A reusable microfluidic chip and methods of using the same

Abstract

The application discloses a reusable micro-fluidic chip and a use method thereof, and the chip comprises a chip body, a sample inlet, an array biological reaction unit and a rotating gating unit are arranged on the chip body; the array biological reaction unit pre-stores a reaction solution, and is used for carrying out biological reaction on a sample entering from the sample inlet; the rotating gating unit is arranged between the sample inlet and the array biological reaction unit, and is used for switching and communicating between the sample inlet and multiple biological reaction chambers in the array biological reaction unit. The array biological reaction unit and the rotating gating unit are integrated on the micro-fluidic chip, switching and communication between the sample inlet and multiple biological reaction chambers in the array biological reaction unit are realized through the rotating gating unit, multiple biological reaction functions are realized on a single micro-fluidic chip, use cost is reduced, and cross contamination is avoided.

Description

Technical Field

[0001] This invention relates to the field of microfluidics, and in particular to a reusable microfluidic chip and its usage method. Background Technology

[0002] Microfluidic chips are a novel analytical platform that integrates basic operational units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes onto a micrometer-scale chip. They have been widely researched and applied in fields such as life sciences, medical testing, materials analysis, and electrical sensing. Traditional microfluidic chips are often used as disposable consumables, losing their function after a single testing cycle. This disposable approach imposes significant cost pressures on applications such as clinical diagnostics (IVD) and environmental monitoring, while also generating environmentally unfriendly plastic chip waste during the testing process.

[0003] Currently, there is a lack of existing technologies that can effectively avoid cross-contamination and ensure detection accuracy for reusable microfluidic chips. Therefore, it is of great significance to develop microfluidic chips that can be recycled multiple times. Summary of the Invention

[0004] In view of the problems existing in the prior art, the purpose of this invention is to overcome the problems of high cost of single use of microfluidic chips and the risk of cross-contamination, and to provide a reusable microfluidic chip and its usage method.

[0005] To achieve the above objectives, the first aspect of the present invention provides a reusable microfluidic chip, comprising a chip body, wherein the chip body is provided with a sample inlet, an array of bioreaction units and a rotational gating unit;

[0006] The array bioreactor unit is pre-stored with a reaction solution for performing a bioreactor on the sample entering through the sample inlet.

[0007] The rotary gate unit is located between the sample inlet and the array bioreaction unit, and is used for switching and connecting the sample inlet and multiple bioreaction chambers in the array bioreaction unit.

[0008] Furthermore, the rotary gating unit includes a main flow channel, a rotary gating valve, and multiple branch flow channels. The input end of the main flow channel is connected to the sample inlet, and the output ends of the multiple branch flow channels are respectively connected to the multiple bioreactor chambers. The rotary gating valve is disposed between the main flow channel and the multiple branch flow channels. By rotating the position of the rotary gating valve, the output end of the main flow channel is connected to the input end of any branch flow channel, thereby realizing the switching connection between the sample inlet and the multiple bioreactor chambers.

[0009] Furthermore, the chip body is provided with multiple sample inlets, and the rotary gating unit includes multiple main channels. The input end of each main channel is connected to a sample inlet. By rotating the position of the rotary gating valve, any one of the multiple main channels can be connected to any one of the multiple branch channels.

[0010] Furthermore, the rotary selector valve includes a valve body and a flexible valve core. The flexible valve core is provided with a transition channel for connecting with the main flow channel and the branch flow channels. The flexible valve core is snapped into the bottom of the valve body. The rotation of the valve body drives the flexible valve core to rotate, thereby driving the transition channel to connect with any of the main flow channel and the multiple branch flow channels.

[0011] Furthermore, the chip body is also provided with a biological detection unit, which is connected to the array biological reaction unit through a first flow channel. The reactants in the array biological reaction unit can flow to the biological detection unit through the first flow channel for biological detection.

[0012] Furthermore, the chip body is also provided with a waste liquid recovery unit, which is connected to the biological detection unit through a second flow channel. The detection products in the biological detection unit can flow through the second flow channel to the waste liquid recovery unit for recovery.

[0013] Furthermore, the chip body is also provided with a detection inlet, which is connected to the first flow channel, and detection liquid is injected into the biological detection unit through the detection inlet.

