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WO2010118637A1 - Dispositif de distribution microfluidique, procédé de production, et application correspondants - Google Patents

Dispositif de distribution microfluidique, procédé de production, et application correspondants Download PDF

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Publication number
WO2010118637A1
WO2010118637A1 PCT/CN2010/000494 CN2010000494W WO2010118637A1 WO 2010118637 A1 WO2010118637 A1 WO 2010118637A1 CN 2010000494 W CN2010000494 W CN 2010000494W WO 2010118637 A1 WO2010118637 A1 WO 2010118637A1
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WO
WIPO (PCT)
Prior art keywords
microfluidic
chip
channel
distribution
microfluidic channel
Prior art date
Application number
PCT/CN2010/000494
Other languages
English (en)
Chinese (zh)
Inventor
黄岩谊
席建忠
王建斌
周莹
Original Assignee
Huang Yanyi
Xi Jianzhong
Wang Jianbin
Zhou Ying
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 Huang Yanyi, Xi Jianzhong, Wang Jianbin, Zhou Ying filed Critical Huang Yanyi
Publication of WO2010118637A1 publication Critical patent/WO2010118637A1/fr

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Classifications

    • 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
    • B01L3/02—Burettes; Pipettes
    • B01L3/0203—Burettes, i.e. for withdrawing and redistributing liquids through different conduits
    • 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
    • B01L3/502715—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 interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/021—Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry
    • 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
    • B01L2200/0642—Filling fluids into wells by specific techniques
    • 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
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting

Definitions

  • Microfluid distribution device preparation method thereof and use thereof
  • the invention relates to the field of micro-test equipment, and more precisely to the field of micro-flow distribution.
  • Microfluidic technology is an ideal platform for upgrading other reactions due to its accurate liquid handling potential.
  • High-volume, miniaturized reaction arrays capable of accurate submicroliter liquid handling have become powerful tools for new drug development, gene detection, protein crystallization, reaction condition screening, and cell-related research.
  • microfluidic pipetting methods that can replace traditional methods, such as highly integrated chips with multi-layer soft lithographically prepared pneumatic valves, and sequential droplet microfluidic chips for parameter screening.
  • the object of the present invention is to solve the above technical problems, and to provide a nanoliter microfluidic distribution device suitable for mass testing, can be used in an open space, low in cost, and convenient to use, and the invention also provides a simple and inexpensive The method of preparing the microfluidic distribution device and providing several applications of the device in different fields.
  • the term "chip” refers to a sheet-like or plate-like object having a certain thickness; it may be a single-layer structure or a multilayer structure; its shape may be any shape, preferably having at least one
  • the shape of the straight side is further preferably trapezoidal, square, or rectangular; the material thereof may be any material, preferably glass, ceramic, silicon, metal, polymer, further preferably a plastic polymer, for example, may be polydimethylsiloxane Alkane (PDMS), acrylonitrile-butadiene-styrene copolymer, polycarbonate (PC), polymethyl methacrylate (PMMA), polyurethane, polyethylene, polypropylene, Polymethylpentene, polytetrafluoroethylene (PTFE), polyvinyl chloride (PVC), cyclic polyolefin copolymer (Cyclic Olefin Copolymers; COC) polyvinylidene fluoride, polystyrene, polysulf
  • microfluidic channel refers to a channel through which a liquid sample disposed inside a microfluidic distribution chip flows, and the liquid sample may flow along the microfluidic channel by capillary force or simultaneously by capillary force and external force, which may be a pumping force. , centrifugal force, vacuum or other similar force that can pull or push the liquid sample along the microfluidic channel.
  • a microfluidic channel has the following meaning: When the microfluidic channel is two or more juxtaposed microfluidic channels, the microfluidic channel between the two openings of the same microfluidic channel on the microfluidic distribution chip "microfluidic channel"; when the microfluidic channel is at least one microfluidic channel tree formed by at least one bifurcation of one microfluidic channel, microcirculation between any two adjacent bifurcation points The microfluidic channel between the channel or any one of its openings and its adjacent bifurcation point is "a microfluidic channel".
  • forked refers to a microfluidic channel divided into two or more microfluidic channels; "bifurcation” refers to a microfluidic channel divided into two microfluidic channels.
