Microfluidic chip and in vitro detection device

Abstract

The present invention relates to a microfluidic chip capable of improving sample processing efficiency and an in vitro detection device containing the microfluidic chip. The microfluidic chip is designed with a sample adding cavity, a first microfluidic channel, a second microfluidic channel, a plurality of separation and quantitative units, a first capillary flow channel and a first waste liquid cavity. After adding a sample solution to the sample adding cavity, the sample solution enters the quantitative cavity under the action of centrifugation through rotation centrifugation, and fills the second waste liquid cavity and the quantitative cavity in turn. Through centrifugation, solid wastes such as blood cells can be further centrifugally deposited in the second waste liquid cavity connected to the quantitative cavity, so as to achieve separation of samples such as whole blood and quantitative in the quantitative cavity. After adding the sample solution, the microfluidic chip only needs one centrifugation to achieve separation and quantification of impurities and target detection liquid in the sample solution, without excessive centrifugation operations, so the operation is simple, the waiting time is short, and the efficiency of sample processing is significantly improved.

Description

Technical Field

[0001] The present invention relates to the technical field of in vitro diagnosis, and in particular to a microfluidic chip and an in vitro detection device. Background Art

[0002] The in vitro diagnostic industry (IVD) belongs to the pharmaceutical and biological industry. It refers to the use of in vitro detection reagents and instruments to detect and calibrate samples such as blood, body fluids, and tissues taken from the human body in order to prevent, diagnose, treat, detect, observe, evaluate health, predict genetic diseases, etc. In vitro diagnosis is divided into three categories according to methodology: biochemical diagnosis, immunological diagnosis, and molecular diagnosis, as well as bedside rapid diagnosis POCT differentiated from biochemical, immunological, and molecular diagnosis. Dry chemical reaction is a type of biochemical diagnosis, which uses biochemical reagents to react with specific substrates, and then quantitatively detects the concentration of the target through instruments to deduce certain biochemical indicators of the human body. Traditional biochemical diagnosis needs to be tested on a large biochemical instrument, which leads to problems such as high reagent consumption and insufficient flexibility; the general dry biochemical POCT diagnostic method has a low test throughput, and generally can only test one or several samples and one or several items at a time. Microfluidics chip technology can integrate basic operating units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes on the chip, automatically completing the entire analysis process and greatly improving detection efficiency. It also has the advantages of miniaturization and automation, and is therefore increasingly widely used in the POCT field.

[0003] In the field of biochemical testing, Abaxis in the United States is the first company to develop microfluidic chips for biochemical testing. Domestic companies such as Tianjin Micro-Nano Chip and Chengdu Smart have developed similar microfluidic chips. The quantification and distribution process of whole blood samples in traditional chips often requires the separation of whole blood and the quantification process of serum to be separated, so multiple centrifugation and quantification are required, which makes the sample processing time longer and causes the detection time to be too extended. Summary of the invention

[0004] Based on this, it is necessary to provide a microfluidic chip that can improve sample processing efficiency and an in vitro detection device containing the microfluidic chip.

[0005] A microfluidic chip comprises a sample loading cavity, a first microfluidic channel, a second microfluidic channel, a separation and quantitative unit, a first capillary channel and a first waste liquid cavity; the sample loading cavity has a sample loading hole, and the sample loading cavity is connected with the second microfluidic channel through the first microfluidic channel; the microfluidic chip has a rotation center, and the second microfluidic channel is arranged around the rotation center; the first waste liquid cavity is connected with the liquid outlet end of the second microfluidic channel through the first capillary channel; there are a plurality of separation and quantitative units, each of which comprises a third microfluidic channel, a quantitative cavity and a second waste liquid cavity, the quantitative cavity is connected with the second microfluidic channel through the third microfluidic channel, the second waste liquid cavity is connected with the quantitative cavity, and a plurality of separation and quantitative units are distributed around the second microfluidic channel on the inner side of the second microfluidic channel;

[0006] The first capillary channel extends from the second microchannel to the direction close to the rotation center on the inner side of the second microchannel and bends to extend away from the rotation center to communicate with the first waste liquid chamber; the third microchannel extends from the second microchannel to the direction close to the rotation center to communicate with the quantitative chamber;

[0007] The distance between the connection position of the quantitative cavity and the third microchannel and the rotation center is not less than the distance between the bending vertex of the first capillary channel and the rotation center, and the second waste liquid cavity is farther from the rotation center than the quantitative cavity.

