EP1637226A1 - Mikrofluide Vorrichtung mit kollinearem elektrischen Feld - Google Patents

Mikrofluide Vorrichtung mit kollinearem elektrischen Feld Download PDF

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Publication number
EP1637226A1
EP1637226A1 EP04292173A EP04292173A EP1637226A1 EP 1637226 A1 EP1637226 A1 EP 1637226A1 EP 04292173 A EP04292173 A EP 04292173A EP 04292173 A EP04292173 A EP 04292173A EP 1637226 A1 EP1637226 A1 EP 1637226A1
Authority
EP
European Patent Office
Prior art keywords
microchannel
packet
electric field
packets
electrodes
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP04292173A
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English (en)
French (fr)
Inventor
Jean-Louis Viovy
Max Chabert
Kevin Dorfman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Centre National de la Recherche Scientifique CNRS
Institut Curie
Original Assignee
Centre National de la Recherche Scientifique CNRS
Institut Curie
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Centre National de la Recherche Scientifique CNRS, Institut Curie filed Critical Centre National de la Recherche Scientifique CNRS
Priority to EP04292173A priority Critical patent/EP1637226A1/de
Priority to PCT/IB2005/052951 priority patent/WO2006027757A2/en
Priority to EP05782951.7A priority patent/EP1802395B1/de
Priority to CN2005800359884A priority patent/CN101052468B/zh
Priority to ES05782951T priority patent/ES2784184T3/es
Priority to CN201110409213.6A priority patent/CN102513170B/zh
Priority to US11/662,362 priority patent/US9566558B2/en
Priority to JP2007530836A priority patent/JP5885901B2/ja
Publication of EP1637226A1 publication Critical patent/EP1637226A1/de
Priority to JP2012237242A priority patent/JP5715999B2/ja
Priority to JP2014243114A priority patent/JP2015096257A/ja
Priority to JP2016135183A priority patent/JP6373308B2/ja
Priority to US15/392,189 priority patent/US10661278B2/en
Priority to US16/784,736 priority patent/US11097275B2/en
Withdrawn legal-status Critical Current

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • 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
    • B01L3/5027—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
    • B01L3/502769—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 multiphase flow arrangements
    • B01L3/502784—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006—Micropumps
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0493—Specific techniques used

Definitions

  • the present invention relates to a device for manipulation of packets in microchannels.
  • « packet » refers to compartmentalized matter and may refer to a fluid packet, an encapsulated packet and/or a solid packet.
  • a fluid packet refers to one or more packets of liquids or gases.
  • a fluid packet may refer to a droplet or bubble of a liquid or gas.
  • a fluid packet may refer to a droplet of water, a droplet of reagent or sample, a droplet of solvent, a droplet of solution, a particle suspension or cell suspension, a droplet of an intermediate product, a droplet of a final reaction product or a droplet of any material.
  • An example of a fluid packet is a droplet of aqueous solution suspended in oil.
  • a fluid packet refers to a droplet of water or a droplet of solution.
  • An encapsulated packet refers to a packet enclosed by a layer of material.
  • the surface of an encapsulated packet may be coated with a reagent, a sample, a particle or cell, an intermediate product, a final reaction product, or any material.
  • An example of an encapsulated packet is a lipid vesicle containing an aqueous solution of reagent suspended in water.
  • a packet may contain for instance a vesicle or other microcapsule of liquid or gas that may contain a reagent, a sample, a particle, a dead cell or alive cell, an intermediate product, a final reaction product, or any material.
  • a solid packet refers to a solid material, for example biological material, that may contain, or be covered with, a reagent, a sample, a particle or cell, an intermediate product, a final reaction product, or any material.
  • An example of a solid packet is a latex microsphere with reagent bound to its surface suspended in an aqueous solution.
  • a packet may contain a crystal, a polycrystalline material or a vitreous material.
  • Packets may be made to vary greatly in size and shape, and may have a maximum dimension between about 100 nm and about 1 cm.
  • US patent 6 294 063 discloses an apparatus for programmably manipulating a plurality of packets, such packets optionally being droplets, said apparatus comprising a reaction surface configured to provide an interaction site for such packets, an inlet port, means to generate manipulation forces upon said packets, the forces being capable of programmably moving said packets about said reaction surface along arbitrarily chosen paths, and a position sensor.
