WO2017186063A1 - 一种离心式多通道微流体芯片 - Google Patents

一种离心式多通道微流体芯片 Download PDF

Info

Publication number
WO2017186063A1
WO2017186063A1 PCT/CN2017/081462 CN2017081462W WO2017186063A1 WO 2017186063 A1 WO2017186063 A1 WO 2017186063A1 CN 2017081462 W CN2017081462 W CN 2017081462W WO 2017186063 A1 WO2017186063 A1 WO 2017186063A1
Authority
WO
WIPO (PCT)
Prior art keywords
solution
reaction
temporary storage
fluid device
reaction cell
Prior art date
Application number
PCT/CN2017/081462
Other languages
English (en)
French (fr)
Inventor
周中人
张玲会
刘波
姜杰
Original Assignee
上海快灵生物科技有限公司
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 上海快灵生物科技有限公司 filed Critical 上海快灵生物科技有限公司
Publication of WO2017186063A1 publication Critical patent/WO2017186063A1/zh

Links

Images

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
    • B01L3/50—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
    • 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
    • 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
    • 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
    • B01L2200/0636—Focussing flows, e.g. to laminate flows
    • 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
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • 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
    • B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • 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
    • B01L2300/0803—Disc shape
    • 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
    • B01L2300/087—Multiple sequential chambers
    • 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
    • B01L2300/0893—Geometry, shape and general structure having a very large number of wells, microfabricated wells
    • 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
    • B01L2300/14—Means for pressure control
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers

