A modularized tubular microfluidic analysis and detection device and detection method

Abstract

The application relates to the technical field of microfluidics, and discloses a modular tubular microfluidic analysis and detection device and a detection method, which comprises the following steps: manufacturing a fluid input module and a reaction and measurement module by using laser cutting, machining, injection molding or 3D printing technology; the fluid input module comprises a plurality of fluid input mechanisms; the fluid input mechanism comprises a liquid storage device, a first micropump and a first microvalve, and each fluid input mechanism is independent of each other; the reaction and measurement module comprises a microreactor and a signal reader; the signal reader is connected with the microreactor; a hose is used to connect the fluid input module and the microreactor; the liquid to be detected is stored in the liquid storage device; the liquid to be detected flows into the microreactor through the hose under the control of the first micropump and the first microvalve; the signal reader acquires signal changes when the liquid to be detected in the microreactor reacts; and analysis and detection results are obtained according to the signal changes. The application can realize a stable pipeline structure, facilitate function expansion and reduce costs.

Description

Technical Field

[0001] This invention relates to the field of microfluidics, and in particular to a modular tubular microfluidic analysis and detection device and method. Background Technology

[0002] Microfluidics is 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). Microfluidics technology has enormous potential in fields such as chemistry, biology, and medicine due to its advantages of low sample consumption, high detection speed, high integration, low cost, ease of operation, and small size and portability. Microfluidic chips, as the primary form of microfluidics, provide a strictly controllable fluid manipulation environment for the flow channels and pumps, valves, chambers, and other structures required for various biochemical reactions, achieving better sealing and contamination resistance than traditional techniques. Microfluidic systems, as the main carriers of microfluidics technology, combine highly integrated electronic and mechanical technologies to drive and control microfluidic chips to achieve their functions, and are now widely used in biochemical detection and clinical diagnostics.

[0003] Currently, microfluidic chips are primarily manufactured using micro- and nanofabrication techniques, such as photolithography and soft photolithography. However, the high cost of micro- and nanofabrication techniques limits the reduction in the cost of microfluidic chips, thus restricting their large-scale replacement of traditional biochemical detection and clinical diagnostics. Furthermore, microfluidic chips manufactured using micro- and nanofabrication techniques are structurally fragile, requiring more precise external equipment and more stringent operating environments, all of which contribute to the high cost and complexity of the entire microfluidic system. In addition, existing microfluidic chips have fixed functions once fabricated, lacking the ability to be versatile and adaptable. These shortcomings all constrain the further expansion of microfluidic technology's application scenarios. Summary of the Invention

[0004] Therefore, the technical problem to be solved by the present invention is to overcome the shortcomings of the prior art and provide a modular tubular microfluidic analysis and detection device and detection method, which can realize a stable pipe structure, facilitate equipment expansion according to actual needs, enhance the reusability of the overall device while meeting different functional requirements, and reduce costs.

[0005] To address the aforementioned technical problems, this invention provides a modular tubular microfluidic analysis and detection device, comprising:

[0006] The fluid input module includes multiple fluid input mechanisms, each fluid input mechanism including a liquid storage device, a first micropump, and a first microvalve, and each fluid input mechanism is independent of the others.

[0007] The reaction measurement module includes a microreactor and a signal reader, wherein the signal reader is connected to the microreactor;

[0008] A flexible hose for connecting the fluid input module and the microreactor;

[0009] The liquid storage device stores the liquid to be tested, which flows into the microreactor through the tubing under the control of the first micropump and the first microvalve. The signal reader acquires the signal change when the liquid to be tested reacts in the microreactor, and obtains the analysis and detection results based on the signal change.

[0010] In one embodiment of the present invention, the microreactor is an enzyme-linked immunosorbent assay (ELISA) reactor, which includes an enzyme-linked reaction chamber, and the enzyme-linked reaction chamber is provided with an enzyme-linked reaction outlet and multiple enzyme-linked reaction inlets.

[0011] The two ends of the tubing are respectively connected to the liquid storage device and the enzyme-linked reaction inlet. The liquid to be tested in the liquid storage device enters the enzyme-linked reaction pool through the enzyme-linked reaction inlet. The first micro valve is installed on the tubing.

[0012] The signal reader is connected to the enzyme-linked reaction chamber and acquires the signal changes in the enzyme-linked reaction chamber in real time. After the analysis and detection are completed, the liquid in the enzyme-linked reaction chamber flows out through the enzyme-linked reaction outlet.

[0013] In one embodiment of the present invention, the microreactor is an electrochemical reactor, the electrochemical reactor includes an electrochemical reaction cell, the electrochemical reaction cell is provided with an electrochemical reaction outlet and multiple electrochemical reaction inlets, and an electrochemical sensing electrode is provided inside the electrochemical reaction cell;

[0014] The two ends of the hose are respectively connected to the liquid storage device and the electrochemical reaction inlet. The liquid to be tested in the liquid storage device enters the electrochemical reaction cell through the electrochemical reaction inlet. The first micro valve is installed on the hose.

[0015] The signal reader is connected to the electrochemical reaction cell and acquires the signal changes in the electrochemical reaction cell in real time. After the analysis and detection are completed, the liquid in the electrochemical reaction cell flows out through the electrochemical reaction outlet.

[0016] The electrochemical sensing electrode is disposed on the inner wall of the electrochemical reaction cell. The electrochemical sensing electrode extends a pin to connect to an external device and transmits the reaction data in the electrochemical reaction cell monitored in real time to the external device.

