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CN109603929A - Manufacturing method of valve on chip, microfluidic chip and liquid flow control method - Google Patents

Manufacturing method of valve on chip, microfluidic chip and liquid flow control method Download PDF

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Publication number
CN109603929A
CN109603929A CN201811330430.4A CN201811330430A CN109603929A CN 109603929 A CN109603929 A CN 109603929A CN 201811330430 A CN201811330430 A CN 201811330430A CN 109603929 A CN109603929 A CN 109603929A
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Prior art keywords
valve
wax
chip
region
manufacturing
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CN201811330430.4A
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CN109603929B (en
Inventor
陈华英
陈畅
沈小双
朱永刚
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Harbin Institute of Technology Shenzhen
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Harbin Institute of Technology Shenzhen
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502738Containers 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 integrated valves

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

Abstract

本发明涉及微流控芯片领域,本发明公开了一种芯片上阀门的制造方法、微流控芯片与液体流动控制方法,芯片制造方法包括以下步骤:在多孔介质基材上设置流道;使蜡液渗透入位于流道上的阀门区域处的多孔介质基材内;待蜡液完全渗透多孔介质基材并经过固化后形成阀门,阀门将流道分隔为互不连通的至少两个区域。本发明同样可以实现流道的阻隔与连通,同时其结构更为简单,操作方便,成本低廉,有助于微流控芯片的推广。

The invention relates to the field of microfluidic chips, and discloses a manufacturing method of a valve on a chip, a microfluidic chip and a liquid flow control method. The chip manufacturing method includes the following steps: setting a flow channel on a porous medium substrate; making The wax liquid penetrates into the porous medium substrate at the valve area on the flow channel; after the wax liquid completely penetrates the porous medium substrate and is cured, a valve is formed, and the valve divides the flow channel into at least two areas that are not connected to each other. The invention can also realize the blocking and communication of the flow channel, and meanwhile, the structure is simpler, the operation is convenient, and the cost is low, which is helpful for the popularization of the microfluidic chip.

