sieve size, vary the distributions of pillars in an array or remove the obstacles completely to release the captured particles or prevent clogging.
  • to achieve reconfiguration of physical obstacles is typically difficult, particularly for integrated microsystems.
  • an electric field pattern is used. This can be useful for integration onto lab-on-a-chip platforms.
  • Some embodiments are based on dielectrophoresis, though in principle other methods can be used, based on charged particles for example.
  • the embodiments based on dielectrophoresis at least can be useful for a wide variety of applications such as for sample preparation, isolation of cells for example from blood, analyte concentration and sorting of cells or functionalized microspheres on the basis of their size.
  • the methods described are especially suited for high conductivity liquids such as blood, but can also be used with fluids of lower conductivity.
  • DEP dielectrophoresis
  • DEP electrostatic field-based approaches are particularly suited for miniaturization because micropatterned electrodes are easy to fabricate and result in high electric fields at modest voltages.
  • DEP has received considerable attention as a method to manipulate and separate micrometer-sized particles.
  • DEP separation methods have been applied to variety of cells including bacteria, yeast, mammalian, and human cells in lab-on-a-chip systems (see H. Morgan and N. Green, AC Electrokinetics: colloids and nanoparticles, Research Studies Press, (Baldock, UK, 2002 ), hereafter Morgan et al).
  • particles are sorted by exploiting differences in their dielectric properties and, consequently, DEP responses.
  • the classic example is separation based on positive vs.
  • negative DEP cells undergoing negative DEP are trapped at field minima, while those experiencing positive DEP are collected at the electrodes tips. As the latter are held by a stronger force than the first, a liquid flow of suitable strength can be used to selectively remove the particles undergoing negative DEP. The remaining particles are then released into the flow when the field is switched off.
  • Another common method for separating particles is based on traveling wave dielectrophoresis (twDEP). In this technique, an array of electrodes is driven by multiphase AC voltage signals, creating a traveling wave potential distribution that can levitate particles and simultaneously propel them along the array. As for conventional DEP separation methods, twDEP methods separate particles based on differences in their dielectric properties.
  • the first term in Eq. (1) is the conventional DEP force, indicating that a particle will be attracted or repelled from regions of stronger electric field depending on whether Re[ f ⁇ CM ] > 0 or Re[ f ⁇ CM ] ⁇ 0, respectively.
  • the second term only occurs when Im[ f ⁇ CM ] ⁇ 0 and when the electric field is rotating ( E I ⁇ 0 ) and is responsible for the phenomena of electro-rotation and twDEP.
  • Figure 1 shows a graph showing four lines representing the real and imaginary parts of the Clausius-Mossotti factor f ⁇ CM for a latex bead with a diameter of 1 ⁇ m, in two conditions.
  • a first case is in a low conductivity fluid medium (10 -3 S/m) and a second case is in a highly conductive medium such as PBS (1.5 S/m).
  • PBS highly conductive medium
  • the field-induced obstacles can be implemented by equipping the device with micropatterned electrodes, which result in a high electric field at specific locations. As explained above, cells or microsphere in highly conductive media experience negative DEP, and will therefore be repelled by these regions.
  • Figure 2 shows for example the electric field created by two round electrodes of 10 ⁇ m diameter in a 10 ⁇ m high microfluidic channel 40 filled with PBS, by assuming a potential difference of 2V between top and bottom electrodes.
  • the top electrode 50 and bottom electrode 60 will be energized with high frequency AC voltage signals with a phase difference of 180° to prevent electrolysis and gas formation.
  • the magnitude of the electric field is high in the volume enclosed by the two electrodes and is negligibly small outside of this region.
  • AC drive circuitry 70 for generating an AC field by applying AC currents of different phases to the electrodes in accordance with conventional DEP systems, e.g.
  • the drive circuitry can include a variable frequency and phase AC field generator.
  • the connections to the electrodes from the variable frequency and phase AC field generator are shown schematically. Such parts that are not shown in detail can be implemented using conventional hardware or circuitry as would be apparent to those skilled in the art, and so need not be described in more detail. They can be integrated on the same chip or located elsewhere.
  • devices can be made with patterned electrodes only on one of the two substrates (top or bottom) and an unstructured electrode on the other substrate ( Fig. 3 ).
  • the substrates are on either side of the channel having the fluid.
  • the unstructured electrode can be either a metallic film or an optically transparent layer of indium tin oxide (ITO) for example.
  • High-field regions can also be created by using exclusively in-plane electrodes, as illustrated in Fig. 4 .
  • the field pattern forms an arch between the electrodes and so extends out of the plane of the electrodes into the channel or part of the channel.
  • Microstructured conductive surfaces can be obtained either by lithographically patterning metallic layers into electrodes or by lithographically defining apertures in an insulating layer deposited on top of an unstructured metal layer.
  • active matrix electronics for example large area electronics based on LTPS technology
  • Electrodes By arranging electrode as the ones described above in an array, one can fabricate devices that selectively filter or trap micrometer-sized particles in a flow along the channel.
  • the flow can be forced by a pump, or by gravity or by centrifugal force for example.
  • the fluid will cause the flow of particles, in other cases, the particles can flow through a static fluid.
  • the sieve size is approximately defined by the gap between the electrodes. A straightforward way to change the sieve size and, consequently, the size of the particles to be trapped is to selectively turn on or off electrodes within the array.
  • Figure 5 shows a representation of a field pattern with small gaps, produced by a line of electrodes.
