Micro-fluidic chip with trace liquid quantitative extraction function and quantitative extraction method

Abstract

The invention discloses a micro-fluidic chip with a micro-liquid quantitative extraction function and a quantitative extraction method. The micro-fluidic chip comprises a quantitative unit, an auxiliary quantitative unit and an extraction and transportation unit, the quantitative unit can be selectively connected with the auxiliary quantitative unit or the extraction and transportation unit, when the quantitative unit is connected with the auxiliary quantitative unit, the quantitative cavity is communicated with the balance cavity through connection of the first micro-channel and the second micro-channel, the quantitative cavity is filled with part of liquid injected from the liquid injection port for liquid quantification, and the quantitative cavity is communicated with the balance cavity through the first micro-channel and the second micro-channel. Redundant liquid flows into the balance cavity to be stored; when the quantitative unit is connected with the extraction and transportation unit, quantitative liquid in the quantitative cavity is extracted from the liquid outlet through connection of the first micro-channel and the third micro-channel. Quantification of the micro liquid is achieved, the requirement for liquid driving precision can be lowered, and quantification accuracy and operation convenience are improved.

Description

Technical Field

[0001] The invention relates to the technical field of biochemical equipment, and in particular to a microfluidic chip with a trace liquid quantitative extraction function and a quantitative extraction method. Background Art

[0002] Microfluidic chip is a rapid analysis platform that can integrate basic operations such as sample preparation, reaction, separation, and detection involved in biological, chemical, and medical analysis. The latest developments in microfluidic technology have made applications related to chip laboratories or micro-total analysis systems possible. It allows small amounts of liquid to be controlled in microfabricated channels, and in some cases, it also allows the effective automatic execution of analysis steps on microchips, including sample pretreatment, reaction, separation, and detection. Based on its small size, low reagent consumption, and high integration, it has great application potential in biology, chemistry, and medicine, and has gradually developed into a highly cross-integrated research field of biochemistry, fluid mechanics, microelectronics, materials, and mechanics. Among them, in the field of medical diagnosis, microfluidic chips are an important implementation platform for POCT (point-of-care testing) diagnostic equipment. And it has been proven to have great potential in a variety of biological applications, including cell sorting, enzyme analysis, immunohybridization reaction, nucleic acid analysis, nucleic acid sequencing, and other applications.

[0003] Since general biochemical reaction processes (such as cell sorting, nucleic acid analysis or other sample processing reactions) involve liquid distribution, extraction, mixing, separation and other steps, they all need to be implemented simultaneously through the structural design of microchannels on microfluidic chips. Among them, due to the influence of equipment control accuracy, the method for extracting small volumes of liquid and transferring them to the next unit has not been effectively solved. Summary of the invention

[0004] In view of the problems existing in the prior art, the object of the present invention is to provide a microfluidic chip and a quantitative extraction method capable of realizing quantitative extraction of a small volume of liquid.

[0005] To achieve the above-mentioned purpose, the first aspect of the present invention provides a microfluidic chip with a function of quantitative extraction of trace liquids, comprising a quantitative unit, an auxiliary quantitative unit and an extraction and transportation unit; the quantitative unit comprises an injection port, a first microchannel and a quantitative cavity; the auxiliary quantitative unit comprises a second microchannel, a balancing cavity and an exhaust port; the extraction and transportation unit comprises a third microchannel and a liquid outlet; wherein the quantitative unit can be selectively connected to the auxiliary quantitative unit or the extraction and transportation unit, and when the quantitative unit is connected to the auxiliary quantitative unit, the first microchannel is connected to the second microchannel so that the quantitative cavity and the balancing cavity are connected, a part of the liquid injected from the injection port fills the quantitative cavity for liquid quantification, and the excess liquid flows into the balancing cavity for storage; when the quantitative unit is connected to the extraction and transportation unit, the first microchannel is connected to the third microchannel so that the quantitative liquid in the quantitative cavity is extracted from the liquid outlet.