  • hydrophilic and hydrophobic refer to the relative concept unless otherwise stated.
  • the inner surface of the microwell of the microwell chip is coated with a hydrophilic material
  • the outer surface of the microwell chip on the side of the microwell is coated with a hydrophobic material
  • the outer surface is coated with a material that is more hydrophobic than the material coated on the inner surface of the microwell.
  • a microfluidic distribution device comprising a microfluidic distribution chip, the microfluidic distribution chip having at least one microfluidic layer; at least two parallel microfluidic channels or at least one of the at least one microfluidic layer a microfluidic channel tree formed by at least one bifurcation of the root microfluidic channel; wherein each of the at least two juxtaposed microfluidic channels has two openings on the microfluidic distribution chip, one of the openings In the microfluidic inlet, the other opening is a microfluidic outlet; in the microfluidic channel tree, the opening of the microfluidic channel on the microfluidic distribution chip is a microfluidic inlet, and the other microfluidic channels formed by the bifurcation are in the microflow
  • the opening on the flow distribution chip is a microfluidic outlet; the microfluidic channel has a cross-sectional area of 1 ⁇ m 2 to 1 mm 2 , and except for the
  • each microfluidic channel can be assigned the same liquid sample or a different liquid sample; the external force applied to the liquid sample in the microfluidic channel and the transverse direction of the microfluidic channel can be adjusted.
  • the cross-sectional area is used to adjust the flow rate of the liquid sample in the microfluidic channel.
  • At least one group of microfluidic channels formed by at least one bifurcation of one microfluidic channel since one microfluidic channel tree has only one microfluidic inlet, the liquid sample in the microfluidic channel of the same microfluidic channel tree is Similarly, the flow rate of the liquid sample in the microfluidic channel can be adjusted by adjusting the magnitude of the external force applied to the liquid sample in the microfluidic channel and the cross-sectional area of the microfluidic channel; while the liquid samples in the different microfluidic channel trees can be the same , can also be different; more than two microfluidic channel trees can be juxtaposed in the same microflow
  • the layers may also be distributed in different microfluidic layers; when more than two microfluidic channel trees are distributed in different microfluidic layers, they may be staggered from each other or may be superimposed on each other.
  • the microfluidic distribution device can also include a microfluidic carrier chip for use with the microfluidic distribution chip for dispensing a liquid sample thereon.
  • a microfluidic carrier chip for use with the microfluidic distribution chip for dispensing a liquid sample thereon.
  • the chip which can accept the liquid sample from the microfluid distribution chip can be used as a microfluidic carrying chip, its shape and material are not required, and may be, for example, a glass piece, a silicon piece, a metal piece, a plastic piece or the like.
  • the microwell can be disposed on the microfluidic carrier chip, and the size of the microwell can be set as needed, for example, several nanoliters to several microliters; the arrangement of the microwells and the microfluidic channel outlet on the microfluid distribution chip The arrangement is adapted, for example, if the microfluidic channel outlets on the microfluidic distribution chip are equally spaced on the side walls of the microfluidic distribution chip, the microwells are also arranged in the same flow at equal intervals in the microflow. Hosted on the chip.
  • the microfluidic bearing chip outer surface of the microwell inner surface and the microwell opening side may be coated with a material having different hydrophilic properties, which has the advantages of facilitating the distribution of the liquid sample and preventing different microwells.
  • the liquid samples in between are contaminated with each other.
  • the inner surface of the microwell is coated with a hydrophilic material
  • the outer surface of the microfluidic bearing chip on the side of the microwell is coated with a hydrophobic material, when flowing from the outlet of the microfluidic channel.
  • the droplets When the liquid sample contacts the inner surface of the microwell, the droplets are confined within the microwell due to surface tension and are not carried to the outer surface of the microfluidic bearing chip or other microwells. Conversely, if the liquid sample to be dispensed is oily, the inner surface of the microwell is coated with a hydrophobic material, and the microfluidic side of the microwell opening side is coated with a hydrophilic material to achieve the same effect.
  • the number of microfluidic channels juxtaposed in the microfluid distribution chip can be set as needed, for example, 10 pieces.
