Valve structure, chip, processing method and system

Abstract

The present application belongs to the field of chip processing, and particularly relates to a valve structure, a chip, a processing method and a system. The valve structure comprises: a liquid outlet layer located between a liquid storage cavity and a micro-pipe, and provided with a liquid outlet; a waterproof film for preventing liquid in the liquid storage cavity from penetrating out of the liquid outlet; and a water-soluble film provided between the waterproof film and the micro-pipe, and used for supporting the waterproof film. The liquid outlet layer provided with the liquid outlet and located between the liquid storage cavity and the micro-pipe can control the liquid flowing from the liquid storage cavity to the micro-pipe. The waterproof film is used for preventing the liquid in the liquid storage cavity from penetrating out of the liquid outlet, so as to prevent uncontrolled penetration. The water-soluble film provided between the waterproof film and the micro-pipe can support the waterproof film, so as to prevent the waterproof film from being abnormal.

Description

Technical Field

[0001] This invention belongs to the field of chip manufacturing, and particularly relates to a valve structure, chip, manufacturing method and system. Background Technology

[0002] Microfluidics refers to the science and technology involved in systems that use microchannels (tens to hundreds of micrometers in size) to process or manipulate tiny fluids (volumes ranging from nanoliters to attoliters). It is an emerging interdisciplinary field involving chemistry, fluid physics, microelectronics, new materials, biology, and biomedical engineering. Due to their miniaturization and integration characteristics, microfluidic devices are often called microfluidic chips, also known as lab-on-a-chip and micro-total analytical systems. One of the key characteristics of microfluidics is the unique fluid properties exhibited at the microscale, such as laminar flow and droplet flow. Utilizing these unique fluid phenomena, microfluidics can achieve a range of microfabrications and micromanipulations that are difficult to accomplish using conventional methods. Currently, microfluidics is considered to have enormous development potential and broad application prospects in biomedical research. For example, POCT (point-of-care testing) refers to clinical testing performed next to the patient and at the bedside, which is not necessarily performed by a clinical laboratory technician. It is a new type of method that allows for immediate analysis at the sampling site, eliminating the complex processing procedures required for specimen testing in the laboratory and quickly obtaining test results.

[0003] Existing POCT microfluidic chips cannot store liquid within the chip and release it automatically, which is not conducive to the development of self-service testing. The bottleneck lies in the lack of suitable microvalves. Summary of the Invention

[0004] To address or improve the aforementioned problems, this invention provides a valve structure and system for a microfluidic chip, the specific technical solution of which is as follows: This invention provides a valve structure suitable for microfluidic chips with a liquid storage chamber and microchannels, comprising: A liquid outlet layer is located between the liquid storage chamber and the microchannel, and is provided with a liquid outlet. A waterproof membrane is used to prevent liquid in the storage chamber from seeping out of the outlet; A water-soluble membrane is disposed between the waterproof membrane and the microchannels to support the waterproof membrane.

[0005] Preferably, the water-soluble membrane is made of polyvinyl alcohol and / or polyethylene oxide; the waterproof membrane is made of perylene and PMMA.

[0006] The present invention provides a microfluidic chip having the above-mentioned valve structure.

[0007] This invention provides a method for processing a valve structure, applicable to the aforementioned valve structure, comprising: The water-soluble membrane is laid on a flat plate, and a waterproof membrane with a thickness of nanometers is vapor-deposited on the surface of the water-soluble membrane to form a composite membrane. The flat plate is connected to the waterproof material board, so that the composite membrane is adhered to the waterproof material board with through holes, and then the flat plate is removed; The liquid storage cavity is formed by the through holes of the waterproof material plate and the composite membrane.

[0008] Preferably, the liquid storage chamber is used to store liquid; correspondingly, the method further includes: when filling the liquid storage chamber, placing a biodegradable capsule that can release gas.

[0009] Preferably, the method further includes: trimming the composite membrane.

[0010] Preferably, the biodegradable capsule is provided with a reactant that can react with the liquid stored in the reservoir to generate a gas.

[0011] Preferably, the surface of the water-soluble film facing the flat plate is further coated with an additional waterproof membrane, the additional waterproof membrane having a perforated area.

