Microfluidic chip with trace liquid quantitative extraction function and quantitative extraction method

Abstract

This invention discloses a microfluidic chip and a quantitative extraction method for trace liquids. The device includes a quantitative unit, an auxiliary quantitative unit, and an extraction and transport unit. The quantitative unit can be selectively connected to either the auxiliary quantitative unit or the extraction and transport unit. When the quantitative unit is connected to the auxiliary quantitative unit, it is connected to a second microfluidic channel via a first microchannel, allowing the quantitative chamber and the equilibrium chamber to communicate. A portion of the liquid injected through the injection port fills the quantitative chamber for quantitative liquid extraction, while excess liquid flows to the equilibrium chamber for storage. When the quantitative unit is connected to the extraction and transport unit, it is connected to a third microfluidic channel via the first microchannel, allowing the quantitative liquid in the quantitative chamber to be extracted from the outlet. This invention achieves quantitative extraction of trace liquids while reducing the requirements for liquid driving precision, thus improving quantitative accuracy and ease of operation.

Description

Technical Field

[0001] This invention relates to the field of biochemical equipment technology, and in particular to a microfluidic chip with micro-liquid quantitative extraction function and a quantitative extraction method. Background Technology

[0002] Microfluidic chips are rapid analytical platforms that integrate basic operations such as sample preparation, reaction, separation, and detection involved in biological, chemical, and medical analysis. Recent advancements in microfluidic technology have enabled applications related to lab-on-a-chip or micro total analysis systems. They allow for the control of small amounts of liquid within microfabricated channels and, in some cases, the efficient automation of analytical steps on the microchip, including sample pretreatment, reaction, separation, and detection. Based on their small size, low reagent consumption, and high integration, they have immense application potential in biology, chemistry, and medicine, and have gradually developed into a highly interdisciplinary research field encompassing biochemistry, fluid mechanics, microelectronics, materials science, and mechanics. In the field of medical diagnostics, microfluidic chips are an important platform for point-of-care testing (POCT) diagnostic devices and have proven to have significant potential in various biological applications, including cell sorting, enzyme analysis, immunohybridization, nucleic acid analysis, and nucleic acid sequencing.

[0003] Since typical biochemical reactions (such as cell sorting, nucleic acid analysis, or other sample processing reactions) involve steps such as liquid distribution, extraction, mixing, and separation, all of which need to be simultaneously implemented on a microfluidic chip through the structural design of microchannels, effective methods for extracting and transferring small volumes of liquid to the next unit remain unsolved due to limitations in device control precision. Summary of the Invention

[0004] To address the problems existing in the prior art, the purpose of this invention is to provide a microfluidic chip and a quantitative extraction method capable of quantitative extraction of small volumes of liquid.

[0005] To achieve the above objectives, a first aspect of the present invention provides a microfluidic chip with a micro-liquid quantitative extraction function, comprising a quantitative unit, an auxiliary quantitative unit, and an extraction and transport unit; the quantitative unit includes an injection port, a first microchannel, and a quantitative chamber; the auxiliary quantitative unit includes a second microchannel, a balance chamber, and an exhaust port; the extraction and transport unit includes a third microchannel and an outlet; wherein, the quantitative unit can be selectively connected to the auxiliary quantitative unit or the extraction and transport unit; when the quantitative unit is connected to the auxiliary quantitative unit, the first microchannel is connected to the second microchannel, thereby connecting the quantitative chamber and the balance chamber; a portion of the liquid injected through the injection port fills the quantitative chamber for quantitative liquid extraction, and excess liquid flows to the balance chamber for storage; when the quantitative unit is connected to the extraction and transport unit, the first microchannel is connected to the third microchannel, thereby extracting the quantitative liquid in the quantitative chamber from the outlet.

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

[0007] Furthermore, the auxiliary quantification unit and the extraction and transport unit are integrated on the second double-layer microfluidic chip structure, and the input end of the second microchannel and the input end of the third microchannel extend to the first side of the second double-layer microfluidic chip structure.

[0008] Furthermore, a sliding structure is provided on the first side of the first dual-layer microfluidic chip structure and the first side of the second dual-layer microfluidic chip structure, which cooperates with each other. The first dual-layer microfluidic chip structure can slide along the first side of the second dual-layer microfluidic chip structure through the sliding structure, so that the quantitative unit can be connected to the auxiliary quantitative unit or the extraction and transport unit.