[0006] Furthermore, the quantitative unit is integrated on the first double-layer microfluidic chip structure, the injection port is arranged on the upper layer of the first double-layer microfluidic chip structure, the first microfluidic channel and the quantitative chamber are arranged on the lower layer of the first double-layer microfluidic chip structure, and the output end of the first microfluidic channel extends to the first side of the first double-layer microfluidic chip structure.

[0007] Furthermore, the auxiliary quantitative unit and the extraction and transportation unit are integrated on a second double-layer microfluidic chip structure, and an input end of the second microfluidic channel and an input end of the third microfluidic channel extend to a first side of the second double-layer microfluidic chip structure.

[0008] Furthermore, a first side edge of the first double-layer microfluidic chip structure and a first side edge of the second double-layer microfluidic chip structure are provided with mutually cooperating sliding structures, and the first double-layer microfluidic chip structure can slide along the first side edge of the second double-layer microfluidic chip structure through the sliding structure to connect the quantitative unit with the auxiliary quantitative unit or the extraction and transportation unit.

[0009] Furthermore, the sliding structure includes a dovetail groove arranged along a first side edge of the first double-layer microfluidic chip structure and a dovetail protrusion arranged along a first side edge of the second double-layer microfluidic chip structure.

[0010] Furthermore, a sealing element is provided at a connection between the first microfluidic channel and the second microfluidic channel and at a connection between the first microfluidic channel and the third microfluidic channel.

[0011] Further, the sealing element is positioned at the output end of the first microchannel in the dovetail groove.

[0012] Furthermore, the first double-layer microfluidic chip structure integrates a plurality of the quantitative units, and each quantitative unit is arranged side by side and spaced apart along the first side of the first double-layer microfluidic chip structure; the second double-layer microfluidic chip structure integrates a plurality of auxiliary quantitative units and a plurality of extraction and transportation units matching the number of the plurality of quantitative units, and each auxiliary quantitative unit and each extraction and transportation unit are arranged side by side and spaced apart along the first side of the second double-layer microfluidic chip structure.

[0013] Furthermore, a sliding positioning structure for positioning the sliding position of the sliding structure is provided at the first side edge of the first double-layer microfluidic chip structure and / or the first side edge of the second double-layer microfluidic chip structure.

[0014] Furthermore, a liquid-resistant and breathable membrane is provided at the exhaust port.

[0015] The second aspect of the present invention provides a method for quantitatively extracting trace amounts of liquid using a microfluidic chip, using the above-mentioned microfluidic chip, the method comprising the following steps:

[0016] Move the quantitative unit to connect the quantitative unit with the auxiliary quantitative unit, and introduce the liquid to be quantitatively extracted from the liquid injection port. At this time, the liquid fills the quantitative cavity through the first microchannel, and enters the balancing cavity through the second microchannel connected to the first microchannel. The excess air in the balancing cavity is discharged through the exhaust port;

[0017] Move the quantitative unit to connect it with the extraction and transportation unit, introduce gas or oil or other liquids for subsequent use into the injection port, and then the trace liquid that needs to be quantitatively extracted can be quantitatively taken out from the liquid outlet for subsequent biological process detection.

[0018] The present invention provides a quantitative unit, an auxiliary quantitative unit and an extraction and transportation unit, and selectively connects the quantitative unit with the auxiliary quantitative unit and the extraction and transportation unit to achieve quantitative extraction and transportation of trace liquids. The balance cavity of the auxiliary quantitative unit is connected with the quantitative cavity of the quantitative unit, which not only achieves the quantification of trace liquids, but also can store excess liquid in the quantification through the balance cavity, which can reduce the requirements for liquid driving accuracy, improve quantitative accuracy and operational convenience, and provide solutions for the extraction of various biochemical reactions and the smooth progress of subsequent reaction steps. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0020] Figure 1It is a schematic diagram of a first double-layer microfluidic chip structure of a microfluidic chip with a trace liquid quantitative extraction function according to an embodiment of the present invention;

[0021] Figure 2 A schematic diagram of a second double-layer microfluidic chip structure of a microfluidic chip with a trace liquid quantitative extraction function according to an embodiment of the present invention;

[0022] Figure 3A and 3B A schematic diagram of a sliding structure according to an embodiment of the present invention;

[0023] Figure 4 This is a schematic diagram of a microfluidic chip with a trace liquid quantitative extraction function under a quantitative working condition according to an embodiment of the present invention;

[0024] Figure 5 Schematic diagram of a microfluidic chip with a trace liquid quantitative extraction function under quantitative working conditions according to an embodiment of the present invention. DETAILED DESCRIPTION

[0025] In order to make the objectives, technical solutions and advantages of the present invention more clear, the embodiments of the present invention will be further described in detail below with reference to the accompanying drawings.