[0012] This invention provides a valve structure processing system, comprising: The first unit is used to lay the water-soluble membrane on a flat plate and vapor-deposit a waterproof membrane with a nanometer-thickness on the surface of the water-soluble membrane to form a composite membrane. The second unit is used to connect the flat plate to the waterproof material board, so that the composite membrane is bonded to the waterproof material board with through holes, and then the flat plate is removed; The third unit is used to form the liquid storage cavity with the composite membrane through the through holes of the waterproof material plate.

[0013] The beneficial effects of the present invention are as follows: by providing an outlet layer with an outlet between the liquid storage chamber and the microchannel, the liquid flowing from the liquid storage chamber to the microchannel can be controlled; a waterproof membrane is used to prevent the liquid in the liquid storage chamber from seeping out from the outlet, so as to prevent uncontrolled seepage; a water-soluble membrane provided between the waterproof membrane and the microchannel can support the waterproof membrane and prevent the waterproof membrane from malfunctioning. Attached Figure Description

[0014] Figure 1 This is a schematic diagram of the valve structure according to the present invention; Figure 2 This is a valve schematic diagram according to the present invention; Figure 3This is a schematic diagram of a three-layer valve according to the present invention.

[0015] Explanation of key figure labels: 1-Liquid storage chamber, 2-Liquid outlet layer, 3-Liquid outlet, 4-Waterproof membrane, 5-Water-soluble membrane, 6-Microchannel, 41-Waterproof film, 51-Degradable thick film, 11-Liquid storage, 61-Sample, 7-Waterproof membrane pattern, 8-Kuaikou area. Detailed Implementation

[0016] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0017] It should be understood that, when used in this specification and the appended claims, the terms "comprising" and "including" indicate the presence of the described features, integrals, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integrals, steps, operations, elements, components and / or collections thereof.

[0018] It should also be understood that the terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to limit the invention. As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms unless the context clearly indicates otherwise.

[0019] It should also be further understood that the term "and / or" as used in this specification and the appended claims refers to any combination of one or more of the associated listed items and all possible combinations, and includes such combinations.

[0020] In order to solve or improve the problems mentioned in the background art, the following are proposed: Figure 1 The valve structure shown is suitable for microfluidic chips with a liquid storage chamber 1 and a microchannel 6, and includes: Liquid outlet layer 2 is located between the liquid storage chamber and the microchannel, and is provided with liquid outlet 3; Waterproof membrane 4 is used to prevent liquid in the storage cavity from seeping out from the outlet; A water-soluble membrane 5 is disposed between the waterproof membrane and the microchannel to support the waterproof membrane.

[0021] This embodiment proposes a normally closed microvalve that can be integrated into microfluidic chips used in POCT and other fields, featuring "sample flow, unidirectional triggering, and automatic delayed opening." A composite membrane consisting of a waterproof thin film and a water-soluble thick film is used as the valve body material. The waterproof membrane side of the valve body faces the liquid reservoir to prevent leakage; the water-soluble thick film provides sufficient support to ensure the valve body remains intact and firmly seals the reservoir during chip storage. The water-soluble membrane side of the valve body faces the sample flow channel (i.e., microchannel) of the chip. When the sample flows through, the water-soluble thick film is wetted by the sample and begins to degrade, causing the waterproof membrane to rupture due to lack of support after a certain period, releasing the reservoir into the sample flow channel. The terms "thin film" and "thick film" only describe relative thickness to indicate functionality; specifically, a film thickness less than a certain threshold is considered a thin film, and vice versa.

[0022] like Figure 2 The valve schematic diagram shows a composite membrane consisting of a waterproof membrane 41 and a biodegradable thick membrane 51 superimposed on top of each other as the valve body material. The waterproof membrane side of the valve body faces the liquid reservoir 11 to prevent liquid leakage; the biodegradable thick membrane provides sufficient support to ensure the valve body remains intact and firmly seals the liquid reservoir during chip storage. The biodegradable membrane side of the valve body faces the sample flow channel of the chip. When sample 61 flows through, the biodegradable thick membrane is wetted by the sample and begins to degrade. After a certain period, the waterproof membrane ruptures due to lack of support, releasing the liquid reservoir into the sample flow channel.