  • the parallel microfluidic channels may be arranged in parallel and equally spaced on the microfluid distribution chip; further preferably, the angle between the sidewall plane where the microfluidic channel exit is located and the plane where the microfluid distribution chip is located is one
  • the acute angle for example, may be from 10 ° to 80 °, such that a liquid sample emerging from the microfluidic channel concentrates to the sharp tip tip under the influence of gravity and surface tension, facilitating the dispensing of the liquid sample to an accurate location.
  • the microfluidic channel tree in the microfluidic distribution chip is formed by bifurcation of the first microfluidic channel (referred to as "root microfluidic channel") connected to the microfluidic inlet to form more than two new micros Flow channels, and each new microfluidic channel can be forked to form a new microfluidic channel, all of which together form a microfluidic channel tree.
  • the bifurcation of the microfluidic channel tree is a bifurcation
  • a microfluidic channel is bifurcated to form two new microfluidic channels, and the three microfluidic channels together form a letter Y or a letter T, new The microfluidic channel can be bifurcated.
  • the microfluidic channel tree is bilaterally symmetric with the root microfluidic channel as an axis, and the new microfluidic channel formed by the bifurcation is turned to a direction parallel to the root microfluidic channel through an arc portion, except for the arc portion
  • the other parts of the microfluidic channel are linear.
  • all of the microfluidic channels have the same cross-sectional area, and the microfluidic outlets are equally spaced on the same sidewall of the microfluidic distribution chip, the plane of the sidewalls and the plane of the microfluid distribution chip
  • the angle is an acute angle, which can be, for example, 10 ° to 80 °.
  • At least one microfluidic control layer may be further disposed in the microfluid distribution chip, the microfluidic control layer has a microfluidic control channel, and the microfluidic control channel is disposed at a position corresponding to the microfluidic channel.
  • the valve that opens or closes the microfluidic channel can be controlled.
  • the valve may be an integrated resilient hydraulic valve, in which case the material of the microfluidic dispensing chip should be a flexible material. In this way, the microfluidic channel can be controlled to open or close the microfluidic channel as needed.
  • microfluidic distribution chip When used with the microfluidic carrier chip, it is preferably carried out by a computer-controlled three-position platform, which ensures that the dispensing of the liquid sample is fast and accurate.
  • the microfluid distribution chip can be prepared by a simple and inexpensive method as follows.
  • step (6) coating a layer of uncured plastic polymer on the substrate and curing it, bonding it to the side of the polymer layer obtained in step (5) having a microfluidic channel, and bonding The polymer layers together are further cured;
  • the cured polymer layer is removed from the substrate, and excess polymer is removed along the end of the microfluidic channel to form a microfluidic outlet.
  • the substrate may be a flat plate having a smooth surface made of any material, for example, a metal sheet, a silicon wafer, a glass sheet, a ceramic sheet, a plastic sheet, etc.; the photoresist is not particularly limited, and the plastic polymer is not particularly limited.
  • PDMS polydimethylsiloxane
  • PC polycarbonate
  • PMMA polymethyl methacrylate
  • Purethane polyethylene
  • PMMA polymethyl methacrylate
  • PVC polyvinyl chloride
  • PVF polyvinylidene fluoride
  • polystyrene polysulfone
  • nylon polystyrene-acrylic acid copolymer
  • any two or more of the above mixture may be polydimethylsiloxane (PDMS), acrylonitrile-butadiene-styrene copolymer, polycarbonate (PC), polymethyl methacrylate (PMMA), polyurethane, polyethylene, poly Propylene, polymethylpentene, polytetrafluoroethylene (PTFE), polyvinyl chloride (PVC), polyvinylidene fluoride, polystyrene, polysulfone, nylon, styrene-acrylic acid copolymer or any two or more of the above mixture.
  • microfluidic distribution device of the present invention can be applied in various fields such as microfluidics, microanalysis, drug screening, cell detection, and combinatorial chemical reactions.