[0026] like Figure 4 and 5 As shown, the microfluidic chip with the function of quantitative extraction of trace liquid of the present invention comprises a quantitative unit 1, an auxiliary quantitative unit 2 and an extraction and transportation unit 3; the quantitative unit 1 comprises a liquid injection port 11, a first microchannel 12 and a quantitative cavity 13; the auxiliary quantitative unit 2 comprises a second microchannel 21, a balancing cavity 22 and an exhaust port 23; the extraction and transportation unit 3 comprises a third microchannel 31 and a liquid outlet 32. The volume of the quantitative cavity 13 is smaller than the volume of the balancing cavity 22. The volume of the quantitative cavity 13 is usually designed to be microliter or submicroliter level to adapt to the quantitative extraction of trace liquid in the field of biochemical analysis. The volume of the balancing cavity 22 is confirmed according to the controllable accuracy of the external liquid driving device. For example, assuming that the controllable accuracy of the external liquid driving device is 50 microliters and the quantitative volume of the quantitative cavity is 10 microliters, the volume of the balancing cavity should be designed to be greater than 40 microliters. The quantitative unit 1 can be selectively connected to the auxiliary quantitative unit 2 or the extraction and transportation unit 3 to realize the switching between the quantitative working condition and the extraction and transportation working condition. When the quantitative unit 1 is connected to the auxiliary quantitative unit 2, it is the quantitative working condition (see Figure 4), under quantitative working conditions, the first microchannel 12 is connected to the second microchannel 21, so that the quantitative chamber 13 and the balancing chamber 22 are connected, and the liquid is injected from the injection port 11 into the quantitative unit 1 through an external driving device. A part of the liquid injected from the injection port 11 fills the quantitative chamber 13 for trace liquid quantification, and the excess liquid flows from the first microchannel 12 and the second microchannel 21 to the balancing chamber 22 for storage. An exhaust port 23 is provided on the balancing chamber 22 to reduce air pressure resistance, so that the external driving device can inject liquid into the quantitative unit 1 for quantitative operation. The interface and microchannel size are as small as possible, for example, the interface size can be designed to be 0.3mm~0.6mm, and the microchannel depth can be designed to be 0.1mm~0.4mm to avoid liquid loss.

[0027] When the quantitative unit 1 is connected to the extraction and transportation unit 3, it is in the extraction and transportation mode (see Figure 5 ), under the extraction and transportation condition, the first microchannel 12 is connected to the third microchannel 31, and is connected to the liquid outlet 32 ​​through an external driving device. The quantitative liquid in the quantitative cavity 13 can be extracted from the first microchannel 12 and the third microchannel 31 from the liquid outlet 32 ​​by driving the external device.

[0028] The present invention realizes the quantitative operation of trace liquids under the cooperation of the quantitative cavity of the quantitative unit and the balance cavity of the auxiliary quantitative unit, which not only ensures the quantitative accuracy, but also reduces the requirements for the driving accuracy of the external driving device, which can greatly reduce the cost of the quantitative operation of trace liquids and provide solutions for the extraction of various biochemical reactions and the smooth progress of subsequent reaction steps.

