Microfluidic chip and detection device and control method thereof

Abstract

The present invention provides a microfluidic chip and its detection device and control method. The microfluidic chip includes a device body and a channel, wherein a first valve body and a second valve body are fixedly arranged in the channel; a first cavity, a second cavity, and a third cavity are formed in the channel; when the first valve body is in a closed state, the first cavity and the second cavity are not connected to each other, and the second cavity contains a reaction reagent; when the second valve body is in a closed state, the second cavity and the third cavity are not connected to each other, and the third cavity contains a sealing liquid; the first valve body is configured to melt and solidify after being heated, thereby forming a first opening; the second valve body is configured to melt and solidify after being heated, thereby forming a second opening; a third valve body is configured to melt and solidify after being heated, thereby forming a second opening; and a third valve body is configured to melt and solidify after being heated, and then melt and solidify in the second cavity, thereby dividing the second cavity into two non-connected parts.

Description

Technical Field

[0001] The invention relates to a microfluidic chip and a detection device and a control method thereof, and belongs to the field of microfluidic chips. Background Art

[0002] Microfluidic chips can effectively accommodate fluids at the micron scale, enabling unique analytical capabilities. Currently, research on these chips is expanding, and their application in medical testing is gaining significant attention. Ensuring more accurate and robust test results is crucial, and maintaining the airtightness of microfluidic chips is crucial. Maintaining a long-term airtight seal within the chip is crucial for protecting reagent storage, preventing interference, preventing contamination, and improving test accuracy.

[0003] Microvalves are a key technology for controlling fluid flow in microfluidic chips. The microvalve's configuration and opening and closing processes must ensure long-term airtightness within the chip. Current microvalves utilize materials such as paraffin. For example, heating a paraffin microvalves can adjust the valve from a normally closed state to an open state, thereby achieving a valve state change.

[0004] However, the valves in the microfluidic chip are often switched between open and closed states. For example, at the beginning, the inside of the chip needs to be in a vacuum state. When the reaction reagent needs to be added, the valve that separates the reaction space inside the chip from the space outside the reaction space is opened, and the reaction reagent and sealing liquid are pushed into the reaction space using a pushing unit (such as a plunger). After the reaction reagent is added, the valve needs to be closed again to ensure that the reaction reagent has good airtightness during the reaction. However, the shape of the existing paraffin microvalve changes after it is heated and melted to become open. Even if the ambient temperature is adjusted, it is difficult to return the opened microvalve to the closed state, so the airtightness of the reaction space where the reaction reagent is located cannot be guaranteed, and thus it cannot meet the needs of the microfluidic chip. Summary of the Invention

[0005] The problem to be solved by the present invention is that the existing normally closed paraffin microvalve is difficult to return to the closed state after being heated and melted into the open state, thereby failing to ensure the air tightness of the reaction space where the reaction reagents are located. A microfluidic chip and its detection device are provided.

[0006] To solve the above technical problems, the present invention adopts a technical solution: a microfluidic chip, comprising a device body, a channel formed in the device body and open at one end, a pushing unit disposed outside the channel opening for pushing reaction reagents and sealing liquid into the channel, and a first valve body and a second valve body fixedly disposed in the channel;

[0007] The channel portion between the end of the channel away from the opening and the first valve body forms a first cavity.

[0008] The channel portion between the first valve body and the second valve body forms a second cavity, and a receiving groove is provided on the lower wall of the channel in the second cavity, and the sample to be tested is received in the receiving groove;

[0009] The passage portion between the second valve body and the pushing end of the pushing unit forms a third cavity;

[0010] The first cavity, the second cavity and the third cavity together form a closed cavity;

[0011] When the first valve body is in a closed state, the first cavity and the second cavity are not connected to each other, and the first cavity contains a reaction reagent;

[0012] When the second valve body is in a closed state, the second cavity and the third cavity are not connected to each other, and the third cavity contains an air column and a sealing liquid for sealing the reaction reagent, and the air column is located between the sealing liquid and the second valve body;

[0013] When the first valve body and the second valve body are both in a closed state, the second cavity is in a vacuum state;

[0014] The first valve body is used to melt and solidify after being heated, thereby forming a first opening between the first cavity and the second cavity;

[0015] The second valve body is used to melt and solidify after being heated, thereby forming a second opening between the second cavity and the third cavity;

[0016] A third valve body is provided on the channel wall in the second cavity. The melting point of the material of the third valve body is higher than the temperature at which the reaction reagent reacts. The third valve body is used to melt after being heated and solidify in the second cavity after melting, thereby separating the second cavity into two parts that are not connected to each other.