[0017] In one embodiment of the present invention, the signal reader is a visible light signal reader, which includes:

[0018] A visible light sensor is installed on the electrochemical reaction cell to convert the changes in light when the liquid to be tested in the electrochemical reaction cell reacts into signal changes.

[0019] The interaction module, connected to the visible light sensor, is used to communicate with external devices and transmit signal changes to the external devices.

[0020] In one embodiment of the present invention, the microreactor is a PCR reactor, and the PCR reactor includes a PCR reaction channel;

[0021] The two ends of the tubing are respectively connected to the liquid storage device and the PCR reaction channel. The test liquid in the liquid storage device enters the PCR reaction channel through the tubing. The first micro valve is disposed on the tubing.

[0022] The PCR reaction channel is equipped with a PCR temperature controller, which includes a mounting base. Multiple integrated electrodes are fixed on the mounting base. The integrated electrodes have heating and sensing functions. The multiple integrated electrodes are mounted on the PCR reaction channel through the mounting base.

[0023] The signal reader is connected to the integrated electrode. The integrated electrode heats the liquid in the PCR reaction channel through a heating function. The integrated electrode extends pins to connect to an external device and transmits the reaction data in the PCR reaction channel monitored in real time to the external device through a sensing function.

[0024] In one embodiment of the present invention, the fluid input module includes three fluid input mechanisms, the PCR reaction channel is a triangular channel, and the PCR temperature controller includes three integrated electrodes, which are respectively disposed on the three sides of the triangle of the PCR reaction channel.

[0025] In one embodiment of the present invention, before the liquid to be tested flows into the microreactor through the hose under the control of the first micropump and the first microvalve, a liquid control mechanism is provided at the inlet of the microreactor. The liquid control mechanism includes an S-shaped hose, a second micropump and a second microvalve. The two ends of the S-shaped hose are respectively connected to the hose and the microreactor. The second micropump and the second microvalve are provided near the inlet of the microreactor on the S-shaped hose.

[0026] The liquid to be tested enters the S-shaped hose after passing through the hose, and flows into the microreactor under the control of the second micropump and the second microvalve.

[0027] In one embodiment of the present invention, the first micropump includes a pump body and a pump base. The first micropump is fixed on the hose through the pump base, and the liquid to be tested flows into the microreactor through the hose under the action of the pump body.

[0028] The first micro-valve includes a valve seat, a moving rod, a valve disc, and a displacement actuator. The first micro-valve is fixed to the hose by the valve seat. The extension direction of the moving rod is perpendicular to the flow direction of the liquid to be tested in the hose. The valve disc moves on the moving rod and controls the flow rate of the liquid to be tested in the hose by pressing it against the hose. The displacement actuator is connected to the valve disc and controls the position of the valve disc pressing against the hose.

[0029] In one embodiment of the present invention, the microreactor is made of a biocompatible material.

[0030] This invention also provides a modular tubular microfluidic analysis and detection method, comprising:

[0031] The fluid input module and reaction measurement module are manufactured using laser cutting, machining, injection molding, or 3D printing technologies. The fluid input module includes multiple fluid input mechanisms, each of which includes a liquid storage device, a first micropump, and a first microvalve, and each fluid input mechanism is independent of the others. The reaction measurement module includes a microreactor and a signal reader, and the signal reader is connected to the microreactor.

[0032] The fluid input module and the microreactor are connected by a hose. The liquid storage device stores the liquid to be tested. The liquid to be tested flows into the microreactor through the hose under the control of the first micropump and the first microvalve. The signal reader acquires the signal change when the liquid to be tested reacts in the microreactor, and obtains the analysis and detection results based on the signal change.

[0033] The technical solution of the present invention has the following advantages compared with the prior art:

[0034] This invention transforms traditional microfluidic chips into a tubular flow control mode by setting up a fluid input module and a reaction measurement module, and connecting the fluid input module and the reaction measurement module with a hose. The fluid input module, reaction measurement module and hose in the flow control mode have low manufacturing costs, effectively reducing costs. Furthermore, the tubular structure connected by the hose is stable and easy to modify, and the equipment can be expanded according to actual needs. While meeting different functional requirements, it enhances the reusability of the overall device and further reduces costs. Attached Figure Description

[0035] To make the content of this invention easier to understand, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings, wherein:

[0036] Figure 1 This is a schematic diagram of the planar structure of Embodiment 1 or Embodiment 2 of the present invention.

[0037] Figure 2 This is a three-dimensional structural schematic diagram of the enzyme-linked immunosorbent assay (ELISA) reactor in Example 1.

[0038] Figure 3 yes Figure 1 A three-dimensional structural diagram of the visible light signal reader in the image.

[0039] Figure 4 This is a three-dimensional structural schematic diagram of the electrochemical reactor in Example 2.

[0040] Figure 5 This is a schematic diagram of the planar structure of Embodiment 3 of the present invention.

[0041] Figure 6 yes Figure 5 A three-dimensional structural diagram of a PCR temperature controller.

[0042] Figure 7 This is a schematic diagram of the structure of the first micro-valve in this invention.