  • US patent 6 565 727 also discloses a device for manipulating a droplet of a polar liquid, comprising an upper and lower surface, defining between them a gap, said upper surface comprising a plurality of interdigitated electrodes, and said lower surface comprising a common counterelectrode.
  • the device further comprises insulating layers between said electrodes and said gap, and a non-polar liquid positioned in the gap.
  • a droplet can be maintained on top of a first electrode on the upper surface, by applying a potential between said electrode and the counterelectrode on the lower surface, making the upper surface wetting for the droplet in the vicinity of said first electrode.
  • the droplet can be moved to a second electrode on the upper surface interdigitated with said first electrode, by suppressing the potential difference between the first electrode and the counterelectrode, and applying a potential difference between the second electrode and the counterelectrode to make said second electrode wetting to the fluid.
  • Electrowetting can also be used to mix two different droplets, as described e.g. in M. Washizu, IEEE Trans. Ind. Appl ., 34, 732-737 (1998). Mixing of droplets containing e.g. two reagents or a sample and a reagent is a key technological step for developing microfluidic integrated systems or "lab-on-chips".
  • Dielectrophoresis is another way of transporting and mixing droplets or solid objects such as cells or latex particles.
  • Schwartz et al . in Lab Chip, 4, 11-17 (2004) discloses a programmable fluid processor, in which droplets can be moved and mixed on top of an array of electrodes, by energizing sequentially electrodes in the array.
  • This method also requires a complex array of electrodes on a planar surface, and thus shares many of the drawbacks of electrowetting.
  • Velev et al ., Nature, 426, 515-516 (2003) describes a process for moving and mixing droplets which are floating on a layer of fluorinated oil, where the oil is in contact with a pattern of electrodes. This eliminates the contamination problems inherent in electrowetting, but still requires fabricating a complex array of electrodes.
  • Transporting and mixing droplets in an elongated microchannel, or in a network of connected microchannels is more robust to the above problems. For instance, it avoids evaporation, and allows transport on long distances by simple hydrodynamic mobilization of a carrier fluid surrounding the droplets. Droplets can thus be transported in capillaries several meters long, and used as microreactors, as disclosed e.g. in Curcio and Roeraade, Anal. Chem., 75, 1-7 (2003). When interaction with the walls is well controlled, all droplets move at the same velocity, and very stable trains are achieved.
  • Dielectrophoresis uses a force exerted on a particle with a dielectric constant different from that of the surrounding medium in a gradient of electric field.
  • Different types of arrangements were used to date for the application of dielectophoresis in microchannels.
  • an array of closely spaced interdigitated electrodes locally creates lines of high field gradient in which particles are attracted.
  • these lines can be shifted in time by alternately energizing different series of electrodes, said method being called " travelling wave dielectrophoresis ".
  • dielectrophoretic devices present some advantages upon planar systems. In particular, they are more robust to tilting or vibration. However, they still require complex microfabrication, and are expensive to fabricate.
  • An object of the present invention among others is to provide such device and method.
  • the present invention relates to a microfluidic device for deforming, in particular splitting, at least one packet, or displacing at least two packets towards each other, in particular for collapsing, said device comprising:
  • the manipulation of the packet(s) with the device according to the present invention may be carried out by generating an appropriate electric field, or by modifying the surface tension of a liquid packet, or by combining both techniques.
  • the interfacial tension may be modified, preferably decreased, by a factor of at least 20%, and more preferably 50%.
  • dipoles are created by the electric field in the packets, said dipoles being oriented substantially along the axis of the microchannel such that the packets attract each other and collapse.
  • substantially collinear means that the average of the direction of the electric field makes with the axis of the microchannel an angle smaller than 45°, for example smaller than 30°, preferably smaller than 20°, and more preferably smaller than 10° or 5°.
  • the invention may be used for inducing the collapse of two packets, and for example the coalescence of two droplets inside the microchannel.
  • electrocoalescence The general physical phenomenon called "electrocoalescence" is disclosed in P. Atten, J. Electrostat. 30, 259 (1993). As electrophoretic forces, and in contrast with dielectrophoresis, electrocoalescence does not require a field gradient.
  • the invention may be used to induce electroporation of such cell or multiplicity of cells.
  • the invention may also be used to split a packet into several packets of smaller size, and for example to extract from a droplet one or several droplets of smaller size.
  • microchannel means a channel that may have a surface/volume ratio substantially greater than 1 mm -1 , preferably greater than 4 mm -1 , for example greater than 10 mm -1 , possibly greater than 1 ⁇ m -1 . Microchannels also encompass nanochannels.