[0017] In the present invention, a first valve body and a second valve body are provided as normally closed valves, and a third valve body is provided as a normally open valve. In the initial state, the first valve body and the second valve body are both in a closed state, so that the first cavity forms a closed space, thereby ensuring the airtightness of the reaction space. When it is necessary to allow the reaction reagent to enter the second cavity, the first valve body can be heated so that the first valve body melts and solidifies after being heated, forming a first opening connecting the first cavity and the second cavity, allowing the reaction reagent to enter the second cavity and be stored in the holding tank. The second valve body can be heated so that the second valve body melts and solidifies after being heated, forming a second opening connecting the second cavity and the third cavity, so that the sealing liquid and the gas column can enter the second cavity from the third cavity, so that the sealing liquid is located above the holding tank to achieve sealing of the reaction reagent located in the holding tank. The pushing unit can push the reaction reagent to the end of the channel away from the opening (i.e., push it into the inside of the channel) by pushing the sealing liquid. When the reaction reagent reaches the set position, the third valve body as a normally open valve can be heated to make it melt and solidify in the second cavity, thereby separating the second cavity into two parts that are not connected to each other, and also separating the air column into two parts that are not connected to each other, wherein the part of the second cavity close to the channel away from the opening end and the first cavity can form a sealed space together through the action of the closed third valve body, and the reaction reagent pushed into the inside of the channel is sealed to ensure air tightness. In the present invention, after the pushing is completed, the third valve body that melts after heating can be solidified to separate the air column into two parts that are not connected to each other, thereby completely blocking the channel at the position of the air column, so that the reaction reagent can be sealed and preserved. The applicant found during the study that since heating is required during the reaction, if the third valve body is not sealed, the sealing liquid will expand due to the heat and squeeze the air column to the left, so that the sealing liquid may move left and right in the direction of channel extension, making its state unstable, which may affect the reaction between the reaction reagent and the sample being tested. In the present invention, since the third valve body is sealed, the sealing liquid is enclosed in the enclosed space between the valve body and the pushing end of the pushing unit, limiting its range of motion and thus maintaining a thermodynamically stable state, thereby avoiding affecting the test results. During research, the applicant discovered that if there are reaction reagents or sealing oil in the pipeline, the heated vaporization of the reaction reagents and the heated flow of the oil will increase the difficulty of sealing the valve body. By providing an air column, the third valve body can be sealed to block the channel at the location of the air column, thereby facilitating sealing, and the sealing process will not contaminate the reaction reagents.

[0018] Furthermore, the number of the containing slots is not less than 2, the containing slots are spaced apart along the extending direction of the channel, and the samples to be tested in the containing slots are the same or different samples.

[0019] The receiving grooves are spaced apart along the extending direction of the channel, and the reaction reagent in one receiving groove is separated from the reaction reagent in the adjacent receiving groove by a sealing liquid.

[0020] Furthermore, the sealing liquid is a liquid having a boiling point higher than that of the reaction reagent.

[0021] In the present invention, the reaction reagent generally needs to be heated when reacting with the sample to be tested, so the heated reaction reagent is likely to generate bubbles on the upper surface of the reaction reagent. By setting the sealing liquid to a liquid with a boiling point higher than that of the reaction reagent, the bubbles can be blocked, thereby preventing the reaction reagent from volatilizing.

[0022] Furthermore, the first valve body, the second valve body, and the third valve body are all made of opaque materials and are all arranged on the inner wall surface of the device body. At least one side wall of the device body located outside the first valve body, at least one side wall located outside the second valve body, and at least one side wall located outside the third valve body are all made of translucent materials.

[0023] Through the above arrangement, the external heating unit can heat the valve body made of opaque material by using the translucent material.

[0024] Furthermore, a first accommodating groove facing the first valve body is formed on the channel wall below the first valve body;

[0025] The first valve body is made of opaque material, and the side wall of the device body located outside the first valve body is made of translucent material;

[0026] When the first valve body is in a closed state, the side wall and the first accommodating groove are respectively located on both sides of the first valve body.

[0027] In the present invention, a first receiving tank is provided so that after the first valve body melts, it can fall into the first receiving tank under its own gravity, thus avoiding excessive obstruction to the flow of liquid between the first and second cavities. When heated by an external light heating unit (such as a laser heating unit), the side wall of the device body on the side of the first valve body away from the first receiving tank is made of a light-transmitting material and therefore does not absorb heat and will not deform due to the heating unit's radiation. However, the first valve body is made of an opaque material and can absorb heat, thereby allowing the first valve body to melt under the heat.

[0028] Furthermore, a second receiving groove facing the second valve body is formed on the channel wall below the second valve body;

[0029] The second valve body is made of opaque material, and the side wall of the device body located outside the second valve body is made of translucent material; when the second valve body is in a closed state, the side wall and the second receiving groove are respectively located on both sides of the second valve body.

[0030] In the present invention, a second receiving groove is provided so that the second valve body can fall into the second receiving groove under its own gravity after melting, thereby avoiding excessive obstruction to the liquid flowing between the second cavity and the third cavity.

[0031] Furthermore, the upper wall surface of the channel in the second cavity is provided with a third accommodating groove arranged toward the channel, and the third valve body is accommodated and fixed in the third accommodating groove;

[0032] The third valve body is made of opaque material, and the side wall of the device body located outside the third valve body is made of translucent material.

[0033] In the present invention, by providing the third receiving groove, the third valve body can fall into the channel below the third receiving groove under its own gravity after melting, thereby completely blocking the channel after melting and solidifying.

[0034] Furthermore, the opaque material and the translucent material are both plastic materials, the opaque material is dark plastic, and the translucent material is transparent plastic.