[0043] Explanation of reference numerals in the accompanying drawings: 1. Fluid input module; 101. Fluid input mechanism; 1011. Liquid storage device; 1012. First micropump; 1013. First microvalve; 10131. Valve seat; 10132. Moving rod; 10133. Valve disc; 10134. Displacement actuator; 2. Reaction measurement module; 201. Microreactor; 202. Signal reader; 3. Tube; 4. Enzyme-linked immunosorbent assay reactor; 401. Enzyme-linked reaction cell; 402. Enzyme-linked reaction outlet; 403. Enzyme-linked reaction inlet; 5. Electrochemical reactor; 501. Electrochemical reactor... 502. Electrochemical reaction outlet; 503. Electrochemical reaction inlet; 504. Electrochemical sensing electrode; 6. Visible light signal reader; 601. Visible light sensor; 602. Interaction module; 603. Housing; 7. PCR reactor; 701. PCR reaction channel; 702. PCR temperature controller; 7021. Mounting base; 7022. Integrated electrode; 8. Liquid control mechanism; 801. S-shaped hose; 802. Second micropump; 803. Second microvalve; 9. Third micropump; 10. Third microvalve; 11. Fourth micropump; 12. Fourth microvalve; Detailed Implementation

[0044] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments described are not intended to limit the present invention.

[0045] Example 1

[0046] Reference Figure 1 As shown, this embodiment discloses a modular tubular microfluidic analysis and detection device for analyzing and detecting enzyme-linked immunosorbent assay (ELISA) reactions, including: a fluid input module 1, a reaction measurement module 2, and a tubular tube 3.

[0047] The fluid input module 1 includes multiple fluid input mechanisms 101, each comprising a liquid storage device 1011, a first micropump 1012, and a first microvalve 1013, with each mechanism operating independently. The reaction measurement module 2 includes a microreactor 201 and a signal reader 202, which are connected to the microreactor 201. A flexible hose 3 connects the fluid input module 1 and the microreactor 201. The function of the microreactor 201 can be determined based on the actual reaction type, and appropriate surface modifications and structural configurations can be made to match different functions.

[0048] The liquid storage device 1011 stores the liquid to be tested. Under the control of the first micro pump 1012 and the first micro valve 1013, the liquid to be tested flows into the microreactor 201 through the hose 3. The first micro pump 1012 controls the flow of the liquid to be tested into the microreactor 201, and the first micro valve 1013 controls the flow rate of the liquid to be tested into the microreactor 201. The signal reader 202 acquires the signal change when the liquid to be tested reacts in the microreactor 201, and obtains the analysis and detection results based on the signal change.

[0049] In this embodiment, the microreactor 201 is the enzyme-linked immunosorbent assay (ELISA) reactor 4, such as... Figure 2As shown, the enzyme-linked immunosorbent assay (ELISA) reactor 4 includes an ELISA chamber 401, which has an ELISA outlet 402 and multiple ELISA inlets 403. The ELISA reactor 4 uses biocompatible materials, such as polyethylene, silica gel, polytetrafluoroethylene (PTFE), ethylene-tetrafluoroethylene copolymer, perfluoropropyl perfluorovinyl ether (PFV) copolymer with PTFE, etc. The inner wall surface of the ELISA reactor 4 is modified with antibodies or antigens, or through surface modification, as required. Modification treatments can give the surface different physical, chemical, and biological properties. For example, physical methods such as plasma etching and micro-polishing can be used to change the surface microstructure, thereby altering its hydrophilicity or hydrophobicity; functional groups can be modified on the surface through chemical grafting, which can provide connection sites for other chemical groups or bioactive substances (antigens, antibodies, ligands, etc.), or can be used to enhance the signal intensity of the sensing reaction.

[0050] The flexible tube 3 is connected at both ends to the liquid storage device 1011 and the enzyme-linked reaction inlet 403, respectively. The test liquid in the liquid storage device 1011 enters the enzyme-linked reaction pool 401 through the enzyme-linked reaction inlet 403. The first microvalve 1013 is installed on the flexible tube 3 and controls the flow rate of the test liquid in the liquid storage device 1011 into the enzyme-linked reaction pool 401. The signal reader 202 is connected to the enzyme-linked reaction pool 401 and acquires the signal changes in the enzyme-linked reaction pool 401 in real time. After the analysis and detection are completed, the liquid in the enzyme-linked reaction pool 401 flows out through the enzyme-linked reaction outlet 402.

[0051] The number of fluid input mechanisms 101 is adjusted according to actual needs. Figure 1 The fluid input mechanism 101 in the example consists of four fluid input mechanisms 101. The four independent fluid input mechanisms 101 are: a first fluid input mechanism 101, a second fluid input mechanism 101, a third fluid input mechanism 101, and a fourth fluid input mechanism 101. The liquid from the first, second, and third fluid input mechanisms 101 flows into the enzyme-linked reaction pool 401 through the hose 3 and then into the enzyme-linked reaction pool 401 from one enzyme-linked reaction inlet 403. The liquid from the fourth fluid input mechanism 101 flows into the enzyme-linked reaction pool 401 from another enzyme-linked reaction inlet 403.

[0052] In this embodiment, the signal reader 202 is a visible light signal reader 6, which includes a visible light sensor 601, an interaction module 602, and a housing 603. The visible light sensor 601 is mounted on the enzyme-linked reaction chamber 401, converting changes in light intensity during the reaction of the test liquid in the chamber 401 into signal changes. The interaction module 602 is connected to the visible light sensor 601 and is used to communicate with external devices via wired or wireless means and transmit signal changes to the external devices. The housing 603 is located outside the visible light sensor 601 and the interaction module 602, protecting them and engaging with the slot plate.