Description

The manufacturing method of valve, micro-fluidic chip and liquid flow control method on chip
Technical field
The present invention relates to micro-fluidic chip field, more particularly, to the micro-fluidic chip field based on porous media substrate, It is specifically related to flow control method of the liquid on micro-fluidic chip, and realizes the micro-fluidic chip of this method.
Background technique
Based on the micro-fluidic chip of porous media substrate, for example paper substrate micro-fluidic chip is a kind of novel microfluidic analysis Device, because it has the characteristics that at low cost, the processing is simple, easy to use, therefore in care diagnostic, food quality control and environment prison There is huge application prospect in the fields such as survey, are increasingly becoming the research hotspot in micro-fluidic chip field in recent years.
When a variety of reactants or reagent participate in detection, generally require to flow in runner using valve to control liquid Precedence.In addition, being received significant attention in recent years using length method in the method that paper base chip is detected, principle is inspection Substrate is surveyed after the conversion zone and predetermined substance of chip chemically react, reaction product is logical as mixed solution flows into miniflow Road, and chromogenic reaction occurs with the color developing agent on channel.After the completion of solution flowing, certain length can be observed in channel Develop the color section, and then can determine the content of reaction product and detectable substance.The device that this method uses is easy, easy to operate, but It is in accuracy there is limitation usually will appear reactant not yet in being related to detection process that is secondary or repeatedly reacting Reaction flows into microchannel completely, influences testing result.It, can be with by the way that hydrophobic valve is arranged in conversion zone and microchannel Control is realized to the flowing of substrate solution, allows substrate sufficiently to react in conversion zone, the solution after fully reacting enters micro- Circulation road carries out subsequent reaction again.Therefore, controlled using valve liquid flowing in paper base chip is that it is answered in detection field Key technology.
The effect of valve is the flowing of control reaction solution, guarantees that detectable substance is reacted completely, and can react in the first step Valve is opened after the completion, and solution is made to can smoothly enter into channel.Its key is to guarantee the closing and opening of valve.It deposits in the prior art Valve closure is reached by the method folded and unfolded such as the three-dimensional paper chip detection device of Pop-up in a variety of valve mechanisms Effect, change the flow path of detectable substance.The method for another example moved using electric textile material as valve controlling flow, positive reason Detectable substance solution cannot flow through textile material under condition, and the method by applying potential between solution and valve enables solution Enough barrier fabrics achieve the effect that open valve, however above-mentioned apparatus all has the shortcomings that structure is complicated, at high cost, it is difficult to full The demand of sufficient people.
Summary of the invention
For overcome the deficiencies in the prior art, the present invention proposes a kind of manufacturing method of valve on chip, existing for solving There are valve device structure complexity, problem at high cost.
The present invention also proposes a kind of micro-fluidic chip and liquid flow control method.
The present invention solves scheme used by its technical problem:
The manufacturing method of valve on a kind of chip, comprising the following steps:
Runner is set on porous media substrate;
Infiltrate through wax liquor in the porous media substrate at the valve region on runner;
Porous media substrate is permeated completely after wax liquor and forms valve after solidification, and runner is divided by valve not to be connected mutually At least two logical regions.
Mode as a further improvement of the foregoing solution, the valve region on porous media substrate applies wax, then right Porous media substrate is heated, so that wax is melted into wax liquor.
Mode as a further improvement of the foregoing solution applies wax in valve region by way of printing.
Runner is divided into mutual disconnected conversion zone and detection by mode as a further improvement of the foregoing solution, valve Region.
A kind of micro-fluidic chip is made by the manufacturing method of valve in said chip.
A kind of liquid flow control method based on above-mentioned micro-fluidic chip a, comprising the following steps: region wherein Interior addition reagent removes the wax of valve region after meeting and imposing a condition so that reagent flowed to from current region it is adjacent another A region.
Mode as a further improvement of the foregoing solution, the method for removing the wax of valve region are as follows: apply to valve solvable Solve the solvent of wax.
Mode as a further improvement of the foregoing solution, solvent are acetone, isopropanol, toluene, acetonitrile or n-hexane.
Mode as a further improvement of the foregoing solution imposes a condition are as follows: the reagent in current region has completely reacted Or it is thoroughly mixed.
The beneficial effects of the present invention are:
Compared with the prior art the present invention equally may be implemented the barrier of runner be connected to, while its structure is more simple, It is easy to operate, it is low in cost, facilitate the popularization of micro-fluidic chip.
Detailed description of the invention
Invention is further explained with reference to the accompanying drawings and examples.
Fig. 1 is the flow chart of micro-fluidic chip manufacturing method embodiment of the present invention;
Fig. 2 is the front view of micro-fluidic chip embodiment of the present invention;
Fig. 3 is that different solvents fully open volume histograms needed for valve;
Fig. 4 is that different solvents are completely dissolved histogram the time required to valve;
Fig. 5 is influence schematic diagram of the valve transparency to valve barriering effect.
Specific embodiment
It is carried out below with reference to technical effect of the embodiment and attached drawing to design of the invention, specific structure and generation clear Chu, complete description, to be completely understood by the purpose of the present invention, scheme and effect.It should be noted that the case where not conflicting Under, the features in the embodiments and the embodiments of the present application can be combined with each other.
It should be noted that unless otherwise specified, when a certain feature referred to as " fixation ", " connection " are in another feature, It can directly fix, be connected to another feature, and can also fix, be connected to another feature indirectly.In addition, this The descriptions such as up, down, left, right, before and after used in invention are only relative to the mutual of each component part of the invention in attached drawing For positional relationship.
In addition, unless otherwise defined, the technology of all technical and scientific terms used herein and the art The normally understood meaning of personnel is identical.Term used in the description is intended merely to description specific embodiment herein, without It is to limit the present invention.Term " and or " used herein includes the arbitrary of one or more relevant listed items Combination.