  • a microfluidic distribution device comprising a microfluidic distribution chip, characterized in that said microfluidic distribution chip has at least one microfluidic layer; said at least one microfluidic layer having at least two juxtaposed microfluidic channels or At least one group consists of a root micro a microfluidic channel tree formed by at least one bifurcation of the flow channel; wherein each of the at least two juxtaposed microfluidic channels has two openings on the microfluidic distribution chip, one of which is micro The flow inlet, the other opening is a micro-flow outlet; in the micro-flow channel tree, the opening of the micro-flow channel on the micro-flow distribution chip is a micro-flow inlet, and the other micro-flow channels formed by the bifurcation are distributed in the micro-flow
  • the opening on the chip is a micro-flow outlet; the micro-flow channel has a cross-sectional area of 1 ⁇ m 2 to 1 mm 2 , and except for the inlet and the outlet communicating with the outside, the
  • microfluidic dispensing device of clause 1, wherein the microfluidic dispensing device further comprises a microfluidic carrier chip for use with the microfluidic distribution chip to accept a liquid sample dispensed by the microfluidic dispensing chip.
  • microfluidic distribution device wherein the microfluidic carrier chip is provided with at least two microwells that can be used to accommodate the liquid sample dispensed by the microfluid distribution chip, and the arrangement of the microwells
  • the mode is adapted to the arrangement of the microfluidic channel outlets on the microfluidic distribution chip.
  • microfluidic distribution device characterized in that the bifurcation of the microfluidic channel tree is a bifurcation, and a microfluidic channel is bifurcated to form two new microfluidic channels, the above three The microfluidic channels together form a letter Y or a letter T, and the new microfluidic channel can be bifurcated.
  • microfluidic distribution device according to Item 3 or 4, wherein the microfluidic channel tree is bilaterally symmetric with the root microfluidic channel as an axis, and the new microfluidic channel formed by the bifurcation is transferred to an arc portion In the direction parallel to the root microfluidic channel, except for the arcuate portion described above, the other portions of the microfluidic channel are linear.
  • microfluidic distribution device characterized in that the inner surface of the microwell is coated with a hydrophilic material, and the outer surface of the microfluidic bearing chip on the side of the microwell opening is coated with a hydrophobic material; or in the microwell The surface is coated with a hydrophobic material, and the outer surface of the microfluidic bearing chip on the side of the microwell opening is coated with a hydrophilic material.
  • microfluidic distribution device according to item 6, wherein the microfluidic outlets are equally spaced on the same side wall of the microfluidic distribution chip.
  • microfluidic distribution device characterized in that all of the microfluidic channels have the same cross-sectional area.
  • microfluidic distribution device according to any one of claims 1 to 4, wherein the microfluid distribution chip is made of a flexible material.
  • microfluidic distribution device further comprises at least one microfluidic control layer, the microfluidic control layer has a microfluidic control channel, and the microfluidic control channel corresponds to the microfluidic channel
  • the position has a valve that can control the opening or closing of the microfluidic channel.
  • microfluidic dispensing device of clause 11 wherein the valve is an integrated resilient hydraulic valve.
  • the method of preparing a microfluidic distribution chip according to Item 1-12 characterized in that the method comprises the following steps:
  • microfluidic distribution chip according to items 1-12 in the fields of microfluidics, microanalysis, drug screening, cell detection, and combinatorial chemical reactions.
  • FIG. 1 Schematic diagram of microfluid distribution chip with multiple parallel microfluidic channels
  • Figure 2 Schematic diagram of a microfluidic distribution chip with a set of microflow channel trees
  • FIG. 3 Schematic diagram of another microfluidic distribution chip with a set of microfluidic channel trees
  • FIG. 4 Schematic diagram of the third microfluidic distribution chip with a set of microfluidic channel trees
  • FIG. 5 Schematic diagram of the fourth microfluidic distribution chip with a set of microfluidic channel trees
  • FIG. 6 Schematic diagram of microfluidic distribution chip with two sets of microfluidic channel trees
  • FIG. 7 Schematic diagram of a microfluid distribution chip with a microfluidic layer and a microfluidic control layer
  • FIG. 8 Schematic diagram of a microfluidic carrier chip with a microwell array
  • Figure 9 Schematic diagram of the preparation process of a microfluid distribution chip with a set of microfluidic channel trees
  • FIG. 11 Schematic diagram of the working process of the microfluidic distribution device
  • FIG. 1(a) is a front view of the microfluid distribution chip
  • Fig. 1(b) is a cross-sectional view along the I - I direction
  • 11 is a microfluidic channel
  • 12 is an inlet of the microfluidic channel
  • 13 is an exit of the microfluidic channel .
