CN112295615A - Micro-fluidic valve and micro-fluidic chip - Google Patents
Micro-fluidic valve and micro-fluidic chip Download PDFInfo
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- CN112295615A CN112295615A CN202010413705.1A CN202010413705A CN112295615A CN 112295615 A CN112295615 A CN 112295615A CN 202010413705 A CN202010413705 A CN 202010413705A CN 112295615 A CN112295615 A CN 112295615A
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
Abstract
The invention relates to the technical field of microfluidics, in particular to a microfluid control valve and a microfluidic chip. The micro-fluid control valve comprises a pipeline and a micro-valve, wherein the micro-valve is positioned in the pipeline, one end of the micro-valve is connected with the pipeline, the micro-valve is in a convex shape, the height of the micro-valve is lower than that of the pipeline, at least one side of the pipeline is made of elastic materials, the other end of the micro-valve is in contact with the pipeline when external force is applied, and the pipeline is closed. The invention has the advantages of simple structure, small volume, few chip assembly steps, easy production and low cost, can realize the closing control of the valve switch by relying on the elastic deformation of the material of the chip without adding an additional film, has small flow interference on liquid in the pipeline due to small deformation of the pipeline when the valve is closed, and has wide application prospect.
Description
Technical Field
The invention relates to the technical field of microfluidics, in particular to a microfluid control valve and a microfluidic chip with the microfluid control valve.
Background
The microfluid control is the operation core of the microfluidic chip, and the processes of sample introduction, mixing, reaction, detection and the like related to the chip are all required to be completed in controllable fluid, so that the microfluidic control valve is one of the main components of the microfluidic system, and the microfluidic controls the fluid through the valve to enable the fluid to flow in a specified direction.
Microfluidic control valves are currently divided into passive valves and active valves. Passive valves do not require external power or control, and can change the state of the valve by changing the flow direction and pressure of the fluid, mainly represented by a two-wafer check valve and a gel valve. Active valves, also known as active valves, operate on the principle of utilizing an external actuating force to open and close the valve. It has a variety of actuation mechanisms including pneumatics, thermal expansion, piezoelectric effects, shape memory alloys, electrostatics, electromagnetism, etc. The most used valves mainly include: phase change valves, mechanical valves, pneumatic valves, and the like.
The phase change valve chip utilizes heating equipment such as laser to heat the easy phase change material pre-installed in the chip, and solid-state material melts and flows into the main pipeline, and blocks the runner after cooling.
The traditional mechanical valve core piece presses a lower layer film through the rotation of a mechanical part, and the film is deformed to block a pipeline. On one hand, if the chip itself is small in size, the mechanical valve size must be minimized to integrate mechanical components into the chip as many as possible, which requires a high machining process and increases the manufacturing cost. On the other hand, if the mechanical valve is too large, the advantage of micro-volume of the chip itself is lost.
Traditional pneumatic valve chip need embedded one deck deformable film, and external pump passes through the gas flow channel in the air flue chip, sends into gas to valve department, and the film receives gas pressure to take place to deform, plugs up the pipeline, realizes that the switch of valve is closed. The mechanical valve and the pneumatic valve both need to cover a layer of chip outside the film, because the film is too thin and easy to break, the air permeability causes poor sealing performance, and the chip layer needs to be additionally added for protection, so that the sealing step of a chip finished product is increased, and the process is complicated.
Disclosure of Invention
It is an object of the present invention to provide a microfluidic control valve.
The micro valve is positioned in the pipeline, one end of the micro valve is connected with the pipeline, the micro valve is in a convex shape, the height of the micro valve is lower than that of the pipeline, at least one side of the pipeline is made of elastic materials, the other end of the micro valve is in contact with the pipeline when external force is applied, and the pipeline is closed.
It is a further object of the present invention to provide a microfluidic chip comprising a microfluidic control valve as described above.