[0053] In this embodiment, the modular tubular microfluidic analysis and detection device also includes a slot plate. The slots include flow channel slots and equipment slots. The slot plate is made of polymethyl methacrylate, polyvinyl chloride, polyethylene, polypropylene, or polystyrene. The hose 3 needs to be cut to a suitable length according to the slot plate. The hose 3, S-type hose 801, and other connecting parts are embedded in the flow channel slots for positioning. The liquid storage device 1011, the first micropump 1012 and other micropumps, the first microvalve 1013 and other microvalves, the microreactor 201, the signal reader 202, and other external equipment are embedded in the equipment slots for positioning, achieving stable installation between the various parts.

[0054] In this embodiment, the first micropump 1012 includes a pump body, a pump base, and a piezoelectric diaphragm. The pump body and the piezoelectric diaphragm form a cavity. The first micropump 1012 is fixed to the hose 3 by snap-fitting the pump base. This snap-fit ​​assembly allows for convenient changes in the assembly position. The liquid to be tested flows into the microreactor 201 through the hose 3 under the action of the pump body. Figure 7 As shown, the first microvalve 1013 includes a valve seat 10131, a moving rod 10132, a valve disc 10133, and a displacement actuator 10134. The first microvalve 1013 is fixed to the hose 3 by the valve seat 10131. The extension direction of the moving rod 10132 is perpendicular to the flow direction of the liquid to be measured in the hose 3. The valve disc 10133 moves on the moving rod 10132 and controls the flow rate of the liquid to be measured in the hose 3 by pressing it against the hose 3. The displacement actuator 10134 is connected to the valve disc 10133 and controls the position of the valve disc 10133 pressing against the hose 3. The displacement actuator 10134 can be a servo motor.

[0055] The first micro-valve 1013 is used to control the flow of the liquid to be tested in the tubing 3. Combined with the power provided by the first micro-pump 1012, the direction and flow rate of the liquid to be tested can be controlled. In this embodiment, when the tubing 3 is connected to various parts such as the liquid storage device 1011 and the enzyme-linked reaction inlet 403, the connection effect is improved by setting a connector between the tubing 3. The tubing 3 and the connector between the tubing 3 are made of polyethylene, silicone, polytetrafluoroethylene, ethylene-tetrafluoroethylene copolymer, perfluoropropyl perfluorovinyl ether, or polytetrafluoroethylene copolymer.

[0056] Example 2

[0057] Reference Figure 1 As shown, this embodiment discloses a modular tubular microfluidic analysis and detection device for analyzing and detecting electrochemical reactions, including: a fluid input module 1, a reaction measurement module 2, and a tubular tube 3.

[0058] The fluid input module 1 includes multiple fluid input mechanisms 101, each comprising a liquid storage device 1011, a first micropump 1012, and a first microvalve 1013, with each mechanism operating independently. The reaction measurement module 2 includes a microreactor 201 and a signal reader 202, which are connected to the microreactor 201. A flexible hose 3 connects the fluid input module 1 and the microreactor 201. The function of the microreactor 201 can be determined based on the actual reaction type, and appropriate surface modifications and structural configurations can be made to match different functions.

[0059] The liquid storage device 1011 stores the liquid to be tested. Under the control of the first micro pump 1012 and the first micro valve 1013, the liquid to be tested flows into the microreactor 201 through the hose 3. The first micro pump 1012 controls the flow of the liquid to be tested into the microreactor 201, and the first micro valve 1013 controls the flow rate of the liquid to be tested into the microreactor 201. The signal reader 202 acquires the signal change when the liquid to be tested reacts in the microreactor 201, and obtains the analysis and detection results based on the signal change.

[0060] In this embodiment, the microreactor 201 is an electrochemical reactor 5. For example... Figure 4 As shown, the electrochemical reactor 5 includes an electrochemical reaction tank 501, which is provided with an electrochemical reaction outlet 502 and multiple electrochemical reaction inlets 503. An electrochemical sensing electrode 504 is provided inside the electrochemical reaction tank 501. The reaction tank uses biocompatible materials, such as polyethylene, silicone, polytetrafluoroethylene, ethylene-tetrafluoroethylene copolymer, perfluoropropyl perfluorovinyl ether copolymer with polytetrafluoroethylene, etc.

[0061] The flexible tube 3 is connected at both ends to the liquid storage device 1011 and the electrochemical reaction inlet 503, respectively. The test liquid in the liquid storage device 1011 enters the electrochemical reaction cell 501 through the electrochemical reaction inlet 503. The first micro valve 1013 is installed on the flexible tube 3 and controls the flow rate of the test liquid in the liquid storage device 1011 into the electrochemical reaction cell 501. The signal reader 202 is connected to the electrochemical reaction cell 501 and acquires the signal changes in the electrochemical reaction cell 501 in real time. After the analysis and detection are completed, the liquid in the electrochemical reaction cell 501 flows out through the electrochemical reaction outlet 502. The electrochemical sensing electrode 504 is installed on the inner wall of the electrochemical reaction cell 501. The electrochemical sensing electrode 504 extends a pin to connect to an external device and transmits the real-time monitored reaction data in the electrochemical reaction cell 501 to the external device, realizing the real-time measurement and analysis of the reaction in the electrochemical reaction cell 501.

[0062] In this embodiment, the signal reader 202 is a visible light signal reader 6, which includes a visible light sensor 601, an interaction module 602, and a housing 603. The visible light sensor 601 is mounted on the electrochemical reaction cell 501, converting changes in light intensity during the reaction of the liquid to be tested in the electrochemical reaction cell 501 into signal changes. The interaction module 602 is connected to the visible light sensor 601 and is used to communicate with external devices via wired or wireless means and transmit signal changes to the external devices. The housing 603 is located outside the visible light sensor 601 and the interaction module 602, protecting them and engaging with the slot plate.