Definitions

  • the present invention relates to a sample analysis fluid chip and a sample analysis method used in the detection or analysis of a biological reaction, and a method of producing a sample analysis fluid chip.
  • a disposable biochip that can be used for protein or DNA analysis and a method of manufacturing the same.
  • reaction cells reaction cells
  • Patent Document 1 discloses a flow device that applies an electric field force to a charged droplet under the action of an external electric field to control the movement of the particles in the microfluidic conduit to the respective branch regions.
  • this method it is necessary to introduce a complicated mechanism and equipment for generating an electric field to the chip; and because the transport liquid needs to be converted into a droplet in the electric field region and is sent to the designated region in the form of droplets, the sample is greatly reduced. Processing speed.
  • Patent Document 2 discloses a device for separating charged substances of different substances to be tested by using an electroosmotic pump that drives a sample.
  • this method is only applicable to samples that must be charged with a charge, and does not work for general biological samples and uncharged samples.
  • Patent Document 3 discloses a centrifugal infusion chip in which liquid is centrifugally dispensed from a storage portion in the center of the chip to each of the surrounding sample wells.
  • the design of the mainstream road that is, the design of the main road with the same width of the mountain and the valley, still fails to solve the problem of uniformity of liquid distribution in each sample hole; in addition, the design of the valley is too wide than the mountain, resulting in the process of loading There is a problem with bubbles in the mainstream road.
  • the internal surface modification treatment is performed internally, that is, the hydrophilic treatment of the inner surface of the branch flow path connected to the sample hole, and the hydrophobic treatment of the inner surface of the branch flow path connected with the waste liquid chamber collecting the remaining solution, which increases the complexity of chip fabrication Sex, processing cost and processing difficulty.
  • a technical solution capable of heating a centrifugal multi-channel microfluidic chip having a centrifugal multi-channel microfluidic chip; a reaction cell or reaction in the first fluid device At least one of the upper and lower substrates of the same or all of the same fluid device of the cartridge, or the second fluid device, is of a thermally conductive material.
  • nucleic acid amplification reaction By using the centrifugal multi-channel microfluidic chip provided by the invention, as long as different substances are pre-loaded in different reaction cells during chip production, nucleic acid amplification reaction, biochemical reaction, immune reaction and the like can be performed on the same designed chip.
  • the detection, or the use of the same reaction format to detect different substances to achieve a variety of applications on a chip platform. For example, if a specific nucleic acid fragment (such as a mutant gene or a gene of a pathogenic microorganism) in a sample is detected by a nucleic acid amplification reaction on a chip, it may be pre-loaded in different reaction cells to be different from the sample to be tested.
  • a primer and an auxiliary component for specifically reacting a nucleic acid fragment if a specific substance or component (such as blood sugar or triglyceride) in the sample is detected by a biochemical reaction on a chip, the sample to be tested may be pre-loaded in different reaction cells.
  • a substance and an auxiliary component that detect a specific immune response of different substances or components in a sample if a specific substance or component (such as blood sugar or triglyceride) in the sample is detected by a biochemical reaction on a chip, the sample to be tested may be pre-loaded in different reaction cells.
  • the innovation of the invention lies in that at least two connecting points are arranged on the reaction cell and the reaction chamber as the channels for the entry and outflow of the solution gas, so that the solution is easily filled, and the reaction is sufficiently performed.
  • the outflow channel of the gas can communicate with a separate air outlet, preventing the solution and the gas from flowing backward on the same flow path.
  • the solution in the temporary storage area of the solution is centrifugally distributed to the fluid device, it can obtain the gas replenishing equilibrium pressure from the flow channel in time, and evenly distribute the solution therein to the respective fluid devices.
  • the upper and lower interconnecting channels enable the reaction device to be at different levels of different heights to prevent unnecessary flow measurement of the solution; it can properly supplement the solution in the reaction device connected at different heights to ensure a solution of a part of the fluid device for biochemical reaction. Fully; it can also isolate the reaction gas or reaction components by providing a hydration membrane in the counterbore of the upper and lower interconnecting channels, but it can be dissolved by the aqueous solution and open the channel, becoming a clever switch device. Since the extra vent hole is provided and can be selectively opened, the first solution temporary storage area can be added to the partial fluid device after the first centrifugation of the solution, and the solution can be added again by centrifugation to drive the newly added solution for mixing reaction and enter more. More fluidic devices.
  • the second solution temporary storage area of the second fluid device can additionally provide a solution addition channel and a connected reaction cell or reaction chamber, so that the solution injected from the first solution temporary storage area and the second solution temporary storage area is respectively
  • the reaction devices are combined and mixed to provide more reaction conditions.
  • FIG. 1 is a schematic top plan view of a centrifugal multi-channel microfluidic chip according to an embodiment of the present invention
  • FIG. 2 is a schematic view showing the flow direction of the liquid extruded air at the time of centrifugation of the centrifugal multi-channel microfluidic chip of the embodiment shown in FIG. 1 , wherein the branch is connected to the first flow path;
  • FIG. 3 is a schematic view showing the flow direction of liquid extrusion air during centrifugation of the centrifugal multi-channel microfluidic chip of the embodiment shown in FIG. 1 , wherein the branch is connected to the solution temporary storage area;
  • FIG. 4 is a schematic view showing the flow direction of liquid extrusion air during centrifugal centrifugation of the centrifugal multi-channel microfluidic chip of the embodiment shown in FIG. 1, wherein the outlet end serves as an independent gas outlet;
  • FIG. 5 is a schematic top plan view of a centrifugal multi-channel microfluidic chip according to another embodiment of the present invention.
  • FIG. 6 is a schematic top plan view of a centrifugal multi-channel microfluidic chip according to still another embodiment of the present invention.
  • FIG. 7 is a schematic top plan view of a centrifugal multi-channel microfluidic chip according to still another embodiment of the present invention.
  • FIG. 8 is a top plan view showing a centrifugal multi-channel microfluidic chip according to a fifth embodiment of the present invention.
  • FIG. 9 is a schematic top plan view of a centrifugal multi-channel microfluidic chip according to a sixth embodiment of the present invention.
  • FIG. 10 is a top plan view showing a centrifugal multi-channel microfluidic chip according to a seventh embodiment of the present invention.
  • FIG. 11 is a partial enlarged view, a partial cross-sectional view of a reaction cell, and a cross-sectional view of a hydrated film structure of a top view of a centrifugal multi-channel microfluidic chip according to an eighth embodiment of the present invention
  • Figure 12 is a partially enlarged perspective view showing a perspective view of the centrifugal multi-channel microfluidic chip of the embodiment shown in Figure 11;
  • FIG. 13 is a top plan view showing a centrifugal multi-channel microfluidic chip according to a ninth embodiment of the present invention.
  • FIG. 14 is a partial perspective structural view of a centrifugal multi-channel microfluidic chip according to a tenth embodiment of the present invention.
  • FIG. 15 is a partial perspective structural view of a centrifugal multi-channel microfluidic chip according to an eleventh embodiment of the present invention.
  • Figure 16 is a partial perspective view of a centrifugal multi-channel microfluidic chip according to an eleventh embodiment of the present invention. Schematic;
  • FIG. 17 is a partial cross-sectional view showing the upper substrate of the centrifugal multi-channel microfluidic chip according to the present invention as a heat conductive material;
  • FIG. 18 is a partial cross-sectional view showing the lower substrate covered with a heat conductive material in the centrifugal multi-channel microfluidic chip of the present invention
  • FIG. 19 is a top plan view showing a centrifugal multi-channel microfluidic chip according to a twelfth embodiment of the present invention.
  • FIG. 20 is a top plan view showing a centrifugal multi-channel microfluidic chip according to a thirteenth embodiment of the present invention.
  • an embodiment or “an embodiment” as used herein refers to a particular feature, structure, or characteristic that can be included in at least one implementation of the invention.
  • FIG. 1 is a plan view showing an embodiment of a centrifugal multi-channel microfluidic chip of the present invention.
  • the chip of the present invention has a plurality of first reaction cells 101 on the chip 100; and a flow path for conveying a solution (solution) for transporting the solution to each of the first reaction cells 101.
  • the flow path includes at least one first solution temporary storage area 102 connected to each of the first reaction cells 101.
  • the first solution temporary storage area 102 passes through the first flow path 103 and the first A reaction cell 101 is connected.
  • the flow path has an injection port for injecting a solution.
  • a first fluid device is disposed on the first layer of the chip 100, and the first fluid device is composed of two upper and lower substrates; the first fluid device comprises a plurality of fluid devices: the first reaction cell 101, and the first reaction cell a 101-connected flow path and a solution injection port 105 for injecting a solution into the flow path, and by rotating the chip 100, the solution is distributed to the first reaction cell 101, and the flow path has a liquid for transporting the liquid to the first reaction cell 101.
  • the flow path includes a first flow path 103 and a branch 104, and the first flow path 103 extends from the valley G to the first
  • a reaction cell 101 forms a first communication point 103a
  • the branch 104 forms a second communication point 104a with the first reaction cell 101 and extends from the second communication point 104a toward the center of rotation to an outlet end 115, which can be Independent, it can also be combined with other stream devices.
  • “first” as described herein The "level” does not emphasize that the depth or height of each fluid device is exactly the same, but multiple fluid devices capable of achieving all the functions of the centrifugal multi-channel microfluidic chip are at a level of similar height.
  • the centrifugal multi-channel microfluidic chip of the present invention distributes liquid to the microfluidic chips of the respective first reaction cells 101 by centrifugal force generated by rotating the chips. Therefore, it is preferable that the central portion has a point penetrating the rotation axis (hereinafter
  • the disk shape is referred to as a center point, but it is not particularly limited as long as it is formed to be rotatable with respect to the rotation axis of the through chip. If the chip has a disk shape, the center can be used as a rotation axis, and the first reaction cell 101 can be arranged concentrically on the disk-shaped chip, thereby effectively utilizing the space.
  • the chip In order to uniformly distribute the liquid to the first reaction cell 101, it is very important to generate a uniform centrifugal force, and the chip can be designed to have rotational symmetry centering on the center point in addition to the injection port, whereby the above object can be easily achieved. That is, assuming that there are N first reaction cells 101, N symmetry is formed, whereby uniform centrifugal force can be generated. Of course, if the amount of liquid to be dispensed in each of the first reaction cells 101 is different, it is not limited thereto. Further, by arranging the first reaction cell 101 in a concentric manner, by rotating the chip 100, analysis of all the first reaction cells 101 can be realized in one detection region.
  • the first solution temporary storage area 102 is formed at a position closer to the center point side than the first reaction cell 101. Moreover, in the centrifugal multi-channel microfluidic chip of the present invention, the first solution temporary storage region 102 is formed as a valley portion G with respect to the center of rotation. Further, having the valley portion G with respect to the center point direction means having a maximum point with respect to the center point direction.
  • each first solution temporary storage area 102 distributes an appropriate amount of solution to the flow path depending on its own volume, in order to ensure uniform solution amount of each first reaction cell 101,
  • the volume of a solution staging area is also designed to be uniform.
  • the flow path further includes a first flow path 103 and a branch 104, the first flow path 103 extending from the valley portion G to the first reaction cell 101 forming a first communication point 103a, and the branch 104 and the first reaction
  • the pool 101 forms a second communication point 104a and extends from the second communication point 104a to the first flow path 103.
  • it may also extend to the first solution temporary storage area 102, and ensure that the distance between the first communication point 103a and the rotation center is greater than The distance between the second connected point 104a and the center of rotation. Therefore, referring to FIG.
  • the centrifugal force generated by rotating the chip when the centrifugal force generated by rotating the chip is rotated, it is ensured that the liquid reagent (solution) in the first solution temporary storage area 102 first enters the first reaction cell 101 through the first flow path 103 and is filled with the first reaction.
  • the pool 101 at this time, the centrifugal force generated by the rotation of the solution will press the gas in the original first reaction cell 101 and the branch 104 to flow back into the first flow path 103 through the second communication point 104a, and then enter the first solution temporary storage area 102 and finally from the solution.
  • the inlet 105 is discharged.
  • the branch 104 forms a second communication point 104a with the first reaction cell 101 and extends from the second communication point 104a to the first solution temporary storage area 102 or the first flow path 103 to the outlet end 115.
  • the first flow path 103 and the branch 104 also function as a buffer pool, thereby not The amount of liquid reagent dispensed in each of the first reaction cells 101 is inconsistent, resulting in each of the first reaction cells
  • the inconsistent reaction results in 101 directly affect the accuracy of the reaction results.