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

[0010] Furthermore, sealing elements are provided at the connection points between the first microchannel and the second microchannel, and at the connection points between the first microchannel and the third microchannel.

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

[0012] Furthermore, the first dual-layer microfluidic chip structure integrates multiple quantitative units, each quantitative unit being arranged side-by-side and spaced apart along the first side of the first dual-layer microfluidic chip structure; the second dual-layer microfluidic chip structure integrates multiple auxiliary quantitative units and multiple extraction and transport units matching the number of quantitative units, each auxiliary quantitative unit and each extraction and transport unit being arranged side-by-side and spaced apart along the first side of the second dual-layer microfluidic chip structure.

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

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

[0015] The second aspect of this invention provides a method for quantitative extraction of trace liquids using a microfluidic chip. Utilizing the aforementioned microfluidic chip, the method includes 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 injection port. At this time, the liquid fills the quantitative chamber through the first microchannel and enters the balance chamber through the second microchannel connected to the first microchannel. Excess air in the balance chamber is discharged through the exhaust port.

[0017] The movable quantitative unit connects to the extraction and transport unit. By introducing gas, oil, or other liquids for subsequent use into the injection port, the required trace amount of liquid can be quantitatively extracted from the outlet for subsequent biological process detection.

[0018] This invention, by setting up a quantitative unit, an auxiliary quantitative unit, and an extraction and transport unit, enables the quantitative extraction and transport of trace liquids by selectively connecting the quantitative unit with the auxiliary quantitative unit and the extraction and transport unit. By connecting the balance chamber of the auxiliary quantitative unit with the quantitative chamber of the quantitative unit, not only is the quantitative analysis of trace liquids achieved, but the excess liquid in the quantitative analysis can also be stored through the balance chamber. This reduces the requirements for liquid driving precision, improves quantitative accuracy and ease of operation, and provides a solution for the extraction of various biochemical reactions and the smooth progress of subsequent reaction steps. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

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

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

[0022] Figure 3A and 3B This is 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 micro-liquid quantitative extraction function under quantitative conditions according to an embodiment of the present invention;

[0024] Figure 5 This is a schematic diagram of a microfluidic chip with micro-liquid quantitative extraction function under quantitative conditions according to an embodiment of the present invention. Detailed Implementation

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

[0026] like Figure 4 and 5 As shown, the microfluidic chip of the present invention, which has the function of quantitative extraction of trace liquids, includes a quantitative unit 1, an auxiliary quantitative unit 2, and an extraction and transport unit 3. The quantitative unit 1 includes an injection port 11, a first microchannel 12, and a quantitative chamber 13. The auxiliary quantitative unit 2 includes a second microchannel 21, a balance chamber 22, and an exhaust port 23. The extraction and transport unit 3 includes a third microchannel 31 and an outlet 32. The volume of the quantitative chamber 13 is smaller than the volume of the balance chamber 22. The volume of the quantitative chamber 13 is usually designed in microliters or submicroliters to adapt to the quantitative extraction of trace liquids in the field of biochemical analysis. The volume of the balance chamber 22 is determined 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 chamber is 10 microliters, then the volume of the balance chamber 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 transport unit 3 to switch between quantitative and extraction and transport modes. When the quantitative unit 1 is connected to the auxiliary quantitative unit 2, it is in quantitative mode (see...). Figure 4In the quantitative operation, the first microchannel 12 and the second microchannel 21 are connected, connecting the quantitative chamber 13 and the balance chamber 22. Liquid is injected into the quantitative unit 1 through the injection port 11 via an external driving device. A portion of the liquid injected through the injection port 11 fills the quantitative chamber 13 for micro-liquid metering. Excess liquid flows from the first microchannel 12 and the second microchannel 21 to the balance chamber 22 for storage. An exhaust port 23 is provided on the balance chamber 22 to reduce air pressure resistance, facilitating the injection of liquid into the quantitative unit 1 by the external driving device for metering operations. The interface and microchannel dimensions are kept as small as possible; for example, the interface size can be designed to be 0.3mm to 0.6mm, and the microchannel depth can be designed to be 0.1mm to 0.4mm to avoid liquid loss.

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

[0028] This invention, through the cooperation of the quantitative chamber of the quantitative unit and the balancing chamber of the auxiliary quantitative unit, achieves quantitative operation of trace liquids. This ensures precise quantification while reducing the requirements for the driving accuracy of external drive equipment, significantly lowering the cost of trace liquid quantification. It also provides a solution for the extraction of various biochemical reactions and the smooth execution of subsequent reaction steps.