[0063] In this embodiment, the modular tubular microfluidic analysis and detection device also includes a slot plate. The slots include flow channel slots and equipment slots. The slot plate is made of polymethyl methacrylate, polyvinyl chloride, polyethylene, polypropylene, or polystyrene. The hose 3 needs to be cut to a suitable length according to the slot plate. The hose 3, S-type hose 801, and other connecting parts are embedded in the flow channel slots for positioning. The liquid storage device 1011, the first micropump 1012 and other micropumps, the first microvalve 1013 and other microvalves, the microreactor 201, the signal reader 202, and other external equipment are embedded in the equipment slots for positioning, achieving stable installation between the various parts.

[0064] In this embodiment, the first micropump 1012 includes a pump body, a pump base, and a piezoelectric diaphragm. The pump body and the piezoelectric diaphragm form a cavity. The first micropump 1012 is fixed to the hose 3 by snap-fitting the pump base. This snap-fit ​​assembly allows for convenient changes in the assembly position. The liquid to be tested flows into the microreactor 201 through the hose 3 under the action of the pump body. Figure 7As shown, the first microvalve 1013 includes a valve seat 10131, a moving rod 10132, a valve disc 10133, and a displacement actuator 10134. The first microvalve 1013 is fixed to the hose 3 by the valve seat 10131. The extension direction of the moving rod 10132 is perpendicular to the flow direction of the liquid to be measured in the hose 3. The valve disc 10133 moves on the moving rod 10132 and controls the flow rate of the liquid to be measured in the hose 3 by pressing it against the hose 3. The displacement actuator 10134 is connected to the valve disc 10133 and controls the position of the valve disc 10133 pressing against the hose 3. The displacement actuator 10134 can be a servo motor.

[0065] The first micro-valve 1013 is used to control the flow of the liquid to be tested in the hose 3. Combined with the power provided by the first micro-pump 1012, the direction and flow rate of the liquid to be tested can be controlled. In this embodiment, when the hose 3 is connected to various parts such as the liquid storage device 1011 and the electrochemical reaction inlet 503, the connection effect is improved by setting a connector between the hoses 3. The hoses 3 and the connectors between the hoses 3 are made of polyethylene, silicone, polytetrafluoroethylene, ethylene-tetrafluoroethylene copolymer, perfluoropropyl perfluorovinyl ether, or polytetrafluoroethylene copolymer.

[0066] Example 3

[0067] Reference Figure 5 As shown, this embodiment discloses a modular tubular microfluidic analysis and detection device for analyzing and detecting polymerase chain reactions, including: a fluid input module 1, a reaction measurement module 2, and a tubular tube 3.

[0068] The fluid input module 1 includes multiple fluid input mechanisms 101, each comprising a liquid storage device 1011, a first micropump 1012, and a first microvalve 1013, with each mechanism operating independently. The reaction measurement module 2 includes a microreactor 201 and a signal reader 202, which are connected to the microreactor 201. A flexible hose 3 connects the fluid input module 1 and the microreactor 201. The function of the microreactor 201 can be determined based on the actual reaction type, and appropriate surface modifications and structural configurations can be made to match different functions.

[0069] The liquid storage device 1011 stores the liquid to be tested. Under the control of the first micro pump 1012 and the first micro valve 1013, the liquid to be tested flows into the microreactor 201 through the hose 3. The first micro pump 1012 controls the flow of the liquid to be tested into the microreactor 201, and the first micro valve 1013 controls the flow rate of the liquid to be tested into the microreactor 201. The signal reader 202 acquires the signal change when the liquid to be tested reacts in the microreactor 201, and obtains the analysis and detection results based on the signal change.

[0070] In this embodiment, the microreactor 201 is a PCR (Polymerase chain reaction) reactor, such as... Figure 5 As shown, the PCR reactor 7 includes a PCR reaction channel 701. The two ends of the flexible tube 3 are connected to the liquid storage device 1011 and the PCR reaction channel 701, respectively. The test liquid in the liquid storage device 1011 enters the PCR reaction channel 701 through the flexible tube 3. The first microvalve 1013 is installed on the flexible tube 3 and controls parameters such as the speed and flow rate of the test liquid flowing from the liquid storage device 1011 into the PCR reaction channel 701.

[0071] like Figure 6 As shown, a PCR temperature controller 702 is provided on the PCR reaction channel 701. The PCR temperature controller 702 includes a mounting base 7021, on which multiple integrated electrodes 7022 are snapped and fixed. The integrated electrodes 7022 have heating and sensing functions. The multiple integrated electrodes 7022 are mounted on the PCR reaction channel 701 through the mounting base 7021. The material of the integrated electrodes 7022 can be metal, graphite, etc. The electrode shape of the integrated electrode 7022 is needle-shaped. It is processed into a suitable needle shape according to requirements and the surface is modified and surface-modified. The needle-shaped electrodes are integrated to form the integrated electrode 7022.