The invention has the beneficial effects that:
1. the micro valve adopts a convex design, so that the pipeline can be closed only by a small amount of deformation, the pipeline sealing is ensured, the accurate control of fluid is realized, the requirement on the material of the pipeline is reduced, and more materials can be applied to the micro-fluidic field.
2. The invention has small deformation of the pipeline when the valve is closed, small flow interference to liquid in the pipeline, no tilting deformation of other areas of the pipeline caused by the deformation of the valve, is especially suitable for the field of molecular detection, and ensures the stability of experimental results.
3. Compared with the traditional pneumatic valve and phase change valve, the micro-valve switching device can realize micro-valve switching without external power supply equipment and a complex control system, greatly reduces the overall use cost, is simple and convenient to operate, and has no limit on application scenes; compared with the traditional mechanical valve, the preparation process is simpler, a plurality of micro valves are easier to integrate on a smaller chip, and the cost is lower.
4. The invention has the advantages of few chip assembly steps, easy production and low cost, does not need to add an additional film, and can realize the closing control of the valve switch by depending on the elastic deformation of the material of the chip.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a schematic cross-sectional view of a microfluidic control valve according to example 1 of the present invention when the valve is open;
FIG. 2 is a schematic cross-sectional view of a microfluidic control valve according to example 1 of the present invention when the valve is closed;
FIG. 3 is a schematic structural view of example 2 of the present invention;
FIG. 4 is a graph showing the results of detection of a positive sample in example 3 of the present invention.
The figures are labeled as follows: 1. a sample inlet; 2. a first microfluidic control valve; 3. a first reaction chamber; 4. a second microfluidic control valve; 5. a second reaction chamber; 6. a micro valve; 7. one side of the pipeline; 8. the other side of the pipeline.
Detailed Description
Reference will now be made in detail to embodiments of the invention, one or more examples of which are described below. Each example is provided by way of explanation, not limitation, of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. For instance, features illustrated or described as part of one embodiment, can be used on another embodiment to yield a still further embodiment.
It is therefore intended that the present invention cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents. Other objects, features and aspects of the present invention are disclosed in or are apparent from the following detailed description. It is to be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only, and is not intended as limiting the broader aspects of the present invention.
As used herein, the term "conduit" is a conduit that carries a fluid (such as steam, gas, water, or oil) from one place to another.
As used herein, the term "resilient material" is a material that recovers its original shape after removal of an external force.
It is an object of the present invention to provide a microfluidic control valve.
The micro valve is positioned in the pipeline, one end of the micro valve is connected with the pipeline, the micro valve is in a convex shape, the height of the micro valve is lower than that of the pipeline, at least one side of the pipeline is made of elastic materials, the other end of the micro valve is in contact with the pipeline when external force is applied, and the pipeline is closed.
In some preferred embodiments, the microvalve cross-sectional width is equal to the conduit width.
In some preferred embodiments, the cross section of the pipeline is any one or more of a rectangle, a circle and an oblate.
In some preferred embodiments, the tube is made of an elastic material on one side and made of any one or two of the following mixed materials, such as silicon, ceramic, glass, plastic, etc., wherein the plastic comprises: polyamide (PA), polybutylene terephthalate (PBT), Polycarbonate (PC), Polyethylene (PE), polymethyl methacrylate (PMMA), Polyoxymethylene (POM), polypropylene (PP), polystyrene diethyl ether (PPE), Polystyrene (PS), Polysulfone (PSU), polyether ether ketone (PEEK), Polydimethylsiloxane (PDMS), and the like.
In some preferred embodiments, the microvalve is cylindrical.
In some preferred embodiments, the microvalve height is 50% to 90% of the tube height.
In some preferred embodiments, the elastomeric material is a polymer.
Among them, polymers are classified into elastomers, thermoplastics, and thermosets.
Elastomers are composed of crosslinked polymer chains that are typically entangled, can stretch or compress when an external force is applied, and recover to an original shape when the external force is withdrawn, which exhibits weaker intermolecular forces, has a lower young's modulus and higher strain to failure than other materials.
