Microfluidic chip component

Abstract

The present invention provides a microfluidic chip assembly, including a microfluidic chip body. Function chambers and / or liquid channels are configured in the microfluidic chip body. When the microfluidic chip assembly is in a horizontal state, the function chambers and the liquid channels extend in a two-dimensional plane within the horizontal plane, and the heights of the function chambers and the liquid channels are equal. In the present invention, since both the function chambers and the fluid channels in the microfluidic chip body extend in a two-dimensional plane and their heights are equal, that is, there is no upward or downward flow deflection and backflow of the sample fluid in the microfluidic chip body, and there is no height difference. Compared with the design in the prior art where each channel presents a three-dimensional flow direction in terms of height and horizontal plane, the design of the chambers and channels in the present invention is simpler, not prone to liquid path blockage, and the probability of generating dead volume is relatively low.

Description

Technical Field

[0001] The present invention belongs to the technical field of microfluidic chip design and application, and particularly relates to a microfluidic chip component. Background Art

[0002] In vitro diagnosis refers to the technology of detecting samples such as blood and tissues outside the human body to determine whether a corresponding disease is present. According to the detection principle, it can be divided into several categories such as biochemical diagnosis, immunoassay, and molecular diagnosis. The field of in vitro diagnosis has a complex branch and numerous technical routes. However, due to its medical diagnosis nature, it generally develops towards precision, integration and portability, and rapid and efficient directions.

[0003] Molecular diagnosis is based on molecular biology technology. Taking the microdroplet digital PCR technology (ddPCR) as an example, this absolute quantitative analysis of nucleic acids based on single molecule PCR is a typical representative of high sensitivity and high accuracy. In recent years, relying on the development of microfluidic chip technology, each link of this technology can be integrated into a small microfluidic chip, gradually moving towards integration to achieve a real lab on a chip. In current market ddPCR systems and some other POCT systems, in the flow path designs of the connection of multiple different functional chips, pipes, cartridges, etc., the three-dimensional flow direction of the flow path is inevitably generated, that is, the fluid does not flow on a single plane, and there will be flow designs such as up and down, inclined, etc. Due to the complexity of biological samples themselves (either viscous or with a large sample diameter), the more complex the liquid path, the higher the probability of liquid path blockage. Especially, the risk at the inlet and outlet positions of the up and down structure is the greatest, and the probability of generating dead volume will increase as the flow path becomes more complex. Summary of the Invention

[0004] Therefore, the technical problem to be solved by the present invention is to provide a microfluidic chip component to overcome the deficiencies in the prior art that the flow path design in the integrated microfluidic chip has a three-dimensional flow direction, with a flow channel design having an up and down direction (generating a height difference), a complex liquid path design, which is prone to liquid path blockage, and a relatively high probability of generating dead volume.

[0005] To solve the above problems, the present invention provides a microfluidic chip component, including a microfluidic chip body. Functional chambers and / or liquid flow channels are constructed in the microfluidic chip body. When the microfluidic chip component is in a horizontal state, the functional chambers and the liquid flow channels extend in a two-dimensional plane within the horizontal plane, and the heights of the functional chambers and the liquid flow channels are equal.

[0006] In some embodiments, at least two microfluidic chip bodies are included, and the flow outlet of the liquid flow channel in one of the microfluidic chip bodies is docked with the flow inlet of the liquid flow channel in another adjacent microfluidic chip body.

[0007] In some embodiments, two adjacent microfluidic chip bodies are a first chip and a second chip respectively. Among them, a first side surface of the first chip is in sealing contact and cooperation with a second side surface of the second chip, so that an outlet of the liquid flow channel of the first chip is horizontally docked with an inlet of the liquid flow channel of the second chip, or so that an inlet of the liquid flow channel of the first chip is horizontally docked with an outlet of the liquid flow channel of the second chip.

[0008] In some embodiments, a sealing gasket is wrapped on the first side surface of the first chip and the second side surface of the second chip respectively. The sealing gasket has a docking hole corresponding to and communicating with the position of the inlet or outlet of the liquid flow channel.

[0009] In some embodiments, an opening size of the docking hole becomes larger and larger in a direction away from the corresponding microfluidic chip body.

[0010] In some embodiments, a set of chip position adjustment devices are respectively arranged corresponding to the microfluidic chip bodies. The chip position adjustment device includes a main shaft and a support arm. A first end of the support arm is connected to an outer circumferential wall of the main shaft, a second end of the support arm is connected with a carrier table, and each microfluidic chip body is fixedly connected to the carrier table. The support arm can be driven to move reciprocally in an axial direction of the main shaft.