  • the excess liquid in the first solution temporary storage zone 102 does not cause the reaction product in the first reaction cell 101. Diffusion into adjacent first reaction cells, causing cross-contamination.
  • the special structure of the branch 104 is such that the solution corresponding to each of the first reaction cells 101 is centrifuged and filled up to the first reaction cell 101 and the first flow path 103 and/or the branch 104, so that the centrifugal distribution can not be caused.
  • the even distribution is only embodied on the first flow path 103 and/or the branch 104, ensuring that the first reaction cell 101 is fully charged.
  • the branch 104 it is assumed that even if the liquid reagent is evenly distributed into each of the first reaction cells 101 even during centrifugation, if the reaction occurring in the first reaction cell 101 needs to be performed at a certain temperature, The liquid reagent in one of the reaction cells 101 is heated and vaporized, resulting in a decrease in the amount of liquid reagent in the first reaction cell 101.
  • the decrease in the amount of the liquid reagent causes the concentration of the solution in the first reaction cell 101 to vary, and the amount of liquid reagent reduction in each of the first reaction cells 101 is also inconsistent.
  • the change in the concentration of the reaction solution and the decrease in the amount of the liquid reagent in the first reaction cell 101 all affect the accuracy of the reaction result.
  • the branch circuit 104 When the branch circuit 104 is disposed in the first reaction cell 101 and communicates with the first flow path 103, the liquid reagent in the first flow path 103 and/or the branch 104 is replenished to the first reaction cell even if there is a loss of liquid amount.
  • the liquid reagent in the first reaction cell 101 is continuously maintained in a full state.
  • the liquid reagent (solution) will preferentially pass through the first communication point 103a into the first reaction cell 101, exhaust the air therein, and fill the first reaction cell 101 until the reaction is sufficiently completed.
  • any point of the first fluid device from the first solution temporary storage region 102 to the rear of the fluid device may extend from the first layer to the upper surface or the lower surface of the first layer of the chip 100 to form a certain depth.
  • the upper and lower interflow paths 114 provide or extend the first fluid device from the first level of the chip 100 to the second level, allowing gases and solutions in the first fluid device to flow from the first level to the fluid devices of the second level.
  • the "second level” described herein also does not emphasize that the depth or height of each fluidic device is completely uniform, but that the fluidic device capable of achieving all of the functions of the centrifugal multi-channel microfluidic chip is at a complete level of similar height.
  • the second fluid cell 106 is further included on the first fluid device, and the second reaction cell 106 is disposed on the branch 104.
  • the first fluid chamber further includes a first reaction chamber 107, and the first reaction chamber 107 is in communication with the first reaction tank 101, or the second reaction tank 106, or the branch 104, and the first reaction chamber 107 and the gas
  • the vent holes 109 are in communication.
  • a second reaction chamber 108 is also disposed between the first reaction chamber 107 and the gas vent 109.
  • the first solution temporary storage area 102 is plural and can communicate with each other, and the solution enters the first first solution temporary storage area 102 from the solution injection port 105, sequentially flows into the other first solution temporary storage area 102, and finally flows into the solution injection. Return port 102a.
  • the first solution temporary storage area 102 is plural and can communicate with each other, the first solution
  • the temporary storage area 102 has a mountain portion S facing in the direction of the center of rotation, and each of the mountain portions S communicates with the air filling passage 110 through the side flow path 113, and the connected air filling passage 110 forms an integrated communication structure and has at least An air hole 110a.
  • the solution temporary storage area 102 is plural and can communicate with each other, and forms an integrated communication structure through the exhaust passage 111, and finally has a common gas exhaust hole 109.
  • FIG. 3 to 16 are plan views showing another embodiment of the centrifugal multi-channel microfluidic chip of the present invention.
  • This embodiment differs from the embodiment shown in FIG. 1 in that the first reaction cell 101 is in communication with the second reaction cell 106.
  • the second reaction cell 106 is disposed on the branch 104, that is, the position of the second reaction cell 106 is between the second communication point 104a and the connection point of the branch 104 and the first flow path 103.
  • the positional relationship between the first communication point 103a and the second communication point 104a of the first reaction cell 101 is not changed, and the distance between the first communication point 103a and the rotation center is always greater than the second communication point 104a and rotation. The distance from the center.
  • the centrifugal force generated by rotating the chip when the centrifugal force generated by rotating the chip is rotated, it is ensured that the liquid reagent (solution) in the first solution temporary storage area 102 first enters the first reaction cell 101 through the first flow path 103 and is filled with the first
  • the reaction cell 101 is then re-entered into the second reaction cell 106 and filled with the second reaction cell 106.
  • the centrifugal force generated by the rotation on the solution will press the gas in the original first reaction cell 101, the second reaction cell 106, and the branch 104.
  • the first solution temporary storage zone 102 is finally discharged through the first flow path 103 and is discharged from the solution injection port 105.
  • the first reaction cell 101 can be used as a buffer pool
  • the second reaction cell 102 can be used as a biochemical reaction cell.
  • the chip of the present invention has: a plurality of first reaction cells 101, a second reaction cell 106 on the chip 100; and a flow for transporting a solution (for example, a liquid reagent) to the reaction cell. road.
  • a solution for example, a liquid reagent
  • the flow path includes at least one first solution temporary storage zone 102 having a valley G connected to each of the reaction cells, and a first flow path connecting the first solution temporary storage zone 102 and the reaction cell. 103 and branch 104.
  • the flow path has an injection port for injecting a solution.
  • the air venting port 109 which is also the air venting at the other end, is actually in communication with the first reaction chamber 107 disposed on the chip 100, and the first reaction chamber 107 is again It is in communication with the second reaction cell 106 for storing the test strip.
  • the reaction solution for completing the amplification is released from the second reaction cell 102, and enters the first reaction chamber in which the immunochromatographic test paper is set, and the nucleic acid reaction liquid layer to be amplified.
  • the nitrocellulose membrane was started to count, and the results were observed at 5 minutes: if the T-line of the test paper has obvious red lines, the detection result of the virus is positive.
  • FIG. 5 is a plan view showing the centrifugal multi-channel microfluidic chip of the present invention in addition to the above embodiment. schematic diagram.
  • the chip of the present invention has a plurality of first reaction cells 101, a second reaction cell 106 on the chip 100, and a flow path for transporting a solution, such as a liquid reagent (solution), to the reaction cell.
  • a solution such as a liquid reagent (solution)
  • the flow path includes at least a first solution temporary storage zone 102 having a valley G connected to each of the reaction cells, and a first flow path 103 connecting the first solution temporary storage zone 102 and the reaction cell.
  • the branch 104 includes at least a first solution temporary storage zone 102 having a valley G connected to each of the reaction cells, and a first flow path 103 connecting the first solution temporary storage zone 102 and the reaction cell.
  • the first solution temporary storage area 102 on the chip 100 of the chip of the present invention is connected to form an integrated communication structure, and is provided with a port for injecting a solution or a gas liquid, for example, having a
  • the solution injection port 105 at one end of the solution temporary storage area 102, the solution of the other end portion are injected into the return port 102a, and the air supply hole 110a located in the air supply passage 110.
  • a gas passage 110 is further provided corresponding to the gas supply hole 110a, and a portion between the valley portion G and the valley portion G of the first solution temporary storage region 102 is a mountain portion S.
  • the mountain portion S refers to a portion of the gas supply passage 110 passing through the side flow passage 113 and the first solution temporary storage region 102 at a portion closest to the center point between the valley portion G and the valley portion G of the first solution temporary storage region 102.
  • the air supply passage 110 communicates with the first solution temporary storage area 102 through the side flow path 113.
  • the air filling passage 110 can pass the side flow.
  • the road 113 can uniformly apply the first solution temporary storage area 102 for gas replenishment.
  • the gas filling passage 110 is formed into a circular structure.
  • the first solution temporary storage area 102 When the first solution temporary storage area 102 is filled with the solution and the liquid distribution is not selected by centrifugation, gas injection can be performed from the air supply hole 110a to the air supply passage 110, thereby respectively for each first solution temporary storage area 102.
  • the solution is pressurized to drive the solution into the first fluid 103.
  • the first solution temporary storage area 102 and the solution injection return port 102a communicate with each other through the storage pool 112.
  • the first solution temporary storage area 102 is formed at a position closer to the center point side than the first reaction cell 101.
  • the centrifugal multi-channel microfluidic chip of the present invention the first solution temporary storage region 102 is formed as a valley portion G with respect to the center of rotation.
  • having the valley portion G with respect to the center point direction means having a maximum point with respect to the center point direction.
  • the valleys G of a solution temporary storage area 102 are collected, so that it is possible to ensure an appropriate amount of solution distribution to the flow path of each of the first solution temporary storage areas 102.
  • the first solution temporary storage area 102 may be disposed in a wave shape, and the wavy first solution temporary storage area 102 forms a circular shape.
  • the reaction cells connected to the first solution temporary storage area 102 are respectively loaded with different substances detected by the same reaction form, for example, can be preloaded in different reaction cells to be specific to different nucleic acid fragments in the sample to be tested.
  • the primers and auxiliary components of the sexual reaction can be used to detect specific nucleic acid fragments in a plurality of samples to be tested on one chip by injection centrifugation and nucleic acid amplification reaction of multiple sets of samples.
  • the flow path further includes a first flow path 103 and a branch 104, the first flow path 103 extending from the valley portion G to the first reaction cell 101 forming a first communication point 103a, and the branch 104 and the first reaction
  • the pool 101 forms a second communication point 104a and extends from the second communication point 104a to the first flow path 103, and ensures that the distance between the first communication point 103a and the rotation center is greater than the distance between the second communication point 104a and the rotation center. from.
  • the first solution temporary storage area 102 has a mountain portion S facing the center of rotation between the reaction cells adjacent to each other (for example, the first reaction cell 101), and each of the mountain portions S passes through the side flow path 113 and refills Channels 110 are in communication.
  • the first reaction cell 101 is connected to the first solution temporary storage zone 102 through the first flow path 103, and the second reaction cell 106 is disposed on the branch circuit 104.
  • the flow path and the second reaction chamber 108 have a peak toward the center of rotation between the adjacent first reaction cells 101, and are connected to the exhaust passage 111.
  • the peak means a portion which is closest to the center point on the second reaction chamber 108.
  • the exhaust passage 111 is disposed concentrically with the chip 100 and is connected to the gas exhaust hole 109.
  • the gas filling passage 110 is also disposed concentrically with the chip 100, and has an air supply hole 110a at one end thereof and is connected to the first solution temporary storage area 102.
  • the second reaction cell 106 is disposed on the branch 104.
  • the second reaction cell 106 is in direct communication with the second reaction chamber 108 and is coupled to the exhaust passage 111.
  • the distance between the connection point formed by the branch 104 and the first flow path 103 and the center of rotation and the distance between the second communication point 104a and the center of rotation are optimized, and when the centrifugal force generated by the chip is rotated, It can be ensured that the liquid reagent (solution) in the first solution temporary storage area 102 first enters the first reaction cell 101 through the first flow path 103 and fills the first reaction cell 101, and then enters the second reaction cell 106, and then rotates to the solution.
  • the generated centrifugal force recirculates the gas in the original first reaction cell 101, the second reaction cell 106, and the branch 104 through the first flow path 103 into the first solution temporary storage area 102 and is finally discharged from the solution injection port 105.
  • FIG. 6 it differs from the embodiment shown in FIG. 5 in that a first reaction chamber 107 is disposed on the chip 100.
  • the first reaction chamber 107 is connected between the second reaction cell 106 and the second reaction chamber 108.
  • the embodiment shown in Figs. 7 and 8 can be seen as a modification of the embodiment shown in Fig. 6, but is not limited thereto.
  • the side flow path 113 is omitted here. That is, the valley portion G is necessary at the time of centrifugation, whereby the liquid injected into the first solution temporary storage region 102 is naturally collected in the valley portion G of the first solution temporary storage region 102 when the chip is rotated. Therefore, it is possible to ensure an appropriate amount of solution distribution to the flow path of each of the first solution temporary storage areas 102.
  • the embodiment provided in Figures 11-20 differs from the prior centrifugal multi-channel microfluidic chip in that it establishes connections between fluidic devices of different levels or different heights or different surfaces.
