CN109603929B

CN109603929B - Manufacturing method of valve on chip, micro-fluidic chip and liquid flow control method

Info

Publication number: CN109603929B
Application number: CN201811330430.4A
Authority: CN
Inventors: 陈华英; 陈畅; 沈小双; 朱永刚
Original assignee: Shenzhen Graduate School Harbin Institute of Technology
Current assignee: Shenzhen Graduate School Harbin Institute of Technology
Priority date: 2018-11-09
Filing date: 2018-11-09
Publication date: 2021-01-05
Anticipated expiration: 2038-11-09
Also published as: CN109603929A

Abstract

The invention relates to the field of microfluidic chips, and discloses a manufacturing method of an on-chip valve, a microfluidic chip and a liquid flow control method, wherein the manufacturing method of the chip comprises the following steps: arranging a flow channel on the porous medium substrate; allowing the wax solution to penetrate into the porous media substrate at the valve region on the flow channel; and forming a valve after the wax liquid completely permeates the porous medium base material and is solidified, and dividing the flow channel into at least two areas which are not communicated with each other by the valve. The invention can also realize the separation and the communication of the flow channel, has simpler structure, convenient operation and low cost and is beneficial to the popularization of the microfluidic chip.

Description

Manufacturing method of valve on chip, micro-fluidic chip and liquid flow control method

Technical Field

The invention relates to the field of microfluidic chips, in particular to the field of microfluidic chips based on porous medium substrates, and specifically relates to a method for controlling the flow of liquid on a microfluidic chip and a microfluidic chip for implementing the method.

Background

The microfluidic chip based on the porous medium substrate, such as a paper-based microfluidic chip, is a novel microfluidic analysis device, and has the characteristics of low cost, simplicity in processing, convenience in use and the like, so that the microfluidic chip has a huge application prospect in the fields of instant diagnosis, food quality control, environmental monitoring and the like, and gradually becomes a research hotspot in the field of microfluidic chips in recent years.

When multiple reactants or reagents participate in the detection, valves are often needed to control the sequence of liquid flows in the flow channels. In addition, in recent years, a method of performing detection on a paper-based chip by using a length method has attracted much attention, and the principle is that after a detection substrate chemically reacts with a specific substance in a reaction region of the chip, a reaction product flows into a microchannel along with a mixed solution and undergoes a color development reaction with a color developing agent on the microchannel. After the solution flows, a color development section with a certain length can be observed in the channel, and then the contents of reaction products and detection substances can be determined. The method has the advantages of simple device and operation, but has limitation on accuracy, and in the detection process involving two or more reactions, the reactants often flow into the microfluidic channel without complete reaction, thereby influencing the detection result. The drain valves are arranged in the reaction area and the microfluidic channel, so that the flow of the substrate solution can be controlled, the substrate can fully react in the reaction area, and the completely reacted solution enters the microfluidic channel to perform subsequent reaction. Therefore, the control of liquid flow in paper-based chips by using valves is a key technology for the application of the paper-based chips in the detection field.

The valve is used for controlling the flow of the reaction solution, ensuring the complete reaction of the detection object and opening the valve after the first step reaction is finished so that the solution can smoothly enter the channel. The key is to ensure the closing and opening of the valve. In the prior art, various valve structures exist, such as a pop-up three-dimensional paper chip detection device, the effect of valve closure is achieved by folding and unfolding, and the flow path of a detected object is changed. For example, the method of controlling the flow by using an electric textile material as a valve, the solution of the detection object can not flow through the textile material under normal conditions, and the solution can permeate the fabric by applying a potential between the solution and the valve to achieve the effect of opening the valve.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention provides a manufacturing method of an on-chip valve, which is used for solving the problems of complex structure and high cost of the conventional valve device.

The invention also provides a micro-fluidic chip and a liquid flow control method.

The technical scheme adopted by the invention for solving the technical problems is as follows:

a method of manufacturing a valve on a chip, comprising the steps of:

arranging a flow channel on the porous medium substrate;

allowing the wax solution to penetrate into the porous media substrate at the valve region on the flow channel;

and forming a valve after the wax liquid completely permeates the porous medium base material and is solidified, and dividing the flow channel into at least two areas which are not communicated with each other by the valve.

As a further improvement to the above, the wax is applied to the valve area on the porous media substrate and then the porous media substrate is heated to melt the wax into a wax liquid.

As a further improvement of the above solution, the wax is applied in the valve area by printing.