[0023] The water-soluble membrane is made of polyvinyl alcohol and / or polyethylene oxide; the waterproof membrane is made of perylene and PMMA.

[0024] To verify the implementation of the sample flow, unidirectional triggering, and automatic delay-based opening function, a sample simulant (commercially purchased fetal bovine serum) was dripped into the inlet of the microfluidic chip. The flow of the sample through the bilayer membrane region and its subsequent flow state were observed under a microscope. The focus was on observing the process of the sample wetting and dissolving the membrane (i.e., the biodegradable membrane), causing it to dissolve, leading to the waterproof membrane bearing the pressure of the stored liquid, and ultimately rupturing to release the stored liquid. The duration of this process was recorded. Because the waterproof membrane does not necessarily open only after the hydrolytic membrane has completely dissolved, the experiment emphasized observing the morphology of the waterproof membrane and the remaining hydrolytic membrane at the time of rupture. This process can be simulated using finite element method (FEM) simulation to understand the key influencing factors affecting this morphology, thereby optimizing the design to achieve the ideal opening state of the microvalve: sudden opening, smooth release of the stored liquid, and entry into the microchannel at a relatively high flow rate and velocity.

[0025] To achieve the above functions, materials with biocompatibility, low water absorption, low vapor permeability, and easy deposition processing are required. The selection of water-soluble materials needs to meet the following requirements: (1) high saturation solubility, requiring only a small amount of sample to dissolve, thereby reducing sample loss; (2) a hydrophilic surface and a water-absorbing internal pore structure, so that the surface can adsorb a certain amount of water when the sample flows through, and gradually penetrate into the interior through the pore capillary structure; (3) a stable and controllable dissolution rate; and (4) biocompatibility, that is, the degradation products will not affect the subsequent detection results.

[0026] The plan is to screen preliminary waterproof membrane materials from various depositable materials through waterproofing and seepage prevention experiments. Then, a pressure-induced rupture experiment will be conducted to further screen suitable waterproof membrane materials. For biodegradable thick films, water-soluble materials such as polyvinyl alcohol (PVA) and polyethylene oxide (PEO) will be considered first, while Parylene and PMMA will be considered for waterproofing materials. A preliminary screening of suitable thick film materials will be conducted by observing the state of the membrane as water and the test sample flow over its surface. If no satisfactory material is found, the screening scope will be expanded.

[0027] The present invention provides a microfluidic chip having the above-mentioned valve structure.

[0028] The microvalve (i.e., the valve in this embodiment) and the reservoir are integrated and fabricated on the chip cover plate. The cover plate is assembled with the base plate containing capillary channels using double-sided adhesive or ultrasonic welding to form a complete microfluidic chip. When a sample (serum) flows through the capillary channels of the chip below the microvalve, the aqueous membrane beneath the valve body begins to dissolve, absorbing a small amount of water from the serum. After a certain period, the serum sample has flowed through the detection area and captured the target protein (tumor marker). At this point, the aqueous membrane of the microvalve has dissolved sufficiently, causing the upper waterproof membrane to lose support and rupture. The microvalve then opens, and the eluent in the reservoir flows through the reservoir outlet into the capillary channels, flushing away non-specifically adsorbed proteins and reducing interference with the detection signal reading, thus achieving a fully automated online cleaning function.

[0029] This invention provides a method for processing a valve structure, applicable to the aforementioned valve structure, comprising: The water-soluble membrane is laid on a flat plate, and a waterproof membrane with a thickness of nanometers is vapor-deposited on the surface of the water-soluble membrane to form a composite membrane. The flat plate is connected to the waterproof material board, so that the composite membrane is adhered to the waterproof material board with through holes, and then the flat plate is removed; The liquid storage cavity is formed by the through holes of the waterproof material plate and the composite membrane.