In some preferred embodiments, the polymer is Polydimethylsiloxane (PDMS), Thermosetting Polyester (TPE), polyethylene glycol diacrylate (PEGDA), perfluoro-compound (PFEP/PFA/PFPE), Polyurethane (PU).
The flow control principle of the micro-fluid control valve is that elastic deformation generated by the action of external force on a pipeline is attached to a micro-valve to cut off micro-fluid.
According to a second aspect of the invention, there is also provided a microfluidic chip comprising a microfluidic control valve as described above.
In some preferred embodiments, the microfluidic chip further comprises a reaction module, the reaction module comprising the microfluidic control valve, a deformable reaction chamber in communication with the microfluidic control valve.
In some preferred embodiments, the number of the microfluidic control valves is n, and the number of the deformable reaction chambers is n + m, where n is an integer > 0, and m is an integer ≧ 0. The reaction module is formed by selecting different numbers of microfluid control valves and deformable reaction chambers, and flow control of different requirements can be realized.
By adopting the reaction module, the following effects can be achieved: the sealing performance of the cavity of the reaction cavity is improved, and the cross reaction risk is reduced; the two ends of the reaction cavity are provided with the microfluid control valves to realize controllable closing, so that the evaporation of liquid in the cavity in the heating process can be obviously reduced, and the performance of a detection product with heating requirements can be obviously improved; the accurate driving of the flowing direction of the fluid and the accurate positioning of the position are realized, and the quantitative distribution of the liquid is realized; but whole manual control reaction process satisfies portable equipment user demand more, cooperates special manual tamp, better realizes the marketization and uses.
In some preferred embodiments, the microfluidic chip includes a sample inlet, a first microfluidic control valve of the reaction module, a first reaction chamber of the reaction module, a second microfluidic control valve of the reaction module, a second reaction chamber of the reaction module, a detection region, and an air outlet, which are sequentially connected.
When the microfluid chip is used, a sample to be detected is added into the microfluid chip from the sample inlet, and the sample to be detected flows into the first reaction cavity and then extrudes the second microfluid control valve, the microfluid control valve is displaced in the vertical direction to plug the pipeline, so that the sample is intercepted, and then the first microfluid control valve is extruded, so that the first reaction cavity is subjected to sealing reaction, and the risk of liquid volatilization by heating or reaction cross is reduced. After the reaction is finished, the valve of the second microfluid control valve is opened, the first reaction cavity is extruded, liquid enters the second reaction cavity, the next-stage reaction is carried out, and different numbers of microfluid control valves and reaction cavities are added according to conditions, so that different requirements are met. After the reaction is finished, the second reaction cavity is extruded, and the liquid enters the detection area to be detected.
When the microfluidic chip is a nucleic acid detection microfluidic chip, the detection display method may be different methods, such as a colloidal gold method, a fluorescence method, a color change reaction, a hybridization method, or a microsphere method.
The invention is further described with reference to the drawings and the following detailed description, which are not intended to limit the invention in any way. It will be appreciated by those skilled in the art that various other changes, modifications, substitutions, combinations, and omissions may be made in the form and detail of the invention without departing from the spirit and scope of the invention.
EXAMPLE 1A microfluidic control valve
The micro valve comprises a pipeline and a micro valve 6, wherein one side 7 of the pipeline is made of elastic materials such as pdms or transparent silica gel, the other side 8 of the pipeline is made of hard materials such as pmma and resin materials, and the two sides of the pipeline are attached by double-sided adhesive.
The micro valve 6 is positioned in the pipeline and is in a column shape, the width of the section of the micro valve 6 is equal to the width of the pipeline, one end of the micro valve is fixedly connected with the pipeline, and the height of the micro valve is 90% of the height of the pipeline. When external force is applied, the other end of the micro valve 6 is in contact with the pipeline, the pipeline is closed, the liquid in the pipeline is intercepted, and the liquid in the pipeline restores to flow when the external force is removed.