As a further improvement mode of the scheme, the valve divides the flow channel into a reaction area and a detection area which are not communicated with each other.

A micro-fluidic chip is prepared by the manufacturing method of the valve on the chip.

A liquid flow control method based on the microfluidic chip comprises the following steps: adding reagent in one zone, and removing wax in the valve zone when set conditions are met so that the reagent flows from the current zone to another adjacent zone.

As a further improvement of the above solution, the method for removing the wax in the valve area comprises: a solvent that dissolves the wax is applied to the valve.

As a further improvement of the scheme, the solvent is acetone, isopropanol, toluene, acetonitrile or n-hexane.

As a further improvement of the above, the setting conditions are: the reagents in the current zone have either fully reacted or fully mixed.

The invention has the beneficial effects that:

compared with the prior art, the invention can also realize the blocking and communication of the flow channel, has simpler structure, convenient operation and low cost, and is beneficial to the popularization of the microfluidic chip.

Drawings

The invention is further illustrated with reference to the following figures and examples.

FIG. 1 is a flow chart of an embodiment of a method of manufacturing a microfluidic chip according to the present invention;

FIG. 2 is a front view of an embodiment of a microfluidic chip according to the present invention;

FIG. 3 is a bar graph of the volumes required for different solvents to fully open the valve;

FIG. 4 is a bar graph of the time required for different solvents to completely dissolve the valve;

fig. 5 is a schematic illustration of the effect of valve transparency on valve barrier effect.

Detailed Description

The conception, the specific structure and the technical effects of the present invention will be clearly and completely described in conjunction with the embodiments and the accompanying drawings to fully understand the objects, the schemes and the effects of the present invention. It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict.

It should be noted that, unless otherwise specified, when a feature is referred to as being "fixed" or "connected" to another feature, it may be directly fixed or connected to the other feature or indirectly fixed or connected to the other feature. Furthermore, the descriptions of up, down, left, right, front, rear, etc. used in the present invention are only relative to the positional relationship of the respective components of the present invention with respect to each other in the drawings.

Furthermore, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. The terminology used in the description herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any combination of one or more of the associated listed items.

The invention discloses a method for manufacturing a micro-fluidic chip with a wax valve and a liquid flow control method based on the micro-fluidic chip, which mainly have the conception that the wax valve penetrating into a porous medium base material is arranged on a flow channel, and when the valve exists, the flow channel is divided into at least two areas so as to realize the complete reaction or the complete mixing of a reagent in one area; and the wax valve can be quickly removed through the organic solvent, so that the communication between the areas is realized, the reagent enters the next area to participate in the reaction, and the detection of the reagent is realized. Compared with the prior art, the invention can also realize the blocking and communication of the flow channel, has simpler structure, convenient operation and low cost, and is beneficial to the popularization of the microfluidic chip.

The following description will be made by specific examples.

Referring to fig. 1, a flow chart of an embodiment of the manufacturing method of the microfluidic chip of the present invention is shown, which comprises the following specific steps:

step one

The flow channel is arranged on the porous medium substrate, the porous medium substrate in this embodiment adopts filter paper, and in this embodiment, the filter paper on which the flow channel is already prepared may be directly adopted, or the step of preparing the flow channel on the filter paper may be included. In an embodiment of the present invention, a curable liquid hydrophobic material is applied on a porous medium substrate, and after the liquid hydrophobic material completely permeates the porous medium substrate, a curing process is performed, so that a hydrophobic channel wall is formed after the liquid hydrophobic material is cured, and the channel wall surrounds the hydrophobic channel wall to form a channel.

Step two

Wax liquid is applied to the valve area of the flow channel and allowed to penetrate into the filter paper at the valve area located above the flow channel. Specifically, in this embodiment, a wax printer is first used to print the wax in a molten state on the valve area, and then the valve area is heated, so that the wax solidified in the valve area is melted again to obtain the wax liquid. In addition, the solid wax can also be dissolved in a volatilizable solvent to form a solution, then the solution is coated on the valve area, the solid wax can be attached to the filter paper after the solvent is volatilized, and finally the valve area is heated, so that the solid wax in the valve area is melted to obtain the wax liquid.

Step three

After the wax liquid completely permeates the filter paper, the wax liquid is cooled and solidified, so that a wax valve can be formed in the flow channel, and the wax valve divides the flow channel into at least two areas which are not communicated with each other. By adding more wax valves, the flow path can be divided into more disconnected regions.