The invention discloses a kind of micro-fluidic chip manufacturing methods with wax valve, and based on the micro-fluidic chip Liquid flow control method, central scope are the wax valves that setting infiltrates through inside porous media substrate on runner, work as valve In the presence of door, runner is divided at least two regions, to realize complete reaction of the reagent in a region or complete Mixing;And wax valve can quickly be removed by organic solvent, so that the connection between region is realized, under entering reagent One region participates in reaction, to realize the detection of reagent.Compared with the prior art, the resistance of runner equally may be implemented in the present invention Every be connected to, while its structure is more simple, easy to operate, low in cost, facilitates the popularization of micro-fluidic chip.
It is illustrated below by way of specific embodiment.
Referring to Fig.1, the flow chart of micro-fluidic chip manufacturing method one embodiment of the present invention is shown comprising following tool Body step:
Step 1
Runner is set on porous media substrate, and the porous media substrate in the present embodiment uses filter paper, in the present embodiment It also may include the step of preparing runner on filter paper either directlying adopt the filter paper for being prepared with runner.This implementation A kind of embodiment of example building runner is that curable liquid hydrophobic material is applied on porous media substrate, is dredged to liquid Water material carries out curing process after permeating porous media substrate completely, can form hydrophobic runner after liquid hydrophobic material solidification Wall, flow path wall is around runner is formed, and in addition to this, the present invention can also construct runner, the present invention couple using other known methods This is without limitation.
Step 2
Apply wax liquor in the valve region of runner, infiltrates through wax liquor in the filter paper at the valve region on runner. Specifically, the present embodiment first uses wax printer that the wax of molten condition is printed upon valve region, then valve region is carried out Heating, so that the wax that valve region has been cured melts again can be obtained above-mentioned wax liquor.In addition it is also possible to which solid state wax is molten Solution forms solution in volatilizable solvent, and solution is then coated in valve region, can be so that solid state wax after solvent volatilization It is attached on filter paper, finally valve region is heated, so that above-mentioned wax can be obtained in the solid state wax thawing of valve region Liquid.
Step 3
Cooling and solidifying is carried out after above-mentioned wax liquor permeates filter paper completely can form wax valve in runner, and wax valve will flow Road is divided into mutual disconnected at least two region, and mutual disconnected conversion zone and detection zone are specifically divided into the present embodiment Domain.By increasing more wax valves, runner can be divided into more disconnected regions.
Step 4
Plastic packaging is carried out to the one side of filter paper, to prevent the leakage of reagent solution.
Referring to Fig. 2, show that the present invention is based on the front views of micro-fluidic chip one embodiment made from the above method.Such as Shown in figure, micro-fluidic chip includes porous media substrate 1, flow path wall 2 and valve region 3, and flow path wall 2 surrounds and forms runner, valve Runner is divided into mutually disconnected conversion zone 101 and detection zone 102 by door region 3.
The invention also discloses a kind of liquid flow control methods based on above-mentioned micro-fluidic chip, comprising the following steps: Reagent is added in conversion zone 101, after the reagent of conversion zone 101 has completely reacted or is thoroughly mixed, removes valve The wax in door region 3, reagent can be detected from 101 flow detection region 102 of conversion zone.
The method that valve is removed in the present embodiment is to apply the solvent that can dissolve wax to valve, and solvent can be acetone, isopropyl Alcohol, toluene, acetonitrile or n-hexane.Referring to Fig. 3, different solvents are shown to the solute effect of valve.As shown, opening same The usage amount of the valve of sample size, toluene and acetonitrile is minimum.
Referring to Fig. 4, the time diagram of different solvents dissolution valve is shown.Under the premise of same dose, toluene tool There is shortest solution rate, therefore consider to shorten the dissolution time of valve region wax, it is preferred to use toluene is as removal valve Solvent.
Referring to Fig. 5, influence schematic diagram of the valve transparency of the present invention to valve barriering effect is shown.Before valve preparation It needs first to draw out design drawing, then valve is printed on porous media substrate according to the pattern on design drawing, wherein designing Each region has different transparencies on figure, and the wax of the higher region printing of transparency is fewer, i.e. the transparency of design drawing (can also Referred to as valve transparency) it is inversely proportional with the wax amount printed, as shown, the wax amount of printing is fewer, then the wax of valve region is fewer, The obstructing capacity of valve is weaker, but solvent volume needed for dissolving valve is fewer;Conversely, the wax amount of printing is more, valve area Domain wax is more, and the obstructing capacity of valve is stronger, and solvent volume needed for dissolving valve is more.On the other hand, the barrier energy of valve Power is also by the effect length of valve, and valve length is longer, and obstructing capacity is stronger, i.e. the longer valve of length, allows less wax Amount, however the wax measurer has lower limit, i.e., after wax amount is less than setting value, even if increasing valve length cannot guarantee that with enough Obstructing capacity.
Usage mode in conjunction with Fig. 2, in the present embodiment are as follows: starch is added dropwise in the detection zone of micro-fluidic chip 102 first Indicator, dropwise reaction object p-methyl benzenesulfonic acid and potassium iodide in nonoverlapping two zonules of 101 internal mutual of conversion zone, really Two solvents are protected not contact.It is separated between conversion zone 101 and detection zone 102 by valve region 3.When detection, Conversion zone 101 instills Potassiumiodate sample, and Potassiumiodate sample generates triiodo yin after sufficiently reacting with the reactant of conversion zone 101 Then ion removes the wax of valve region 3, the sample with triiodo anion flows into detection zone 102, anti-with starch indicator It answers and develops the color.If not set valve, Potassiumiodate sample will flow into detection zone 102 before complete reaction, cause to generate Triiodo anion amount substantially reduce, thus significantly reduced with the react length of colour developing of starch indicator, influence detection effect Fruit.
It is to be illustrated to what preferable implementation of the invention carried out, but the invention is not limited to the implementation above Example, those skilled in the art can also make various equivalent variations on the premise of without prejudice to spirit of the invention or replace It changes, these equivalent deformations or replacement are all included in the scope defined by the claims of the present application.