  • the microchannel is preferably elongated, i.e. the dimension along its axis is larger by a factor of 3, preferably by a factor of 10, for example by a factor of 100 or 1000, than along any other direction perpendicular to said axis.
  • the axis of the microchannel may be rectilinear or not.
  • the microchannel may have a cross-section which is constant or not.
  • the section may be for example circular, ellipsoidal, rectangular, square or with a bowl shape.
  • thickness means the smallest inner distance in cross section between two opposite sides of the microchannel.
  • the thickness is the diameter.
  • the thickness is the length of the small side of the rectangle.
  • the thickness of the microchannel can take any value between a few nm and a few mm. Preferably, the thickness is comprised between 1 ⁇ m and 1mm. Still preferably, the length of the microchannel along its axis, may be chosen to be at least 10 times larger than the thickness. The microchannel may have a length chosen between 10 mm and several meters, for example between 1 cm and 50 cm.
  • the portion of the microchannel in which the electric field is substantially collinear to the axis of the microchannel has a length along said axis at least as large as the thickness of the microchannel, and smaller than the total length of the microchannel.
  • the length of said portion of the microchannel is comprised between about 1 and about 100 times the thickness of said portion, and preferably between about 1 and about 10 times the thickness of said portion.
  • the microchannel may be rigid or flexible and comprises for example a tube made of a flexible non-electrically-conducting material.
  • the microchannel is made of fused silica glass, polydimethylsiloxane, polymethylmethacrylate, or any kind of elastomer or plastic.
  • the microchannel has at least one inlet port, and/or at least one outlet port.
  • at least one of said ports can be connected to one or several reservoirs, to one or several pumps, to one or several detectors or sensors or to one or several sampling devices.
  • the microchannel may be part of a network of connected microchannels.
  • said electrode assembly is electrically insulated from an inside surface of the microchannel, for example by an insulating material.
  • the insulating material may have a thickness of at least 1 nm, for example at least 10 nm, preferably at least 100 nm, most preferably of at least 1 ⁇ m, for example up to several tens or hundreds ⁇ m. Typically, thicker insulating layers may be preferred for larger microchannels.
  • This insulating material may be made out of for example polymeric material, e.g.
  • non-conducting oxide such as, for example, glass, silicon dioxide, diamond, non-conductive ceramics.
  • the electrode assembly comprises at least two electrodes axially spaced along the axis of the microchannel by a distance long enough for the electric field between the electrodes to be substantially collinear to the axis of the microchannel.
  • Each electrode may be symmetric relative to the axis of the microchannel.
  • at least one of said electrodes comprises at least two equipotential portions facing each other across the microchannel.
  • At least one of said electrodes may be monolithic having for example a cylindrical surface surrounding the microchannel.
  • at least one of said electrodes is composite, i.e. made out of a plurality of pieces, comprising for example at least two substantially parallel equipotential plates sandwiching the microchannel.
  • the electrodes may also have a shape other than those described above.
  • the electrodes are spaced by a gap having a length that is greater than the thickness of the microchannel, preferably greater than twice the thickness.
  • the generator unit comprises advantageously at least one of a current and a voltage generator, configured to create a difference of potential between said two electrodes, preferably an alternating potential.
  • the electrode assembly is configured so that in at least one cross section of the microchannel the amplitude of the electric field varies less than a factor 10, preferably less than a factor 5, better less than a factor 2, and preferably is substantially uniform, in particular in the gap between the electrodes.
  • the electric field generated by the generator unit via the electrode assembly may have any temporal profile, for example continuous, variable or alternating (AC), or a combination of such temporal profiles.
  • the electric field may be an AC field with variable frequency or root mean squared (RMS) amplitude, or a superposition of continuous and AC components.
  • RMS root mean squared
  • AC field we mean any field periodic in time and with a zero time average.
  • Non limiting examples of AC fields according to the invention are sinusoidal, square or sawtooth AC fields.
  • the generator unit is preferably capable of generating an AC electric field with a frequency ranging from about 0.01 Hz to about 1 GHz, preferably from about 1 Hz to about 10 MHz.
  • the coalescence of droplets is efficiently achieved, for instance, with frequencies between 100 Hz and 10 kHz.
  • the aliquoting of at least one droplet is preferably achieved at frequencies lower than 50 Hz.