Step four

One side of the filter paper is plastically packaged to prevent leakage of the reagent solution.

Referring to fig. 2, a front view of an embodiment of the microfluidic chip according to the present invention manufactured based on the above method is shown. As shown in the figure, the microfluidic chip includes a porous medium substrate 1, a channel wall 2 and a valve area 3, the channel wall 2 surrounds to form a channel, and the valve area 3 divides the channel into a reaction area 101 and a detection area 102 which are not communicated with each other.

The invention also discloses a liquid flow control method based on the microfluidic chip, which comprises the following steps: reagent is added to the reaction area 101, and when the reagents in the reaction area 101 have completely reacted or completely mixed, the wax in the valve area 3 is removed, and the reagents can flow from the reaction area 101 to the detection area 102 for detection.

The method for removing the valve in this embodiment is to apply a solvent capable of dissolving the wax to the valve, and the solvent may be acetone, isopropanol, toluene, acetonitrile or n-hexane. Referring to fig. 3, the dissolving effect of different solvents on the valve is shown. As shown, the same size valve was opened and the amount of toluene and acetonitrile used was minimal.

Referring to fig. 4, a time diagram of different solvent dissolution valves is shown. Toluene has the shortest dissolution rate under the premise of the same dosage, so that toluene is preferably used as a solvent for removing the valve in view of shortening the dissolution time of wax in the valve area.

Referring to fig. 5, a schematic diagram illustrating the effect of the transparency of the valve of the present invention on the barrier effect of the valve is shown. Before the valve is prepared, a design drawing needs to be drawn, and then the valve is printed on the porous medium substrate according to a pattern on the design drawing, wherein each area on the design drawing has different transparency, the more transparent areas print less wax, namely the transparency (also called valve transparency) of the design drawing is inversely proportional to the amount of the printed wax, as shown in the figure, the less wax is printed, the less wax is in the valve area, the weaker barrier capability of the valve is, and the less solvent volume is needed for dissolving the valve; conversely, the more wax is printed and the more wax is in the valve area, the greater the barrier capability of the valve and the greater the volume of solvent required to dissolve the valve. On the other hand, the blocking capability of the valve is also influenced by the length of the valve, the longer the length of the valve, the stronger the blocking capability, i.e. the longer the valve, the less amount of wax is allowed, however the amount of wax has a lower limit, i.e. the amount of wax is less than the set value, even if the length of the valve is increased, the sufficient blocking capability cannot be guaranteed.

With reference to fig. 2, the usage in this embodiment is as follows: firstly, a starch indicator is dripped into a detection area 102 of the microfluidic chip, and reactants of p-toluenesulfonic acid and potassium iodide are dripped into two non-overlapping small areas in a reaction area 101 to ensure that two solvents are not contacted. The reaction region 101 is separated from the detection region 102 by a valve region 3. During detection, a potassium iodate sample is dripped into the reaction area 101, the potassium iodate sample and reactants in the reaction area 101 fully react to generate triiodide anions, then wax in the valve area 3 is removed, and the sample with the triiodide anions flows into the detection area 102 to react with the starch indicator to develop color. If no valve is arranged, the potassium iodate sample flows into the detection area 102 before completely reacting, so that the amount of the generated triiodide anions is obviously reduced, and the length of the color development of the reaction with the starch indicator is obviously reduced, thereby influencing the detection effect.

While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

Claims

1. A liquid flow control method of a microfluidic chip comprises the following steps:

arranging a flow channel on the porous medium substrate;

dissolving solid wax in a volatilizable solvent to form a solution, coating the solution on a valve area on the flow channel, volatilizing the solvent to enable the solid wax to be attached to the porous medium substrate, heating the valve area to enable the solid wax in the valve area to be melted to form a wax liquid, and finally enabling the wax liquid to permeate into the porous medium substrate at the valve area;

forming a valve after the wax liquid completely permeates the porous medium base material and is solidified, wherein the valve divides the flow channel into at least two areas which are not communicated with each other;

adding a reagent in one zone, and applying toluene capable of dissolving wax to the valve to remove the wax in the valve zone when a set condition is met so that the reagent flows from the current zone to another adjacent zone.

2. The liquid flow control method of a microfluidic chip according to claim 1, wherein the valve divides the flow channel into a reaction region and a detection region which are not communicated with each other.

3. The method for controlling liquid flow of a microfluidic chip according to claim 1, wherein the setting conditions are: the reagents in the current zone have either fully reacted or fully mixed.