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

[0030] In one embodiment of the present invention, such as Figure 2 As shown, the auxiliary quantitative unit 2 and the extraction and transport unit 3 are integrated on the second double-layer microfluidic chip structure. The exhaust port 23 and the liquid outlet 32 ​​are located on the upper layer of the chip, while the second microchannel 21 and the balance chamber 22 are located on the lower layer. The input ends of the second microchannel 21 and 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 rigid polymer thermoplastic materials such as PP, PC, PET, PTFE, and COC, and processed by injection molding or other methods. The bonding of the upper and lower layers can be achieved through laser bonding, ultrasonic bonding, hot-press bonding, adhesive bonding, etc. In this embodiment, the auxiliary quantitative unit and the extraction and transport unit are integrated together, and the design is a two-layer structure. On the one hand, this ensures reliable process implementation; the two-layer structure can be achieved through traditional processes such as injection molding and bonding, resulting in higher cost and yield. On the other hand, it allows for convenient connection and switching between the quantitative unit and the auxiliary quantitative unit and the extraction and transport unit. It should be noted that the structure of the present invention is not limited to this, and it is also designed as a three-layer structure according to the actual chip function requirements.

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

[0032] In one embodiment of the present invention, sealing elements 5 are provided at the connection points of the first microchannel 12 and the second microchannel 21, and at the connection points of 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. The sealing element is deformed and compressed to achieve a seal at the fluid channel interface, ensuring the sealing performance when the first microchannel is connected to the second and third microchannels respectively. The sealing element material can be selected from materials such as fluororubber, liquid silicone, TPE, and TPU.

[0033] In one embodiment of the present invention, a plurality of quantitative units 1 are integrated on the first dual-layer microfluidic chip structure, each quantitative unit 1 being arranged side-by-side at intervals along the first side of the first dual-layer microfluidic chip structure; a plurality of auxiliary quantitative units 2 and a plurality of extraction and transport units 3 are integrated on the second dual-layer microfluidic chip structure, matching the number of the plurality of quantitative units 1, each auxiliary quantitative unit 2 and each extraction and transport unit 3 being arranged side-by-side at intervals along the first side of the second dual-layer microfluidic chip structure. The intervals between the plurality of quantitative units 1 are respectively matched with the intervals between the plurality of auxiliary quantitative units 2 and the plurality of extraction and transport units 3, so as to ensure that after one quantitative unit 1 is connected to an auxiliary quantitative unit 2 or an extraction and transport unit 3, the other quantitative units can also be connected to the auxiliary quantitative unit 2 or the extraction and transport unit 3 precisely, allowing multiple channels to work simultaneously, greatly improving the efficiency of quantitative extraction operations.

[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 on the first side of the first dual-layer microfluidic chip structure and / or the first side of the second dual-layer microfluidic chip structure. For example, a positioning protrusion is provided on the first side of the first dual-layer microfluidic chip structure near the output end of the first microchannel, and positioning grooves are provided on the first sides of the second dual-layer microfluidic chip structure near the input end of the second microchannel and the input end of the third microchannel. During the sliding process of the first dual-layer microfluidic chip structure on the first side of the second dual-layer microfluidic chip structure via the sliding structure, when the positioning protrusion is sensed to move into the positioning groove, it indicates that the quantitative unit 1 has moved to the accurate connection position with the auxiliary quantitative unit 2 or the extraction and transport unit 3. It should be noted that the connection and positioning method of the quantitative unit, the auxiliary quantitative unit, and the extraction and transport unit of the present invention is not limited to this, and the movement position can also be precisely controlled by an external motion driving device.

[0035] In one embodiment of the present invention, a liquid-resistant 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 metering operation.

[0036] This invention also provides a method for quantitative extraction of trace liquids using a microfluidic chip. Utilizing the aforementioned microfluidic chip, the method includes 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 injection port. At this time, the liquid fills the quantitative chamber through the first microchannel and enters the balance chamber through the second microchannel connected to the first microchannel. Excess air in the balance chamber is discharged through the exhaust port.

[0038] The movable quantitative unit connects to the extraction and transport unit. By introducing gas, oil, or other liquids for subsequent use into the injection port, the required trace amount of liquid can be quantitatively extracted from the outlet for subsequent biological process detection.