  • the generator unit may be configured for delivering a RMS voltage ranging between 1V and 30 kV, preferably between 60 V and 2 kV, depending on the nature of the packet, of the fluid surrounding the packet, of the microchannel, and on the size of the device.
  • the voltage may increase as the size of the device increases.
  • the RMS electric field inside the microchannel in the gap between the electrodes may range for instance between 100 V/cm and 100 kV/cm, and preferably between 500 V/cm and 20 kV/cm.
  • the generator unit may be configured to deliver a voltage with at least one of the amplitude and the frequency being time-related variable.
  • the amplitude and/or the frequency of the electric field may be modified as two packets come into close contact.
  • the electrode assembly is housed in a support, the latter having two separated support members assembled together via a fixing element, each support member carrying one electrode of the electrode assembly.
  • the support may comprise at least one orifice for receiving the microchannel.
  • said side channel When the microchannel is connected to a side channel, said side channel may have a cross-section with dimensions comparable to those of the microchannel.
  • the cross-section of the side channel is smaller than this of the microchannel.
  • the cross-section of the side channel is larger than this of the microchannel.
  • the delivery system associated with said side channel may comprise pressure control means or flow control means.
  • said side channel and said delivery system are configured for delivering in the microchannel a solution containing a surfactant.
  • surfactant designs any species, molecules or combination of molecules capable of modifying the interfacial tension between two fluids.
  • a surfactant may be for instance a tensioactive or an amphiphilic species.
  • the surfactant may be chosen to favor the formation of oil-in-water emulsions.
  • said surfactants are typically surfactants with a high HLB (Hydrophilic/Lipophilic Balance), for example with HLB values larger than 15.
  • HLB Hydrophilic/Lipophilic Balance
  • Non-limiting examples of such surfactants are Sodium Dodecyl Sulfate (SDS), oleic acid, and CTAB.
  • the solution preferably contains at least one surfactant with a low HLB, for example a HLB lower than 15, and preferably lower than 10.
  • the device for coalescing or splitting two droplets, the device comprising a first side channel connected to the delivery system, the microchannel may be connected to a second side channel, preferably connected in regard or in close vicinity of the first side channel and configured for collecting packets formed by the coalescence or splitting of original packets.
  • the microchannel may be made out of a wide variety of homogeneous or composite materials.
  • the wall of the microchannel according to the present invention may be made of a material, or treated with a material, reducing the risk of interaction of the packets with the wall of the microchannel in the presence of the embedding fluid. There may be no chemical interaction at all between the packets and the microchannel.
  • the interfacial tension between the droplet and the microchannel wall is made larger than the interfacial tension between the water between the droplet and the surrounding fluid, by treating the microchannel wall and/or by including in the droplet and/or in the fluid additives.
  • a naturally hydrophobic surface such as fluorocarbon or polyethylene.
  • hydrophobic materials such as Teflon® AF, silane or fluorosilane.
  • the surface tension between water and hydrogenated oil-based fluids can be decreased by the presence of surface-active molecules.
  • surface active molecules Numerous such surface active molecules are known in the art, and we list here only a few as a matter of examples: surfactants such as Pluronics® and Symperionics®, Triton®, Tween®, Span® 80, Tergitol®, Sodium Dodecyl Sulfate(SDS), oleic acid, methyl cellulose, hydroxyethyl and hydroxy propyl cellulose, or Coatex®.
  • surfactants such as Pluronics® and Symperionics®, Triton®, Tween®, Span® 80, Tergitol®, Sodium Dodecyl Sulfate(SDS), oleic acid, methyl cellulose, hydroxyethyl and hydroxy propyl cellulose, or Coatex®.
  • fluorinated surfactants such as 1H,1H,2H,2H perfluorodecan-1-ol or 1H,1H,2H,2H perfluorooctan-1-ol, are particularly suitable.
  • the microchannel is filled with a fluid surrounding at least one packet, said fluid may be any liquid or gaseous fluid, provided it is not miscible in the packet or with the wall of the microchannel.
  • the fluid surrounding the packet may be a liquid, for example a water-immiscible organic or inorganic liquid.
  • the fluid may be a fluorinated liquid or gas, and the droplet may be an organic or hydroorganic liquid, optionally containing species.
  • the packet and the surrounding fluid have different conductivities and/or different dielectric constants.
  • the packet may have a conductivity higher than the surrounding fluid conductivity.
  • the packet is a droplet of a first liquid suspended in an immiscible second liquid, said first liquid being more electrically conductive than the first.