[0072] The signal reader 202 is connected to the integrated electrode 7022. The integrated electrode 7022 heats the liquid in the PCR reaction channel 701 through its heating function, providing the temperature conditions required for PCR detection. The polymerase chain reaction (PCR) mainly consists of three steps: denaturation, annealing, and extension. Each step requires a different temperature, and different reaction temperatures can be achieved through the heating functions of multiple integrated electrodes 7022. The integrated electrode 7022 extends pins to connect to an external device and transmits the reaction data in the PCR reaction channel 701, monitored in real time through its sensing function, to the external device, enabling real-time measurement and analysis of the reaction within the PCR reaction channel 701.

[0073] The final result of the polymerase chain reaction is displayed in the form of fluorescence; therefore, in this embodiment, the signal reader 202 is a fluorescence signal reader. The structure of the fluorescence signal reader is similar to that of the visible light signal reader 6, except that the visible light sensor 601 is replaced with a fluorescence sensor.

[0074] In this embodiment, the modular tubular microfluidic analysis and detection device also includes a slot plate. The slots include flow channel slots and equipment slots. The slot plate is made of polymethyl methacrylate, polyvinyl chloride, polyethylene, polypropylene, or polystyrene. The hose 3 needs to be cut to a suitable length according to the slot plate. The hose 3, S-type hose 801, and other connecting parts are embedded in the flow channel slots for positioning. The liquid storage device 1011, the first micropump 1012 and other micropumps, the first microvalve 1013 and other microvalves, the microreactor 201, the signal reader 202, and other external equipment are embedded in the equipment slots for positioning, achieving stable installation between the various parts.

[0075] like Figure 5 As shown, the fluid input module 1 in this embodiment includes three fluid input mechanisms 101. The PCR reaction channel 701 is a triangular channel, and the PCR temperature controller 702 includes three integrated electrodes 7022, which are respectively located on the three sides of the triangle of the PCR reaction channel 701. The three fluid input mechanisms 101 are independent of each other. The three different test liquids in the three liquid storage devices 1011 circulate unidirectionally in the triangular PCR reaction channel 701 under the control of the three first microvalves 1013, and pass through the three PCR temperature controllers 702 in sequence for polymerase chain reaction determination.

[0076] In this embodiment, before the liquid to be tested flows into the microreactor 201 through the hose 3 under the control of the first micropump 1012 and the first microvalve 1013, a liquid control mechanism 8 is provided at the inlet of the microreactor 201. The liquid control mechanism 8 includes an S-shaped hose 801, a second micropump 802, and a second microvalve 803. The two ends of the S-shaped hose 801 are respectively connected to the hose 3 and the microreactor 201. The second micropump 802 and the second microvalve 803 are located near the inlet of the microreactor 201 on the S-shaped hose 801. After passing through the hose 3, the liquid to be tested enters the S-shaped hose 801, where it is mixed and / or slowed down. Under the control of the second micropump 802 and the second microvalve 803, it flows into the microreactor 201 through the S-shaped hose 801. By setting the liquid control mechanism 8, the flow rate and velocity of the liquid to be tested can be controlled again before entering the microreactor 201, further improving the reaction accuracy.

[0077] Figure 5The reaction measurement module 2 further includes two micropumps and microvalves: a third micropump 9, a third microvalves 10, a fourth micropump 11, and a fourth microvalves 12. The second micropump 802 and the second microvalves 803, the third micropump 9 and the third microvalves 10, and the third micropump 9 and the third microvalves 10 are each a group, respectively positioned on the triangle of the triangular flow channel, for precise control of the liquid flow rate in the triangular flow channel. The structures of the second micropump 802, the third micropump 9, and the fourth micropump 11 are the same as those of the first micropump 1012, and the structures of the second microvalves 803, the third microvalves 10, and the fourth microvalves 12 are the same as those of the first microvalves 1013.

[0078] In this embodiment, the first micropump 1012 includes a pump body, a pump base, and a piezoelectric diaphragm. The pump body and the piezoelectric diaphragm form a cavity. The first micropump 1012 is fixed to the hose 3 by snap-fitting the pump base. This snap-fit ​​assembly allows for convenient changes in the assembly position. The liquid to be tested flows into the microreactor 201 through the hose 3 under the action of the pump body. Figure 7 As shown, the first microvalve 1013 includes a valve seat 10131, a moving rod 10132, a valve disc 10133, and a displacement actuator 10134. The first microvalve 1013 is fixed to the hose 3 by the valve seat 10131. The extension direction of the moving rod 10132 is perpendicular to the flow direction of the liquid to be measured in the hose 3. The valve disc 10133 moves on the moving rod 10132 and controls the flow rate of the liquid to be measured in the hose 3 by pressing it against the hose 3. The displacement actuator 10134 is connected to the valve disc 10133 and controls the position of the valve disc 10133 pressing against the hose 3. The displacement actuator 10134 can be a servo motor.

[0079] The first micro-valve 1013 is used to control the flow of the liquid to be tested in the tubing 3. Combined with the power provided by the first micro-pump 1012, it can control the direction and flow rate of the liquid to be tested. In this embodiment, when the tubing 3 is connected to various parts such as the PCR reaction channel 701 of the liquid storage device 1011 and the S-shaped tubing 801, the connection effect is improved by setting a connector between the tubing 3. The tubing 3 and the connector between the tubing 3 are made of polyethylene, silicone, polytetrafluoroethylene, ethylene-tetrafluoroethylene copolymer, perfluoropropyl perfluorovinyl ether, or polytetrafluoroethylene copolymer.