[0029] In one embodiment of the present invention, Figure 1 As shown, the quantitative unit 1 is integrated on the first double-layer microfluidic chip structure, the injection port 11 is arranged on the upper layer of the first double-layer microfluidic chip structure, the first microchannel 12 and the quantitative cavity 13 are arranged on the lower layer of the first double-layer microfluidic chip structure, and the output end of the first microchannel 12 extends to the first side of the first double-layer microfluidic chip structure. The liquid injected from the injection port 11 by the external driving device falls to the lower layer of the chip, and can flow into the quantitative cavity 13 through the input end of the first microchannel 12 and flow out through the output end of the first microchannel 12. The material of the first double-layer microfluidic chip structure can be selected from hard polymer thermoplastic materials such as PP, PC, PET, PTFE, COC, etc., and processed by injection molding and other methods. The combination of the corresponding upper and lower layers can be achieved by laser bonding, ultrasonic bonding, hot pressing bonding, adhesive bonding, etc. In this embodiment, the quantitative unit is designed as a two-layer structure mainly for reliable process realization. The two-layer structure can be achieved by traditional process means such as injection molding and bonding, and the cost yield rate is high. It should be noted that the structure of the present invention is not limited thereto, and it can also be designed as three layers according to the actual chip function requirements.

[0030] In one embodiment of the present invention, Figure 2 As shown, the auxiliary quantitative unit 2 and the extraction and transportation unit 3 are integrated on the second double-layer microfluidic chip structure, the exhaust port 23 and the liquid outlet 32 ​​are arranged on the upper layer of the chip, the second microchannel 21 and the balance chamber 22 are arranged on the lower layer of the chip, and the input end of the second microchannel 21 and the input end of the third microchannel 31 extend to the first side of the second double-layer microfluidic chip structure. The material of the second double-layer microfluidic chip structure can be selected from hard polymer thermoplastic materials such as PP, PC, PET, PTFE, COC, etc., and processed by injection molding and other methods. The combination of the corresponding upper and lower layers can be achieved by laser bonding, ultrasonic bonding, hot pressing bonding, adhesive bonding, etc. In this embodiment, the auxiliary quantitative unit and the extraction and transportation unit are integrated together, and the design is a two-layer structure. On the one hand, for reliable process realization, the two-layer structure can be realized by traditional process means such as injection molding and bonding, and the cost yield rate is high. On the other hand, it is convenient to connect and switch between the quantitative unit and the auxiliary quantitative unit and the extraction and transportation unit. It should be noted that the structure of the present invention is not limited thereto, and it can also be designed as three layers according to the actual chip function requirements.

[0031] In one embodiment of the present invention, Figure 3A and 3B As shown, the first side edge of the first double-layer microfluidic chip structure and the first side edge of the second double-layer microfluidic chip structure are provided with a sliding structure 4 that cooperates with each other, and the first double-layer microfluidic chip structure can slide along the first side edge of the second double-layer microfluidic chip structure through the sliding structure 4, so that the quantitative unit 1 is connected with the auxiliary quantitative unit 2 or the extraction and transportation unit 3. Specifically, the sliding structure 4 includes a dovetail groove 41 arranged along the first side edge of the first double-layer microfluidic chip structure and a dovetail protrusion 42 arranged along the first side edge of the second double-layer microfluidic chip structure. The connection and fixation of the first double-layer microfluidic chip structure and the second double-layer microfluidic chip structure are achieved by the interference fit of the wedge-shaped structure. It should be noted that the shape and configuration of the above-mentioned sliding structure are only a preferred embodiment, and the present invention is not limited thereto.

[0032] In one embodiment of the present invention, a sealing element 5 is provided at the connection between the first microchannel 12 and the second microchannel 21 and at the connection between the first microchannel 12 and the third microchannel 31. Specifically, the sealing element 5 is positioned at the output end of the first microchannel 12 in the dovetail groove 41, and the sealing of the fluid channel interface is achieved by deforming and extruding the sealing element to ensure the sealing performance when the first microchannel is connected to the second microchannel and the third microchannel respectively. The sealing element material can be selected from materials such as fluororubber, liquid silicone, TPE, TPU, etc.