[0008] In one embodiment, the sample loading chamber is arranged around the rotation center, one end of which is provided with the sample loading hole, and the other end is connected to the first microchannel.

[0009] In one embodiment, the sample loading chamber is further provided with a first vent hole at one end connected to the first microfluidic channel, and the first vent hole is closer to the rotation center than the connection position between the sample loading chamber and the first microfluidic channel.

[0010] In one embodiment, the microfluidic chip further includes a fifth microchannel, one end of the fifth microchannel is connected to the first waste liquid chamber, and the other end has a second air hole, and the second air hole is closer to the rotation center than the first waste liquid chamber.

[0011] In one embodiment, the first waste liquid chamber is arranged outside the second microfluidic channel and around the rotation center; and / or

[0012] A radial dimension of a section of the fifth microfluidic channel connected to the first waste liquid chamber is greater than a radial dimension of a section close to the second air permeable hole.

[0013] In one embodiment, each of the separation and quantitative units further includes a sixth microfluidic channel, and the quantitative chamber is connected to the third microfluidic channel through the sixth microfluidic channel;

[0014] The connection position between the sixth microfluidic channel and the third microfluidic channel is closer to the rotation center than the quantitative cavity; the distance between the connection position between the sixth microfluidic channel and the third microfluidic channel and the rotation center is not less than the distance between the bending vertex position of the first capillary channel and the rotation center.

[0015] In one embodiment, the microfluidic chip further comprises a gas permeable microchannel, the gas permeable microchannel is connected to the sixth microchannel of each quantitative cavity, and a third gas permeable hole is provided on the gas permeable microchannel;

[0016] The air-permeable microchannel is closer to the rotation center than the connection position between the sixth microchannel and the third microchannel.

[0017] In one embodiment, the air-permeable microchannel is annularly arranged around the rotation center on the inner side of the plurality of separation and quantitative units, and there are a plurality of third air holes, which are distributed around the air-permeable microchannel.

[0018] In one embodiment, one end of the sixth microfluidic channel is connected to the air-permeable microfluidic channel, and the other end is connected to the quantitative chamber, and the third microfluidic channel is connected to the middle of the sixth microfluidic channel.

[0019] In one embodiment, each of the separation and quantitative units further includes a seventh microfluidic channel, and the second waste liquid chamber is connected to the quantitative chamber through the seventh microfluidic channel.

[0020] In one embodiment, the separation and quantitative unit further includes a liquid outlet microchannel, one end of which is connected to the quantitative cavity, and the other end of which is provided with a permeation hole.

[0021] In one embodiment, the liquid outlet microchannel includes a second capillary channel, one end of the second capillary channel is connected to the seventh microchannel, and the other end is provided with the permeation hole;

[0022] The second capillary channel extends toward the direction close to the rotation center after being connected to the seventh microchannel and bends to extend toward the direction away from the rotation center;

[0023] The distance between the connection position of the quantitative cavity and the third microfluidic channel and the rotation center is greater than the distance between the bending vertex position of the second capillary channel and the rotation center, and the distance between the bending vertex position of the first capillary channel and the rotation center is greater than the distance between the bending vertex position of the second capillary channel and the rotation center.

[0024] In one embodiment, the liquid outlet microfluidic channel further includes an eighth microfluidic channel, the eighth microfluidic channel is connected to the seventh microfluidic channel, and the second capillary channel is connected to the seventh microfluidic channel through the eighth microfluidic channel.

[0025] In one embodiment, the microfluidic chip includes a chip body and a transparent cover film covering the chip body, and the chip body and the transparent cover film cooperate to form various cavity structures and flow channel structures of the microfluidic chip.

[0026] In one embodiment, the transparent cover film is a transparent pressure-sensitive adhesive film.

[0027] An in vitro detection device comprises the microfluidic chip and a detection mechanism as described in any one of the above embodiments, wherein the detection mechanism is connected to the quantitative cavity and is used to detect a sample in the quantitative cavity.