  • Figure 6 shows the field pattern after some of the electrodes are switched off, to increase the size of the gaps.
  • devices based on the disclosed method can block or filter particles as long as the negative DEP force experienced by the particles is higher than the drag force caused by the fluid flow. Therefore, the sieve size can be continuously tuned by adjusting the voltage applied on the electrodes or by varying the strength of the fluid flow.
  • the method allows reconfiguring the arrangement of the electrodes in an array. For example, rows of obstacles with different gap sizes can be placed in succession. The rows can be perpendicular to the flow direction ( Fig. 7 ), in which case particles of different sizes would be trapped in the different sections of the device. After that, the electrodes can be turned-off (e.g., starting from the bottom) to release the trapped particles selectively. Alternatively, the activated electrode configuration can be changed in order do tilt the filtering rows with respect to the flow direction (as shown in Fig. 8 ). This would enable, for example, sorting particles of different sizes into separate micro fluidic exit channels.
  • Size-sorting of particles can also be obtained with the method described in Huang et al, i.e., by using rows of obstacles with the same gap and shifting each successive row horizontally with respect to the previous one by a fraction of the gap between the obstacles.
  • CMOS complementary metal-oxide-semiconductor
  • LTPS layered nitride-semiconductor
  • ITO unpatterned counter electrode
  • Each electrode in the array can be activated individually.
  • a high-field region i.e., an obstacle
  • Low-field regions can be created by grounding the electrodes or by driving them with in-phase voltage signals.
  • a pillar can be obtained by activating a single electrode or by energizing multiple adjacent "pixels". The last option would allow creating larger obstacles of arbitrary shape.
  • An array based on CMOS technology has been used by the company Silicon Biosystems (see www.siliconbiosystems.com) to trap, levitate and transport individual cells across the array. But there is no suggestion of using the technology for reconfigurable microfluidic filters.
  • the method described above according to embodiments of the present invention may be implemented in a processing system, e.g. a micorcontroller.
  • a processing system e.g. a micorcontroller.
  • One configuration of such a processing system includes at least one customisable or programmable processor coupled to a memory subsystem that includes at least one form of memory, e.g., RAM, ROM, and so forth.
  • the processor or processors may be a general purpose, or a special purpose processor, and may be for inclusion in a device, e.g., a chip that has other components that perform other functions.
  • one or more aspects of the method according to embodiments of the present invention can be implemented in digital electronic circuitry, or in computer hardware, firmware, software, or in combinations of them.
  • the processing system may include a storage subsystem that has at least one disk drive and/or CD-ROM drive and/or DVD drive and/or solid state memory.
  • a display system, a keyboard, and a pointing device may be included as part of a user interface subsystem to provide for a user to manually input information, such as parameter values.
  • More elements such as network connections, interfaces to various devices, and so forth, may be included.
  • the various elements of the processing system may be coupled in various ways, including via a bus subsystem, e.g. for simplicity as a single bus, but will be understood to those in the art to include a system of at least one bus.
  • the memory of the memory subsystem may at some time hold part or all of a set of instructions that when executed on the processing system implement the steps of the method embodiments described herein.
  • the present invention also includes a computer program product which provides the functionality of any of the methods according to the present invention when executed on a computing device.
  • Such computer program product can be tangibly embodied in a carrier medium carrying machine-readable code for execution by a programmable processor.
  • the present invention thus relates to a carrier medium carrying a computer program product that, when executed on computing means, provides instructions for executing any of the methods as described above.
  • carrier medium refers to any medium that participates in providing instructions to a processor for execution. Such a medium may take many forms, including but not limited to, non-volatile media, and transmission media.
  • Non-volatile media includes, for example, optical or magnetic disks, such as a storage device which is part of mass storage.
  • Computer readable media include, a CD-ROM, a DVD, a flexible disk or floppy disk, a tape, a memory chip or cartridge or any other medium from which a computer can read.
  • Various forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.
  • the computer program product can also be transmitted via a carrier wave in a network, such as a LAN, a WAN or the Internet.
  • Transmission media can take the form of acoustic or light waves, such as those generated during radio wave and infrared data communications. Transmission media include coaxial cables, copper wire and fibre optics, including the wires that comprise a bus within a computer.
  • Control circuitry to control the individual electrodes according to a desired sequence can be implemented using conventional digital logic circuits in the form of integrated circuitry, ASICs, microprocessors and so on. Such circuitry can execute instructions coded in conventional software languages. The control can be made dependent on external conditions, or inputs from local sensors as desired.
  • the embodiments described above can be applied essentially to any application involving arrays of obstacles to selectively filter or block micrometer-sized particles such as cells or dielectric beads in a liquid flow. It can also be applied to define microreactors for bead-based processes, as described above.
  • the method is expected to have important applications for sample preparation and filtration, isolation of cells for example from blood, extraction and purification of an analyte (e.g., nucleic acids or proteins) and size-sorting of cells or functionalized microspheres. In particular the filtering or trapping of micro-carrier beads loaded with cells.
  • analyte e.g., nucleic acids or proteins