[0039] In summary, this invention is applicable to scenarios involving the extraction and transport of quantitative trace amounts of liquid in biological reaction processes. It reduces the precision requirements for liquid-driven extraction and is suitable for simultaneous parallel liquid extraction via single or multiple channels, improving accuracy and ease of operation. This provides a solution for the smooth progress of extraction and subsequent reaction steps in various biochemical reactions.

[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 principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A microfluidic chip with micro-liquid quantitative extraction function, characterized in that, The device includes a quantitative unit, an auxiliary quantitative unit, and an extraction and transport unit. The quantitative unit is integrated on a first double-layer microfluidic chip structure, and the auxiliary quantitative unit and the extraction and transport unit are integrated on a second double-layer microfluidic chip structure. The quantitative unit includes an injection port, a first microchannel, and a quantitative chamber. The auxiliary quantitative unit includes a second microchannel, a balance chamber, and an exhaust port. The extraction and transport unit includes a third microchannel and an outlet. The quantitative unit can be selectively connected to either the auxiliary quantitative unit or the extraction and transport unit. When the quantitative unit is connected to the auxiliary quantitative unit, it connects the quantitative chamber and the balance chamber through the first microchannel and the second microchannel. A portion of the liquid injected through the injection port fills the quantitative chamber for quantitative liquid measurement, and the excess liquid flows to the balance chamber for storage. When the quantitative unit is connected to the extraction and transport unit, it connects the quantitative liquid in the quantitative chamber through the first microchannel and the third microchannel, allowing the quantitative liquid to be extracted from the outlet.

2. The microfluidic chip with micro-liquid quantitative extraction function as described in claim 1, characterized in that, The injection port is located on the upper layer of the first dual-layer microfluidic chip structure, the first microchannel and the metering chamber are located on the lower layer of the first dual-layer microfluidic chip structure, and the output end of the first microchannel extends to the first side of the first dual-layer microfluidic chip structure.

3. The microfluidic chip with micro-liquid quantitative extraction function as described in claim 2, characterized in that, The input ends of the second microchannel and the third microchannel extend to the first side of the second dual-layer microfluidic chip structure.

4. The microfluidic chip with micro-liquid quantitative extraction function as described in claim 3, characterized in that, The first side of the first dual-layer microfluidic chip structure and the first side of the second dual-layer microfluidic chip structure are provided with mutually cooperating sliding structures. The first dual-layer microfluidic chip structure can slide along the first side of the second dual-layer microfluidic chip structure through the sliding structures, so that the quantitative unit can be connected to the auxiliary quantitative unit or the extraction and transport unit.

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

6. The microfluidic chip with micro-liquid quantitative extraction function as described in claim 5, characterized in that, A sealing element is provided at the connection between the first microchannel and the second microchannel, and at the connection between the first microchannel and the third microchannel.

7. The microfluidic chip with micro-liquid quantitative extraction function as described in claim 6, characterized in that, The sealing element is positioned at the output end of the first microchannel in the dovetail groove.

8. The microfluidic chip with micro-liquid quantitative extraction function as described in claim 3, characterized in that, The first dual-layer microfluidic chip structure integrates multiple quantitative units, each of which is arranged side-by-side and spaced apart along the first side of the first dual-layer microfluidic chip structure; the second dual-layer microfluidic chip structure integrates multiple auxiliary quantitative units and multiple extraction and transport units that match the number of quantitative units, each of which is arranged side-by-side and spaced apart along the first side of the second dual-layer microfluidic chip structure.

9. The microfluidic chip with micro-liquid quantitative extraction function as described in claim 4, characterized in that, A sliding positioning structure for positioning the sliding position of the sliding structure is provided on the first side of the first dual-layer microfluidic chip structure and / or the first side of the second dual-layer microfluidic chip structure.

10. The microfluidic chip with micro-liquid quantitative extraction function as described in claim 1, characterized in that, A liquid-resistant and breathable membrane is provided at the exhaust port.

11. A method for quantitative extraction of trace liquids using a microfluidic chip, characterized in that, Using the microfluidic chip as described in any one of claims 1-10, the method includes 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 injection port. At this time, the liquid fills the quantitative chamber through the first microchannel and enters the balance chamber through the second microchannel connected to the first microchannel. Excess air in the balance chamber is discharged through the exhaust port. The movable quantitative unit connects to the extraction and transport unit. By introducing gas, oil, or other liquids for subsequent use into the injection port, the required trace amount of liquid can be quantitatively extracted from the outlet for subsequent biological process detection.

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