[0028] In one embodiment, the detection mechanism is a dry chemical test paper.

[0029] In one embodiment, the dry chemical test paper includes a support layer and a reaction indicator layer and a diffusion layer stacked in sequence on the support layer, the reaction indicator layer contains a reaction reagent and an indicator reagent that can react with a target substance in a sample to be tested, and the diffusion layer faces the permeation hole through the injection port.

[0030] In one embodiment, the microfluidic chip is provided with mounting grooves around the permeation holes of each separation and quantitative unit, and the detection mechanism is embedded in each mounting groove.

[0031] The above-mentioned microfluidic chip is designed by designing a sample addition chamber, a first microfluidic channel, a second microfluidic channel, multiple separation and quantitative units, a first capillary channel and a first waste liquid chamber, wherein the first microfluidic channel, the second microfluidic channel, the third microfluidic channel of each separation and quantitative unit and the first capillary channel constitute a communicating vessel structure. After adding the sample solution to the sample adding chamber, the sample solution enters the second microchannel through the first microchannel through rotation centrifugation, and is divided in the second microchannel to enter the third microchannel of each separation and quantitative unit respectively, so that the sample solution will enter the quantitative chamber under the action of centrifugation, and fill the second waste liquid chamber and the quantitative chamber in turn, and solid wastes such as blood cells can be further centrifugally deposited in the second waste liquid chamber connected to the quantitative chamber through centrifugation, so as to achieve the separation of samples such as whole blood and the quantification in the quantitative chamber, and the excess sample solution enters the first capillary channel through the second microchannel, because the distance between the connection position of the quantitative chamber and the third microchannel in the separation and quantitative unit and the rotation center of the microfluidic chip is equal to the distance between the bending vertex position of the first capillary channel and the rotation center, so when the sample solution reaches the bending vertex of the first microchannel, it will continue to move forward, and under the action of centrifugal force, a siphon effect is formed to introduce the excess sample solution into the first waste liquid chamber.

[0032] After adding the sample solution, the microfluidic chip only needs one centrifugation to separate and quantify the impurities and target detection solution in the sample solution, without requiring excessive centrifugation operations. Therefore, the operation is simple, the waiting time is short, and the efficiency of sample processing is significantly improved.

[0033] Further, the microfluidic chip is also designed with a liquid outlet microchannel including a second capillary channel, one end of the second capillary channel is connected to the seventh microchannel, and the other end is provided with a permeation hole, the second capillary channel extends in a direction close to the rotation center after being connected to the seventh microchannel and extends in a direction away from the rotation center after being bent, and the distance between the connection position of the quantitative cavity and the third microchannel and the rotation center is greater than the distance between the bending vertex position of the second capillary channel and the rotation center, so that during centrifugation, because the centrifugal force is greater than the capillary suction force of the capillary, the sample solution will not break through the bending position of the second capillary channel, and the second capillary channel can play the role of a "valve" to close the sample solution in the quantitative cavity and prevent it from flowing out; after the subsequent centrifugation is completed, the liquid in the second capillary channel moves forward along the second capillary channel under the action of the capillary suction force, the "valve" is opened, and the liquid continues to flow to the permeation hole and can seep out from the permeation hole. Preferably, it can be combined with low-speed centrifugation, and under the action of siphon, the liquid continuously seeps out from the permeation hole to the detection mechanism to complete the detection of the sample.

[0034] The second capillary channel is used as a valve to control the contact reaction between the sample and the detection mechanism, which can replace the traditional delayed opening mechanism such as water-soluble membrane or valve, making the sampling detection process more stable and reliable, while simplifying the chip assembly process, which is conducive to reducing production costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 , Figure 2 and Figure 3 The front, back and side structural schematic diagrams of the microfluidic chip according to an embodiment of the present invention are shown respectively.

[0036] Figure 4-1 , Figure 4-2 , Figure 4-3 , Figure 4-4 They are Figure 1 The schematic diagram of the separation and quantification process of the sample solution using the microfluidic chip shown. Figure 4-3-1 , Figure 4-3-2 It is a local enlarged schematic diagram.