  • FIG. 1 is a front view of the microfluid distribution chip
  • Figure 2 (b) is a cross-sectional view along the I - I direction
  • 21a is the root microfluidic channel
  • 21b is formed by the root microfluidic channel through the bifurcation
  • the new microfluidic channel, 22 is the inlet of the microfluidic channel
  • 23 is the outlet of the microfluidic channel.
  • Two new microfluidic channels 21b formed by the bifurcation of the root microfluidic channel form a letter Y shape with the root microfluidic channel 21a.
  • FIG. 3 (a) is a front view of the microfluid distribution chip
  • Figure 3 (b) is a cross-sectional view along the I - I direction
  • 31a is the root microfluidic channel
  • 31b is formed by the root microfluidic channel through the bifurcation
  • the new microfluidic channel, 32 is the inlet of the microfluidic channel
  • 33 is the outlet of the microfluidic channel.
  • Two new microfluidic channels 31b formed by the bifurcation of the root microfluidic channel form a letter T shape with the root microfluidic channel 31a.
  • FIG. 4 (a) is a front view of the microfluid distribution chip
  • Figure 4 (b) is a cross-sectional view along the I - I direction
  • 41a is the root microfluidic channel
  • 41b is formed by the root microfluidic channel through the bifurcation
  • the new microfluidic channel, 42 is the inlet of the microfluidic channel
  • 43 is the outlet of the microfluidic channel.
  • Two new microfluidic channels 31b formed by the bifurcation of the root microfluidic channel form a letter T shape with the root microfluidic channel 31a.
  • the entire microfluidic channel tree is bilaterally symmetric with the root microfluidic channel 41a as an axis, and 41b is turned by an arcuate portion 44 in a direction parallel to the root microfluidic channel. Except for the curved portion 44, the other portions of the microfluidic channel are It is linear.
  • FIG. Fig. 5(a) is a front view of the microfluid distribution chip
  • Fig. 5(b) is a cross-sectional view along the I - I direction
  • Fig. 5(c) is a cross-sectional view along the ⁇ - ⁇ direction.
  • the structure of the microfluidic distribution chip in this embodiment is similar to that in the embodiment 4. The difference is that the plane of the sidewall of the microfluidic channel exit is at an acute angle ⁇ from the plane where the microfluid distribution chip is located, and flows out from the microfluidic channel.
  • the liquid sample concentrates on the tip of the acute angle under the action of surface tension and gravity, which facilitates the dispensing of the liquid sample to an accurate position.
  • Fig. 6(a) is a front view of the microfluid distribution chip
  • Fig. 6(b) is a cross-sectional view along the 1-1 direction
  • Fig. 6(c) is a cross-sectional view along the ⁇ - ⁇ direction.
  • the microfluidic channels in the upper microfluidic layer are indicated by solid black lines, while the microfluidic channels in the lower microfluidic layer are indicated by solid gray lines.
  • Two sets of microfluidic channel trees can be assigned different liquid samples, as shown in Figure 6(c). During operation, two different liquid samples are collected and mixed at the lower end of the microfluidic distribution chip.
  • FIG. Fig. 7 (a) is a front view of the microfluid distribution chip
  • Fig. 7 (b) is a cross-sectional view taken along the line I - I
  • Fig. 7 (c) is a cross-sectional view along the ⁇ - ⁇ direction.
  • the upper layer is a microfluidic control layer, wherein the microfluidic control channel is indicated by a solid black line
  • the lower layer is a microfluidic layer, wherein the microfluidic channel is indicated by a solid gray line.
  • microfluidic control channels There are four microfluidic control channels, namely 751, 752, 753 and 754, and there are four microfluidic channels with outlets, namely 731, 732, 733 and 734.
  • the microfluidic control channel has only one opening on the microfluid distribution chip, and the other end is sealed inside the microfluid distribution chip, in which the gas is introduced, and the pressure of the gas can be adjusted as needed.
  • the microfluidic control channel is provided with an enlarged cavity at some locations intersecting the microfluidic channel (as shown by the black square in Figure 7(a), the expanded cavity is the integrated elastic hydraulic pressure of claim 12. Valve), so at these locations, the wall between the microfluidic channel and the microfluidic control channel is thin (as shown in Figure 7(b)).