[0080] Example 4

[0081] This invention also discloses a modular tubular microfluidic analysis and detection method, comprising:

[0082] The fluid input module 1 and reaction measurement module 2 are manufactured using technologies such as laser cutting, machining, injection molding, and 3D printing. The fluid input module 1 includes multiple fluid input mechanisms 101, each comprising a liquid storage device 1011, a first micropump 1012, and a first microvalve 1013, with each mechanism operating independently. The reaction measurement module 2 includes a microreactor 201 and a signal reader 202, which is connected to the microreactor 201. A flexible tube 3 connects the fluid input module 1 and the microreactor 201. The liquid storage device 11 stores the liquid to be tested, which flows into the microreactor 201 through the flexible tube 3 under the control of the first micropump 1012 and the first microvalve 1013. The signal reader 202 acquires signal changes when the liquid to be tested reacts within the microreactor 201, and obtains analytical results based on these signal changes.

[0083] The advantages of this invention compared to the prior art are:

[0084] 1. By incorporating a fluid input module and a reaction measurement module, and connecting them with a flexible tube, the traditional microfluidic chip is transformed into a tubular flow channel control mode. This mode offers the advantages of current microfluidic technology, including low sample consumption, fast detection speed, high integration, low cost, ease of operation, and small size for portability. The fluid input module, reaction measurement module, and flexible tube in the flow channel control mode have low manufacturing costs, effectively reducing overall costs.

[0085] 2. In view of the shortcomings of existing microfluidic technology in terms of processing technology and functional implementation, this invention uses manufacturing technologies such as laser cutting, machining, injection molding, and 3D printing to improve the strength of the components in each module while further reducing manufacturing costs.

[0086] 3. The tubular structure connected by flexible hoses is stable and highly robust. Furthermore, the tubular structure with flexible hose connections is easy to modify, allowing for equipment expansion according to actual needs. This enhances the reusability of the overall device while meeting different functional requirements and further reducing costs. This invention achieves low manufacturing costs, high robustness, multiple functions, and variable applications, opening up new application scenarios and market needs for microfluidics technology.

[0087] Those skilled in the art will understand that embodiments of this application can be provided as methods, systems, or computer program products. Therefore, this application can take the form of a completely hardware embodiment, a completely software embodiment, or an embodiment combining software and hardware aspects. Furthermore, this application can take the form of a computer program product embodied on one or more computer-usable storage media (including but not limited to disk storage, CD-ROM, optical storage, etc.) containing computer-usable program code.

[0088] This application is described with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of this application. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, special-purpose computer, embedded processor, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, generate instructions for implementing the flowchart... Figure 1 One or more processes and / or boxes Figure 1 A device that provides the functions specified in one or more boxes.

[0089] These computer program instructions may also be stored in a computer-readable storage medium that can direct a computer or other programmable data processing device to function in a particular manner, such that the instructions stored in the computer-readable storage medium produce an article of manufacture including instruction means, which are implemented in a process Figure 1 One or more processes and / or boxes Figure 1 The function specified in one or more boxes.

[0090] These computer program instructions may also be loaded onto a computer or other programmable data processing equipment to cause a series of operational steps to be performed on the computer or other programmable equipment to produce a computer-implemented process, thereby providing instructions that execute on the computer or other programmable equipment for implementing the process. Figure 1 One or more processes and / or boxes Figure 1 The steps of the function specified in one or more boxes.

[0091] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A modular tubular microfluidic analysis and detection device, characterized in that, include: The fluid input module includes multiple fluid input mechanisms, each fluid input mechanism including a liquid storage device, a first micropump, and a first microvalve, and each fluid input mechanism is independent of the others. The reaction measurement module includes a microreactor and a signal reader, wherein the signal reader is connected to the microreactor; A flexible hose for connecting the fluid input module and the microreactor; The liquid storage device stores the liquid to be tested, and the liquid to be tested flows into the microreactor through the tubing under the control of the first micropump and the first microvalve; the signal reader acquires the signal change when the liquid to be tested reacts in the microreactor, and obtains the analysis and detection results based on the signal change. The microreactor is a PCR reactor, which includes a PCR reaction channel. The two ends of the flexible tube are connected to the liquid storage device and the PCR reaction channel, respectively. The test liquid in the liquid storage device enters the PCR reaction channel through the flexible tube. A first microvalve is disposed on the flexible tube. A PCR temperature controller is provided on the PCR reaction channel. The PCR temperature controller includes a mounting base, on which multiple integrated electrodes are fixed. Each integrated electrode has heating and sensing functions. The multiple integrated electrodes are mounted on the PCR reaction channel via the mounting base. A signal reader is connected to the integrated electrodes. The integrated electrodes heat the liquid in the PCR reaction channel through the heating function. Pins extended from the integrated electrodes connect to an external device, and the reaction data in the PCR reaction channel monitored in real time through the sensing function is transmitted to the external device. The fluid input module includes three fluid input mechanisms, the PCR reaction channel is a triangular channel, and the PCR temperature controller includes three integrated electrodes, which are respectively located on the three sides of the triangle of the PCR reaction channel. Before the liquid to be tested flows into the microreactor through the tubing under the control of the first micropump and the first microvalve, a liquid control mechanism is provided at the inlet of the microreactor. The liquid control mechanism includes an S-shaped tubing, a second micropump, and a second microvalve. The two ends of the S-shaped tubing are respectively connected to the tubing and the microreactor. The second micropump and the second microvalve are provided near the inlet of the microreactor on the S-shaped tubing. After passing through the tubing, the liquid to be tested enters the S-shaped tubing and flows into the microreactor through the S-shaped tubing under the control of the second micropump and the second microvalve.