[0030] The proposed solution is to use commercially available water-soluble PVA film as the biodegradable material for the valve body and Piriton film as the waterproof membrane. The commercially available water-soluble PVA film is laid flat and fixed on a plate approximately 30mm wide. A nanometer-thick Piriton film is then vapor-deposited onto its surface, forming a composite membrane with a PVA water-soluble film on one side and a Piriton waterproof membrane on the other. The plate with the composite membrane is then firmly glued to a PMMA board with through-holes. Finally, the plate is removed, and the composite membrane is trimmed. The holes (through-holes, which do not need to penetrate the PMMA board) on the PMMA board and the bonded composite membrane together form the liquid storage chamber. The commercially available water-soluble PVA film has good toughness, providing sufficient support for the Piriton film. The through-holes on the PMMA are made into stepped holes, with a small diameter at the end encapsulated by the composite membrane, which reduces the deformation of the composite membrane and facilitates subsequent integration with microfluidic chips.

[0031] The liquid storage chamber is used to store liquid; correspondingly, the method further includes: when filling the liquid storage chamber, placing a biodegradable capsule that can release gas. For example, a capsule containing compressed air; after a period of time, degradation causes the capsule to be unable to withstand the pressure of the compressed air, allowing the compressed air to be released.

[0032] The method also includes: trimming the composite membrane.

[0033] The biodegradable capsule is provided with a reactant that can react with the liquid stored in the reservoir to generate gas.

[0034] This embodiment proposes a method for applying precise gas pressure to a reservoir chamber. A substance that can chemically react with water to produce gas is encapsulated in a biodegradable capsule and placed into the reservoir chamber during filling. The reservoir chamber can be sealed with a PMMA cap and adhesive, eliminating the need for elastic material components and gas injection. The capsule slowly degrades, and after several days, the solid material inside is gradually exposed, reacting chemically with the reservoir to produce gas, thereby increasing the pressure in the reservoir chamber. The gas pressure in the reservoir chamber can be precisely controlled by adjusting the amount of material encapsulated in the capsule. Due to the capsule's slow-release effect, gas production begins several days after encapsulation, making it fully compatible with existing chip packaging processes. It is simple, reliable, and provides excellent sealing, requiring no additional equipment and suitable for mass production. Moreover, the amount of gas produced increases gradually, with the entire process lasting several days or even weeks, minimizing impact on the valve diaphragm. Biodegradable capsule encapsulation technology is already very mature; capsule shells can be purchased directly as finished products. The capsule is intended to contain disintegrants (such as citric acid C6H8O7, sodium carboxymethyl starch, etc.) that can react with water to produce a large amount of gas.

[0035] The surface of the water-soluble film facing the flat plate is also coated with an additional waterproof membrane, which has a perforated area.

[0036] like Figure 3The diagram shows a three-layer valve. If the above optimizations are insufficient to achieve the required delay length, the fabrication process of the double-layer membrane can be improved by vapor-depositing a waterproof membrane pattern 7 (i.e., another waterproof membrane with a pattern) on the back side (facing the microchannel) of the water-soluble membrane (i.e., the water-soluble membrane 5), forming a sandwich-like composite membrane structure of a waterproof membrane sandwiching a water-soluble membrane. In the areas with open patterns, the water-soluble membrane is exposed, and the sample can still dissolve the water-soluble membrane through these open areas 8, but the dissolution rate is slowed down by the pattern of the waterproof membrane. Moreover, this patterned waterproof membrane can also improve the overall strength of the valve body and prevent large pieces of the top waterproof membrane from falling and clogging the microchannel. Changing the pattern design of the waterproof membrane can optimize the delay time of the microvalve and the state of liquid release when the valve opens. Fabricating a patterned waterproof membrane is not difficult; simply cover the surface of the water-soluble membrane with a thin metal sheet mask engraved with a pattern during vapor deposition. The pattern of the thin metal sheet mask can be obtained by laser engraving.

[0037] This embodiment aims to achieve a controllable delay time for the valve by optimizing the thickness of the biodegradable membrane and depositing a patterned waterproof membrane on its surface. Furthermore, it addresses the challenge of balancing good sealing performance and rupture resistance of the waterproof membrane by injecting gas into the reservoir chamber to apply a specific pre-pressure to the valve body membrane.

[0038] This invention provides a valve structure processing system, comprising: The first unit is used to lay the water-soluble membrane on a flat plate and vapor-deposit a waterproof membrane with a nanometer-thickness on the surface of the water-soluble membrane to form a composite membrane. The second unit is used to connect the flat plate to the waterproof material board, so that the composite membrane is bonded to the waterproof material board with through holes, and then the flat plate is removed; The third unit is used to form the liquid storage cavity with the composite membrane through the through holes of the waterproof material plate.