  • the centrifugal multi-channel microfluidic chip, the first layer or the second layer of the chip 100 is provided with a second fluid device, including a second solution temporary storage region, connected to the second solution temporary storage region and All or part of the same fluid device in the first fluid device; the second fluid device is in communication with the first fluid device and leads to a common gas vent 109.
  • Test papers showing biochemical reaction results are provided in at least one reaction cell or reaction chamber in the reaction cell and the reaction chamber, and the test papers include dry chemical test papers, dry biochemical test papers or immunochromatographic test papers.
  • the centrifugal multi-channel microfluidic chip is provided with a detecting instrument capable of detecting a specific spectral signal generated by a solution in a certain reaction cell of the chip 100, and obtaining an analysis result of the detected sample.
  • the plurality of branches 104 are interconnected by a plurality of The flow path 114 is in communication with an exhaust passage on another layer that communicates with the uniform outlet end 115.
  • the first intercom flow path 114 is provided with a counterbore 120 capable of forming a hydration film, which can isolate the air in the flow channel so that the air cannot pass, and when a solution flows, the solution It is capable of dissolving the hydrated film.
  • the main component of the hydrated film is a mixture of one or several of polyethylene glycol, ethylene-vinyl acetate polymer, polyacrylic acid, polyacrylamide chitosan, hyaluronic acid, polyvinyl alcohol, sucrose, and the like.
  • the centrifugal multi-channel microfluidic chip has a chip 100 formed with a reaction cell, an injection hole and a flow path, which is composed of a substrate which is fitted or fitted up and down.
  • the substrate is not particularly limited as long as it does not affect the reagent.
  • a resin material containing any one of polypropylene, polycarbonate, and acrylic is used, good visible light transmittance can be ensured.
  • polypropylene homopolypropylene or a random copolymer of polypropylene and polyethylene can be used.
  • acrylic acid polymethyl methacrylate or a copolymer of methyl methacrylate and another monomer such as methacrylate, acrylate or styrene may be used.
  • resin materials the heat resistance and strength of the chip can be ensured.
  • the material other than the resin material include metal materials such as aluminum, copper, silver, nickel, brass, and gold. When using a metal material, it is also excellent in thermal conductivity and sealing performance. Further, by keeping the substrate of at least one side of the reaction cell transparent, it is possible to detect and analyze fluorescence or the like from the outside.
  • transparent and “light transmittance” mean a case where the average transmittance in the wavelength region of the detection light is 70% or more.
  • a light-transmitting material in a visible light region wavelength: 350 to 780 nm
  • the state of the reagent in the chip can be easily recognized, but the present invention is not limited thereto.
  • a processing method of forming a substrate for a sample insertion hole, a flow path, and a waste liquid portion when it is a resin material, various resin molding methods such as injection molding, vacuum molding, or mechanical cutting can be employed.
  • it is a metal material, it can be formed by performing a press working or etching using a thick substrate, and performing press working or drawing processing on a thin metal sheet.
  • the resin material containing any of polypropylene, polycarbonate, and acrylic is used as the chip 100, it is possible to ensure good light transmittance, heat resistance, and strength.
  • the thickness of the base material is in the range of 50 ⁇ m to 3 mm, good light transmittance, heat resistance, and strength can be ensured, and the concave portion can be reliably processed.
  • the thickness of the substrate is in the range of 10 ⁇ m to 300 ⁇ m, the thermal conductivity and sealing property of the substrate can be simultaneously satisfied.
  • a method of bonding the base material a method of providing a resin coating layer as an adhesive layer on one base material and melting the same to bond the two base materials is exemplified.
  • the resin coating layer is provided on a metal material substrate having a high thermal conductivity and is melt-bonded.
  • a resin material such as PET, polyacetal, polyester or polypropylene can be used.
  • tape fixing and paraffin bonding it is also possible to use tape fixing and paraffin bonding.
  • a light-transmitting resin material which is easy to be finely processed and suitable for fluorescence measurement, and has a high thermal conductivity as a substrate, and it is easy to provide a resin coating layer and paste it by fusion bonding.
  • Combined metal material by forming a resin coating on the surface of the metal substrate, the chemical resistance of the metal substrate itself can be ignored in selecting the material.
  • tackification is formed by the underlayer as a resin coating layer.
  • An anchor layer whereby a laser can be used for fusion bonding.
  • Carbon black (light absorbing material) that absorbs laser wavelength light is mixed in the adhesion-promoting layer, and heat is generated by irradiation of the laser light, whereby the resin coating layer can be melt-bonded.
  • it is also possible to efficiently melt the resin coating by irradiating light of an infrared laser diode having a wavelength of about 900 nm. Unlike thermal fusion, laser welding does not require heating of the chip, so that the bonding of the substrate can be carried out without affecting the chip or the reagent immobilized on the chip.
  • a solution containing a nucleic acid primer and an amplification enzyme is separately added to the second reaction cell 106, and the chip is dried to obtain a solid primer, an amplification enzyme, etc., and the nucleic acid immunization is placed in the first reaction chamber 107.
  • the test strip is attached, the chip 100 and the second substrate 200 are attached, and the gas vent 109 is sealed with a tape or other articles, and the solution with the nucleic acid template to be detected is injected from the solution injection port 105 and gradually filled with the first In the solution temporary storage area 102, at this time, as shown in the embodiment shown in FIG. 5 to FIG.
  • the solution injection return port 102a functions to discharge the gas in the first solution temporary storage area 102 in the whole process, and if the injection solution is too much, it is redundant. It will be assigned to the storage pool when it is centrifuged.
  • the whole chip is placed on a centrifuge for centrifugation, and the solution with the nucleic acid template in the first solution temporary storage area 102 is sequentially flowed into the first reaction cell 101 and the second reaction cell 106 by centrifugal force, and the solution with the nucleic acid template is dried.
  • the primer and the amplification enzyme are dissolved and mixed, and after the chip is placed under a certain temperature condition for nucleic acid amplification reaction, the first solution temporary storage area 102 is injected into the diluted solution, and the gas vent hole 109 is opened, and the gas can be injected from the gas supply hole 110a.
  • the pressure will be transferred from the gas supply passage 110 to the side flow passage 113 and the first solution temporary storage area 102. Since the fluid device such as the first reaction tank 101 is connected to the gas vent hole 109, the diluted solution will enter the second reaction.
  • the pool 106 dilutes and squeezes the amplified nucleic acid solution into the test strip of the first reaction chamber 107, and the test strip reaction shows the result.
  • the first solution temporary storage area 102 can also be injected into the diluted solution, and the injected solution is driven into each fluid device through the centrifugal chip disk, and the diluted solution will enter the second reaction cell 106 and dilute the amplified nucleic acid solution. And it is squeezed into the test strip of the second reaction chamber 108, and the test strip reaction shows the result.
  • the second solution temporary storage area may be injected into the diluted solution, and the injected solution is driven into each fluid device through the centrifugal chip disk, and the diluted solution will enter the second reaction cell 106 and dilute the amplified nucleic acid solution.
  • the second solution temporary storage area of the first solution temporary storage area may be simultaneously injected into the diluted solution, and the injected solution is driven into each fluid device through the centrifugal chip disk, and the diluted solution will enter the second reaction cell 106 and be expanded.
  • the good nucleic acid solution is diluted and squeezed into the test strip of the first reaction chamber 107, and the test strip reaction shows the result.
  • the chip disk in addition to the nucleic acid primer and the amplification enzyme, if the immunoreactive antibody is added in advance in the second reaction cell of the first fluid device, the chip disk can be used for immunofluorescence detection, etc. test. If a biochemical reaction phase is previously added to the second reaction cell of the first fluid device The reaction chip can be used to perform a variety of biochemical divisions.
  • the above nucleic acid reaction, immune reaction, and biochemical reaction are also set in one of the reaction cells or the reaction chamber.
  • the diluted solution drives the first fluid device and the second fluid device to complete the reaction, and the liquid flows out after the flow, so that the subsequent Further reaction in the reaction cell or reaction chamber.
  • the results of the nucleic acid reaction, the immune reaction, and the biochemical reaction in the chip tray can be visually interpreted by means of a test strip, or by a spectroscopic instrument for a solution of a reaction cell or a reaction chamber provided with a transparent substrate. Interpretation.
  • a plurality of first reaction cells 101 on the chip 100 and a flow path for transporting a solution, such as a liquid reagent, are supplied to the respective first reaction cells 101.
  • the flow path includes at least one first solution temporary storage area 102 connected to each of the first reaction cells 101.
  • the first solution temporary storage area 102 passes through the first flow path 103 and the first A reaction cell 101 is connected.
  • the first reaction cell 101 side is in communication with the gas vent 109, and the flow path has an injection port for injecting a solution.
  • the injected liquid reagent (solution) is transferred to the first solution temporary storage area 102, and the liquid reagent (solution) enters the first reaction cell 101 from the first flow path 103 by the centrifugal movement, and the air flow of the first flow path 103 and the first reaction cell 101
  • the gas vent 109 is discharged, the test strip is placed in the first reaction cell 101, the test strip absorbs the liquid reagent (solution), and the test strip reaction shows the result.
  • each first reaction cell 101 side is connected to one unit.
  • the exhaust circuit may be disposed on the front side of the chip 100, or on the reverse side, as long as the liquid reagent (solution) is injected from the uniform injection port, and the liquid reagent (solution) is moved by centrifugation. All the first reaction cells 101 are entered by the first flow path 103, and all the air of the first flow path 103 and the first reaction cell 101 are discharged through the uniform gas vent 109, and the test strip is placed in the first reaction cell 101. The test strip absorbs the liquid reagent (solution), and the test strip reaction shows the result.
  • the second reaction cell 106 is disposed at another level of the chip relative to the first reaction cell 101, and the second reaction cell 106 is in communication with the branch 104 through the inter-flow path 114 when the centrifugation operation is completed.
  • the first reaction cell 101 and the second reaction cell 106 are filled with the liquid reagent (solution)
  • the first reaction cell 101 is laid up upward, since the second reaction cell 106 is connected to the vertical flow path 114, The liquid reagent (solution) in the second reaction cell 106 at the lower level is not diffused by the branch 104 by gravity or shaking.
  • the liquid reagent (solution) in the second reaction cell 106 is reduced by the diffusion of the vaporized gas to the branch 104 and other fluid devices connected thereto because the first reaction cell 101 is in the second reaction.
  • the pool 106 is at a high horizontal position, so the liquid reagent (solution) in the first reaction tank 101 may be appropriately flowed into the second reaction tank 106 for replenishment due to gravity or the like, so that the second reaction tank can be laid flat on the chip and reacted.
  • the liquid is always filled during the process and will not be affected by the liquid in the second reaction tank 106.
  • the reagent (solution) is reduced and the effect is shown.
  • the main component of the counterbore 120 is a mixture of one or several of polyethylene glycol, ethylene-vinyl acetate polymer, polyacrylic acid, polyacrylamide chitosan, hyaluronic acid, polyvinyl alcohol, sucrose, and the like. After drying, a hydration film 120a is formed at the bottom of the counterbore 120.
  • the plane of the hydration film 120a is disposed parallel to the plane of the chip. Further, the plane of the hydrated film 120a may also be disposed perpendicular to the plane of the chip, that is, without passing through the inter-flow path 114.
  • the branch 104 functions as a gas barrier.
  • the hydrating film 120a functions to block the first reaction chamber 107 and the second reaction cell 106 when the liquid-free reagent (solution) comes over, preventing the reaction gas or the reaction component from flowing, affecting the experimental result, when the liquid reagent ( When the solution) flows to the hydration film 120a, the hydration film 120a is dissolved, and the liquid reagent (solution) can flow from the second reaction cell 106 to the first reaction chamber 107, the test strip absorber reagent (solution), the test paper The strip reaction shows the result.
  • the injection port of the uniform injection solution is connected to each other, and the first reaction chamber 107 side is connected to one.
  • the bottom substrate of the second reaction cell 106 may be previously provided as a heat conductive material aluminum foil. Then, the partial aluminum foil is subjected to the same 55-95 degree heat treatment of the temperature cycle of the biological PCR instrument with a specific heat conductive metal. Since the depth of the second reaction cell 106 is very thin, the heat conduction performance of the aluminum foil is particularly good and can be The solution is sufficiently conducted to the second reaction cell 106 at a temperature.
  • the second reaction cell 106 can undergo a complete PCR nucleic acid amplification reaction.
  • the first solution temporary storage zone diluent is driven into the second reaction cell 106 by centrifugal force, the PCR amplification reaction solution will enter the first reaction chamber 107, and the reaction result is displayed through the test strip.
  • the signal of the PCR nucleic acid amplification reaction can be directly detected in the second reaction cell 106, and the reaction result can be obtained by analyzing the instrument.
  • the whole chip can be placed in a specific temperature environment for constant temperature nucleic acid amplification, and the reaction result is judged by a test strip or a spectrometer.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