[0014] Furthermore, the bioreactor chamber includes a bio-insulating zone and a magnetic separation zone. The bio-insulating zone is located between the branch flow channel and the magnetic separation zone and is used to regulate the temperature of the sample flowing in from the branch flow channel. The magnetic separation zone is used to achieve sample filtration and separation. A one-way valve is also provided after the magnetic separation zone to prevent the sample from flowing back into the bioreactor chamber.

[0015] Furthermore, the one-way valve includes a valve cover and a flexible valve plate. The valve cover presses the flexible valve plate between the flow channel of the bioreactor chamber and the downstream flow channel of the bioreactor chamber. The cross-sectional dimension of the flow channel of the bioreactor chamber is larger than that of the downstream flow channel. Through the flow resistance difference between the flow channel of the bioreactor chamber and the downstream flow channel, the flexible valve plate opens when the fluid in the bioreactor chamber flows to the downstream flow channel, and closes when the fluid in the downstream flow channel flows to the bioreactor chamber.

[0016] A second aspect of the present invention provides a method of using the above-mentioned microfluidic chip, comprising the following steps:

[0017] Step S110: Rotate the rotary gate unit to connect the sample inlet to any one of the multiple bioreactor chambers;

[0018] Step S120: Inject sample solution into the bioreactor chamber through the sample inlet;

[0019] Step S130: The sample undergoes a biological reaction in the bioreactor chamber;

[0020] Step S140: The bioreaction products and detection solution enter the biodetection unit for biodetection;

[0021] Step S150: After detection, the product enters the waste liquid recovery unit for recycling;

[0022] Repeat steps S110-S150 until all bioreactor chambers have completed their reaction operations.

[0023] This invention integrates an array bioreaction unit and a rotation gating unit on a microfluidic chip. The rotation gating unit enables switching and communication between the sample inlet and multiple bioreaction chambers in the array bioreaction unit, realizing multiple bioreaction functions on a single microfluidic chip, reducing usage costs and avoiding cross-contamination problems. Attached Figure Description

[0024] 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.

[0025] Figure 1 This is a schematic diagram of the structure of a reusable microfluidic chip according to an embodiment of the present invention;

[0026] Figure 2 This is a schematic diagram of the structure of a rotating gating unit in a microfluidic chip according to an embodiment of the present invention;

[0027] Figure 3 This is a cross-sectional schematic diagram of a rotary gating unit according to an embodiment of the present invention;

[0028] Figure 4 This is a schematic diagram of the structure of an array of bioreactor units in a microfluidic chip according to an embodiment of the present invention;

[0029] Figure 5 This is a cross-sectional schematic diagram of a one-way valve in an array bioreactor unit according to an embodiment of the present invention. Detailed Implementation

[0030] 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.

[0031] like Figure 1 As shown, the reusable microfluidic chip of the present invention includes a chip body 1, on which a sample inlet 2, an array bioreaction unit 3, and a rotation gate unit 4 are disposed; the array bioreaction unit 3 is pre-stored with a reaction solution for performing a bioreaction on the sample entering through the sample inlet 2; the rotation gate unit 4 is disposed between the sample inlet 2 and the array bioreaction unit 3 for switching communication between the sample inlet 2 and multiple bioreaction chambers in the array bioreaction unit 3.