  • the droplet may be a water based droplet.
  • Said water based droplet may contain any kind of natural, artificial, organic or inorganic species such as, for example, biological molecules, proteins, protein complexes, enzymes, haptens, antigens, antibodies, aptamers, epitopes, nucleic acids, peptides, polysaccharides, glycopeptides, cells, cell aggregates, drugs, chemicals, latexes, living or dead organisms, viruses, organelles, liposomes, vesicles, micelles, synthetic or natural polymers, nanoparticles, luminescent molecules, quantum dots, chemical reagents, buffers, surfactants, and any combination of such species.
  • the packet is a droplet of a water-immiscible liquid
  • the surrounding fluid is a water based solution
  • the invention may allow for the manipulation of packets having a size comparable with the section of the microchannel.
  • the area of the smallest section of said packet is at least equal to one half of the area of the section of the microchannel at the location of a first electrode or at the location of a second electrode, whichever is smaller.
  • the packet may be a spherical droplet with a diameter comparable with the diameter of the microchannel, or an elongated droplet spanning the whole section of the microchannel.
  • the device according to the present invention may be used to fuse colloids to form a chain, for instance.
  • the device may also be used for screening processing.
  • the invention also relates to, according to another of its aspects, a method for displacing at least two packets towards each other in a microchannel, in particular in order to collapse the at least two packets, the microchannel having a longitudinal axis, said method comprising:
  • the method may comprise:
  • the packets for collapsing may be placed initially in a flowing stream such as to perform an in-flight operation of collapsing.
  • the method may thus comprise:
  • At least one of said packets contains biological material, for example a cell or a cytoplasm nucleus.
  • the method for collapsing at least two packets is particularly advantageous when the packets contain a biological membrane.
  • Said method may be carried out in order to form hybridoma or to manipulate embryonic founder cells.
  • the invention also relates to, according to another of its aspects, a method for displacing at least two packets towards each other in a microchannel, in particular in order to collapse them, or for splitting at least one packet, the microchannel having an axis, said method comprising:
  • the invention also relates to, according to another of its aspects, a method for splitting at least one packet in a microchannel having a longitudinal axis, said method comprising:
  • the invention also relates to, according to another of its aspects, a method of monitoring the collapsing of at least two packets or splitting of at least one packet, the method comprising:
  • the invention also relates to, according to another of its aspects, a method for displacing at least one packet in a microchannel having an axis, said method comprising:
  • Said electric field may be continuous.
  • the operation of displacing at least one packet in the microchannel may be performed independently from an operation of collapsing or splitting.
  • said operation of displacing at least one packet in the microchannel may be carried out in order to position appropriately said at least one packet in the microchannel before performing the operation of collapsing or splitting.
  • Figure 1 shows a microfluidic device 1 according to the invention, said device comprising a microchannel 2 and an electrode assembly 3.
  • the microchannel 2 has a longitudinal axis X and an internal cross section that is circular.
  • the electrode assembly 3 comprises a pair of electrodes 4, each electrode 4 comprising a metal cylinder, for example aluminium.
  • the length of each electrode 4 is for example 4 mm and the inner diameter 1.5 mm and the outer diameter 1.9 mm.
  • the electrodes 4 are placed around the microchannel 2 and are spaced along the axis X by a gap 6.
  • the electrodes 4 are connected to a generator unit 9 via connection elements 8 comprising electrical wires.
  • the electrodes 4 are housed in a support 10 comprising two support members 11, each being a substantially rectangular parallelepiped made of Plexiglas®, for example with a width of 24 mm, a height of 20 mm and a depth of 20 mm.
  • the first hole 12 extends from a front face 13 towards a rear face 14 of the support member 11, opposite to the front face 13.
  • a second hole 17 is drilled perpendicular to the first hole 12 for receiving a connection element 8 connecting the corresponding electrode 4 to the generator unit 9.
  • Each support member 11 further comprises two holes 20 and 21 whose axes are parallel to the axis of hole 12 and configured for receiving respectively a Teflon® screw 22 and a metal rod 23 in order to maintain the support members 11 assembled with the holes 12 being collinear.
  • Each electrode 4 is mounted in the corresponding support member 11 such that the electrode 4 is flush with the front face 13, as illustrated in Figure 2.
  • the front faces 13 of the support members 11 are spaced for example by a length of 2 mm defining a 2 mm gap 6 between the electrodes 4.