一种离心式多通道微流体芯片（100），在芯片（100）第一层面设置有第一流体器件，包括：第一反应池（101）、与第一反应池（101）连接的流路和向流路注入溶液的溶液注入口（105），并通过旋转该芯片（100），将溶液分配给第一反应池（101），流路具有用于向第一反应池（101）输送液体的第一溶液暂存区(102)，第一溶液暂存区(102)具有相对于旋转中心方向的一个谷部（G）；流路包括第一流路（103）和支路（104），第一流路（103）自谷部（G）延伸至第一反应池（101）形成第一连通点（103a），支路（104）与第一反应池（101）形成第二连通点（104a）并自此第二连通点（104a）朝向旋转中心的方向延伸至一个出口端（115）。第一层面的流体器件与第二层面的可通过上下互联通道联通，第一流体器件与第二流体器件可相互连通。

Description

一种离心式多通道微流体芯片 技术领域
本发明涉及生物反应的检测或分析等中使用的试样分析流体芯片和试样分析方法、以及试样分析流体芯片的制造方法。特别是，涉及能够用于蛋白或DNA分析的生物芯片(disposable biochip)及其制造方法。
背景技术
以往，例如在DNA反应、蛋白质反应等的生化反应领域中，作为处理微量试样溶液的反应装置，公知的有被称为微全分析系统(μ-TAS；TotalAnalysis System)或片上实验室(Lab-on-Chip)的技术。该技术是向一个芯片或反应盒提供多个反应室(以下也称为“反应池”)或流路的技术，能够对多个检测队形进行分析，或能够进行多个反应。这些技术通过使芯片和反应盒小型化，由此可以减少药品的使用量，一直被认为具有各种优点。
专利文献1(CN 101609088A)公开了在外部电场的作用下，对带电液滴施加电场力，控制微粒子在微流体管道中向各个分支区域移动的送流装置。但是，在该方法中，需要向芯片引入生成电场的复杂机构和设备；又因为输送液体在电场区域需要先转换成液滴，并以液滴的方式向指定区域送流，大大降低了样品的处理速度。
专利文献2(CN 103055973A)公开了利用驱动样品的电渗泵，将带电不同的待测物质分离的装置。但该方法仅适用于必须带有电荷被测样品，对一般生物样品及不带电荷的样品不起作用。
专利文献3(CN 102369443A)披露了一种离心式输液芯片，即液体从芯片中央的存储部向周围的各个加样孔进行离心配送。该主流路的设计，即山部与谷部同宽的主流路的设计仍未能解决各加样孔配液均匀性的问题；另外谷部比山部过宽的设计，造成加样过程中主流路有气泡产生的问题。此外，通过添加废液室承载过量的溶液，虽在一定程度上实现了各加样孔分配液体体积的一致性，但并不能保证反应过程中液体始终充满加样孔，并且需要在微流体管道内部进行局部表面改性处理，即与加样孔连接的分支流路内表面的亲水处理，与收集剩余溶液的废液室相连的分支流路内表面的疏水处理，增加了芯片制造的复杂性，加工成本及加工难度。
发明内容
本部分的目的在于概述本发明的实施例的一些方面以及简要介绍一些较佳实施例。在本部分以及本申请的说明书摘要和发明名称中可能会做些简化或省略以避免使本部分、说明书摘要和发明名称的目的模糊，而这种简化或省略不能用于限制本发明的范围。
鉴于上述和/或现有离心式多通道微流体芯片及其方法中存在的问题，提 出了本发明。
因此，本发明其中一个目的是，提供一种在向加样孔送液的试样分析流体芯片中，送液方法简单、各加样孔的液量之间不存在偏差、且成本低的离心式多通道微流体芯片。
根据本发明的再一个方面，提供了如下技术方案：一种能够加热的离心式多通道微流体芯片，其具有离心式多通道微流体芯片；在所述第一流体器件中的反应池或反应仓、或第二流体器件的相同的全部或部分的流体器件的上下基材中至少有一个基材属于导热材料。
使用本发明提供的离心式多通道微流体芯片，只要在芯片生产时在不同反应池内预先装载不同的物质就可以在同一设计的芯片上进行核酸扩增反应、生化反应、免疫反应等多种形式的检测，或者利用同一种反应形式检测不同的物质，从而在一种芯片平台上实现多种应用。举例来说，若要在芯片上通过核酸扩增反应检测样品中的特定核酸片段(比如某个突变型基因或病原微生物的基因)，可以在不同反应池中预先装载可与待检样品中不同核酸片段发生特异性反应的引物及辅助成分；若要在芯片上通过生化反应检测样品中的特定物质或成分(比如血糖或甘油三酯)，可以在不同反应池中预先装载可与待检样品中不同物质或成分发生特异性生化反应的物质及辅助成分；若要在芯片上通过免疫反应检测样品中的特定成分(比如某种抗原或抗体)，可以在不同反应池中预先装载可与待检样品中不同物质或成分发生特异性免疫反应的物质及辅助成分。
本发明的创新点在于在反应池和反应仓上设置了至少两个连通点分别作为溶液气体进入与流出的通道，使其溶液容易充满，保证反应充分进行。溶液进入时，其气体的流出通道可连通一个独立的出气口，避免了溶液与气体在同一个流路上逆向流动。当溶液暂存区的溶液被离心分配到流体器件时，它能从测流道及时得到气体补充平衡压力，更能使其内的溶液均匀分配到各个流体器件。上下互联通道能使反应器件处于不同高度的不同层面，可防止溶液不必要的测流；它能对在不同高度连通的反应器件内的溶液进行适当补充，保证部分进行生化反应的流体器件的溶液充满；它也能通过在上下互联通道的沉孔设置水化膜对反应气体或反应成分进行隔离封闭，却能被水溶液溶解后开放通道，成为一个巧妙的开关装置。由于设置了额外的排气孔并能选择性打开，第一溶液暂存区能在首次离心分配溶液进入部分流体器件后，可再次添加溶液，离心驱动新加的溶液进行混合反应，并进入更多的流体器件。第二流体器件的第二溶液暂存区能额外提供一个溶液添加通道及其连通的反应池或反应仓，让从第一溶液暂存区与第二溶液暂存区分别注入的溶液在某个反应器件汇合混合，提供更多的反应条件。
附图说明
为了更清楚地说明本发明实施例的技术方案，下面将对实施例描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，还可以根据这些附图获得其它的附图。其中：
图1为本发明一个实施例所述离心式多通道微流体芯片的俯视结构示意图；
图2为本发明图1所示实施例所述离心式多通道微流体芯片离心时液体挤压空气排出流向示意图，此时所述支路连接至所述第一流路；
图3为本发明图1所示实施例所述离心式多通道微流体芯片离心时液体挤压空气排出流向示意图，此时所述支路连接至所述溶液暂存区；
图4为本发明图1所示实施例所述离心式多通道微流体芯片离心时液体挤压空气排出流向示意图，此时所述出口端作为独立的气体出口；
图5为本发明另一个实施例所述离心式多通道微流体芯片的俯视结构示意图；
图6为本发明再一个实施例所述离心式多通道微流体芯片的俯视结构示意图；
图7为本发明还一个实施例所述离心式多通道微流体芯片的俯视结构示意图；
图8为本发明第五个实施例所述离心式多通道微流体芯片的俯视结构示意图；
图9为本发明第六个实施例所述离心式多通道微流体芯片的俯视结构示意图；
图10为本发明第七个实施例所述离心式多通道微流体芯片的俯视结构示意图；
图11为本发明第八个实施例所述离心式多通道微流体芯片俯视图部分局部放大视图、反应池部分剖视图和水化膜结构剖视示意图；
图12为本发明图11所示实施例所述离心式多通道微流体芯片透视图部分局部放大示意图；
图13为本发明第九个实施例所述离心式多通道微流体芯片的俯视结构示意图；
图14为本发明第十个实施例所述离心式多通道微流体芯片的部分透视结构示意图；
图15为本发明第十一个实施例所述离心式多通道微流体芯片的部分透视结构示意图；
图16为本发明第十一个实施例所述离心式多通道微流体芯片的部分透视 结构示意图；
图17为本发明与上述实施例所述离心式多通道微流体芯片中上部基材为导热材料的部分剖视示意图；
图18为本发明与上述实施例所述离心式多通道微流体芯片中下部基材覆盖导热材料的部分剖视示意图；
图19为本发明第十二个实施例所述离心式多通道微流体芯片的俯视结构示意图；
图20为本发明第十三个实施例所述离心式多通道微流体芯片的俯视结构示意图。
具体实施方式
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合说明书附图对本发明的具体实施方式做详细的说明。
在下面的描述中阐述了很多具体细节以便于充分理解本发明，但是本发明还可以采用其他不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似推广，因此本发明不受下面公开的具体实施例的限制。
其次，此处所称的“一个实施例”或“实施例”是指可包含于本发明至少一个实现方式中的特定特征、结构或特性。在本说明书中不同地方出现的“在一个实施例中”并非均指同一个实施例，也不是单独的或选择性的与其他实施例互相排斥的实施例。
图1是表示本发明离心式多通道微流体芯片的一实施方式的俯视图。本发明的芯片具有：位于芯片100上的多个第一反应池101；以及用于向各个第一反应池101输送溶液的、例如输送液体试剂(溶液)的流路。为了将液体输送到各个第一反应池101，流路至少包括与各个第一反应池101连接的一个第一溶液暂存区102，当然，第一溶液暂存区102通过第一流路103与第一反应池101相连。流路上具有用于注入溶液的注入口。在图1的实施方式中，具有与第一溶液暂存区102相连的溶液注入口105。
具体地，在芯片100第一层面设置有第一流体器件，第一流体器件由上下两个基材配合组成；第一流体器件包含多个流体器件：第一反应池101、与第一反应池101连接的流路和向流路注入溶液的溶液注入口105，并通过旋转该芯片100，将溶液分配给第一反应池101，流路具有用于向上述第一反应池101输送液体的第一溶液暂存区102，该第一溶液暂存区102具有相对于旋转中心方向的一个谷部G；流路包括第一流路103和支路104，第一流路103自谷部G延伸至第一反应池101形成第一连通点103a，支路104与第一反应池101形成第二连通点104a并自此第二连通点104a朝向旋转中心的方向延伸至一个出口端115，该出口端可独立，也可以与其他流路器件合并。在此所述的“第一 层面”并非强调各个流体器件的深度或高度完全一致，而是能够实现离心式多通道微流体芯片所有功能的多个流体器件处在相似高度的一个层面。
本发明的离心式多通道微流体芯片，其是通过旋转该芯片而产生的离心力将液体分配给各个第一反应池101的微流体芯片，因此，优选为中央部具有贯穿旋转轴的点(以下，称为中心点)的圆盘状，但是，只要其形成为能够相对于贯穿芯片的旋转轴旋转即可，没有特别的限制。如果芯片为圆盘状，则能够以其中心为旋转轴，并可在该圆盘状芯片上以同心圆状配置第一反应池101，由此有效地利用空间。为了将液体均匀分配给第一反应池101，产生均匀离心力是非常重要的，可将芯片设计成除了注入口之外，以中心点为轴具有旋转对称性，由此可以容易实现上述目的。即，假设有N个第一反应池101，则就形成N个对称，由此可产生均匀的离心力。当然，要想各第一反应池101的配液量不同时，则并不限定于此。另外，通过以同心圆状配置第一反应池101，由此，通过旋转芯片100，可在一处检测区域实现所有第一反应池101的分析。
第一溶液暂存区102形成在比第一反应池101更接近于中心点侧的位置上。而且，本发明的离心式多通道微流体芯片中，该第一溶液暂存区102形成为相对于旋转中心方向的一个谷部G。另外，具有相对于中心点方向的谷部G，是指具有相对于中心点方向的最大点。如此地，通过在第一溶液暂存区102之间具有相对于中心点方向的一个谷部G，由此，被注入到第一溶液暂存区102的液体在芯片旋转时，自然而然地在第一溶液暂存区102谷部G被汇集，因此各个第一溶液暂存区102向流路进行适量溶液分配取决于它自身的容积大小，为了保证各个第一反应池101的溶液量均匀，第一溶液暂存区的容积也就设计为统一大小。
在这一实施例中，流路还包括第一流路103以及支路104，第一流路103自谷部G延伸至第一反应池101形成第一连通点103a，而支路104与第一反应池101形成第二连通点104a并自此第二连通点104a延伸至第一流路103，当然，也可以延伸至第一溶液暂存区102，并且保证第一连通点103a与旋转中心的距离大于第二连通点104a与旋转中心的距离。由此，参见图2，旋转该芯片而产生的离心力时，能够保证第一溶液暂存区102内的液体试剂(溶液)经第一流路103先进入第一反应池101内并充满第一反应池101，此时旋转对溶液产生的离心力将压迫原第一反应池101以及支路104内的气体通过第二连通点104a回流入第一流路103后进入第一溶液暂存区102最终由溶液注入口105排出。在一个实施例中，支路104与第一反应池101形成第二连通点104a并自此第二连通点104a延伸至第一溶液暂存区102或第一流路103后通向出口端115。
此时，因为原第一溶液暂存区102内的液体试剂(溶液)量大于第一反应池101的容量，则第一流路103以及支路104还充当了缓冲池的作用，由此不会发生每个第一反应池101内分配的液体试剂量不一致从而导致各第一反应池 101内的反应结果不一致现象，直接影响反应结果的准确性。在这一实施例中，由于各个第一反应池101彼此之间是独立的，并无连通，所以，第一溶液暂存区102内多余的液体不会导致第一反应池101内的反应产物向相邻第一反应池内扩散，造成交叉污染。
支路104的特殊结构设置使存储在每个第一反应池101对应的溶液离心后填满至第一反应池101以及第一流路103和/或支路104，这样可以使离心分配造成的不均匀分配仅体现在第一流路103和/或支路104上，而确保第一反应池101是全满的。
如果没有支路104的特殊结构设置，假设即使在离心分配时液体试剂均匀分配到每个第一反应池101内，但是如果第一反应池101内发生的反应需要在一定温度下进行时，第一反应池101内的液体试剂受热气化，造成第一反应池101内液体试剂量减少。液体试剂量的减少使第一反应池101内溶液浓度发生变化，而且每个第一反应池101内液体试剂减少量也并不一致。反应液浓度的变化以及第一反应池101液体试剂量的减少都会影响反应结果的准确性。而第一反应池101上设置支路104与第一流路103相通后，即使有液体量的损耗，第一流路103和/或支路104内的液体试剂也会向第一反应池补充，使第一反应池101内液体试剂持续保持全满状态。
同时，由于第一连通点103a与旋转中心的距离大于第二连通点104a与旋转中心的距离，则意味着离心时，第一连通点103a处产生的离心力将大于第二连通点104a处的离心力。故，液体试剂(溶液)将优先顺利通过第一连通点103a进入第一反应池101内，排走其内的空气，充满第一反应池101，直至反应充分完成。
在另一个实施方式中，第一流体器件中从第一溶液暂存区102向后的流体器件的任何一个点，可从所述芯片100的第一层向上表面或下表面一定深度延伸，形成上下互通流路114，将第一流体器件从芯片100的第一层面设置或延伸到第二层面，让第一流体器件中的气体和溶液从第一层面流动到第二层面的流体器件。在此所述的“第二层面”也并非强调各个流体器件的深度或高度完全一致，而是能够实现离心式多通道微流体芯片所有功能的流体器件处于类似高度的一个完整层面。第一流体器件上还包括有第二反应池106，第二反应池106设置于支路104上。第一流体器件上还包括有第一反应仓107，第一反应仓107与所述第一反应池101、或第二反应池106、或支路104相连通，且第一反应仓107与气体排气孔109相连通。第一反应仓107与气体排气孔109之间还设置有第二反应仓108。第一溶液暂存区102为多个且能够彼此相互连通，溶液从溶液注入口105进入到最近第一溶液暂存区102后，依次流入其他第一溶液暂存区102，最后通向溶液注入回流口102a。
在此实施方式中，第一溶液暂存区102为多个且能够彼此连通，第一溶液 暂存区102具有相向于旋转中心方向的一个山部S，且每一山部S通过侧流路113与加气通道110相连通，相连的加气通道110形成一体式连通结构，且具有至少一个加气孔110a。所溶液暂存区102为多个且能够彼此连通，并通过排气通道111形成一体式连通结构，最终具有共同的气体排气孔109。
如图3～图16所示，其示出了本发明离心式多通道微流体芯片的另一实施方式的俯视图。这一实施方式与图1所示实施方式的不同在于：第一反应池101与第二反应池106相连通。当然，第二反应池106设置在支路104上，即第二反应池106的位置介于第二连通点104a与支路104和第一流路103的连通点之间。在这一结构中，并没有改变第一反应池101的第一连通点103a和第二连通点104a的位置关系，始终保证第一连通点103a与旋转中心的距离大于第二连通点104a与旋转中心的距离。因此，参见上一实施方式，旋转该芯片而产生的离心力时，能够保证第一溶液暂存区102内的液体试剂(溶液)经第一流路103先进入第一反应池101内并充满第一反应池101，而后再进入第二反应池106内并充满第二反应池106，此时旋转对溶液产生的离心力将压迫原第一反应池101、第二反应池106以及支路104内的气体通过第一流路103进入第一溶液暂存区102最终由溶液注入口105排出，在这里，第一反应池101可以被用作缓冲液池，第二反应池102可以被生化反应池。
本领域技术人员应该能够知道，本发明在此列举的两种实施方式，其涵盖了只有第一反应池101以及同时具有第一反应池101和第二反应池106的两种情况。但，具有第一反应池101和第二反应池106意味着还可能具有第三、第四等等反应池，类似结构及其变形，也应该涵盖在我方发明的保护范围之内。