[0035] The present invention also provides a microfluidic chip detection device, which includes a control unit and a detection unit for detecting the position of a reaction reagent in a channel of a microfluidic chip to be detected as described in any of the above items. The control unit and the detection unit are both arranged on the outside of the microfluidic chip to be detected, and the output end of the detection unit and the control end of the pushing unit of the microfluidic chip to be detected are electrically connected to the control unit respectively.

[0036] By setting up the detection unit, the position of the reaction reagent in the channel can be determined, so that after the reaction reagent reaches the set position, the pushing unit can be stopped, thereby facilitating the sealing of the valve body.

[0037] In a preferred embodiment, the detection unit is used to detect the position of the pushing end of the pushing unit.

[0038] In the present invention, since the channel size, the volume of the sealing liquid, the volume of the reaction reagent, and the speed of the pushing unit can all be determined, the position of the air column can be estimated by detecting the position of the pushing end.

[0039] In a preferred embodiment, the detection unit is a visual detection unit, and the image acquisition end of the visual detection unit is arranged toward the channel.

[0040] The present invention also provides a microfluidic chip control method, wherein the controlled microfluidic chip is any one of the microfluidic chips described above;

[0041] The microfluidic chip control method comprises the following steps:

[0042] Step (A): heating the first valve body for a first preset time so that the first valve body melts and solidifies after being heated, thereby forming a first opening between the first cavity and the second cavity;

[0043] Step (B): After waiting for a first preset waiting time, heating the second valve body for a second preset time, so that the second valve body melts and solidifies after being heated, thereby forming a second opening between the second cavity and the third cavity;

[0044] Step (C): After waiting for a second preset waiting time, the reaction reagent and the sealing liquid are pushed into the inner side of the channel by using the pushing unit;

[0045] Step (D): If it is determined that the third valve body is between the first position and the second position, then the pushing is stopped;

[0046] Step (E): heating the third valve body for a third preset time, so that the third valve body melts after being heated and solidifies in the second cavity, thereby separating the second cavity into two parts that are not connected to each other. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0048] Figure 1 is a schematic cross-sectional view of a first state of the microfluidic chip according to an embodiment of the present invention;

[0049] Figure 2 is a schematic cross-sectional view of the microfluidic chip in the second state according to an embodiment of the present invention;

[0050] Figure 3 is a schematic cross-sectional view of the microfluidic chip in the third state according to an embodiment of the present invention;

[0051] Figure 4 is a schematic cross-sectional view of the microfluidic chip in the fourth state according to an embodiment of the present invention;

[0052] Figure 5 yes Figure 1 A1-A1 cross-sectional schematic diagram;

[0053] Figure 6 yes Figure 2 A2-A2 cross-sectional schematic diagram;

[0054] Figure 7 yes Figure 1 B1-B1 cross-sectional view;

[0055] Figure 8 yes Figure 3 B2-B2 cross-sectional view of FIG;

[0056] Figure 9 yes Figure 1 C1-C1 cross-sectional view;

[0057] Figure 10 yes Figure 4 C2-C2 cross-sectional view;

[0058] Figure 11 Flowchart of the working process of the microfluidic chip control method according to an embodiment of the present invention. DETAILED DESCRIPTION

[0059] The following will be combined with the drawings of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments of this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0060] Example 1

[0061] like Figure 1-4 As shown, this embodiment 1 provides a microfluidic chip, including a device body 10, a channel formed in the device body 10 and open at one end, a pushing unit 7 for pushing the reaction reagent 8 and the sealing liquid 6 into the inside of the channel is provided on the outside of the channel opening, and a first valve body 1 and a second valve body 2 are fixedly provided in the channel.

[0062] The device body 10 is provided with a barrel 71. The pushing unit 7 can slide along the inner wall of the barrel 71 toward the channel opening, thereby pushing the reaction reagent 8 and sealing liquid 6 into the channel. The space enclosed by the barrel 71, the outer wall of the device body 10, and the pushing end of the pushing unit 7 is connected to the channel.

[0063] The channel portion between the end of the channel away from the opening and the first valve body 1 forms a first cavity 601.

[0064] The channel portion between the first valve body 1 and the second valve body 2 forms a second cavity 602. A receiving groove 61 (also called a microchamber) is formed on the lower wall of the channel in the second cavity 602. The receiving groove 61 receives the sample to be tested.

[0065] The channel portion between the second valve body 2 and the pushing end of the pushing unit 7 forms a third cavity 603 .

[0066] The first cavity 601 , the second cavity 602 , and the third cavity 603 together form a closed cavity.

[0067] In the present invention, the channel includes the first cavity 601 , the second cavity 602 , and the portion of the third cavity 603 located inside the channel opening.

[0068] When the first valve body 1 is in a closed state (the first valve body 1 is not heated), the first cavity 601 and the second cavity 602 are not connected to each other, and the first cavity 601 contains the reaction reagent 8. In other words, the closed first valve body 1 separates the first cavity 601 and the second cavity 602, preventing them from communicating with each other.

[0069] When the second valve body 2 is in a closed state (the second valve body 2 is not heated), the second cavity 602 and the third cavity 603 are not connected to each other. The third cavity 603 contains a gas column 5 and a sealing liquid 6 for sealing the reaction reagent 8. The gas column 5 is located between the sealing liquid 6 and the second valve body 2. In other words, the closed second valve body 2 separates the second cavity 602 and the third cavity 603, preventing them from communicating.