[0037] Figure 5-1 and Figure 5-2 They are Figure 1 Schematic diagram of the detection process of the microfluidic chip shown. Figure 5-1-1 It is a local enlarged schematic diagram.

[0038] Description of reference numerals:

[0039] 10: microfluidic chip, 101: rotation center, 102: mounting part, 103: chip body, 104: transparent cover film, 11: sample loading chamber, 111: sample loading hole, 112: first air permeable hole, 12: first microfluidic channel, 13: second microfluidic channel, 14: separation quantitative unit, 141: third microfluidic channel, 142: quantitative chamber, 143: second waste liquid chamber, 144: outlet microfluidic channel, 145: permeation hole, 146: sixth microfluidic channel, 1 47: seventh microfluidic channel, 148: second capillary channel, 148a, 148b and 148c are different positions on the second capillary channel, 149: eighth microfluidic channel, 15: first capillary channel, 15a, 15b and 15c are different positions on the first capillary channel, 16: first waste liquid chamber, 17: fourth microfluidic channel, 18, fifth microfluidic channel, 181: second air hole, 19: air-permeable microfluidic channel, 191: third air hole, 20: mounting groove. DETAILED DESCRIPTION

[0040] In order to facilitate the understanding of the present invention, the present invention will be described more fully below with reference to the relevant drawings. The preferred embodiments of the present invention are given in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0041] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art of the present invention. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0042] Please combine Figure 1 and Figure 2 An embodiment of the present invention provides a microfluidic chip 10 , which has a sample addition chamber 11 , a first microfluidic channel 12 , a second microfluidic channel 13 , a separation and quantitative unit 14 , a first capillary channel 15 and a first waste liquid chamber 16 .

[0043] The sample loading chamber 11 has a sample loading hole 111. The sample solution can be added to the sample loading chamber 11 from the sample loading hole 111. The sample loading chamber 11 is connected to the second microchannel 13 through the first microchannel 12. The microfluidic chip 10 has a rotation center 101. During rotation centrifugation, the microfluidic chip 10 rotates around the rotation center 101. The second microchannel 13 is arranged around the rotation center 101. The first waste liquid chamber 16 is connected to the liquid outlet end of the second microchannel 13 through the first capillary channel 15.

[0044] There are multiple separation and quantitative units 14. Each separation and quantitative unit 14 includes a third microfluidic channel 141, a quantitative chamber 142, and a second waste liquid chamber 143. The quantitative chamber 142 is connected to the second microfluidic channel 13 through the third microfluidic channel 141, and the second waste liquid chamber 143 is connected to the quantitative chamber 142. Multiple separation and quantitative units 14 are distributed around the second microfluidic channel 13 on the inner side of the second microfluidic channel 13. Preferably, multiple separation and quantitative units 14 are evenly spaced around the second microfluidic channel 13.

[0045] The “surrounding” mentioned in this article may form a closed loop or not, for example, it may surround in the shape of a sector with an angle greater than 180°.

[0046] In this embodiment, the first capillary channel 15 extends from the inner side of the second microchannel 13 to the direction close to the rotation center 101 (which may be the direction gradually close to the rotation center 101, for example, but not limited to the radial direction toward the rotation center 101) after being connected to the second microchannel 13, and then bends to extend from the rotation center 101 (which may be the direction gradually away from the rotation center 101, for example, but not limited to the radial direction away from the rotation center 101) to communicate with the first waste liquid chamber 16. The third microchannel 141 is located on the inner side of the second microchannel 13, and the third microchannel 141 extends from the direction close to the rotation center 101 after being connected to the second microchannel 13 to communicate with the quantitative chamber 142.

[0047] Furthermore, in this embodiment, the distance between the connection position of the quantitative chamber 142 and the third microchannel 141 and the rotation center 101 is not less than the distance between the bending vertex of the first capillary channel 15 and the rotation center 101, and the second waste liquid chamber 143 is farther away from the rotation center 101 than the quantitative chamber 142.

[0048] By designing a microfluidic chip 10 with the above structure, the sample solution can be separated and quantified by one centrifugation, and the sample solution can be distributed to multiple separation and quantification units 14 with good consistency and high integration, which significantly improves the throughput of a single detection.