如图4所示，本发明的芯片具有：位于芯片100上的多个第一反应池101、第二反应池106；以及用于向反应池输送溶液的、例如输送液体试剂(溶液)的流路。为了将液体输送到各个反应池，流路至少包括与各个反应池连接的一个具有谷部G的第一溶液暂存区102，还包括连接第一溶液暂存区102和反应池的第一流路103以及支路104。流路上具有用于注入溶液的注入口。在图4的实施方式中，具有位于第一溶液暂存区102端部的溶液注入口105和位于另一侧端部的、兼任空气排出的气体排气孔109。
在这一实施例中，位于另一侧端部的、兼任空气排出的气体排气孔109其实际上与设置于芯片100上的第一反应仓107相连通，而该第一反应仓107又与第二反应池106相连通，用于存放试纸条。例如，在病毒细菌的核酸扩增检测实验中，从第二反应池102释放出完成扩增的反应液，进入设置了免疫层析试纸的第一反应仓中，待扩增的核酸反应液层析上硝酸纤维素膜开始计时，5分钟时观察结果：如试纸的检测T线有明显红色线条，说明该病毒细菌的的检测结果为阳性
图5是表示本发明除上述实施例外的离心式多通道微流体芯片的俯视结构 示意图。本发明的芯片具有：位于芯片100上的多个第一反应池101、第二反应池106；以及用于向反应池输送溶液的、例如输送液体试剂(溶液)的流路。为了将液体输送到各个反应池，流路至少包括与各个反应池连接的具有谷部G的第一溶液暂存区102，还包括连接第一溶液暂存区102和反应池的第一流路103以及支路104。
在图7这一实施方式中，在本发明芯片的芯片100上第一溶液暂存区102相连通形成一体式连通结构，还设置有用于注入溶液或气体液体流出的通口，如具有位于第一溶液暂存区102一端部的溶液注入口105、另一端部的溶液注入回流口102a、以及位于加气通道110上的加气孔110a。对应加气孔110a还设置了加气通道110，在第一溶液暂存区102的谷部G和谷部G之间的部位为山部S。此处山部S是指，在第一溶液暂存区102的谷部G与谷部G之间离中心点距离最近的部位加气通道110通过侧流路113和第一溶液暂存区102相连通。加气通道110通过侧流路113和第一溶液暂存区102相连通，当芯片进行离心时，当谷部G的溶液被离心力驱使流入第一流路103时，加气通道110可通过侧流路113可均匀给予第一溶液暂存区102进行气体补充，较佳地，加气通道110形成为圆形结构。当第一溶液暂存区102内部注满溶液而不选择离心方式进行液体分配时，可通过从加气孔110a向加气通道110进行气体注入，从而分别对每个第一溶液暂存区102内的溶液进行加压，驱动溶液进入第一流体103。在此实施例中，第一溶液暂存区102与溶液注入回流口102a之间通过存储池112相连通。第一溶液暂存区102形成在比第一反应池101更接近于中心点侧的位置上。而且，本发明的离心式多通道微流体芯片中，该第一溶液暂存区102形成为相对于旋转中心方向的一个谷部G。另外，具有相对于中心点方向的谷部G，是指具有相对于中心点方向的最大点。如此地，通过在第一溶液暂存区102之间具有相对于中心点方向的一个谷部G，由此，被注入到第一溶液暂存区102的液体在芯片旋转时，自然而然地在第一溶液暂存区102谷部G被汇集，因此可以保证各个第一溶液暂存区102的向流路进行适量溶液分配。第一溶液暂存区102可以设置为波浪形，波浪形的第一溶液暂存区102形成一个圆形。在本发明中，与第一溶液暂存区102相连的反应池内分别预先装载利用同一种反应形式检测的不同物质，例如可以在不同反应池中预先装载可与待测样品中不同核酸片段发生特异性反应的引物及辅助成分，通过多组样品的进样离心且核酸扩增反应，便可在一张芯片上对多组待测样品中的特定核酸片段进行检测。
在这一实施例中，流路还包括第一流路103以及支路104，第一流路103自谷部G延伸至第一反应池101形成第一连通点103a，而支路104与第一反应池101形成第二连通点104a并自此第二连通点104a延伸至第一流路103，并且保证第一连通点103a与旋转中心的距离大于第二连通点104a与旋转中心的距 离。
第一溶液暂存区102在彼此相邻的反应池(例如第一反应池101)之间具有相向于旋转中心方向的一个山部S，且每一山部S通过侧流路113与加气通道110相连通。在这一实施例中，第一反应池101通过第一流路103和第一溶液暂存区102相连，而第二反应池106设置在支路104上。为了更好的利用空间，如图5所示，流路与第二反应仓108在相邻第一反应池101之间具有朝向旋转中心方向的一个波峰，且与排气通道111相连。在此，波峰是指，在连接第二反应仓108上离中心点距离最近的部位。排气通道111配置成与芯片100呈同心圆状，与气体排气孔109相连。加气通道110也配置成与芯片100呈同心圆状，其一端设置有加气孔110a，且与第一溶液暂存区102相连。
第二反应池106设置于所述支路104上。在这一实施例中，第二反应池106直接与第二反应仓108相连通并连接排气通道111。为了更好的离心进行液体分配，支路104与第一流路103形成的连通点与旋转中心的距离与第二连通点104a与旋转中心的距离要优化设计，旋转该芯片而产生的离心力时，能够保证第一溶液暂存区102内的液体试剂(溶液)经第一流路103先进入第一反应池101内并充满第一反应池101，而后进入第二反应池106，此时旋转对溶液产生的离心力将压迫原第一反应池101、第二反应池106以及支路104内的气体通过第一流路103回流进入第一溶液暂存区102最终由溶液注入口105排出。
如图6所示，其与图5所示实施例的区别在于，在芯片100上设置有第一反应仓107。第一反应仓107连接在第二反应池106与第二反应仓108之间。
图7和图8所示实施方式，都可以看作为图6所示实施例的变形，但并不局限于此。如图，侧流路113在此被省略了。也即，在进行离心时，谷部G是必须的，由此，被注入到第一溶液暂存区102的液体在芯片旋转时，自然而然地在第一溶液暂存区102谷部G被汇集，因此可以保证各个第一溶液暂存区102的向流路进行适量溶液分配。
图11～图20提供的实施例不同于之前的离心式多通道微流体芯片之处在于，其建立了不同层面或不同高度或不同表面的流体器件之间的连接。在这一实施方式中，离心式多通道微流体芯片，芯片100的第一层面或第二层面设置有第二流体器件，包含有第二溶液暂存区、连通第二溶液暂存区且与第一流体器件中相同的全部或部分的流体器件；第二流体器件与第一流体器件相连通，且通向一个共同的气体排气孔109。在反应池及反应仓中至少一个反应池或反应仓中设置有显示生物化学反应结果的试纸，所述试纸包括干式化学试纸、干式生化试纸或免疫层析试纸。较佳地，离心式多通道微流体芯片中配套设置有检测仪器，其能对芯片100的某一个反应池中的溶液产生的特定光谱信号进行检测，得到被检测样品的分析结果。
如图15和图16，在如图4的实施例基础上，多个支路104通过多个互通 流路114与另一层上的一个排气通道联通，该排气通道联通统一的出口端115。
参见图11和图12，第一互通流路114上设置有能够形成水化膜的沉孔120，该水化膜能够将流道内的空气隔离使得空气不能通过，而当有溶液流过来，溶液能够溶解水化膜。水化膜的主要成分是聚乙二醇、乙烯-醋酸乙烯聚合物、聚丙烯酸、聚丙烯酰胺壳聚糖、透明质酸、聚乙烯醇、蔗糖等产品中的一个或若干个的混合物。
离心式多通道微流体芯片具有：形成有反应池、注入孔和流路的芯片100，其通过上下相配合或贴合设置的基材组成。作为基材，只要是不影响试剂的基材就没有特别的限制，特别是，如果使用含有聚丙烯、聚碳酸酯、丙烯酸中的任一种的树脂材料，则能够确保良好的可见光透过性。作为聚丙烯，可以使用均聚丙烯或聚丙烯与聚乙烯的无规共聚物。另外，作为丙烯酸，可以使用聚甲基丙烯酸甲酯、或者可以使用甲基丙烯酸甲酯与其他的甲基丙烯酸酯、丙烯酸酯、苯乙烯等单体的共聚体。另外，使用这些树脂材料的情况下，也可以确保芯片的耐热性和强度。作为除树脂材料以外的材料，可举出铝、铜、银、镍、黄铜、金等的金属材料。使用金属材料时，还在热传导率和密封性能方面优异。而且，通过使反应池的至少一侧基材的保持透明，由此能够从外部进行荧光等的检测和分析。其中，本发明中的“透明”和“光透过性”是指，在检测光的波长区域下的平均透过率为70％以上的情况。如果使用可见光区域(波长350～780nm)的光透过性材料，则易于辨认芯片内的试剂状态，但并不限定于此。
作为形成加样孔、流路和废液部的基材的加工方法，当为树脂材料时，可以采用注塑成型、真空成型等的各种树脂成型方法或机械切割等。当为金属材料时，可通过实施利用较厚基材的研磨加工或蚀刻、在较薄金属片上实施压力加工或拉伸加工而形成。另外，作为芯片100，特别是使用含有聚丙烯、聚碳酸酯、丙烯酸中的任一种的树脂材料时，能够确保良好的光透过性、耐热性和强度。另外，当基材的厚度为50μm～3mm范围时，能够确保良好的光透过性、耐热性和强度，且能够可靠地进行凹部加工。另外，当基材的厚度为10μm～300μm范围时，可以同时满足基材的热传导性和密封性。
作为贴合基材方法，可举出在一个基材上设置作为粘接层的树脂涂层，并使其熔融而粘接两个基材的方法。优选树脂涂层设置在热传导率高的金属材料基材上并进行熔融粘接。作为树脂涂层的材料，可以使用PET、聚缩醛、聚酯或聚丙烯等的树脂材料。当然，还可以采用胶带固定以及石蜡黏合的方式。
在上述的贴合方法中，优选作为基材使用容易进行微细加工且适合荧光测量的光透过性树脂材料，作为基材使用热传导率高、且容易设置树脂涂层并通过熔融粘接进行贴合的金属材料。另外，通过在金属基材表面形成树脂涂层，在选定材料时可以不考虑金属基材自身的耐药品性。
另外，在基材表面形成树脂涂层时，通过作为树脂涂层的底层形成增粘(锚 固，anchor)层，由此可采用激光来进行熔融粘接。在增粘层中混合有吸收激光波长光的碳黑(光吸收性材料)，通过照射激光产生热，由此能够对树脂涂层进行熔融粘接。或者，也可以通过在树脂涂层中添加碳黑、或将树脂涂层的表面涂覆为黑色的方式来代替在增粘层中添加碳黑。例如，在照射波长为900nm左右的红外激光二极管的光，也可以有效地熔融树脂涂层。与热熔接不同，激光熔接无需加热芯片，因此，可在几乎不会影响到芯片或被固定在芯片上的试剂的情况下，实施基材的贴合。
实际操作时，先在第二反应池106中分别滴加带有核酸引物及扩增酶等溶液，将芯片进行干燥，得到固态的引物及扩增酶等，第一反应仓107内放置核酸免疫层析试纸条，将芯片100和第二基材200贴合，并用胶带或其他物品封住气体排气孔109和，由溶液注入口105注入带有待检测核酸模板的溶液并逐渐充满第一溶液暂存区102，此时，如图5～图8所示实施例，溶液注入回流口102a在整个过程的作用为排出第一溶液暂存区102内的气体，若是注入溶液过多，多余的会在离心时会被分配到存储池。将整个芯片放在离心机上离心处理，利用离心力，第一溶液暂存区102中带有核酸模板的溶液依次流入第一反应池101和第二反应池106，带有核酸模板的溶液将干燥的引物及扩增酶溶解混合，将芯片放置在一定的温度条件下进行核酸扩增反应后，将第一溶液暂存区102注入稀释溶液，打开气体排气孔109，可从加气孔110a注入气体，压力将从加气通道110传递到侧流道113及第一溶液暂存区102，因为第一反应池101等流体器件与气体排气孔109是相连接的，稀释溶液将进入第二反应池106并将扩增的核酸溶液稀释并挤压流进第一反应仓107的试纸条上，试纸条反应显示结果。
此外，也可以将第一溶液暂存区102注入稀释溶液，通过离心芯片盘，将注入的溶液驱动进入各流体器件，稀释溶液将进入第二反应池106并将扩增好的核酸溶液进行稀释并挤压流进第二反应仓108的试纸条上，试纸条反应显示结果。
此外，还可以将第二溶液暂存区注入稀释溶液，通过离心芯片盘，将注入的溶液驱动进入各流体器件，稀释溶液将进入第二反应池106并将扩增好的核酸溶液进行稀释并挤压流进第一反应仓107的试纸条上，试纸条反应显示结果。
此外，还可以将第一溶液暂存区第二溶液暂存区同时注入稀释溶液，通过离心芯片盘，将注入的溶液驱动进入各流体器件，稀释溶液将进入第二反应池106并将扩增好的核酸溶液进行稀释并挤压流进第一反应仓107的试纸条上，试纸条反应显示结果。
在以上的三种稀释液注入案例中，除核酸引物及扩增酶外，如果在第一流体器件的第二反应池内预先加入免疫反应的抗体，则该芯片盘可以用来进行免疫荧光检测等试验。如果在第一流体器件的第二反应池预先加入生化反应的相 关反应成分，则该芯片盘可以用来进行多种生化分院。
相应地，如果第二流体器件中的第二溶液暂存区还连通有反应池或反应仓，也在其中一个反应池或反应仓中设置了以上的核酸反应，免疫反应，生化反应的相关反应成分，则当同时在第一溶液暂存区第二溶液暂存区注入稀释溶液后，稀释溶液会驱使第一流体器件何第二流体器件的反应完成的液体流出后合流，从而可以在后续的反应池或反应仓中进一步反应。
相应地芯片盘内的核酸反应，免疫反应，生化反应的结果可以通过试纸条的方式进行肉眼颜色判读，或者通过光谱仪器对某个设置了透明基材的反应池或反应仓的溶液进行光谱判读。
如图19所示，位于芯片100上的多个第一反应池101以及用于向各个第一反应池101输送溶液的、例如输送液体试剂(溶液)的流路。为了将液体输送到各个第一反应池101，流路至少包括与各个第一反应池101连接的一个第一溶液暂存区102，当然，第一溶液暂存区102通过第一流路103与第一反应池101相连。第一反应池101一侧与气体排气孔109联通，流路上具有用于注入溶液的注入口。注入的液体试剂(溶液)到第一溶液暂存区102，通过离心运动，液体试剂(溶液)由第一流路103进入第一反应池101，第一流路103和第一反应池101的空气经气体排气孔109排出，第一反应池101中装有试纸条，试纸条吸收液体试剂(溶液)，试纸条反应显示结果。
如图20所示，为将图19所述实施例中的各个第一溶液暂存区102首尾联通起来有统一的注入溶液的注入口、将各个第一反应池101一侧联通至一个有统一的气体排气孔109的排气回路的实施例，排气回路可以设置在芯片100正面，也可以在反面，只要从统一的注入口注入液体试剂(溶液)，通过离心运动，液体试剂(溶液)由第一流路103进入所有的第一反应池101，所有的第一流路103和第一反应池101的空气经统一的气体排气孔109排出，第一反应池101中装有试纸条，试纸条吸收液体试剂(溶液)，试纸条反应显示结果。
如图11、12所示一实施方式，第二反应池106设置在芯片相对第一反应池101的另一层面，第二反应池106通过互通流路114与支路104联通，当完成离心操作，第一反应池101和第二反应池106充满液体试剂(溶液)时，第一反应池101朝上平放时，因为联通第二反应池106都是竖直方向的互通流路114，故处在低位层面的第二反应池106中的液体试剂(溶液)不会因重力或晃动，而通过支路104扩散测流。
将芯片加热处理时，第二反应池106中的液体试剂(溶液)会因蒸发后的气体扩散至支路104及其连通的其他流体器件而变少，因为第一反应池101处于第二反应池106偏高的水平位置，所以第一反应池101中的液体试剂(溶液)会因为重力等原因适当流入第二反应池106中进行补充，从而能使第二反应池在芯片平放且反应过程中始终保持液体充满，不会因第二反应池106中的液体 试剂(溶液)减少而影响显示反应结果。
在支路104一处有互通流路114，在互通流路114上有沉孔120，沉孔120底部通过互通流路114与支路104联通，沉孔120上部与第一反应仓107联通，沉孔120中加入主要成分是聚乙二醇、乙烯-醋酸乙烯聚合物、聚丙烯酸、聚丙烯酰胺壳聚糖、透明质酸、聚乙烯醇、蔗糖等产品中的一个或若干个的混合物，干燥后在沉孔120底部形成水化膜120a,此状态下水化膜120a平面是与芯片平面平行设置，此外，水化膜120a平面还可以与芯片平面垂直设置，即不经过互通流路114对支路104起到气体隔断效果。
水化膜120a在无液体试剂(溶液)过来时，起到能将第一反应仓107和第二反应池106之间隔离封闭起来，防止反应气体或反应成分流动影响实验结果，当液体试剂(溶液)流到水化膜120a处时，水化膜120a溶解，液体试剂(溶液)可从第二反应池106流到第一反应仓107中，试纸条吸收体试剂(溶液)，试纸条反应显示结果。
如图13所示，为将图11、12所述实施例中的各个第一溶液暂存区102首尾联通起来有统一的注入溶液的注入口、将各个第一反应仓107一侧联通至一个有统一的气体排气孔109的排气回路的实施例，且在支路104(图中未示出)通过互通流路114(图中未示出)与第二溶液暂存区(102)联通，第二溶液暂存区(102)(图中未示出)既可以作为排气功能，又可以注入第二种液体试剂(溶液)。
当芯片平放且第二反应池106处于下表面时，第二反应池106的底部基材可预先设置为导热材料铝箔。然后用特定的导热金属对该部分铝箔进行生物学PCR仪的温度循环设置完全相同的55-95度的加热处理，鉴于第二反应池106的深度很薄，铝箔的热传导性能特别好，能将温度充分第传导至第二反应池106的溶液。当预先在第二反应池106中放置了PCR核酸扩增的引物及扩增酶，溶液中也存在待扩增的核酸模板时，第二反应池106能发生完整的PCR核酸扩增反应。当第一溶液暂存区稀释液被离心力驱动进入第二反应池106后，PCR扩增反应溶液将进入第一反应仓107，通过试纸条显示反应结果。
如果配置了适当的光谱检测仪器时，则可以直接对第二反应池106进行PCR核酸扩增反应的信号检测，通过仪器进行分析得出反应结果。
如果第二反应池106的下表面不设置为导热材料时，可将芯片整体放置在特定的温度环境中进行恒温核酸扩增，通过是试纸条或光谱仪器进行反应结果判读。
应说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的精神和范围，其均应涵盖在本发明的权利要求范围当中。