  • the generator unit 9 comprises for example a function generator connected to an amplifier such as to deliver sinusoidal voltages up to 2 kV with frequencies up to 1 kHz.
  • the generator unit 9 may also comprise a central processing unit such as a computer to programmably control the voltage delivered to the electrodes 4.
  • Figure 3 shows diagrammatically the orientation of electric field given by the arrows together with the equipotential lines.
  • the electric field is substantially collinear to the axis X of the microchannel 2 and thus favors electrocoalescence and minimizes any effect of dielectrophoresis.
  • the device 1 may be mounted on an observation stage of a binocular microscope 30 connected to a CCD camera 31 and a video recorder 32, as illustrated on Figure 1, thus enabling the monitoring of the collapsing of two packets or the splitting of a packet in the microchannel.
  • the device may be configured such that after the collapsing or splitting, the packet(s) are drained off.
  • Figure 8 shows an electrode assembly 3' comprising two composite electrodes 35 each having a pair of substantially parallel equipotential plates 36 facing each other and sandwiching a microchannel 2' which has a rectangular cross-section. Each pair of plates 36 is connected to a respective pole of the generator unit 9.
  • the droplet fluid is TBE 5x buffer (0.45 M Trisbase®, 0.45 M boric acid and 0.01 M EDTA; Sigma®) dyed with 0.25 wt% bromophenol blue for observation in a carrier fluid of fluorinated oil (FC-40, 3M) with 0.5 wt% 1H,1H,2H,2H perfluorodecan-1-ol (Fluorochem®) added to prevent interactions with the wall of the microchannel 2.
  • FC-40 fluorinated oil
  • FC-40 carrier fluid of fluorinated oil
  • Fluorochem® perfluorodecan-1-ol
  • the two fluids are layered in a 1.5 ml Eppendorf® tube so that the bottom layer consists of approximately 0.6 ml of the carrier fluid (FC-40/1H,1H,2H,2H perfluorodecan-1-ol) and the upper layer consists of approximately 0.6 ml of the droplet fluid (TBE 5x/bromophenol blue).
  • the carrier fluid FC-40/1H,1H,2H,2H perfluorodecan-1-ol
  • TBE 5x/bromophenol blue approximately 0.6 ml of the droplet fluid
  • the microchannel 2 is filled from a syringe pump (commercialised by KD Scientific) using for example a Hamilton® Gas-Tight 250 ⁇ l syringe filled with the carrier fluid.
  • the excess fluid pumped into the microchannel may be collected in a waste reservoir.
  • the microchannel 2 is placed into the carrier fluid phase of the layered Eppendorf® tube. The pump is then aspirated at a rate of 1 ml/hr. Droplets are formed by oscillating the microchannel between the carrier phase and the droplet phase, either manually or by attaching the microchannel to a mechanical oscillator, at for example approximately 2 Hz. Droplets formed by this method have approximately the same diameter as the channel.
  • the method may be carried out with any of the devices defined above.
  • a single droplet is formed by the oscillation method described above. Using the syringe pump, the droplet is aspirated into the gap 6 between the electrodes 4. When the droplet has reached the section of the gap just before the upstream electrode, the flow is stopped and the system allowed to settle to equilibrium. A continuous voltage is then applied, with the positive voltage applied to the electrode 4 closest to the droplet and with the farthest electrode grounded. The motion of the droplet towards the grounded electrode can be recorded on video and the time for a given displacement measured. The droplet only moves when it is between the electrodes 4 and stops when it is under the grounded electrode.
  • the static coalescence may be performed by any of the devices defined above.
  • Droplets are formed by the oscillation method described above such that the spacing between the two droplets is larger than the gap 6 between the electrodes 4.
  • a first droplet is initially brought into the gap 6 between the electrodes 4 using the syringe pump.
  • the flow is stopped.
  • the droplet is moved against the direction of the previously applied flow using the electric field actuation described above until it reaches the downstream electrode.
  • the flow is restarted until the first droplet returns to the upstream electrode. This procedure is repeated until a second droplet appears between the electrodes 4.
  • the microchannel position in the electrodes is then adjusted so that the second droplet is outside of the gap 6 between the electrodes.
  • the first droplet is moved against the direction of the previously applied flow until the gap between the two droplets is for example 0.5 mm.
  • the microchannel is then repositioned such that the midpoint between the two closest edges of the droplets is centered between the two electrodes and the system is allowed to settle to equilibrium.