[0070] When the first valve body 1 and the second valve body 2 are both in a closed state, the second cavity 602 is in a vacuum state.

[0071] The first valve body 1 is used to melt and solidify after being heated, thereby forming a first opening 201 between the first cavity 601 and the second cavity 602;

[0072] The second valve body 2 is used to melt and solidify after being heated, thereby forming a second opening 202 between the second cavity 602 and the third cavity 603;

[0073] A third valve body 3 is provided on the channel wall in the second cavity 602. The melting point of the material of the third valve body 3 is higher than the temperature at which the reaction reagent 8 reacts. The third valve body 3 is used to melt after being heated and solidify in the second cavity 602 after melting, thereby separating the second cavity 602 into two parts that are not connected to each other.

[0074] The number of the containing slots 61 is not less than 2, and the containing slots 61 are spaced apart along the extending direction of the channel. The samples to be tested in the containing slots 61 are the same or different samples.

[0075] The sealing liquid 6 is a liquid having a boiling point higher than that of the reaction reagent 8 .

[0076] When the third valve body 3 is solidified in the second cavity 602 , the third valve body 3 separates the gas column 5 into two parts that are not connected to each other.

[0077] The device body 10 is provided with a control unit and a detection unit for detecting the position of the air column 5 in the channel. The output end of the detection unit and the control end of the pushing unit 7 are electrically connected to the control unit. The control unit can be a PLC controller, a single chip microcomputer, a DSP or an FPGA.

[0078] Preferably, the detection unit is used to detect the position of the pushing end of the pushing unit 7 .

[0079] Preferably, the detection unit detects the position of the reaction reagent in the channel by detecting the position of the gas column in the channel; the detection unit is a visual detection unit, the image acquisition end of the visual detection unit is set toward the channel, the part of the device body 10 between the visual detection unit and the channel is a transparent material, the color difference and / or brightness difference between the gas column 5 and the reaction reagent 8 can be distinguished by the visual detection unit, and the color difference and / or brightness difference between the gas column 5 and the sealing liquid 6 can be distinguished by the visual detection unit. The visual detection unit can use CCD or CMOS. In the present invention, through the above-mentioned setting, the visual detection unit can detect the position of the interface between the gas column and the reaction reagent, and the position of the interface between the gas column and the sealing liquid, so that the position of the gas column can be detected.

[0080] The present invention blocks the air column at the front end of the sealing liquid 6 and uses a visual detection unit to identify the position of the air column, thereby controlling its movement to a specified position. This allows for accurate and rapid control of the air column's position, and its presence facilitates the closing of the normally open valve. The air column's position is monitored and accurately controlled, with position visualization, enabling precise and rapid control.

[0081] The melting points of the materials of the first valve body 1, second valve body 2, and third valve body 3 are all higher than the reaction temperature of the reagent (generally 10°C). Since the melting points of the valve body materials are higher than the reaction temperature of the reagent (generally 100°C), the valve bodies will not melt when the reaction temperature of the reagent is reached.

[0082] like Figure 1-8 As shown, the device body 10 includes oppositely disposed sidewalls 101 and 102, and sidewalls 103 and 104 sandwiched between sidewalls 101 and 102. Sidewalls 101, 102, 103, and 104 form a channel that can be connected by vacuum bonding or conventional bonding followed by vacuum extraction to form the device body 10, thereby creating a vacuum-sealed environment. Sidewalls 101 and 102 can be made of a dark, opaque material, preferably black, while sidewalls 103 and 104 can be made of either opaque or transparent materials.

[0083] The first valve body 1 and the second valve body 2 are sealed in the channel. The material of the first valve body 1 and the second valve body 2 can be the same as that of the side wall 101 and can be integrally formed with the side wall 101. The first valve body 1 and the second valve body 2 can be made of plastic. The third valve body 3 is arranged on the side wall 101 above the microfluidic channel near the position where the fluid needs to be controlled. The third valve body 3 can be made of a material with a high melting point and good fluidity, such as Fischer-Tropsch wax, hot melt adhesive, etc. The material of the third valve body 3 can also be the same as that of the side wall 101.

[0084] Working process: The first valve body 1 (normally closed valve) is heated (preferably by laser heating) by the external first heating unit 51, and the first valve body 1 melts or vaporizes and opens. Since the second cavity 602 is initially in a vacuum state, the reaction reagent 8 enters the second cavity 602 from the first cavity 601; then the second valve body 2 (normally closed valve) is heated (preferably by laser heating) by the second heating unit 52, and the second valve body 2 opens. Subsequently, the plunger (i.e., the pushing unit 7) connected to the upper end is pressed down, and a sealing liquid 6 is stored in the plunger pipeline. The sealing liquid 6 is a high-boiling-point heat-conducting oil such as mineral oil, which is used to seal the reaction reagent. At the point where the front end of the sealing liquid 6 meets the valve body 2 is a 10-15 mm long gas column. This column facilitates the melt sealing of the normally open valve. As the plunger is pressed downward, the column moves, pushing the reagents forward. A visual inspection unit continuously identifies the position of the column in the channel by identifying the interfaces between the column and the sealing liquid 6, as well as the interface between the column and the reagents. This information is fed back to the control system, which then assesses the position. When the column approaches a designated position, the control system brakes the motor and decelerates until it reaches the designated pipeline position below the normally open valve. The motor brake stops, and the plunger stops pressing downward. At this point, the third heating unit 53 (preferably laser heating) heats the third valve body 3 (normally open valve), causing the melted material to flow into the pipe below, where it solidifies and shuts off the liquid flow. This composite microvalve can achieve "normally closed-normally open-normally closed" functionality.