[0032] In one embodiment of the present invention, such as Figure 2 and 3As shown, the rotary gating unit 4 includes a main channel 41, a rotary gating valve 42, and multiple branch channels 43. The input end of the main channel 41 is connected to the sample inlet 2, and the output ends of the multiple branch channels 43 are respectively connected to the multiple bioreactor chambers. The main channel 41 includes a first channel, a second channel, and a third channel. The first channel is arranged vertically along the chip body 1 and located below the vertical projection of the sample inlet 2. The third channel is arranged vertically along the chip body 1 and located below the vertical projection of the rotary gating valve 42. The second channel is arranged horizontally along the chip body 1, with one end connected to the first channel and the other end connected to the third channel, so that the sample liquid injected into the sample inlet 2 is guided sequentially through the first channel, the second channel, and the third channel of the main channel 41 to the rotary gating valve 42. The branch channel 43 includes a first channel and a second channel. The first channel of the branch channel 43 is arranged vertically along the chip body 1 and located below the vertical projection of the rotary gate valve 42. The second channel of the branch channel 43 is arranged horizontally along the chip body 1, with one end connected to the first channel of the branch channel 43 and the other end connected to the bioreactor chamber. The rotary gate valve 42 is located between the main channel 41 and the plurality of branch channels 43. By rotating the position of the rotary gate valve 42, the output end of the main channel 41 is connected to the input end of any branch channel 43. Specifically, the third channel of the main channel 41 is connected to the first channel of the branch channel 43 through the rotary gate valve 42, so that the sample liquid injected into the sample injection port 2 is sequentially injected into the bioreactor chamber through the first channel, second channel, third channel of the main channel 41, rotary gate valve 42, first channel of the branch channel 43, and second channel of the branch channel 43. Rotating the rotary selector valve 42 to different positions allows the main flow channel 41 to be connected to multiple branch flow channels 43 respectively, so as to realize the switching connection between the sample inlet 2 and multiple bioreactor chambers and realize the cyclic use of multiple bioreactor chambers.

[0033] In one embodiment of the present invention, the rotary selector valve 42 includes a valve cover 421, a valve body 422, a flexible valve core 423, and a rotary valve buckle 424. The valve body 422 and the flexible valve core 423 are disposed on the chip body 1 through the cooperation of the valve cover 421 and the rotary valve buckle 424. The valve cover 421 and the rotary valve buckle 424 achieve the pressing and fixing of the valve body 422 and the flexible valve core 423 through a locking structure. The flexible valve core 423 is provided with a transition channel 425 for connecting with the main flow channel 41 and the branch flow channels 43. The flexible valve core 423 has a slot, and the bottom of the valve body 422 has a boss. The slot and the boss cooperate to engage the flexible valve core 423 with the bottom of the valve body 422. The rotation of the valve body 422 drives the flexible valve core 423 to rotate, thereby driving the transition channel 425 to connect with any one of the main flow channel 41 and the multiple branch flow channels 43. The rotary selector valve 42 can control which branch of the main flow channel 41 is connected to the multiple branch flow channels 43 by rotating at a designed angle within the water surface. The flexible valve core 423 can be made of graphic soft rubber coating, and the transition channel 425 is formed by drilling holes in the graphic soft rubber coating. This achieves both the connection between the main flow channel 41 and the branch flow channels 43 and ensures the sealing of the main flow channel and the branch flow channels 43 after connection. The clamping distance between the valve cover 421 and the rotary valve latch 424 is adjustable. By adjusting the clamping distance between the flexible valve core 423 and the valve cover 421 and the rotary valve latch 424, the torque of the rotary gate 42 in the horizontal direction can be adjusted. This prevents the torque from being too small, which would cause cross-contamination between the main flow channel 41 and multiple branch flow channels 43, resulting in the failure of the rotary gate function; and too large a torque would increase the load torque pressure on the external drive motor, affecting the motor selection and power consumption of the matching equipment. The valve body 422 is made of rigid materials such as PP (polypropylene polymer) and PC (polycarbonate polymer), and the graphic soft overlay is made of soft materials such as TPE (thermoplastic elastomer) and TPC (thermoplastic polyurethane), achieving an integral structure production through a two-color injection molding process.

[0034] In one embodiment of the present invention, the third section of the main flow channel 41 is located below the vertical projection of the flexible valve core 423, and the first section of the multiple branch flow channels 43 is arranged around the third section of the main flow channel 41. The flexible valve core 423 can be rotated to different angles to connect the transition flow channel 4 with the main flow channel 41 and the multiple branch flow channels 43 respectively.

[0035] In one embodiment of the present invention, the chip body 1 is provided with multiple sample inlets 2, and the rotary gating unit 4 is provided with multiple main channels 41. The number of sample inlets 2, main channels 41 and branch channels 43 are the same. The input end of each main channel is connected to a sample inlet. By rotating the position of the rotary gating valve 42, any one of the multiple main channels can be connected to any one of the multiple branch channels. In this way, selective connection between multiple main channels and multiple branch channels can be realized, further improving efficiency.