[0011] In some embodiments, the main shaft can be driven to rotate around its central axis; and / or, the support arm is telescopic; and / or, there are two support arms, and the two support arms are arranged at intervals along the axial direction of the main shaft.

[0012] In some embodiments, the first chip is a micro-droplet generation chip. For the first chip, a liquid flow channel is constructed in the microfluidic chip body. The liquid flow channel includes a first-phase introduction flow channel, a second-phase introduction flow channel, and a micro-droplet flow channel. The second-phase introduction flow channel and the micro-droplet flow channel are collinearly connected and connected to a first intersection point. The first-phase introduction flow channel forms a cross intersection with the second-phase introduction flow channel and the micro-droplet flow channel at the first intersection point.

[0013] In some embodiments, the second chip is an amplification chip. For the second chip, the functional chamber and the liquid flow channel are constructed in the microfluidic chip body. Among them, the functional chamber includes an amplification chamber, a first waste liquid chamber upstream of the amplification chamber, and a second waste liquid chamber downstream of the amplification chamber. The first waste liquid chamber, the amplification chamber, and the second waste liquid chamber are connected through the liquid flow channel. A first cut-off valve is provided on the liquid flow channel between the downstream of the first waste liquid chamber and the amplification chamber and / or on the liquid flow channel between the upstream of the second waste liquid chamber and the amplification chamber.

[0014] In some embodiments, a second cut-off valve is provided on the liquid flow channel upstream of the first waste liquid chamber and / or on the liquid flow channel downstream of the second waste liquid chamber.

[0015] In the microfluidic chip assembly provided by the present invention, since the functional chamber and the fluid flow channel in the microfluidic chip body both extend in a two-dimensional plane and have the same height, that is, there is no up-and-down baffle and backflow of the sample fluid in the microfluidic chip body, and there is no height difference. Compared with the design in the prior art where each flow channel presents a three-dimensional flow direction in terms of height and horizontal plane, the design of the chamber and the flow channel of the present invention is simpler, not prone to liquid path blockage, and at the same time, the probability of generating dead volume is lower. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is a schematic structural diagram (top view) of the microfluidic chip assembly according to an embodiment of the present invention;

[0017] Figure 2 It is a three-dimensional structural diagram of the microfluidic chip assembly according to an embodiment of the present invention;

[0018] Figure 3 is Figure 1 a three-dimensional structural diagram of the sealing gasket in

[0019] The reference numerals are shown as:

[0020] 1. Microfluidic chip body; 2. Sealing gasket; 21. Docking hole; 31. Main shaft; 32. Support arm; 33. Carrying platform; 100. First chip; 101. First-phase introduction flow channel; 102. Second-phase introduction flow channel; 103. Micro-droplet flow channel; 200. Second chip; 201. Amplification chamber; 202. First waste liquid chamber; 203. Second waste liquid chamber; 204. First cut-off valve; 205. Second cut-off valve. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0021] Refer to Figures 1 to 3As shown, according to an embodiment of the present invention, a microfluidic chip assembly is provided, including a microfluidic chip body 1. Functional chambers and / or liquid channels are constructed in the microfluidic chip body 1. When the microfluidic chip assembly is in a horizontal state, specifically, for example, the microfluidic chip body 1 is formed by bonding a substrate and a cover plate. When the microfluidic chip assembly is in a horizontal state, that is, the bottom surface and the top surface of the cover plate and the substrate are parallel to the horizontal plane. The functional chambers and the liquid channels extend in a two-dimensional plane within the horizontal plane, and the heights of the functional chambers and the liquid channels are equal. In this technical solution, since both the functional chambers and the fluid channels in the microfluidic chip body 1 extend in a two-dimensional plane and their heights are equal, that is, there is no up-and-down folding flow and backflow of the sample fluid in the microfluidic chip body 1, and there is no height difference. Compared with the design in the prior art where each flow channel presents a three-dimensional flow direction in terms of height and horizontal plane, the design of the chambers and channels of the present invention is simpler, not prone to liquid path blockage, and at the same time, the probability of generating dead volume is lower.