[0039] Those skilled in the art will recognize that the units of the various examples described in connection with the embodiments disclosed herein can be implemented in electronic hardware, computer software, or a combination of both. To clearly illustrate the interchangeability of hardware and software, the components of the various examples have been generally described in terms of functionality in the foregoing description. Whether these functions are implemented in hardware or software depends on the specific application and design constraints of the technical solution. Those skilled in the art can use different methods to implement the described functions for each specific application, but such implementations should not be considered beyond the scope of the invention.

[0040] In the embodiments provided in this application, it should be understood that the division of units is only a logical functional division. In actual implementation, there may be other division methods, such as multiple units can be combined into one unit, one unit can be split into multiple units, or some features can be ignored.

[0041] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be covered within the scope of the claims and specification of the present invention.

Claims

1. A valve structure suitable for microfluidic chips with a liquid reservoir and microchannels, comprising: The liquid outlet layer, located between the liquid storage chamber and the microchannel, is provided with a liquid outlet. A waterproof membrane is used to prevent liquid in the storage chamber from seeping out of the outlet; A water-soluble membrane is disposed between the waterproof membrane and the microchannels to support the waterproof membrane; The waterproof membrane is characterized in that it is a thin film with a nanometer-thickness formed by vapor deposition on the surface of the water-soluble membrane; It also includes a biodegradable capsule disposed in the liquid storage cavity, wherein the biodegradable capsule is provided with a reactant that can react with the liquid stored in the liquid storage cavity to generate a gas, so as to generate a preset pressure in the liquid storage cavity to act on the waterproof membrane. An additional waterproof membrane with a perforated area is also vapor-deposited on the side of the water-soluble membrane facing the microchannel to form a sandwich-like composite membrane structure of a waterproof membrane sandwiching a water-soluble membrane. The water-soluble membrane is dissolved by the sample fluid flowing through the microchannel through the perforated area, thereby removing the support for the waterproof membrane.

2. The valve structure according to claim 1, characterized in that, The water-soluble membrane is made of polyvinyl alcohol and / or polyethylene oxide; the waterproof membrane is made of perylene and PMMA.

3. A microfluidic chip, characterized in that, The valve structure described in claim 1 or 2 is provided.

4. A method for processing a valve structure, applicable to the valve structure described in claim 1 or 2, characterized in that, include: The water-soluble membrane is laid on a flat plate, and a waterproof membrane with a nanometer-thickness is vapor-deposited on the surface of the water-soluble membrane. An additional waterproof membrane with a hollowed-out area is also vapor-deposited on the side of the water-soluble membrane facing the flat plate, forming a composite membrane. The flat plate is connected to a waterproof material board, so that the composite membrane is bonded to the waterproof material board with stepped holes. Then the flat plate is removed. The liquid storage cavity is formed by the stepped holes of the waterproof material board and the composite membrane.

5. The processing method of the valve structure according to claim 4, characterized in that, The liquid storage chamber is used to store liquid; Correspondingly, the method also includes: when filling the liquid storage chamber, placing a biodegradable capsule that can release gas.

6. The processing method of the valve structure according to claim 4, characterized in that, Also includes: Trim the composite membrane.

7. The processing method of the valve structure according to claim 5, characterized in that, The biodegradable capsule is provided with a reactant that can react with the liquid stored in the reservoir to generate gas.

8. A processing system for a valve structure, based on the valve structure as described in claim 1 or 2, characterized in that, include: The first unit is used to lay the water-soluble membrane on a flat plate, vapor deposit a waterproof membrane of nanometer thickness on the surface of the water-soluble membrane, and vapor deposit an additional waterproof membrane with a hollow area on the other side of the water-soluble membrane to form a composite membrane. The second unit is used to connect the flat plate to the waterproof material board, so that the composite membrane is bonded to the waterproof material board with stepped holes, and then the flat plate is removed. The third unit is used to form the liquid storage cavity with the composite membrane through the stepped holes of the waterproof material plate.

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