  • FIG. 7(c) shows the case where the air pressure in the 751 channel does not exceed P e and the air pressure in the 753 channel exceeds P e .
  • FIG. Fig. 8(a) is a front view of the microfluidic carrying chip
  • Fig. 8(b) is a cross-sectional view along the I - I direction.
  • 81 is a microwell
  • 82 is the inner surface of the microwell
  • 83 is the outer surface of the microwell carrying chip.
  • the arrangement of the microwell on the microfluidic carrier chip should be compatible with the microfluidic distribution chip used. For example, if the microfluid distribution outlets of the microfluidic distribution chip are arranged at equal intervals, the microwell should also be the same.
  • the pitch is arranged on the microfluidic carrier chip.
  • 82 and 83 are coated with materials having opposite hydrophilic properties.
  • Preparation of a microfluidic distribution chip A method of preparing a microfluid distribution chip including only one microfluidic layer (such as the microfluid distribution chip in the embodiment 1-5) will be described in detail below with reference to FIG.
  • (a) Prepare a 3'' wafer and clean and dry the surface.
  • (b) Apply a layer of photoresist SU-8 of about 100 m on the silicon wafer; prepare a hollowed-out visor with a microfluidic channel pattern, and use 300 mJ/ for the SU-8 under the visor.
  • the preparation method is similar to the preparation method of the microfluidic distribution chip in Example 9. If the structures of the channels of different layers are different, the steps (a) and (b) in Embodiment 9 should be repeated to obtain templates of different patterns, and then the PDMS layers of channels having different structures are respectively prepared by using the respective templates. Finally, the PDMS layers are bonded together and fully cured to form a microfluidic outlet and an inlet. If the channels of the different layers are of the same structure, the same number of PDMS layers can be prepared using the same template, and then the PDMS layers are bonded together and fully cured to form a microfluidic outlet and an inlet.
  • Preparation of a microfluidic carrier chip with a microwell Prepare a glass plate coated with a chrome film, spin a layer of SU-8 on the chrome film, and use a 150 mJ/cm 2 center wavelength of 365 nm for SU-8 under the occlusion of a well-designed visor. Irradiation with ultraviolet light, then baking SU-8 at 65 ° C for 3 minutes, baking at 95 ° C for 10 minutes, developing with a developer, and then baking the glass piece at 150 ° C for 3 hours to make SU-8 fully Cross-linking. The chrome film is etched with an etchant, and the etched chrome film is then used as a mask for etching the glass.
  • a microwell is formed on the glass plate, and the size of the microwell capacity can be controlled by the size of the mask pattern and the etching time.
  • the outer surface of the microwell carrier chip was modified with 1H, 1H, 2H, 2H-perfluorodecyltriethoxysilane to form a hydrophobic outer surface.
  • microfluidic distribution chip and a microfluidic carrier chip having a microwell array were prepared in accordance with the methods of Examples 9 and 11, respectively.
  • Microfluidic core with microwell array The structure of the chip is shown in Figure 8.
  • the structure of the micro-flow distribution chip is shown in Figure 4.
  • the microfluidic channel has a cross-sectional dimension of 100 ⁇ m ⁇ 100 m and the microwell has a volume of approximately 120 nanoliters. Since the relative position of the microfluidic distribution chip and the microfluidic carrier chip is critical to the operational accuracy during the operation of the microfluidic distribution device, a computer controlled three-dimensional mobile platform is used to control the movement of the chip.
  • FIG. 10 (a) is the state before the distribution of the microfluid
  • Figure 10 (b) is the state of the microfluid distribution process, from which it can be clearly seen that the droplets of the liquid sample are hung at the exit of the microfluidic channel
  • c) is a microfluidic carrier chip to which a liquid sample is dispensed, and the distribution mode is interlaced
  • FIG. 10(d) is an enlarged view of a portion of the dotted line in FIG. 10(c)
  • FIG. 10(e) is a solution of a fluorescein solution.
  • Fluorescence micrograph of a microfluidic carrier chip The liquid sample of a few nanoliters to several hundred nanoliters can be accurately dispensed using the microfluidic dispensing device of this embodiment, and when 115 nanoliters of the liquid sample is dispensed at a time, the error between the different channels is less than 6%.