  • the first droplet 40 has a diameter of about 540 ⁇ m and the second droplet 41 has a diameter of about 560 ⁇ m.
  • initial droplet motion is steady, with the smaller droplet 40 moving at a slightly higher velocity ( Figures 4A and 4B).
  • Figure 4C When the droplets 40 and 41 come into close contact they rapidly accelerate and drain the intervening film ( Figure 4C), which indicates that the device 1 should provide essentially instantaneous coalescence of droplets which are initially close together, such as occurs after two droplets arrive simultaneously at a T-junction.
  • the in-flight coalescence may be performed by any of the devices defined above.
  • the first droplet 43 may have a diameter of about 580 ⁇ m and the second droplet may have a diameter of about 560 ⁇ m.
  • the microchannel is displaced such that both droplets are outside the gap 6 between the electrodes 4.
  • a 2 kV, 1kHz sinusoidal voltage is then applied to the 2 mm-spaced electrodes and kept on throughout the duration of the experiment. After applying the electric field, the flow is started by aspirating with the syringe pump at 50 ⁇ L/hr.
  • the droplet 42 enters the gap 6 between the electrodes 4 and moves at a constant velocity in the absence of the droplet 43 (Figure 5A).
  • the leading interface of the droplet 43 appears after 13 sec, but has no effect on the droplet 42.
  • Only when the trailing droplet is well inside the gap 6 between the electrodes does the dipolar force manifest itself.
  • the coalescence time is essentially the same as in the static case (approximately 8 sec) for these widely separated droplets, but the dynamics are slightly different due to the flow.
  • the dipolar force is sufficiently strong to stop the droplet 42 (Figure 5B), whereupon the droplet 43 moves toward it at a constant rate, closing the distance at essentially the same rate as in the static case. Once the droplets are close together, the strong dipolar force rapidly drains the intervening fluid and coalescence is achieved (Figure 5C).
  • a single large droplet 46 is formed by oscillating the interface as described above but at a lower frequency.
  • the droplet 46 is brought into the gap 6 between the electrodes, by aspirating with the syringe pump (Figure 6A).
  • the drop depicted in the present embodiment is an ellipsoid of revolution with a 2.5 mm long axis.
  • the drop 46 splits into two smaller, stable drops 47 ( Figures 6B and 6C) that are ejected from the gap 6.
  • Typical operating conditions for achieving a clean droplet splitting may consist in a square voltage with a frequency between 0.1 and 1 Hz and an amplitude between 1kV and 2 kV. Under such condition, the droplet may break in less than 1 minute. The lowest the voltage applied, the "cleanest" the splitting but the longer it may take. The droplet length may be about the length of gap 6.
  • the microchannel portion 50 between the electrodes 4 may form a T-intersection with a transverse channel 51.
  • the resulting droplet 52 may be driven in the transverse channel 51, for example by using a syringe pump connected to the transverse channel 51.
  • the droplet splitting may be performed by extracting a droplet 53 from a relatively large mass of fluid 54 by applying the electric field between the two electrodes 4.
  • droplets 53 can be formed when desired, for example by programmably controlling the electrodes 4.
  • Figure 13 shows a device 60 according to the invention, said device 60 comprising a microchannel 61 connected in a portion 62 to first and second side channels 63 and 64.
  • Portion 62 may for instance be situated substantially at the middle of the microchannel.
  • the microchannel 61 may have a thickness of about 100 ⁇ m and a width of about 300 ⁇ m and the side channel 63 a thickness of about 100 ⁇ m and a width of about 50 ⁇ m.
  • the side channel 63 is connected to a delivery system 66 comprising a syringe pump having a reservoir 67 containing a solution of surfactant of oleic acid and SDS in hexadecane, at a concentration superior to the critical micellar concentration.
  • the microchannel 61 is filled with a solution containing hexadecane containing SPAN®80 at a concentration adjusted to avoid interaction of aqueous droplets with the microchannel walls.
  • the side channel 64 is connected to a springe pump 68 in aspiration mode configured to aspirate the solution from the microchannel 61.
  • Two droplets 70 of a 5X TBE Buffer are introduced and displaced in the microchannel 61 by its both ends.
  • the aspiration of droplets 70 by both ends is synchronized so that the droplets 70 arrive from both sides at the same time at the portion 62.
  • a solution of surfactant contained in the reservoir 67 is delivered by the delivery system 66 into the portion 62 of the microchannel with a predetermined flow rate such as droplets 70 coalesce.