2. The modular tubular microfluidic analysis and detection device according to claim 1, characterized in that: The microreactor is an enzyme-linked immunosorbent assay (ELISA) reactor, which includes an enzyme-linked reaction chamber, and the enzyme-linked reaction chamber is provided with an enzyme-linked reaction outlet and multiple enzyme-linked reaction inlets. The two ends of the tubing are respectively connected to the liquid storage device and the enzyme-linked reaction inlet. The liquid to be tested in the liquid storage device enters the enzyme-linked reaction pool through the enzyme-linked reaction inlet. The first micro valve is installed on the tubing. The signal reader is connected to the enzyme-linked reaction chamber and acquires the signal changes in the enzyme-linked reaction chamber in real time. After the analysis and detection are completed, the liquid in the enzyme-linked reaction chamber flows out through the enzyme-linked reaction outlet.

3. The modular tubular microfluidic analysis and detection device according to claim 1, characterized in that: The microreactor is an electrochemical reactor, which includes an electrochemical reaction cell. The electrochemical reaction cell is provided with an electrochemical reaction outlet and multiple electrochemical reaction inlets. An electrochemical sensing electrode is provided inside the electrochemical reaction cell. The two ends of the hose are respectively connected to the liquid storage device and the electrochemical reaction inlet. The liquid to be tested in the liquid storage device enters the electrochemical reaction cell through the electrochemical reaction inlet. The first micro valve is installed on the hose. The signal reader is connected to the electrochemical reaction cell and acquires the signal changes in the electrochemical reaction cell in real time. After the analysis and detection are completed, the liquid in the electrochemical reaction cell flows out through the electrochemical reaction outlet. The electrochemical sensing electrode is disposed on the inner wall of the electrochemical reaction cell. The electrochemical sensing electrode extends a pin to connect to an external device and transmits the reaction data in the electrochemical reaction cell monitored in real time to the external device.

4. The modular tubular microfluidic analysis and detection device according to claim 3, characterized in that: The signal reader is a visible light signal reader, which includes: A visible light sensor is installed on the electrochemical reaction cell to convert the changes in light when the liquid to be tested in the electrochemical reaction cell reacts into signal changes. The interaction module, connected to the visible light sensor, is used to communicate with external devices and transmit signal changes to the external devices.

5. The modular tubular microfluidic analysis and detection device according to claim 1, characterized in that: The first micropump includes a pump body and a pump base. The first micropump is fixed to the hose through the pump base. The liquid to be tested flows into the microreactor through the hose under the action of the pump body. The first micro-valve includes a valve seat, a moving rod, a valve disc, and a displacement actuator. The first micro-valve is fixed to the hose by the valve seat. The extension direction of the moving rod is perpendicular to the flow direction of the liquid to be tested in the hose. The valve disc moves on the moving rod and controls the flow rate of the liquid to be tested in the hose by pressing it against the hose. The displacement actuator is connected to the valve disc and controls the position of the valve disc pressing against the hose.

6. A modular tubular microfluidic analysis and detection device according to any one of claims 1-5, characterized in that: The microreactor is made of biocompatible material.

7. A modular tubular microfluidic analysis and detection method, characterized in that, include: The fluid input module and reaction measurement module are manufactured using laser cutting, machining, injection molding, or 3D printing technologies. The fluid input module includes multiple fluid input mechanisms, each of which includes a liquid storage device, a first micropump, and a first microvalve, and each fluid input mechanism is independent of the others. The reaction measurement module includes a microreactor and a signal reader, and the signal reader is connected to the microreactor. The fluid input module and the microreactor are connected by a hose. The liquid storage device stores the liquid to be tested. The liquid to be tested flows into the microreactor through the hose under the control of the first micropump and the first microvalve. The signal reader acquires the signal change when the liquid to be tested reacts in the microreactor and obtains the analysis and detection results based on the signal change. The microreactor is a PCR reactor, which includes a PCR reaction channel. The two ends of the flexible tube are connected to the liquid storage device and the PCR reaction channel, respectively. The test liquid in the liquid storage device enters the PCR reaction channel through the flexible tube. A first microvalve is disposed on the flexible tube. A PCR temperature controller is provided on the PCR reaction channel. The PCR temperature controller includes a mounting base, on which multiple integrated electrodes are fixed. Each integrated electrode has heating and sensing functions. The multiple integrated electrodes are mounted on the PCR reaction channel via the mounting base. A signal reader is connected to the integrated electrodes. The integrated electrodes heat the liquid in the PCR reaction channel through the heating function. Pins extended from the integrated electrodes connect to an external device, and the reaction data in the PCR reaction channel monitored in real time through the sensing function is transmitted to the external device. The fluid input module includes three fluid input mechanisms, the PCR reaction channel is a triangular channel, and the PCR temperature controller includes three integrated electrodes, which are respectively located on the three sides of the triangle of the PCR reaction channel. Before the liquid to be tested flows into the microreactor through the tubing under the control of the first micropump and the first microvalve, a liquid control mechanism is provided at the inlet of the microreactor. The liquid control mechanism includes an S-shaped tubing, a second micropump, and a second microvalve. The two ends of the S-shaped tubing are respectively connected to the tubing and the microreactor. The second micropump and the second microvalve are provided near the inlet of the microreactor on the S-shaped tubing. After passing through the tubing, the liquid to be tested enters the S-shaped tubing and flows into the microreactor through the S-shaped tubing under the control of the second micropump and the second microvalve.

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