Claims (15)

  1. 一种离心式多通道微流体芯片，在芯片(100)第一层面设置有第一流体器件，所述第一流体器件由上下两个基材配合组成；第一流体器件包含多个流体器件：第一反应池(101)、与第一反应池(101)连接的流路和向流路注入溶液的溶液注入口(105)，并通过旋转该芯片(100)，将溶液分配给第一反应池(101)，其特征在于：
    所述流路具有用于向上述第一反应池(101)输送液体的第一溶液暂存区(102)，该第一溶液暂存区(102)具有相对于旋转中心方向的一个谷部(G)；
    所述流路包括第一流路(103)和支路(104)，第一流路(103)自所述谷部(G)延伸至所述第一反应池(101)形成第一连通点(103a)，所述支路(104)与所述第一反应池(101)形成第二连通点(104a)并自此第二连通点(104a)朝向旋转中心的方向延伸至一个出口端(115),该出口端(115)可独立，也可以与其他流路器件合并。
  2. 如权利要求1所述的离心式多通道微流体芯片，其特征在于：所述支路(104)与所述第一反应池(101)形成第二连通点(104a)并自此第二连通点(104a)延伸至所述第一溶液暂存区(102)或第一流路(103)后通向出口端(115)。
  3. 如权利要求1或2所述的离心式多通道微流体芯片，其特征在于：所述第一流体器件中从第一溶液暂存区(102)及其向后的流体器件的任何一个点，可从所述芯片(100)的第一层面向上表面或下表面的一定深度延伸，形成上下互通流路(114)，将第一流体器件从芯片(100)的第一层面设置或延伸到第二层面，让第一流体器件中的气体和溶液从第一层面流动到第二层面的流体器件。
  4. 如权利要求1或2所述的离心式多通道微流体芯片，其特征在于：所述第一流体器件上还包括有第二反应池(106)，所述第二反应池(106)设置于所述支路(104)上。
  5. 如权利要求4所述的离心式多通道微流体芯片，其特征在于：所述第一流体器件上还包括有第一反应仓(107)，所述第一反应仓(107)与所述第一反应池(101)、或第二反应池(106)、或支路(104)相连通，且所述第一反应仓(107)与气体排气孔(109)相连通。
  6. 如权利要求5所述的离心式多通道微流体芯片，其特征在于：所述第一反应仓(107)与气体排气孔(109)之间还设置有第二反应仓(108)。
  7. 如权利要求1、2、4～6任一所述的离心式多通道微流体芯片，其特征在于：所述第一溶液暂存区(102)为多个且能够彼此相互连通，溶液从溶液注入口(105)进入到最近第一溶液暂存区(102)后，依次流入其他第一溶液暂存区(102)，最后通向溶液注入回流口(102a)。
  8. 如权利要求7所述的离心式多通道微流体芯片，其特征在于：所述第一溶液暂存区(102)为多个且能够彼此连通，第一溶液暂存区(102)具有相向于旋转中心方向的一个山部(S)，且每一山部(S)通过侧流路(113)与加气通道 (110)相连通，相连的加气通道(110)形成一体式连通结构，且具有至少一个加气孔(110a)。
  9. 如权利要求7所述的离心式多通道微流体芯片，其特征在于：所述溶液暂存区(102)为多个且能够彼此连通，并通过排气通道(111)形成一体式连通结构，最终具有共同的气体排气孔(109)。
  10. 一种如权利要求3所述的离心式多通道微流体芯片，其特征在于：所述芯片的第一层面或第二层面设置有第二流体器件包含有第二溶液暂存区、连通第二溶液暂存区且与第一流体器件中相同的全部或部分的流体器件；第二流体器件与第一流体器件相连通。
  11. 如权利要求1、2、4～6、8～10任一所述的离心式多通道微流体芯片，其特征在于：所述反应池及反应仓中至少一个反应池或反应仓中设置有显示生物化学反应结果的试纸，所述试纸包括干式化学试纸、干式生化试纸或免疫层析试纸。
  12. 如权利要求1、2、4～6、8～10任一所述的离心式多通道微流体芯片，其特征在于：配套设置有检测仪器，其能对芯片(100)的某一个反应池中的溶液产生的特定光谱信号进行检测，得到被检测样品的分析结果。
  13. 如权利要求3所述的离心式多通道微流体芯片，其特征在于：所述第一上下互通流路(114)上有能够设置水化膜的沉孔(120)，所述水化膜能够将所述流道内的空气隔离使得空气不能通过，而当有溶液流过来，溶液能够溶解所述水化膜。
  14. 如权利要求13所述的离心式多通道微流体芯片，其特征在于：所述水化膜的主要成分是聚乙二醇、乙烯-醋酸乙烯聚合物、聚丙烯酸、聚丙烯酰胺壳聚糖、透明质酸、聚乙烯醇、蔗糖产品中的一个或若干个的混合物。
  15. 一种能够加热的离心式多通道微流体芯片，其特征在于：具有结构如权利要求1、2、4～6、8～10、13或14任一所述的离心式多通道微流体芯片；
    在所述第一流体器件中的反应池或反应仓、或第二流体器件的相同的全部或部分的流体器件的上下基材中至少有一个基材属于导热材料。
PCT/CN2017/081462 2016-01-22 2017-04-21 一种离心式多通道微流体芯片 WO2017186063A1 (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201610045669 2016-01-22
CN201610261848.9 2016-04-25
CN201610261848.9A CN105964313B (zh) 2016-01-22 2016-04-25 一种离心式多通道微流体芯片

Publications (1)

Publication Number Publication Date
WO2017186063A1 true WO2017186063A1 (zh) 2017-11-02

Family

ID=56993262

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2017/081462 WO2017186063A1 (zh) 2016-01-22 2017-04-21 一种离心式多通道微流体芯片

Country Status (2)

Country Link
CN (1) CN105964313B (zh)
WO (1) WO2017186063A1 (zh)