[0022] The aforementioned two-dimensional plane extension is specifically, for example, the fluid channel flows in a single direction from left to right along the horizontal direction. It has no rise or fall in the height direction and only has a straight or a certain degree of zigzag progression in the horizontal direction; the functional chamber extends around in the horizontal plane. The chamber has the same height as the corresponding fluid channel. The bottom surface of the fluid channel is flush with the bottom surface of the functional chamber, and the top surfaces are also correspondingly flush. The volume of the functional chamber is determined by the degree of its expansion around in the horizontal plane.

[0023] In some embodiments, there are at least two microfluidic chip bodies 1. The flow outlet (not labeled in the figure) of the liquid channel in one of the microfluidic chip bodies 1 is docked with the flow inlet (not labeled in the figure) of the liquid channel in another adjacent one. In a feasible implementation, the docked flow outlet and flow inlet can be hermetically docked through a connecting pipe, for example, so as to realize the integrated and spliceable processing of different liquid channels and / or functional chambers on different microfluidic chip bodies 1 to achieve different processing procedures for biological samples.

[0024] The above-mentioned method of sealing and docking with a connecting pipe cannot meet the working conditions where at least one of the multiple spliced microfluidic chip bodies 1 needs to be disassembled and post-processed individually. In order to enable the microfluidic chip assembly to be applicable to the above-mentioned working conditions, in some embodiments, two adjacent microfluidic chip bodies 1 are respectively a first chip 100 and a second chip 200. Among them, the first side surface of the first chip 100 is in sealing contact and cooperation with the second side surface of the second chip 200 so that the outflow port of the liquid flow channel of the first chip 100 is horizontally docked with the inflow port of the liquid flow channel of the second chip 200, or so that the inflow port of the liquid flow channel of the first chip 100 is horizontally docked with the outflow port of the liquid flow channel of the second chip 200. That is, when it is necessary to connect two adjacent microfluidic chip bodies 1 to convey the corresponding sample fluid to each other, the corresponding sides of the two chips can be made to contact each other. And when it is necessary to separate the two, they can be made to be out of contact, and any one of the chips can be operated independently. For example, one of the chips can be transferred to another detection device for relevant process operations.

[0025] Refer to in combination Figure 1 and Figure 2 As shown, a sealing gasket 2 is wrapped on the first side surface of the first chip 100 and the second side surface of the second chip 200 respectively. The sealing gasket 2 has a docking hole 21 corresponding to and communicating with the position of the inflow port or the outflow port of the liquid flow channel. By respectively sleeving the above-mentioned sealing gasket 2 on the corresponding end side surfaces of two adjacent chips, the elastic deformation ability of the sealing gasket 2 can be used to ensure the sealing of the flow channels after the two chips are connected in contact under force, and the sealing is simple and feasible. The above-mentioned sealing gasket 2 can specifically be made of silica gel.

[0026] Refer to Figure 3 As shown, the opening size of the docking hole 21 becomes larger and larger along the direction away from the corresponding microfluidic chip body 1, that is, the opening size of the docking hole 21 on the opposite side is the largest. This is beneficial to improving the error tolerance rate of the docking flow channels of the two chips and ensuring the smooth flow of the sample liquid. In addition, the design with an increasingly larger opening size can prevent the formation of steps in the docking hole 21 and further reduce the dead volume.

[0027] Refer to in combination Figure 1 and Figure 2As shown in the figure, each microfluidic chip body 1 is respectively provided with a set of chip position adjustment devices, which are used to drive the position adjustment of the microfluidic chips placed thereon. In a specific embodiment, the chip position adjustment device includes a main shaft 31 and a support arm 32. The first end of the support arm 32 is connected to the outer circumferential wall of the main shaft 31, and the second end of the support arm 32 is connected with a stage 33. Each microfluidic chip body 1 is respectively fixedly connected to the stage 33. The support arm 32 can be driven to reciprocate in the axial direction of the main shaft 31. The reciprocating motion of the foregoing support arm 32 can be, for example, a manner driven by manual force, or a mechanical drive adjustment manner implemented by a corresponding electric push rod. The present invention does not intend to limit its specific implementation manner. The purpose of setting the foregoing stage 33 is to fix the position of the chip placed thereon. For example, a corresponding clamping structure (such as an elastic jaw) can be provided thereon to clamp and position the chip to prevent it from detaching from the stage 33. When two chips need to be docked, only need to place the two chips on the corresponding stages 33 for positioning respectively, and then control the two support arms 32 to approach each other, thereby driving the two chips to approach each other and dock on the side. At this time, the docking holes 21 of the sealing rubber pads 2 respectively provided on the two chips correspond and communicate with each other. After that, other corresponding devices can be controlled to perform necessary control on each chip. In a preferred embodiment, there are two support arms 32, and the two support arms 32 are arranged at intervals along the axial direction of the main shaft 31 to be able to reliably support the stage 33. In another preferred embodiment, the main shaft 31 can be driven to rotate around its central axis, that is, the main shaft 31 is a rotating shaft, and it can be specifically driven to rotate by a rotating motor. Specifically, after the main shaft 31 corresponding to one chip is controlled to rotate a certain angle when it is necessary to separate adjacent two chips, it is convenient to take out one of the chips. On the other hand, in some working conditions that require high-speed centrifugal oscillation, the main shaft 31 can also be controlled to rotate at a high speed; in order to prevent structural interference from occurring between one of the adjacent two chips and the other when one of the chips is controlled to rotate, in a preferred embodiment, the support arm 32 is telescopic, and it can be controlled to rise and extend, or descend and retract. When it is in the state of rising and extending, the chip on the stage 33 connected thereto can be driven to rotate independently by the rotating main shaft 31 to achieve specific purposes such as centrifugal oscillation.