[0033] In one embodiment of the present invention, the first double-layer microfluidic chip structure integrates a plurality of the quantitative units 1, and each quantitative unit 1 is arranged side by side and spaced along the first side of the first double-layer microfluidic chip structure; the second double-layer microfluidic chip structure integrates a plurality of auxiliary quantitative units 2 and a plurality of extraction and transportation units 3 that match the number of the plurality of quantitative units 1, and each auxiliary quantitative unit 2 and each extraction and transportation unit 3 are arranged side by side and spaced along the first side of the second double-layer microfluidic chip structure. The intervals between the plurality of quantitative units 1 match the intervals between the plurality of auxiliary quantitative units 2 and the plurality of extraction and transportation units 3, respectively, to ensure that after one quantitative unit 1 is connected to the auxiliary quantitative unit 2 or the extraction and transportation unit 3, the other quantitative units can also be connected to the auxiliary quantitative unit 2 or the extraction and transportation unit 3, and multiple channels can work simultaneously, greatly improving the efficiency of the quantitative extraction operation. .

[0034] In one embodiment of the present invention, a sliding positioning structure (not shown in the figure) for positioning the sliding position of the sliding structure is provided at the first side of the first double-layer microfluidic chip structure and / or the first side of the second double-layer microfluidic chip structure. For example, a positioning protrusion is provided on the first side of the first double-layer microfluidic chip structure close to the output end of the first microchannel, and a positioning groove is provided on the first side of the second double-layer microfluidic chip structure close to the input end of the second microchannel and the input end of the third microchannel. When the first double-layer microfluidic chip structure slides on the first side of the second double-layer microfluidic chip structure through the sliding structure, when the positioning protrusion is felt to move into the positioning groove, it indicates that the quantitative unit 1 moves to the accurate connection position with the auxiliary quantitative unit 2 or the extraction and transportation unit 3. It should be noted that the connection and positioning method of the quantitative unit, the auxiliary quantitative unit and the extraction and transportation unit of the present invention is not limited to this, and the moving position can also be accurately controlled by an external mobile drive device.

[0035] In one embodiment of the present invention, a liquid-blocking and breathable membrane is provided at the exhaust port 23 to prevent liquid from leaking from the exhaust port due to excessive driving force during liquid quantitative operation.

[0036] The present invention also provides a method for quantitatively extracting trace amounts of liquid using a microfluidic chip, using the above-mentioned microfluidic chip, the method comprising the following steps:

[0037] Move the quantitative unit to connect the quantitative unit with the auxiliary quantitative unit, and introduce the liquid to be quantitatively extracted from the liquid injection port. At this time, the liquid fills the quantitative cavity through the first microchannel, and enters the balancing cavity through the second microchannel connected to the first microchannel. The excess air in the balancing cavity is discharged through the exhaust port;

[0038] Move the quantitative unit to connect it with the extraction and transportation unit, introduce gas or oil or other liquids for subsequent use into the injection port, and then the trace liquid that needs to be quantitatively extracted can be quantitatively taken out from the liquid outlet for subsequent biological process detection.

[0039] In summary, the present invention is applicable to scenarios involving the extraction and transportation of quantitative trace liquids in biological reaction processes. It reduces the requirements for liquid driving accuracy and is applicable to liquid extraction in a single channel or multiple channels at the same time, improving accuracy and ease of operation, and providing solutions for the extraction of various biochemical reactions and the smooth progress of subsequent reaction steps.

[0040] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A microfluidic chip with a function of quantitatively extracting trace amounts of liquid, characterized in that: It includes a quantitative unit, an auxiliary quantitative unit and an extraction and transportation unit; the quantitative unit includes a liquid injection port, a first microfluidic channel and a quantitative cavity; the auxiliary quantitative unit includes a second microfluidic channel, a balancing cavity and an exhaust port; the extraction and transportation unit includes a third microfluidic channel and a liquid outlet; wherein the quantitative unit can be selectively connected to the auxiliary quantitative unit or the extraction and transportation unit, and when the quantitative unit is connected to the auxiliary quantitative unit, the first microfluidic channel is connected to the second microfluidic channel so that the quantitative cavity and the balancing cavity are connected, a part of the liquid injected from the liquid injection port fills the quantitative cavity for liquid quantification, and the excess liquid flows into the balancing cavity for storage; when the quantitative unit is connected to the extraction and transportation unit, the first microfluidic channel is connected to the third microfluidic channel so that the quantitative liquid in the quantitative cavity is extracted from the liquid outlet.