Claims (9)

1.一种芯片上阀门的制造方法,包括以下步骤:1. A method for manufacturing a valve on a chip, comprising the following steps: 在多孔介质基材上设置流道;A flow channel is arranged on the porous medium substrate; 使蜡液渗透入位于所述流道上的阀门区域处的所述多孔介质基材内;infiltrating the wax liquid into the porous media substrate at the valve region on the flow channel; 待所述蜡液完全渗透所述多孔介质基材并经过固化后形成阀门,所述阀门将所述流道分隔为互不连通的至少两个区域。After the wax liquid completely penetrates the porous medium substrate and is cured, a valve is formed, and the valve divides the flow channel into at least two regions that are not connected to each other. 2.根据权利要求1所述的芯片上阀门的制造方法,其特征在于,向所述多孔介质基材上的所述阀门区域施加蜡,然后对所述多孔介质基材进行加热,以使所述蜡融化成所述蜡液。2 . The method for manufacturing a valve on a chip according to claim 1 , wherein wax is applied to the valve region on the porous medium substrate, and then the porous medium substrate is heated so that the The wax melts into the wax liquid. 3.根据权利要求2所述的芯片上阀门的制造方法,其特征在于,通过打印的方式在所述阀门区域施加所述蜡。3 . The method for manufacturing a valve on a chip according to claim 2 , wherein the wax is applied to the valve region by printing. 4 . 4.根据权利要求1至3中任一项所述的芯片上阀门的制造方法,其特征在于,所述阀门将所述流道分隔为互不连通的反应区域与检测区域。4 . The method for manufacturing a valve on a chip according to claim 1 , wherein the valve divides the flow channel into a reaction area and a detection area that are not connected to each other. 5 . 5.一种微流控芯片,其特征在于,由权利要求1至4中任一项所述的芯片上阀门的制造方法制得。5 . A microfluidic chip, characterized in that, it is obtained by the method for manufacturing an on-chip valve according to any one of claims 1 to 4 . 6.一种基于权利要求5所述的微流控芯片的液体流动控制方法,包括以下步骤:在其中一个区域内添加试剂,当满足设定条件后去除所述阀门区域的所述蜡,以使所述试剂从当前区域流向相邻的另一个区域。6. A liquid flow control method based on the microfluidic chip according to claim 5, comprising the steps of: adding a reagent in one of the regions, removing the wax in the valve region when a set condition is met, to The reagents are flowed from the current region to another adjacent region. 7.根据权利要求6所述的液体流动控制方法,其特征在于,去除所述阀门区域上的所述蜡的方法为:向所述阀门施加可溶解蜡的溶剂。7 . The liquid flow control method of claim 6 , wherein the method for removing the wax on the valve region is: applying a wax-dissolving solvent to the valve. 8 . 8.根据权利要求7所述的液体流动控制方法,其特征在于,所述溶剂为丙酮、异丙醇、甲苯、乙腈或者正己烷。8. The liquid flow control method according to claim 7, wherein the solvent is acetone, isopropanol, toluene, acetonitrile or n-hexane. 9.根据权利要求6所述的液体流动控制方法,其特征在于,所述设定条件为:当前区域内的所述试剂已经完全反应或者完全混合。9 . The liquid flow control method according to claim 6 , wherein the setting condition is: the reagents in the current region have been completely reacted or completely mixed. 10 .
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CN113198552A (en) * 2021-03-29 2021-08-03 苏州深得源健康科技有限公司 Micro-fluidic chip for extracting nucleic acid and preparation method and application method thereof
CN114235793A (en) * 2021-12-09 2022-03-25 汪开继 Noninvasive uric acid instant detection device, detection system and detection method
CN117000323A (en) * 2023-09-22 2023-11-07 北京芯迈微生物技术有限公司 Microfluidic chip

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