[0085] Figure 1 This is a schematic diagram of the microfluidic chip in its first state, where the first and second valve bodies 1 and 2 remain closed, and the third valve body 3 remains open. In this first state, the reaction reagent 8 is sealed within the first cavity 601. Specifically, the channel is divided into the first, second, and third cavities 601, 602, and 603, which are not interconnected. The first cavity 601 is sealed, maintaining a vacuum state for extended periods, facilitating storage of the reaction reagent 601.

[0086] Figure 2 This is a schematic diagram of the microfluidic chip in its second state, wherein the first valve body 1 is open, the second valve body 2 remains closed, and the third valve body 3 remains open, connecting the first cavity 601 and the second cavity 602. In the second state, the reaction reagent 8 enters the second cavity 602 from the first cavity 601 through the first opening 201, thereby allowing the reaction reagent 8 to enter and be contained in the holding tank 61. The purpose of the second state is to allow the reaction reagent 8 to enter the reaction cavity (the second cavity).

[0087] Figure 3This is a schematic diagram of the microfluidic chip in its third state, wherein the first valve body 1 is open, the second valve body 2 is open, and the third valve body 3 remains open. The first cavity 601, the second cavity 602, and the third cavity 603 are interconnected. In the third state, the pushing end of the pushing unit 7 (preferably a plunger) is pressed downward (preferably to the lowest point), and the gas column 5 and sealing liquid 6 enter the second cavity 602 from the third cavity 603 through the second opening 202. At this time, the receiving grooves 61 still contain reaction reagents 8, and the sealing liquid 6 is placed above each receiving groove 61. The receiving grooves 61 are spaced apart along the direction of the channel extension, and the reaction reagent 8 in one receiving groove 61 is separated from the reaction reagent 8 in the adjacent receiving groove by the sealing liquid 6. The third state is to push the sealing liquid 6 (preferably oil) into the second cavity 602. The purpose of this is to seal the surface of the reaction reagent 8 in each microchamber with the oil.

[0088] Figure 4 Figure 2 is a schematic diagram of the microfluidic chip in the fourth state. The first valve body 1 is open, the second valve body 2 is open, and the third valve body 3 is closed. This means that the second cavity 602 and the third cavity 603 are connected, while the gas column 5 is separated into two disconnected parts by the third valve body 3, thereby forming a closed cavity between the third valve body 3 and the pushing end of the pushing unit 7. In this state, the reaction reagent 8 in the holding tank 61 can react with the sample being tested. In the fourth state, one end of the chip is sealed with a plunger, and the other end is sealed with a normally open valve. The chip as a whole returns to a sealed state, facilitating subsequent reactions.

[0089] Figure 4 In the embodiment, there is a sealing liquid 6 above each holding tank 61. Therefore, when the reaction reagent 8 in each holding tank 61 reacts with the sample to be detected, the reaction reagents 8 in each holding tank 61 will not affect each other, and therefore will not affect the detection results of the sample to be detected in each holding tank 61 (will not affect the fluorescent labeling results).

[0090] Reaction reagent 8 typically requires heating when reacting with the sample being tested. Therefore, heating of reaction reagent 7 can easily generate bubbles on the surface of reaction reagent 8. By using sealing liquid 6 with a higher boiling point than that of reaction reagent 8, bubbles can be blocked, thereby preventing the volatilization of reaction reagent 8. Sealing liquid 6 is preferably sealing oil.

[0091] When heating during the reaction, if the third valve body 3 is not sealed, the sealing liquid 6 will expand due to the heat and squeeze the gas column 5 to the left, causing the sealing liquid 6 to move left and right in the extension direction of the channel, making its state unstable and possibly affecting the reaction between the reaction reagent 8 and the sample to be tested.

[0092] exist Figure 4In the embodiment, since the third valve body 3 is sealed, the sealing liquid 6 is enclosed in the closed cavity between the third valve body 3 and the pushing end of the pushing unit 7, so that its range of movement is limited, thereby keeping it in a thermodynamically stable state and avoiding affecting the detection results.

[0093] When the reaction reagent is added, the state changes from the first state to the second state. When the sealing oil is pushed in, the state changes from the second state to the third state. When the sealing oil is pushed out and the gas column reaches the position facing the third valve body 3 (the lower end of the third valve body 3), the state changes from the third state to the fourth state.

[0094] The normally closed valve heating time can be 0.5-1.5 seconds, while the normally open valve heating time can be 1-5 seconds. Heating is performed using a laser, which shines through the transparent sidewall 101 onto the black surface of the normally closed valve. The sidewall does not absorb heat and therefore does not melt, while the normally closed valve absorbs the laser energy, melting and vaporizing. The heating unit can utilize a laser light source, preferably a blue-violet laser light source. The blue-violet laser light source parameters can be: power of 1-5W and wavelength of 450nm.