  • Figure 11 details the operation of the microfluidic distribution device, the liquid sample dispensed being an aqueous solution of potassium thiocyanate.
  • Fig. 11(a) Under the control of the three-dimensional platform, the microfluidic outlet of the microfluidic distribution chip moves toward the microwell;
  • Fig. 11(b) generates a droplet driven by pulse pressure;
  • Fig. 11(c) liquid The droplets continue to increase, contact and infiltrate into the hydrophilic inner surface of the microwell;
  • Figure 11(d) The microfluidic distribution chip continues to move forward and the droplets remain in the microwell. It can be seen from this process that liquid samples in adjacent microwells do not contaminate each other.
  • FIG. Figure 12 clearly shows the operation of the microfluidic distribution device.
  • Figure 12(d)-(f) The graphic letter "N” formed by dispensing the liquid sample at different locations using the microfluidic distribution chip ", jagged and "PKU”.

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  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

La présente invention concerne un dispositif de distribution microfluidique. Ce dispositif de distribution microfluidique comporte une puce de distribution microfluidique. La puce comprend une ou plusieurs couches microfluidiques dont chacune comporte au moins deux canaux microfluidiques parallèles ou un ensemble de canaux microfluidiques constitué d'un unique canal microfluidique racine et de ses bifurcations. La superficie en coupe du canal microfluidique va de 1 µm2 à 1 mm2. Les orifices d'entrée et de sortie des canaux microfluidiques sont en communication avec l'extérieur, alors que les autres parties des canaux microfluidiques sont à l'intérieur de la puce de distribution microfluidique. L'invention concerne également un procédé et une application du dispositif de distribution microfluidique.
PCT/CN2010/000494 2009-04-14 2010-04-14 Dispositif de distribution microfluidique, procédé de production, et application correspondants WO2010118637A1 (fr)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013180494A1 (fr) * 2012-05-30 2013-12-05 나노바이오시스(주) Dispositif à multicanaux pour la distribution de fluide, appareil pour l'extraction d'acide nucléique le comprenant, et procédé d'extraction d'acide nucléique par l'utilisation de celui-ci
CN105903501A (zh) * 2016-04-18 2016-08-31 南京大学 一种聚二甲基硅氧烷-纸复合芯片及其制法和用途
CN111057649A (zh) * 2019-12-31 2020-04-24 复旦大学 一种微流控芯片及其制备方法与应用
WO2022233937A3 (fr) * 2021-05-06 2023-03-09 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e. V. Tête de dosage et système fluidique servant à la réception et au dosage d'au moins un milieu
US12337312B2 (en) 2019-10-10 2025-06-24 Hewlett-Packard Development Company, L.P. Microfluidic dispensers for limiting dilution

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101533005B (zh) * 2009-04-14 2012-10-10 北京大学 微流分配装置、其制备方法及用途
JP5250574B2 (ja) * 2010-02-10 2013-07-31 富士フイルム株式会社 マイクロ流路デバイス
CN101907631B (zh) * 2010-07-19 2012-07-25 中国科学院长春光学精密机械与物理研究所 微流控芯片内的双液体毛细微流控制阀及其制作方法
CN102553506A (zh) * 2010-12-30 2012-07-11 国家纳米技术与工程研究院 一种利用光刻在pdms上直接形成图形的方法
US9386948B2 (en) 2012-12-05 2016-07-12 Theranos, Inc. Systems, devices, and methods for bodily fluid sample transport
US10248765B1 (en) 2012-12-05 2019-04-02 Theranos Ip Company, Llc Systems, devices, and methods for bodily fluid sample collection, transport, and handling
WO2014145330A2 (fr) * 2013-03-15 2014-09-18 Theranos, Inc. Procédés et dispositifs pour collecte d'échantillons et séparation d'échantillons
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US9604209B2 (en) * 2015-03-19 2017-03-28 International Business Machines Corporation Microfluidic device with anti-wetting, venting areas