[0049] In a specific example, the sample loading chamber 11 is arranged around the rotation center 101, one end of which is provided with a sample loading hole 111, and the other end is connected to the first microchannel 12, and preferably, the sample loading chamber 11 gradually widens from the end provided with the sample loading hole 111 to the other end, so that the added sample loading solution can flow smoothly to the first microchannel 12. Further, the end of the sample loading chamber 11 connected to the first microchannel 12 extends in a direction away from the rotation center 101, and is connected to the first microchannel 12 at the bottom, so as to introduce the sample solution into the first microchannel 12 during centrifugation.

[0050] Furthermore, the sample adding chamber 11 is further provided with a first vent hole 112 at one end connected to the first microchannel 12, and the first vent hole 112 is closer to the rotation center 101 than the connection position between the sample adding chamber 11 and the first microchannel 12. By providing the first vent hole 112, when adding the sample solution to the sample adding chamber 11, the gas can be discharged in time, which facilitates the addition of the sample solution.

[0051] In a specific example, one end of the second microchannel 13 is connected to the first microchannel 12 , and extends around the rotation center 101 to the other end connected to the first capillary channel 15 .

[0052] In a specific example, the microfluidic chip 10 further includes a fourth microchannel 17. The first capillary channel 15 is connected to the second microchannel 13 through the fourth microchannel 17, and the fourth microchannel 17 extends toward the rotation center 101 after being connected to the second microchannel 13 to connect to the first capillary channel 15.

[0053] Further, in a specific example, the microfluidic chip 10 further includes a fifth microchannel 18. One end of the fifth microchannel 18 is connected to the first waste liquid chamber 16, and the other end has a second vent 181. The second vent 181 is closer to the rotation center 101 than the first waste liquid chamber 16. Preferably, the fifth microchannel 18 extends in a direction close to the rotation center 101 after being connected to the first waste liquid chamber 16.

[0054] In the specific example shown in the figure, the first waste liquid chamber 16 is arranged around the rotation center 101 at the periphery of the second microfluidic channel 13, and the volume of the entire first waste liquid chamber 16 is guaranteed to be large enough to fully accommodate the excess sample solution. Preferably, the radial dimension of a section of the fifth microfluidic channel 18 connected to the first waste liquid chamber 16 is larger than the radial dimension of a section close to the second vent hole 181, so as to prevent the liquid from entering the fifth microfluidic channel 18 and blocking the fifth microfluidic channel 18, thereby causing the problem of untimely ventilation.

[0055] In a specific example, each separation and quantitative unit 14 further includes a sixth microchannel 146. The quantitative chamber 142 is connected to the third microchannel 141 through the sixth microchannel 146.

[0056] The connection position between the sixth microchannel 146 and the third microchannel 141 is closer to the rotation center 101 than the quantitative chamber 142. The distance between the connection position between the sixth microchannel 146 and the third microchannel 141 and the rotation center 101 is not less than the distance between the bending vertex of the first capillary channel 15 and the rotation center 101.

[0057] Furthermore, the microfluidic chip 10 further includes a gas permeable microchannel 19. The gas permeable microchannel 19 is connected to the sixth microchannel 146 of each quantitative cavity 142. The gas permeable microchannel 19 is provided with a third gas permeable hole 191. The gas permeable microchannel 19 is closer to the rotation center 101 than the connection position between the sixth microchannel 146 and the third microchannel 141.

[0058] In the specific example shown in the figure, the air-permeable microchannel 19 is arranged in a ring shape around the rotation center 101 on the inner side of the plurality of separation and quantitative units 14. Preferably, there are a plurality of third air holes 191, and the plurality of third air holes 191 are distributed around the air-permeable microchannel 19. By providing a plurality of air holes 191, in coordination with the plurality of separation and quantitative units 14, the air in each separation and quantitative unit 14 can be discharged in time, facilitating the introduction of the sample solution.

[0059] In the specific example shown in the figure, one end of the sixth microchannel 146 is connected to the air-permeable microchannel 19, and the other end is connected to the quantitative chamber 142, and the third microchannel 141 is connected to the middle of the sixth microchannel 146. The "middle" described herein can be, but is not limited to, the center or midpoint in a geometric sense, or a position close to the center or midpoint, preferably a non-end position.