[0095] like Figure 2-4 As shown, a first heating unit 51 for heating the first valve body 1, a second heating unit 52 for heating the second valve body 2, and a third heating unit 53 for heating the third valve body 3 are provided on the outside of the device body 10, and the control end of the first heating unit 51, the control end of the second heating unit 52, and the control end of the third heating unit 53 are electrically connected to the control unit respectively.

[0096] Preferably, the first heating unit 51, the second heating unit 52, and the third heating unit 53 are all laser heating units. The first valve body, the second valve body, and the third valve body are all made of opaque material and are all arranged on the inner wall surface of the device body. The portion of the device body located between the first valve body and the first heating unit, the portion located between the second valve body and the second heating unit, and the portion located between the third valve body and the third heating unit are made of translucent material.

[0097] In the present invention, through the above-mentioned arrangement, the control unit can determine whether the designated position has been reached based on the position of the air column in the channel detected by the detection unit, thereby stopping the pushing unit when the designated position is reached, and controlling the first, second, and third heating units to perform heating, thereby realizing automatic control of the device. Preferably, the outer side wall of the device body of the first valve body away from the first receiving groove is close to or in contact with the first heating unit. Preferably, the outer side wall of the device body of the second valve body away from the second receiving groove is close to or in contact with the second heating unit. Preferably, the outer side wall of the device body of the third valve body away from the channel is close to or in contact with the third heating unit.

[0098] Preferably, the first heating unit 51, the second heating unit 52, and the third heating unit 53 are the same heating unit, that is, the same heating unit heats each valve body respectively in different time periods.

[0099] The first heating unit 51 can be arranged at a position corresponding to the first valve body 1 outside the device body 10. The first heating unit 51 can be arranged at a position corresponding to the first valve body 1 outside the device body 10. Figure 2 The side wall 101 is in contact with or has a certain distance therefrom.

[0100] The second heating unit 52 can be arranged at a position corresponding to the second valve body 2 outside the device body 10. The first heating unit 51 can be arranged at a position corresponding to the outer wall surface ( Figure 3 The side wall 101 is in contact with or has a certain distance therefrom.

[0101] The third heating unit 53 can be arranged at a position corresponding to the third valve body 3 outside the device body 10. The first heating unit 51 can be connected to the outer wall surface ( Figure 4 The side wall 101 is in contact with or has a certain distance therefrom.

[0102] Since the side wall 101 is made of a translucent material, when heated by each heating unit, the side wall 101 will not absorb heat and will not be deformed by the irradiation of the heating unit; while the valve body is made of an opaque material and can absorb heat, so that the valve body is heated and melted to block the channel.

[0103] Figure 5 、 Figure 6 They are cross-sectional schematic diagrams of the first valve body 1 in the closed and open states respectively. Figure 5-6 As shown, the channel wall below the first valve body 1 is provided with a first receiving groove 11 facing the first valve body 1;

[0104] The first valve body 1 is made of an opaque material, while the sidewalls 101 of the device body 10, located outside the first valve body 1, are made of a translucent material. When the first valve body 1 is closed, the sidewalls 101 and the first receiving groove 11 are located on either side of the first valve body 1. The first valve body 1 can be fixed to the inner wall of the device body 10 above the first valve body 1. Preferably, the first receiving groove 11 is positioned directly opposite the first valve body 1. Preferably, the opening of the first receiving groove 11 is no smaller than the size of the first valve body 1.

[0105] The first holding tank 11 serves as an overflow pool (located below the pipe, on the chip substrate). After heating the first valve body 1 by the first heating unit 51, the material of the first valve body 1 melts and flows into the overflow pool below the pipe, thus ensuring fluid flow. A high-melting-point, highly fluid material is pre-sealed in the pipe, creating a normally closed valve.

[0106] Figure 7 、 Figure 8They are cross-sectional schematic diagrams of the second valve body 2 in the closed and open states respectively. Figure 7-8 As shown, the channel wall below the second valve body 2 is provided with a second receiving groove 21 facing the second valve body 2;

[0107] The second valve body 2 is made of an opaque material, while the sidewall 101 of the device body 10, located outside the second valve body 2, is made of a translucent material. When the second valve body 2 is closed, the sidewall 101 and the second receiving groove 21 are located on either side of the second valve body 2. The second valve body 2 can be fixed to the inner wall of the device body 10 above the second valve body 2. Preferably, the second receiving groove 21 is positioned directly opposite the second valve body 2. Preferably, the opening of the second receiving groove 21 is no smaller than the size of the second valve body 2.

[0108] Figure 9 、 Figure 10 They are cross-sectional schematic diagrams of the third valve body 3 in the open and closed states respectively. Figure 9-10 As shown, the upper wall surface of the channel in the second cavity 602 is provided with a third receiving groove 31 arranged toward the channel, and the third valve body 3 is received and fixed in the third receiving groove 31;

[0109] The third valve body 3 is made of opaque material, and the side wall 101 of the device body 10 located outside the third valve body 3 is made of translucent material.