Example 2A microfluidic chip
As shown in fig. 3, the device comprises a sample inlet 1, a first microfluidic control valve 2 of the reaction module, a first reaction chamber 3 of the reaction module, a second microfluidic control valve 4 of the reaction module, a second reaction chamber 5 of the reaction module, a detection region and an air outlet which are sequentially communicated. The structure of the microfluidic control valve is the same as that of example 1.
The chip channel depth is 1000 microns and the width is 600 microns.
(1) Chip fabrication
A chip bottom layer structure integrating a sample inlet 1, a first micro-fluid control valve 2 of a reaction module, a first reaction cavity 3 of the reaction module, a second micro-fluid control valve 4 of the reaction module, a second reaction cavity 5 of the reaction module, a detection area and an air outlet is made of resin materials.
The top layer of the chip is made of an elastic material such as pdms or transparent silica gel, and the top layer and the bottom layer of the chip are attached by double-sided adhesive tape.
The chip sealing steps are few, the production is easy, and the cost is low. Compared with the valve device which is directly contacted by controlling the upper and lower parallel base layer films in the prior report, the valve switch closing control can be realized by depending on the elastic deformation of the self materials of the upper and lower layers of the chip without adding an additional film.
(2) Microfluidic control valve effect verification
Experiment one: the 100 qualified microfluidic chips are prepared by the process, and the microfluidic chips are divided into two groups, namely an experimental group and a control group at random
The specific experimental method is as follows: injecting a certain volume of liquid into the first reaction cavity 3 through the chip sample inlet 1, and applying a certain external force to press the first microfluid control valve 2;
experimental groups: and applying a certain external force to press the right upper part of the second microfluidic control valve 4 to extrude the liquid in the first reaction chamber 3, and observing the liquid flowing condition at the second microfluidic control valve 4.
Control group: and applying a certain external force to press a certain position (namely a position not right above the second microfluidic control valve 4) between the second microfluidic control valve 4 and the connecting pipeline of the first reaction cavity 3, so as to extrude the liquid in the first reaction cavity 3 and observe the liquid flowing condition at the second microfluidic control valve 4.
The experimental results are as follows: the liquid of the experimental group did not flow through the second microfluidic control valve 4; the control liquid passes through the second microfluidic control valve 4 and flows to the second reaction chamber 5.
Experimental results prove that the sealing performance of the micro-fluid control valve is better and the interception effect is obvious by adding the convex micro-valve 6 structure.
Experiment two: the bottom material of the chip is changed into the same material as the upper layer elastic material to be directly attached to the chip, and the experiment is repeated to obtain the same experiment result.
EXAMPLE 3 use case of a microfluidic chip for nucleic acid detection
When the microfluidic chip is applied to nucleic acid detection, the structure of the microfluidic chip for nucleic acid detection is the same as that of the embodiment 2. In this embodiment, the present invention is a microfluidic chip for detecting African Swine Fever Virus (ASFV), and specific amplification primers and grnas of the microfluidic chip are designed for the African Swine Fever Virus (ASFV).
The design of the convex micro valve of the micro-fluidic chip ensures that the pipeline can be closed only by a small amount of deformation, ensures the pipeline sealing, and avoids the influence on the experimental result caused by the volatilization of liquid in the reaction cavity to other areas in the chip during heating. Especially in the pipeline with a large depth-to-width ratio, the intercepting sealing effect is more obvious.
The first reaction chamber is pre-filled with a freeze-dried reagent for isothermal amplification, and the reagent composition is as follows: 120ng/ul of Ys40 UvsX, 60ng/ul of Ys40 UvsaK, 300ng/ul of T4 gp32, 200uM of dNTP, 500nM of Primers, 2mM of DTT, 50mM of inositol, 200ng/ul of Ckase, 1.5mM of ATP, 14mM of MgAc, 2U of Bsu, 100mM of Tris-acetic acid, 50mM of sodium acetate and 5% of PEG 20000.