US10371606B2 (en) 2015-07-21 2019-08-06 Theraos IP Company, LLC Bodily fluid sample collection and transport
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Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001075176A2 (fr) * 2000-04-04 2001-10-11 California Institute Of Technology Methodes et systemes pour releves d'empreinte moleculaire
CN1326549A (zh) * 1998-10-13 2001-12-12 微生物系统公司 基于无源流体动力学的流体管路元件
WO2003098218A1 (fr) * 2002-05-10 2003-11-27 Biomicro Systems, Inc. Conception de systeme microfluidique a canaux multiples avec distribution d'ecoulement fluidique equilibree
WO2004011365A2 (fr) * 2002-07-26 2004-02-05 Applera Corporation Caracteristiques de conception de micro-canal facilitant un transfert de fluide centripete
US6737026B1 (en) * 1999-03-03 2004-05-18 Symyx Technologies, Inc. Methods for identifying and optimizing materials in microfluidic systems
CN1928534A (zh) * 2006-09-29 2007-03-14 西安交通大学 微流动注射式化学发光芯片的制备方法
CN1948966A (zh) * 2005-10-13 2007-04-18 财团法人工业技术研究院 微流道生物芯片
WO2007062666A1 (fr) * 2005-12-02 2007-06-07 Technical University Of Denmark Dispositif fluidique pour dosage
CN101218019A (zh) * 2005-04-08 2008-07-09 维罗西股份有限公司 通过多个平行的连接通道流向/来自歧管的流体控制
CN101533005A (zh) * 2009-04-14 2009-09-16 北京大学 微流分配装置、其制备方法及用途

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1326549A (zh) * 1998-10-13 2001-12-12 微生物系统公司 基于无源流体动力学的流体管路元件
US6737026B1 (en) * 1999-03-03 2004-05-18 Symyx Technologies, Inc. Methods for identifying and optimizing materials in microfluidic systems
WO2001075176A2 (fr) * 2000-04-04 2001-10-11 California Institute Of Technology Methodes et systemes pour releves d'empreinte moleculaire
WO2003098218A1 (fr) * 2002-05-10 2003-11-27 Biomicro Systems, Inc. Conception de systeme microfluidique a canaux multiples avec distribution d'ecoulement fluidique equilibree
WO2004011365A2 (fr) * 2002-07-26 2004-02-05 Applera Corporation Caracteristiques de conception de micro-canal facilitant un transfert de fluide centripete
CN101218019A (zh) * 2005-04-08 2008-07-09 维罗西股份有限公司 通过多个平行的连接通道流向/来自歧管的流体控制
CN1948966A (zh) * 2005-10-13 2007-04-18 财团法人工业技术研究院 微流道生物芯片
WO2007062666A1 (fr) * 2005-12-02 2007-06-07 Technical University Of Denmark Dispositif fluidique pour dosage
CN1928534A (zh) * 2006-09-29 2007-03-14 西安交通大学 微流动注射式化学发光芯片的制备方法
CN101533005A (zh) * 2009-04-14 2009-09-16 北京大学 微流分配装置、其制备方法及用途

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JIANBIN, WANG ET AL.: "A chip-to-chip nanoliter microfluidic dispenser", LAB ON A CHIP, vol. 9, no. 13, 7 July 2009 (2009-07-07), pages 1831 - 1835 *
LE, JUN ET AL.: "Mass transfer in gas-liquid flow in microchannels", JOURNAL OF CHEMICAL INDUSTRY AND ENGINEERING, vol. 57, no. 6, June 2006 (2006-06-01), CHINA, pages 1296 - 1303 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013180494A1 (fr) * 2012-05-30 2013-12-05 나노바이오시스(주) Dispositif à multicanaux pour la distribution de fluide, appareil pour l'extraction d'acide nucléique le comprenant, et procédé d'extraction d'acide nucléique par l'utilisation de celui-ci
CN105903501A (zh) * 2016-04-18 2016-08-31 南京大学 一种聚二甲基硅氧烷-纸复合芯片及其制法和用途
US12337312B2 (en) 2019-10-10 2025-06-24 Hewlett-Packard Development Company, L.P. Microfluidic dispensers for limiting dilution
CN111057649A (zh) * 2019-12-31 2020-04-24 复旦大学 一种微流控芯片及其制备方法与应用
CN111057649B (zh) * 2019-12-31 2023-02-07 复旦大学 一种微流控芯片及其制备方法与应用
WO2022233937A3 (fr) * 2021-05-06 2023-03-09 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e. V. Tête de dosage et système fluidique servant à la réception et au dosage d'au moins un milieu

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