[0110] The first valve body 1 , the second valve body 2 , the third valve body 3 and the device body 10 are all made of polymer plastic materials, the opaque material is dark plastic, and the translucent material is transparent plastic.

[0111] In this invention, a material with a high melting point and good fluidity is selected as the valve body. A normally closed valve (first valve body 1, second valve body 2) and a normally open valve (third valve body 3) are combined to form a composite microvalve structure, achieving the microvalve's "normally closed-normally open-normally closed" function. This ensures that the chip maintains a high degree of airtightness for a long period of time during the microvalve's setup and after opening and closing.

[0112] Each valve body in the present invention can maintain a long-term stable vacuum inside the chip before use, and after the valve body is opened and closed, the inside of the chip can maintain a high degree of airtightness for a long time, which is stable and reliable. The valve body material can be pre-bonded to a specified position in the chip, and the melting point needs to be higher than the chip material temperature (i.e., the melting point of the chip material), the softening temperature is higher than the reagent reaction temperature, and the fluidity is good after melting. When the third valve body 3 needs to be closed, the material of the third valve body 3 can flow to the specified position in the channel, solidify according to the required time, and completely block the channel. The melting point of the valve body can be higher or lower than the temperature of the chip material. If laser heating is used, it is also acceptable for the melting point of the valve body to be equal to or higher than the melting point of the chip material. Because the side wall is transparent and does not absorb heat, the heating temperature of the heating unit needs to be lower than the temperature of the chip material.

[0113] This invention simplifies the overall microvalve manufacturing process, making it easier to integrate the microvalve with the microfluidic chip, reducing chip production costs and making it suitable for mass production. The normally open valve's closing time is controllable. By selecting and adjusting the material formula, the fluid closing time can be adjusted from 1 to 5 seconds as needed. The normally closed valve opens quickly, opening the microvalve in about 1 second.

[0114] The use of an external heating device separates the power source from the chip, simplifying chip processing and production, making installation and removal of the chip in the instrument more flexible during testing and improving testing efficiency. An external heating device (laser heating or micro-heating pad) heats the valve body to open and close the microvalve. The advantages of this combination of a microvalve and heating are: After the microvalve is opened and closed, the chip interior maintains a high degree of airtightness for extended periods; the microvalve is less susceptible to environmental fluctuations, does not contaminate reagents, and is stable and reliable; it simplifies chip processing, facilitating chip integration; and it reduces production costs, making it suitable for mass production. Due to the extremely small area of ​​the microvalve, the size of the heating device required to melt the valve body material is limited, ensuring that heating does not affect the reagents in the pipeline. The external heating device provides highly concentrated energy and precise heating position control.

[0115] This embodiment 1 also provides a microfluidic chip control method, which includes the following steps:

[0116] Step (A): heating the first valve body 1 for a first preset time, so that the first valve body 1 melts and solidifies after being heated, thereby forming a first opening 201 between the first cavity 601 and the second cavity 602;

[0117] Step (B): After waiting for a first preset waiting time, the second valve body 2 is heated for a second preset time, so that the second valve body 2 melts and solidifies after being heated, thereby forming a second opening 202 between the second cavity 602 and the third cavity 603;

[0118] Step (C): After waiting for a second preset waiting time, the reaction reagent 8, the gas column 5 and the sealing liquid 6 are pushed into the inner side of the channel by the pushing unit 7;

[0119] Step (D1): If it is determined that the third valve body 3 is between the first position and the second position, then the pushing is stopped;

[0120] Step (E): heating the third valve body 3 for a third preset time, so that the third valve body 3 melts after being heated and solidifies in the second cavity 602, thereby separating the second cavity 602 into two parts that are not connected to each other.

[0121] The first and second positions are defined as the intersection of the gas column 5 and the reaction reagent 8 in the channel, and the intersection of the gas column 5 and the sealing liquid 6 in the channel, respectively. The detection unit is configured to detect the first and second positions and stop pushing if it determines that the third valve body 3 is between the first and second positions. The third valve body 3 is located between the first valve body 1 and the innermost receiving groove 61.

[0122] Example 2

[0123] This embodiment 2 differs from embodiment 1 in that no detection device is provided, only a timing device. Based on the channel dimensions, the volume of the reaction reagent, the volume of the gas column, the volume of the sealing liquid, and the speed of the pushing unit, an estimate is made of how long the pushing unit will need to operate from the start of operation until the gas column 5 reaches a position directly opposite the third valve body 3. This allows heating of the third valve body 3 after the pushing unit stops.

[0124] It should be noted that the various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same and similar parts between the various embodiments can be referenced to each other.

[0125] The embodiments of the present invention are described in detail above, but the contents are only preferred embodiments of the present invention and cannot be considered to limit the scope of implementation of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the scope of this patent. After reading this invention, modifications of various equivalent forms of the present invention by those skilled in the art fall within the scope defined by the claims attached to this application. In the absence of conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other.