[0028] As a specific embodiment, the first chip 100 is a micro-droplet generation chip, and the second chip 200 is an amplification chip. At this time, refer to Figure 1As shown in the figure, for the first chip 100, a liquid flow channel is constructed in the microfluidic chip body 1. The liquid flow channel includes a first-phase introduction flow channel 101, a second-phase introduction flow channel 102, and a micro-droplet flow channel 103. The second-phase introduction flow channel 102 and the micro-droplet flow channel 103 are collinearly connected and connected to a first intersection point. The first-phase introduction flow channel 101 forms a cross intersection with the second-phase introduction flow channel 102 and the micro-droplet flow channel 103 at the first intersection point. It can be understood that the bottom walls of the aforementioned first-phase introduction flow channel 101, second-phase introduction flow channel 102, and micro-droplet flow channel 103 are at the same height, and the top walls are at the same height. Among them, the first-phase introduction flow channel 101 can specifically be an oil-phase fluid, which forms a closed square flow channel. The second-phase introduction flow channel 102 is a sample fluid. In the two flows, the corresponding oil phase and sample fluid are introduced according to a preset flow rate. The oil phase will cut the sample fluid at the first intersection point, and then form water-in-oil micro-droplets and enter the micro-droplet flow channel 103. Using the cross-intersection method to generate micro-droplets is common knowledge in the industry and will not be elaborated here. For the second chip 200, a functional chamber and a liquid flow channel are constructed in the microfluidic chip body 1. Among them, the functional chamber includes an amplification chamber 201, a first waste liquid chamber 202 upstream of the amplification chamber 201, and a second waste liquid chamber 203 downstream of the amplification chamber 201. The first waste liquid chamber 202, the amplification chamber 201, and the second waste liquid chamber 203 are connected through a liquid flow channel. A first cut-off valve 204 is provided on the liquid flow channel between the downstream of the first waste liquid chamber 202 and the amplification chamber 201 and / or on the liquid flow channel between the upstream of the second waste liquid chamber 203 and the amplification chamber 201. In the specific application process, when the upstream sample micro-droplets (or through a separately provided sample injection port) flow into the amplification chamber 201 through the liquid flow channel, the two first cut-off valves 204 can be controlled in a timely manner to cut off according to the actual situation of the sample liquid in the first waste liquid chamber 202 and the second waste liquid chamber 203, so as to ensure that there are no bubbles in the sample liquid in the amplification chamber 201 and guarantee the sample amplification quality.

[0029] Furthermore, a second cut-off valve 205 is provided on the liquid flow channel upstream of the first waste liquid chamber 202 and / or on the liquid flow channel downstream of the second waste liquid chamber 203. At this time, when part of the volume in the first waste liquid chamber 202 and the second waste liquid chamber 203 is occupied by gas, the two second cut-off valves 205 can be cut off. At this time, the second chip 200 can be disassembled without causing cross-contamination due to the overflow of the sample liquid. It can be understood that when there is only part of the air in the first waste liquid chamber 202 and the second waste liquid chamber 203, this indicates that there is no longer sample liquid in the upstream flow channel of the first waste liquid chamber 202, and the sample liquid has not yet flowed into the downstream flow channel of the second waste liquid chamber 203. Therefore, cutting off the two second cut-off valves 205 at this time can effectively prevent the outflow of the sample liquid when the second chip 200 is disassembled. At this time, the second chip 200 can specifically be removed and transferred to the corresponding amplification station for amplification.