[0036] In one embodiment of the present invention, the chip body 1 is further provided with a biodetection unit 5. The biodetection unit 5 is connected to the array bioreaction unit 3 through a first flow channel 53. The reactants in the array bioreaction unit 3 can flow to the biodetection unit 5 through the first flow channel 53 for biodetection. The first flow channel 53 may include multiple parallel branch channels and a main flow channel. One end of each of the parallel branch channels is connected to multiple bioreaction chambers in the array reaction unit 3, and the other end is connected to the input end of the main flow channel. The output end of the main flow channel is connected to the biodetection unit 5. Thus, the reactants in the multiple bioreaction chambers can enter the biodetection unit 5 sequentially for biodetection, improving detection efficiency while reducing costs. The chip body 1 is also provided with a detection inlet 6, which is connected to the first flow channel 53. Detection liquid is injected into the biodetection unit 5 through the detection inlet 6.

[0037] In one embodiment of the present invention, the chip body 1 is further provided with a waste liquid recovery unit 7. The waste liquid recovery unit 7 is connected to the biological detection unit 5 through a second flow channel 75. The detection products in the biological detection unit 5 can flow through the second flow channel 75 to the waste liquid recovery unit 7 for recovery.

[0038] In one embodiment of the present invention, such as Figure 4 As shown, the bioreactor chamber of the array bioreactor unit 3 includes a bio-insulating zone 31 and a magnetic separation zone 32. The bio-insulating zone 31 is located between the branch channel 43 and the magnetic separation zone 32 and is used to regulate the temperature of the sample flowing in from the branch channel 43. The magnetic separation zone 32 is used to filter and separate the sample. A one-way valve 8 is also provided after the magnetic separation zone 32 to prevent the sample from flowing back into the bioreactor chamber.

[0039] In one embodiment of the present invention, such as Figure 5As shown, the one-way valve 8 includes a valve cover 81 and a flexible valve plate 82. The valve cover 81 presses the flexible valve plate 82 between the flow channel 33 of the bioreactor chamber and the downstream flow channel of the bioreactor chamber. The cross-sectional dimension of the flow channel 33 of the bioreactor chamber is larger than that of the downstream flow channel. Through the flow resistance difference between the flow channel 33 of the bioreactor chamber and the downstream flow channel, the flexible valve plate 82 opens when fluid flows from the bioreactor chamber to the downstream flow channel and closes when fluid flows from the downstream flow channel to the bioreactor chamber. The downstream flow channel refers to the flow channel downstream of the bioreactor chamber, such as the first flow channel 53. The area of ​​the output port of the flow channel 33 pressed by the flexible valve plate 82 in the bioreactor chamber is larger than the area pressed at the input port of the downstream flow channel, and a gap is reserved between the valve cover 81 and the flexible valve plate 82 for the flexible valve plate 82 to flip upwards. The one-way valve 8 can effectively prevent the failure of material flow function caused by cross-contamination between the downstream flow channel and the bioreactor chamber. In the corresponding microchannel, when the drive unit drives the fluid to move in the forward direction, the forward flow velocity of the fluid will be greater than the reverse free diffusion velocity of the fluid. Under the action of the flexible valve plate 82, the forward flow resistance of the fluid is less than the reverse flow resistance. The forward conduction and reverse cut-off functions are achieved through the difference in flow resistance.

[0040] A second aspect of the present invention provides a method of using the above-mentioned microfluidic chip, comprising the following steps:

[0041] Step S110: Rotate the rotary gate unit to connect the sample inlet to any one of the multiple bioreactor chambers;

[0042] Step S120: Inject sample solution into the bioreactor chamber through the sample inlet;

[0043] Step S130: The sample undergoes a biological reaction in the bioreactor chamber;

[0044] Step S140: The bioreaction products and detection solution enter the biodetection unit for biodetection;

[0045] Step S150: After detection, the product enters the waste liquid recovery unit for recycling;

[0046] After steps S110-S150 are completed, the next sample is injected, and steps S110-S150 are repeated until all bioreactor chambers have completed the reaction. Multiple bioreactor functions are achieved using a single microfluidic chip, reducing operating costs and avoiding cross-contamination.

[0047] In summary, this invention integrates an array bioreaction unit and a rotation gating unit on a microfluidic chip. The rotation gating unit enables switching and communication between the sample inlet and multiple bioreaction chambers in the array bioreaction unit, achieving multiple bioreaction functions on a single microfluidic chip, reducing usage costs and avoiding cross-contamination issues.