Claims

1. A microfluidic chip comprising a device body, a channel formed in the device body (10) and open at one end, a pushing unit (7) for pushing a reaction reagent (8) and a sealing liquid (6) into the inner side of the channel is provided on the outer side of the channel opening, characterized in that: A first valve body (1) and a second valve body (2) are fixedly arranged in the channel; The channel portion between the end of the channel away from the opening and the first valve body (1) forms a first cavity (601). The channel portion between the first valve body (1) and the second valve body (2) forms a second cavity (602), and a receiving groove (61) is provided on the lower wall of the channel in the second cavity (602), wherein the receiving groove (61) receives a sample to be tested; The channel portion between the second valve body (2) and the pushing end of the pushing unit (7) forms a third cavity (603); The first cavity (601), the second cavity (602), and the third cavity (603) together form a closed cavity; When the first valve body (1) is in a closed state, the first cavity (601) and the second cavity (602) are not connected to each other, and the first cavity (601) contains a reaction reagent (8); When the second valve body (2) is in a closed state, the second cavity (602) and the third cavity (603) are not connected to each other, and the third cavity (603) contains an air column (5) and a sealing liquid (6) for sealing a reaction reagent (8), and the air column (5) is located between the sealing liquid (6) and the second valve body (2); When the first valve body (1) and the second valve body (2) are both in a closed state, the second cavity (602) is in a vacuum state; The first valve body (1) is used to melt and solidify after being heated, thereby forming a first opening (201) between the first cavity (601) and the second cavity (602); The second valve body (2) is used to melt and solidify after being heated, thereby forming a second opening (202) between the second cavity (602) and the third cavity (603); A third valve body (3) is provided on the channel wall surface in the second cavity (602); the melting point of the material of the third valve body (3) is higher than the temperature at which the reaction reagent (8) reacts; the third valve body (3) is used to melt after being heated and solidify in the second cavity (602), thereby separating the second cavity (602) into two parts that are not connected to each other; The number of the containing grooves (61) is not less than 2, and the containing grooves (61) are arranged at intervals along the extension direction of the channel, and the samples to be tested in the containing grooves (61) are the same or different samples; The first valve body (1), the second valve body (2), and the third valve body (3) are all made of opaque materials and are all arranged on the inner wall surface of the device body (10); at least one side wall (101) located outside the first valve body (1), at least one side wall (101) located outside the second valve body (2), and at least one side wall (101) located outside the third valve body (3) of the device body (10) are all made of translucent materials.

2. The microfluidic chip according to claim 1, characterized in that The sealing liquid (6) is a liquid having a boiling point higher than that of the reaction reagent (8).

3. The microfluidic chip according to claim 1 or 2, characterized in that: A first receiving groove (11) facing the first valve body (1) is formed on the channel wall below the first valve body (1); The first valve body (1) is made of opaque material, and the side wall (101) of the device body (10) located outside the first valve body (1) is made of translucent material; When the first valve body (1) is in a closed state, the side wall (101) and the first accommodating groove (11) are respectively located on both sides of the first valve body (1).

4. The microfluidic chip according to claim 1 or 2, characterized in that: A second receiving groove (21) facing the second valve body (2) is formed on the channel wall below the second valve body (2); The second valve body (2) is made of opaque material, and the side wall (101) of the device body (10) located outside the second valve body (2) is made of translucent material; When the second valve body (2) is in a closed state, the side wall (101) and the second accommodating groove (21) are respectively located on both sides of the second valve body (2).

5. The microfluidic chip according to claim 1 or 2, characterized in that: A third accommodating groove (31) is provided on the upper wall surface of the channel in the second cavity (602) and is arranged toward the channel, and the third valve body (3) is accommodated and fixed in the third accommodating groove (31); The third valve body (3) is made of opaque material, and the side wall (101) of the device body (10) located outside the third valve body (3) is made of translucent material.

6. A microfluidic chip detection device, characterized in that: The microfluidic chip detection device comprises a control unit and a detection unit for detecting the position of a reaction reagent (8) in a channel of the microfluidic chip according to any one of claims 1 to 5, wherein the control unit and the detection unit are both arranged on the outside of the microfluidic chip, and the output end of the detection unit and the control end of the pushing unit (7) of the microfluidic chip are electrically connected to the control unit respectively.

7. The microfluidic chip detection device according to claim 6, characterized in that: The detection unit is used to detect the position of the pushing end of the pushing unit (7); or The detection unit is a visual detection unit, and the image acquisition end of the visual detection unit is arranged toward the channel.

8. A microfluidic chip control method, characterized in that: The controlled microfluidic chip is the microfluidic chip according to any one of claims 1 to 5; The microfluidic chip control method comprises the following steps: Step (A): heating the first valve body (1) for a first preset time, so that the first valve body (1) melts and solidifies after being heated, thereby forming a first opening (201) between the first cavity (601) and the second cavity (602); Step (B): after waiting for a first preset waiting time, heating the second valve body (2) for a second preset time, so that the second valve body (2) melts and solidifies after being heated, thereby forming a second opening (202) between the second cavity (602) and the third cavity (603); Step (C): After waiting for a second preset waiting time, the sealing liquid (6) is pushed into the inner side of the channel by using the pushing unit (7); Step (D): If it is determined that the third valve body (3) is located between the first position and the second position, the pushing is stopped; Step (E): heating the third valve body (3) for a third preset time, so that the third valve body (3) melts after being heated and solidifies in the second cavity (602), thereby separating the second cavity (602) into two parts that are not connected to each other.

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