[0030] Those skilled in the art can easily understand that, on the premise of no conflict, the above advantageous ways can be freely combined and superimposed.

[0031] The above are only the preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the present invention shall be included within the protection scope of the present invention. The above is only the preferred implementation manner of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the technical principle of the present invention, several improvements and modifications can also be made, and these improvements and modifications should also be regarded as the protection scope of the present invention.

Claims

1. A microfluidic chip assembly, characterized in that, it includes a microfluidic chip body (1), and functional chambers and / or liquid channels are constructed in the microfluidic chip body (1). When the microfluidic chip assembly is in a horizontal state, the functional chambers and the liquid channels extend in a two-dimensional plane within the horizontal plane, and the heights of the functional chambers and the liquid channels are equal; at least two microfluidic chip bodies (1) are included, and the outlet of the liquid channel in one of each microfluidic chip body (1) is docked with the inlet of the liquid channel in another adjacent one; two adjacent microfluidic chip bodies (1) are respectively a first chip (100) and a second chip (200); the second chip (200) is an amplification chip. For the second chip (200), functional chambers and the liquid channels are constructed in the microfluidic chip body (1), wherein the functional chambers include an amplification chamber (201), a first waste liquid chamber (202) upstream of the amplification chamber (201), and a second waste liquid chamber (203) downstream of the amplification chamber (201), and the first waste liquid chamber (202), the amplification chamber (201), and the second waste liquid chamber (203) are communicated through the liquid channels.

2. The microfluidic chip assembly according to claim 1, characterized in that, the first side surface of the first chip (100) is in sealing contact and cooperation with the second side surface of the second chip (200) so that the outlet of the liquid channel in the first chip (100) is horizontally docked with the inlet of the liquid channel in the second chip (200), or so that the inlet of the liquid channel in the first chip (100) is horizontally docked with the outlet of the liquid channel in the second chip (200).

3. The microfluidic chip assembly according to claim 2, characterized in that, sealing rubber pads (2) are respectively wrapped on the first side surface of the first chip (100) and the second side surface of the second chip (200), and the sealing rubber pads (2) are provided with docking holes (21) corresponding to and communicated with the positions of the inlets or outlets of the liquid channels.

4. The microfluidic chip assembly according to claim 3, characterized in that, the opening size of the docking hole (21) becomes larger and larger along the direction away from the corresponding microfluidic chip body (1).

5. The microfluidic chip assembly according to claim 2, characterized in that, each microfluidic chip body (1) is respectively provided with a set of chip position adjustment devices, and the chip position adjustment devices include a main shaft (31) and a support arm (32). The first end of the support arm (32) is connected to the outer circumferential wall of the main shaft (31), the second end of the support arm (32) is connected with a carrier platform (33), and each microfluidic chip body (1) is respectively fixedly connected to the carrier platform (33), and the support arm (32) can be driven to move reciprocally in the axial direction of the main shaft (31).

6. The microfluidic chip assembly according to claim 5, wherein, the main shaft (31) can be driven to rotate around its central axis; and / or, the support arm (32) is telescopic; and / or, there are two support arms (32), and the two support arms (32) are arranged at intervals along the axial direction of the main shaft (31).

7. The microfluidic chip assembly according to claim 2, wherein, the first chip (100) is a micro-droplet generating chip. For the first chip (100), a liquid flow channel is constructed in the microfluidic chip body (1). The liquid flow channel includes a first-phase introduction flow channel (101), a second-phase introduction flow channel (102), and a micro-droplet flow channel (103). The second-phase introduction flow channel (102) and the micro-droplet flow channel (103) are collinearly connected and connected to a first intersection point. The first-phase introduction flow channel (101) forms a cross intersection with the second-phase introduction flow channel (102) and the micro-droplet flow channel (103) at the first intersection point.

8. The microfluidic chip assembly according to claim 2, wherein, a first cut-off valve (204) is provided on the liquid flow channel between the downstream of the first waste liquid chamber (202) and the amplification chamber (201) and / or on the liquid flow channel between the upstream of the second waste liquid chamber (203) and the amplification chamber (201).

9. The microfluidic chip assembly according to claim 8, wherein, a second cut-off valve (205) is provided on the liquid flow channel upstream of the first waste liquid chamber (202) and / or on the liquid flow channel downstream of the second waste liquid chamber (203).

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