2. The microfluidic chip with a trace liquid quantitative extraction function as claimed in claim 1, characterized in that: The quantitative unit is integrated on the first double-layer microfluidic chip structure, the injection port is arranged on the upper layer of the first double-layer microfluidic chip structure, the first microfluidic channel and the quantitative chamber are arranged on the lower layer of the first double-layer microfluidic chip structure, and the output end of the first microfluidic channel extends to the first side of the first double-layer microfluidic chip structure.

3. The microfluidic chip with a trace liquid quantitative extraction function as claimed in claim 2, characterized in that: The auxiliary quantitative unit and the extraction and transportation unit are integrated on a second double-layer microfluidic chip structure, and an input end of the second microfluidic channel and an input end of the third microfluidic channel extend to a first side of the second double-layer microfluidic chip structure.

4. The microfluidic chip with a trace liquid quantitative extraction function as claimed in claim 3, characterized in that: The first side edge of the first double-layer microfluidic chip structure and the first side edge of the second double-layer microfluidic chip structure are provided with mutually cooperating sliding structures, and the first double-layer microfluidic chip structure can slide along the first side edge of the second double-layer microfluidic chip structure through the sliding structure to connect the quantitative unit with the auxiliary quantitative unit or the extraction and transportation unit.

5. The microfluidic chip with a trace liquid quantitative extraction function as claimed in claim 4, characterized in that: The sliding structure includes a dovetail groove arranged along a first side edge of the first double-layer microfluidic chip structure and a dovetail protrusion arranged along a first side edge of the second double-layer microfluidic chip structure.

6. The microfluidic chip with a trace liquid quantitative extraction function as claimed in claim 1 or 5, characterized in that: A sealing element is provided at a connection between the first microfluidic channel and the second microfluidic channel and at a connection between the first microfluidic channel and the third microfluidic channel.

7. The microfluidic chip with a trace liquid quantitative extraction function as claimed in claim 6, characterized in that: The sealing element is positioned at an output end of the first micro-channel in the dovetail groove.

8. The microfluidic chip with a trace liquid quantitative extraction function as claimed in claim 3, characterized in that: The first double-layer microfluidic chip structure is integrated with a plurality of the quantitative units, and each quantitative unit is arranged side by side and spaced apart along the first side of the first double-layer microfluidic chip structure; the second double-layer microfluidic chip structure is integrated with a plurality of auxiliary quantitative units and a plurality of extraction and transportation units matching the number of the plurality of quantitative units, and each auxiliary quantitative unit and each extraction and transportation unit is arranged side by side and spaced apart along the first side of the second double-layer microfluidic chip structure.

9. The microfluidic chip with the function of quantitatively extracting trace amounts of liquid as claimed in claim 4, characterized in that: A sliding positioning structure for positioning the sliding position of the sliding structure is arranged at the first side edge of the first double-layer microfluidic chip structure and / or the first side edge of the second double-layer microfluidic chip structure.

10. The microfluidic chip with a trace liquid quantitative extraction function as claimed in claim 1, characterized in that: A liquid-blocking and breathable membrane is arranged at the exhaust port.

11. A method for quantitatively extracting trace amounts of liquid using a microfluidic chip, characterized in that: Using the microfluidic chip according to any one of claims 1 to 10, the method comprises the following steps: Move the quantitative unit to connect the quantitative unit with the auxiliary quantitative unit, and introduce the liquid to be quantitatively extracted from the liquid injection port. At this time, the liquid fills the quantitative cavity through the first microchannel, and enters the balancing cavity through the second microchannel connected to the first microchannel. The excess air in the balancing cavity is discharged through the exhaust port; Move the quantitative unit to connect it with the extraction and transportation unit, introduce gas or oil or other liquids for subsequent use into the injection port, and then the trace liquid that needs to be quantitatively extracted can be quantitatively taken out from the liquid outlet for subsequent biological process detection.

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