[0048] 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 reusable microfluidic chip, characterized by, The chip body includes a sample inlet, an array of bioreactor units, and a rotation gate unit. The array bioreactor unit is pre-stored with a reaction solution for performing a bioreactor on the sample entering through the sample inlet. The rotary gate unit is located between the sample inlet and the array bioreactor unit, and is used for switching communication between the sample inlet and multiple bioreactor chambers in the array bioreactor unit. Each bioreactor chamber includes a bio-insulating zone and a magnetic separation zone. The bio-insulating zone is located between the branch channel and the magnetic separation zone, and is used to regulate the temperature of the sample flowing in from the branch channel. The magnetic separation zone is used to filter and separate the sample. A one-way valve is also provided downstream of the magnetic separation zone to prevent backflow of the sample from the bioreactor chamber. The one-way valve includes a valve cover and a flexible valve plate, and the valve cover presses the flexible valve plate against the bioreactor unit. Between the flow channel of the bioreactor chamber and the downstream flow channel of the bioreactor chamber, the cross-sectional dimension of the flow channel of the bioreactor chamber is larger than that of the downstream flow channel. Through the flow resistance difference between the flow channel of the bioreactor chamber and the downstream flow channel, the flexible valve plate opens when the fluid in the bioreactor chamber flows to the downstream flow channel, and closes when the fluid in the downstream flow channel flows to the bioreactor chamber. The downstream flow channel refers to the flow channel downstream of the bioreactor chamber. The area of ​​the flexible valve plate pressed against the output port of the flow channel in the bioreactor chamber is larger than the area pressed against the input port of the downstream flow channel, and a gap is reserved between the valve cover and the flexible valve plate for the flexible valve plate to flip up.

2. The microfluidic chip of claim 1, wherein, The rotary gating unit includes a main channel, a rotary gating valve, and multiple branch channels. The input end of the main channel is connected to the sample inlet, and the output ends of the multiple branch channels are respectively connected to the multiple bioreactor chambers. The rotary gating valve is located between the main channel and the multiple branch channels. By rotating the position of the rotary gating valve, the output end of the main channel is connected to the input end of any branch channel, thereby realizing the switching connection between the sample inlet and the multiple bioreactor chambers.

3. The microfluidic chip of claim 2, wherein, The chip body is provided with multiple sample inlets, and the rotary gating unit includes multiple main channels. The input end of each main channel is connected to a sample inlet. By rotating the position of the rotary gating valve, any one of the multiple main channels can be connected to any one of the multiple branch channels.

4. The microfluidic chip of claim 2, wherein, The rotary selector valve includes a valve body and a flexible valve core. The flexible valve core is provided with a transition channel for connecting with the main flow channel and the branch flow channels. The flexible valve core is snapped into the bottom of the valve body. The rotation of the valve body drives the flexible valve core to rotate, thereby driving the transition channel to connect with any of the main flow channel and the multiple branch flow channels.

5. The microfluidic chip of claim 1, wherein, The chip body is also provided with a biological detection unit, which is connected to the array biological reaction unit through a first flow channel. The reactants in the array biological reaction unit can flow to the biological detection unit through the first flow channel for biological detection.

6. The microfluidic chip as described in claim 5, characterized in that, The chip body is also provided with a waste liquid recovery unit, which is connected to the biological detection unit through a second flow channel. The detection products in the biological detection unit can flow through the second flow channel to the waste liquid recovery unit for recovery.

7. The microfluidic chip of claim 5, wherein, The chip body is also provided with a detection inlet, which is connected to the first flow channel, and a detection liquid is injected into the biological detection unit through the detection inlet.

8. A method of using a microfluidic chip according to any one of claims 1-7, characterized in that, Includes the following steps: Step S110: Rotate the rotary gate unit to connect the sample inlet to any one of the multiple bioreactor chambers; Step S120: Inject sample solution into the bioreactor chamber through the sample inlet; Step S130: The sample undergoes a biological reaction in the bioreactor chamber; Step S140: The bioreaction products and detection solution enter the biodetection unit for biodetection; Step S150: After detection, the product enters the waste liquid recovery unit for recycling; Repeat steps S110-S150 until all bioreactor chambers have completed their reaction operations.

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