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EP07119287A 2007-10-25 2007-10-25 Filtre microfluidique reconfigurable basé sur des champs électriques Ceased EP2078958A1 (fr)

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WO2012054904A2 (fr) * 2010-10-21 2012-04-26 The Regents Of The University Of California Dispositifs microfluidiques avec circuits électroniques alimentés par une liaison sans fil
WO2014066888A1 (fr) * 2012-10-27 2014-05-01 The Texas A&M University System Système de criblage de cellule mutagénisée à haut rendement pour l'extraction sélective de cellule unique
TWI499778B (zh) * 2013-12-25 2015-09-11 Univ Nat Taiwan 微流體裝置
US10324018B2 (en) 2009-03-10 2019-06-18 The Regents Of The University Of California Fluidic flow cytometry devices and particle sensing based on signal-encoding
US10816550B2 (en) 2012-10-15 2020-10-27 Nanocellect Biomedical, Inc. Systems, apparatus, and methods for sorting particles
CN112858670A (zh) * 2021-01-26 2021-05-28 深圳市科瑞达生物技术有限公司 一种多重数字化elisa检测方法及微流控芯片

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WO2010115167A2 (fr) 2009-04-03 2010-10-07 The Regents Of The University Of California Procédés et dispositifs adaptés pour trier des cellules et d'autres particules biologiques
US9857333B2 (en) 2012-10-31 2018-01-02 Berkeley Lights, Inc. Pens for biological micro-objects
GB201312035D0 (en) * 2013-07-04 2013-08-21 Cytomos Ltd Biological sensing apparatus
EP3783094B1 (fr) 2013-10-22 2023-10-11 Berkeley Lights, Inc. Dispositifs microfluidiques pour dosage d'activité biologique

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WO2012054904A2 (fr) * 2010-10-21 2012-04-26 The Regents Of The University Of California Dispositifs microfluidiques avec circuits électroniques alimentés par une liaison sans fil
WO2012054904A3 (fr) * 2010-10-21 2012-08-30 The Regents Of The University Of California Dispositifs microfluidiques avec circuits électroniques alimentés par une liaison sans fil
US10024819B2 (en) 2010-10-21 2018-07-17 The Regents Of The University Of California Microfluidics with wirelessly powered electronic circuits
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WO2014066888A1 (fr) * 2012-10-27 2014-05-01 The Texas A&M University System Système de criblage de cellule mutagénisée à haut rendement pour l'extraction sélective de cellule unique
US9822390B2 (en) 2012-10-27 2017-11-21 The Texas A&M University System High-throughput mutagenized cell screening system for selective single cell extraction
TWI499778B (zh) * 2013-12-25 2015-09-11 Univ Nat Taiwan 微流體裝置
CN112858670A (zh) * 2021-01-26 2021-05-28 深圳市科瑞达生物技术有限公司 一种多重数字化elisa检测方法及微流控芯片
CN112858670B (zh) * 2021-01-26 2021-12-17 深圳市科瑞达生物技术有限公司 一种多重数字化elisa检测方法及微流控芯片

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