The second reaction cavity is pre-filled with a freeze-dried reagent of a detection system of CRISPR/Cas12a, and the reagent composition is as follows: scCas12a 45nM, gRNA 22.5nM, digoxin and biotin labeled nucleic acid probe 100nM, Tris 20 mM, NaCl 60 mM, MgCl 210 mM, pH 7.3.
A detection step of the microfluidic detection chip:
(1) the sample to be detected is added into the detection chip from the sample inlet, the sample to be detected flows into the first reaction cavity, the second microfluid control valve is extruded, the microfluid control valve is displaced in the vertical direction to plug the pipeline, the sample is intercepted, and then the first microfluid control valve is extruded, so that the sample to be detected and the pre-installed reagent in the first reaction cavity are subjected to sealing reaction, and the risk of heating volatilization or reaction cross risk of the sample to be detected is reduced.
(2) After the reaction is finished, opening a valve of a second micro-fluid control valve, extruding the first reaction cavity, and allowing the sample to be detected to enter the second reaction cavity to react with a reagent pre-filled in the second reaction cavity;
(3) after the reaction is finished, the second reaction cavity is extruded, so that the sample to be detected enters the detection area for detection.
(4) The detection area is prepared by using immunochromatographic test paper, and the result of the detection area is judged: the colloidal gold particles mark the mouse digoxin antibody; the detection line is a T line and marks streptavidin; the control line, i.e., line C, labeled goat anti-mouse antibody. Analyzing the result, wherein if the blood sample contains African swine fever virus under the condition that the C line of the detection chip is developed, the T line of the detection chip is not developed, and the result is judged to be positive; if the African swine fever virus does not exist, the T line of the detection chip is developed, and the result is judged to be negative.
The detection result shows that the detection line and the control line of the negative sample appear, and the detection line and the control line are correspondingly negative; the result of the positive sample is shown in FIG. 4, in which the control line appeared but the detection line disappeared, and the result is positive. The result shows that the detection chip can accurately detect the virus nucleic acid in the African swine fever sample.
Claims (8)
1. The micro-fluid control valve is characterized by comprising a pipeline and a micro-valve, wherein the micro-valve is positioned in the pipeline, one end of the micro-valve is connected with the pipeline and is in a convex shape, the height of the micro-valve is lower than that of the pipeline, at least one side of the pipeline is made of an elastic material, the other end of the micro-valve is in contact with the pipeline when external force is applied, and the pipeline is closed.
2. The microfluidic control valve of claim 1, wherein the microvalve cross-sectional width is equal to the conduit width.
3. The microfluidic control valve of claim 1, wherein the elastomeric material is a polymer.
4. The microfluidic control valve of claim 1, wherein the elastomeric material is polydimethylsiloxane or transparent silicone.
5. The microfluidic control valve of claim 1, wherein the microvalve height is 50% -95% of the conduit height.
6. A microfluidic chip comprising the microfluidic control valve of any one of claims 1-4.
7. The microfluidic chip of claim 6, further comprising a reaction module comprising said microfluidic control valve, a deformable reaction chamber in communication with said microfluidic control valve.
8. The microfluidic chip of claim 6 or 7, comprising a sample inlet, a first microfluidic control valve, a first reaction chamber, a second microfluidic control valve, a second reaction chamber, a detection region, and a gas outlet, which are sequentially connected.
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| CN202010413705.1A CN112295615A (en) | 2020-05-15 | 2020-05-15 | Micro-fluidic valve and micro-fluidic chip |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113528295A (en) * | 2021-09-10 | 2021-10-22 | 中国医学科学院北京协和医院 | Microfluidic chip capable of carrying out multi-step time sequence reaction, microfluidic method and application thereof |
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