  • the optimal flow rate may be determined by progressively increasing the flow until droplets coalesce at each collision, which sets the optimal flow rate.
  • the solution of surfactant may be delivered in pulses synchronized with the arrival of the pair of droplets at the connection portion 62.
  • the resulting droplet 71 is collected in syringe pump 68 for further use, or e.g. transferred to another microchannel for detection.
  • a device made in accordance with the invention may be used to carry out, for instance:

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EP04292173A 2004-09-09 2004-09-09 Mikrofluide Vorrichtung mit kollinearem elektrischen Feld Withdrawn EP1637226A1 (de)

Priority Applications (13)

Application Number Priority Date Filing Date Title
EP04292173A EP1637226A1 (de) 2004-09-09 2004-09-09 Mikrofluide Vorrichtung mit kollinearem elektrischen Feld
US11/662,362 US9566558B2 (en) 2004-09-09 2005-09-09 Device for manipulation of packets in micro-containers, in particular in microchannels
JP2007530836A JP5885901B2 (ja) 2004-09-09 2005-09-09 マイクロチャネルまたは他のマイクロ容器中でパケットを操作するためのデバイス
EP05782951.7A EP1802395B1 (de) 2004-09-09 2005-09-09 Ein kollineares elektrisches feld verwendende mikrofluidvorrichtung
CN2005800359884A CN101052468B (zh) 2004-09-09 2005-09-09 采用共线电场的微流控装置
ES05782951T ES2784184T3 (es) 2004-09-09 2005-09-09 Dispositivo microfluídico que utiliza un campo eléctrico colinear
CN201110409213.6A CN102513170B (zh) 2004-09-09 2005-09-09 用于在微容器特别是微通道中操纵小包的装置
PCT/IB2005/052951 WO2006027757A2 (en) 2004-09-09 2005-09-09 Microfluidic device using a collinear electric field
JP2012237242A JP5715999B2 (ja) 2004-09-09 2012-10-26 マイクロチャネルまたは他のマイクロ容器中でパケットを操作するためのデバイス
JP2014243114A JP2015096257A (ja) 2004-09-09 2014-12-01 マイクロチャネルまたは他のマイクロ容器中でパケットを操作するためのデバイス
JP2016135183A JP6373308B2 (ja) 2004-09-09 2016-07-07 マイクロチャネルまたは他のマイクロ容器中でパケットを操作するためのデバイス
US15/392,189 US10661278B2 (en) 2004-09-09 2016-12-28 Device for manipulation of packets in micro-containers, in particular in microchannels
US16/784,736 US11097275B2 (en) 2004-09-09 2020-02-07 Device for manipulation of packets in micro-containers, in particular in microchannels

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WO2009037680A2 (en) 2007-09-20 2009-03-26 Jean-Louis Viovy Encapsulation microfluidic device
US8741661B2 (en) 2006-09-13 2014-06-03 Institut Curie Methods and devices for sampling flowable materials
CN107188306A (zh) * 2017-07-12 2017-09-22 同济大学 固定化微生物生产设备及生产方法
EP3586964A1 (de) 2018-06-27 2020-01-01 Inorevia Verfahren zur manipulation von tröpfchen in einem kanal
WO2020002197A1 (en) 2018-06-27 2020-01-02 Institut Curie Method of inducing or preventing the merging of droplets

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EP1348546A2 (de) * 2002-03-28 2003-10-01 Toyo Ink Mfg. Co., Ltd. Elektrokoagulationsdruckverfahren zur Erzeugung von Bildern mit erhöhter optischer Dichte

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8741661B2 (en) 2006-09-13 2014-06-03 Institut Curie Methods and devices for sampling flowable materials
WO2009037680A2 (en) 2007-09-20 2009-03-26 Jean-Louis Viovy Encapsulation microfluidic device
US9744513B2 (en) 2007-09-20 2017-08-29 Jean-Louis Viovy Encapsulation microfluidic device
CN107188306A (zh) * 2017-07-12 2017-09-22 同济大学 固定化微生物生产设备及生产方法
EP3586964A1 (de) 2018-06-27 2020-01-01 Inorevia Verfahren zur manipulation von tröpfchen in einem kanal
WO2020002196A1 (en) 2018-06-27 2020-01-02 Inorevia Method of manipulating droplets in a channel
WO2020002197A1 (en) 2018-06-27 2020-01-02 Institut Curie Method of inducing or preventing the merging of droplets

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