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108642146A (zh) * 2018-06-01 2018-10-12 广州双螺旋基因技术有限公司 一种可预装试剂的s型微管道式核酸扩增密闭反应管
CN109894166A (zh) * 2019-03-14 2019-06-18 杭州霆科生物科技有限公司 一种真菌毒素多指标检测微流控芯片
CN110531068A (zh) * 2019-09-09 2019-12-03 河南格悦检测技术有限公司 一种动物疫病胶体金检测卡
CN110849868A (zh) * 2019-10-21 2020-02-28 江苏大学 基于微流控芯片的面粉中臭酸钾智能检测装置与方法
CN110872558A (zh) * 2019-12-13 2020-03-10 天津诺迈科技有限公司 光激化学发光及分子检测用微流控芯片系统及使用方法
CN111487229A (zh) * 2020-04-20 2020-08-04 中国农业科学院烟草研究所 一种基于背光激发原理的植物病菌检测装置
CN112791645A (zh) * 2021-01-26 2021-05-14 驻马店职业技术学院 流体驱动控制阀
US20210291166A1 (en) * 2019-04-19 2021-09-23 Lg Chem, Ltd. Microdevice for detecting aldehydes or ketones
CN113649095A (zh) * 2021-09-13 2021-11-16 大连理工大学 一种用于核酸检测的高度集成式微流控芯片及使用方法
CN113846174A (zh) * 2021-09-15 2021-12-28 北京源景泰科生物科技有限公司 用于检测艰难梭菌的试剂盒和检测方法
CN114618600A (zh) * 2022-02-25 2022-06-14 南昌大学 微流控离心盘
CN114931987A (zh) * 2022-06-13 2022-08-23 中科合肥智慧农业协同创新研究院 用于土壤多种离子同步检测的离心式微流控芯片及方法
CN115646563A (zh) * 2022-10-14 2023-01-31 广州迪澳医疗科技有限公司 一种微流控芯片及其制备方法

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105964313B (zh) * 2016-01-22 2019-04-09 上海快灵生物科技有限公司 一种离心式多通道微流体芯片
CN106434320A (zh) * 2016-11-15 2017-02-22 上海快灵生物科技有限公司 一种微量溶液反应器
EP3541518A4 (en) * 2016-11-17 2020-09-30 Cleveland State University CHIP PLATFORMS FOR THREE-DIMENSIONAL MICROARRAY BIOPRINTING
US11262349B2 (en) 2017-10-11 2022-03-01 Cleveland State University Multiplexed immune cell assays on a micropillar/microwell chip platform
CN108982824B (zh) * 2018-05-11 2023-11-10 石家庄禾柏生物技术股份有限公司 一种试剂盘测试装置
DE102018212930B3 (de) * 2018-08-02 2019-11-07 Hahn-Schickard-Gesellschaft für angewandte Forschung e.V. Vorrichtung und Verfahren zum Leiten einer Flüssigkeit durch ein poröses Medium
CN109283174A (zh) * 2018-09-29 2019-01-29 厦门大学 一种定量检测光盘和检测方法
CN109613286A (zh) * 2018-12-27 2019-04-12 宁波大学 一种定性/定量生物芯片检测装置
CN109821667A (zh) * 2019-02-27 2019-05-31 广西民族大学 一种便携式手动高速血液离心装置
CN109884328A (zh) * 2019-03-01 2019-06-14 清华大学 基于离心式微流控系统的侧向流免疫检测系统
CN109894165B (zh) * 2019-03-14 2021-05-18 杭州霆科生物科技有限公司 一种瘦肉精三联检测微流控芯片
CN110295107A (zh) * 2019-07-01 2019-10-01 贵州金玖生物技术有限公司 一种用于核酸检测的多通量微流控芯片
CN110568203B (zh) * 2019-09-12 2022-05-24 重庆科技学院 一种多通道荧光免疫层析微流控芯片的使用方法
TWI754838B (zh) * 2019-09-25 2022-02-11 財團法人工業技術研究院 觀測裝置及其觀測載具
CN110684640B (zh) * 2019-10-15 2024-06-11 深圳清华大学研究院 微流体装置及基因测序仪
CN110643502A (zh) * 2019-10-27 2020-01-03 苏州济研生物医药科技有限公司 一种单细胞微流控检测芯片及其制备方法和使用方法
CN111558402B (zh) * 2020-03-10 2021-05-11 青岛英赛特生物科技有限公司 一种气压驱动的离心式微流控检测芯片
CN111269827A (zh) * 2020-03-22 2020-06-12 大连保税区金宝至电子有限公司 一种不锈钢蚀刻加工核酸检测微流道控制芯片
CN117420299A (zh) * 2023-12-18 2024-01-19 南京海关工业产品检测中心 基于CRISPR-Cas12a系统的可穿戴生物传感器及其应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN2585691Y (zh) * 2002-12-20 2003-11-12 上海博昇微晶科技有限公司 变轴心微流体系统
CN101850231A (zh) * 2009-07-03 2010-10-06 中国科学院上海微系统与信息技术研究所 一种微流体反应器、使用方法及其应用
CN102369443A (zh) * 2009-03-31 2012-03-07 凸版印刷株式会社 试样分析芯片、采用该试样分析芯片的试样分析装置和试样分析方法、以及试样分析芯片的制造方法
WO2013077391A1 (ja) * 2011-11-25 2013-05-30 凸版印刷株式会社 試料分析チップ並びに試料分析方法及び遺伝子解析方法
CN105964313A (zh) * 2016-01-22 2016-09-28 上海快灵生物科技有限公司 一种离心式多通道微流体芯片

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2256501B1 (en) * 2008-02-05 2021-07-07 PHC Holdings Corporation Analyzing device, and analyzing apparatus and analyzing method using the device
CN103041880A (zh) * 2012-12-31 2013-04-17 苏州汶颢芯片科技有限公司 一种检测土壤中酚类化合物的离心式微流控芯片及其制备方法
CN103398961A (zh) * 2013-08-07 2013-11-20 苏州扬清芯片科技有限公司 一种检测化学需氧量的微流控玻璃芯片及其制备方法
CN104497099B (zh) * 2014-12-02 2017-08-11 中国科学院上海微系统与信息技术研究所 一种气相扩散型结晶芯片及使用方法
CN206229376U (zh) * 2016-01-22 2017-06-09 上海快灵生物科技有限公司 一种离心式多通道微流体芯片

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN2585691Y (zh) * 2002-12-20 2003-11-12 上海博昇微晶科技有限公司 变轴心微流体系统
CN102369443A (zh) * 2009-03-31 2012-03-07 凸版印刷株式会社 试样分析芯片、采用该试样分析芯片的试样分析装置和试样分析方法、以及试样分析芯片的制造方法
CN101850231A (zh) * 2009-07-03 2010-10-06 中国科学院上海微系统与信息技术研究所 一种微流体反应器、使用方法及其应用
WO2013077391A1 (ja) * 2011-11-25 2013-05-30 凸版印刷株式会社 試料分析チップ並びに試料分析方法及び遺伝子解析方法
CN105964313A (zh) * 2016-01-22 2016-09-28 上海快灵生物科技有限公司 一种离心式多通道微流体芯片

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108642146A (zh) * 2018-06-01 2018-10-12 广州双螺旋基因技术有限公司 一种可预装试剂的s型微管道式核酸扩增密闭反应管
CN108642146B (zh) * 2018-06-01 2024-02-02 广州双螺旋基因技术有限公司 一种可预装试剂的s型微管道式核酸扩增密闭反应管
CN109894166A (zh) * 2019-03-14 2019-06-18 杭州霆科生物科技有限公司 一种真菌毒素多指标检测微流控芯片
US20210291166A1 (en) * 2019-04-19 2021-09-23 Lg Chem, Ltd. Microdevice for detecting aldehydes or ketones
US11969729B2 (en) * 2019-04-19 2024-04-30 Lg Chem, Ltd. Microdevice for detecting aldehydes or ketones
CN110531068A (zh) * 2019-09-09 2019-12-03 河南格悦检测技术有限公司 一种动物疫病胶体金检测卡
CN110531068B (zh) * 2019-09-09 2022-06-10 河南格悦检测技术有限公司 一种动物疫病胶体金检测卡
CN110849868A (zh) * 2019-10-21 2020-02-28 江苏大学 基于微流控芯片的面粉中臭酸钾智能检测装置与方法
CN110872558A (zh) * 2019-12-13 2020-03-10 天津诺迈科技有限公司 光激化学发光及分子检测用微流控芯片系统及使用方法
CN111487229A (zh) * 2020-04-20 2020-08-04 中国农业科学院烟草研究所 一种基于背光激发原理的植物病菌检测装置
CN111487229B (zh) * 2020-04-20 2023-05-23 中国农业科学院烟草研究所 一种基于背光激发原理的植物病菌检测装置
CN112791645A (zh) * 2021-01-26 2021-05-14 驻马店职业技术学院 流体驱动控制阀
CN112791645B (zh) * 2021-01-26 2022-05-13 驻马店职业技术学院 流体驱动控制阀
CN113649095B (zh) * 2021-09-13 2022-04-08 大连理工大学 一种用于核酸检测的高度集成式微流控芯片及使用方法
CN113649095A (zh) * 2021-09-13 2021-11-16 大连理工大学 一种用于核酸检测的高度集成式微流控芯片及使用方法
CN113846174A (zh) * 2021-09-15 2021-12-28 北京源景泰科生物科技有限公司 用于检测艰难梭菌的试剂盒和检测方法
CN113846174B (zh) * 2021-09-15 2024-06-11 北京源景泰科生物科技有限公司 用于检测艰难梭菌的试剂盒和检测方法
CN114618600B (zh) * 2022-02-25 2023-03-24 南昌大学 微流控离心盘
CN114618600A (zh) * 2022-02-25 2022-06-14 南昌大学 微流控离心盘
CN114931987A (zh) * 2022-06-13 2022-08-23 中科合肥智慧农业协同创新研究院 用于土壤多种离子同步检测的离心式微流控芯片及方法
CN114931987B (zh) * 2022-06-13 2024-06-07 中科合肥智慧农业协同创新研究院 用于土壤多种离子同步检测的离心式微流控芯片及方法
CN115646563A (zh) * 2022-10-14 2023-01-31 广州迪澳医疗科技有限公司 一种微流控芯片及其制备方法

Also Published As

Publication number Publication date
CN105964313B (zh) 2019-04-09
CN105964313A (zh) 2016-09-28

Similar Documents

Publication Publication Date Title
WO2017186063A1 (zh) 一种离心式多通道微流体芯片
TWI582425B (zh) 樣本分析晶片、樣本分析方法及基因解析方法
US10252267B2 (en) Microfluidic device for simultaneously conducting multiple analyses
CN109825426B (zh) 一体式液滴微流控芯片结构及制备方法、微流控芯片组件
JP4962658B2 (ja) 試料分析チップ、これを用いた試料分析装置、試料分析方法及び遺伝子解析方法、並びに試料分析チップの製造方法
US9897596B2 (en) Microfluidic disc for use in with bead-based immunoassays
CN107583692B (zh) 液滴微流控芯片及其制备方法
US20020187564A1 (en) Microfluidic library analysis
AU756710B2 (en) Apparatus for, and method of, varying the rate of flow of fluid along a pathway
US20090155125A1 (en) Microchip
TWI447393B (zh) 反應晶片及其製造方法
KR20110088746A (ko) 원심력기반의 미세유동장치 및 이를 이용한 유체시료 내 분석대상물질 검출방법
US8058072B2 (en) Microanalysis measuring apparatus and microanalysis measuring method using the same
WO2024067695A1 (zh) 微流控芯片及检测方法
US20140311910A1 (en) Microchip and method of manufacturing microchip
EP1356303B1 (fr) Procede et systeme permettant de realiser en flux continu un protocole biologique, chimique ou biochimique.
CN111957360A (zh) 液滴微流控芯片及微液滴的制备方法
JP5521454B2 (ja) 試料分析チップ、これを用いた試料分析装置及び試料分析方法
CN206229376U (zh) 一种离心式多通道微流体芯片
JP5177533B2 (ja) マイクロチップ
JP2012185000A (ja) 試料分析チップ及びこれを用いた試料分析方法
JP2013509578A (ja) 異種アッセイの洗浄方法及び装置としてのサイフォン吸引
JP2011214943A (ja) 試料分析チップ、試料分析方法及び試料分析装置
US20130209329A1 (en) Microchip

Legal Events

Date Code Title Description
NENP Non-entry into the national phase

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17788715

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 17788715

Country of ref document: EP

Kind code of ref document: A1