[0060] In a specific example, each separation and quantitative unit 14 further includes a seventh microchannel 147. The second waste liquid chamber 143 is connected to the quantitative chamber 142 via the seventh microchannel 147. The outlet microchannel 144 is connected to the seventh microchannel 147.

[0061] In a specific example, the separation and quantification unit 14 further includes a liquid outlet microchannel 144. One end of the liquid outlet microchannel 144 is connected to the quantitative cavity 142, and the other end is provided with a permeation hole 145. The quantitative sample solution in the quantitative cavity 142 can be permeated out through the permeation hole 145.

[0062] Further, the liquid outlet microchannel 144 includes a second capillary channel 148. One end of the second capillary channel 148 is connected to the seventh microchannel 147, and the other end is provided with a permeation hole 145. In this specific example, the second capillary channel 148 extends in a direction close to the rotation center 101 after being connected to the seventh microchannel 147 and extends in a direction away from the rotation center 101 after being bent, and the distance between the connection position of the quantitative cavity 142 and the third microchannel 141 and the rotation center 101 is greater than the distance between the bending vertex position of the second capillary channel 148 and the rotation center 101, and the distance between the bending vertex position of the first capillary channel 15 and the rotation center 101 is greater than the distance between the bending vertex position of the second capillary channel 148 and the rotation center 101. In this way, during centrifugation, the sample solution after impurities are separated flows along the second capillary channel 148, but because the centrifugal force is greater than the capillary force, the sample solution will not flow to the bending apex of the second capillary channel 148, so the second capillary channel 148 can act as a valve to achieve a closing effect when the sample solution is separated and quantified.

[0063] Further, in a specific example, the outlet microchannel 144 further includes an eighth microchannel 149 . The eighth microchannel 149 is connected to the middle of the seventh microchannel 147 , and the second capillary channel 148 is connected to the seventh microchannel 147 through the eighth microchannel 149 .

[0064] The microfluidic chip 10 is further provided with a mounting portion 102 in the middle thereof. The center of the mounting portion 102 is the rotation center 101 of the microfluidic chip 10 .

[0065] The capillary flow channel described herein is a flow channel structure that is smaller than the size (e.g., width and / or depth) of the microchannel. In a specific example, the first capillary flow channel 15 and the second capillary flow channel 148 are in a V-shape, and the bending portion thereof is close to the rotation center 101. Preferably, the width of the first capillary flow channel 15 and the second capillary flow channel 148 is 0.1 mm to 0.2 mm, and the depth is 0.1 mm to 0.2 mm; or the width of the first capillary flow channel 15 and the second capillary flow channel 148 is 0.2 mm to 0.5 mm, and the depth is 0.2 mm to 0.5 mm. When the width of the first capillary channel 15 and the second capillary channel 148 is 0.1 mm to 0.2 mm and the depth is 0.1 mm to 0.2 mm, no surface treatment is required. When the width of the first capillary channel 15 and the second capillary channel 148 is 0.2 mm to 0.5 mm and the depth is 0.2 mm to 0.5 mm, the channel walls of the first capillary channel 15 and the second capillary channel 148 are preferably surface treated with PEG4000. Further preferably, the width of the first capillary channel 15 and the second capillary channel 148 is 0.2 mm and the depth is also 0.2 mm. After the sample solution enters the first capillary channel 15 and the second capillary channel 148, the sample solution can flow to the other end thereof by capillary action. Further preferably, the first capillary channel 15 and the second capillary channel 148 have different sizes in different sections. For example, the width of the first capillary channel 15 and the second capillary channel 148 at the bending part is 0.2 mm, and the depth is also 0.2 mm, and the width of other parts is 0.5 mm, and the depth is also 0.2 mm, so as to facilitate liquid flow and local formation of siphon and capillary action.

[0066] The PEG4000 surface treatment may be, but is not limited to, adding a 1wt% PEG4000 solution into the capillary channel and drying it naturally. The PEG4000 surface treatment is beneficial to increasing the capillary force of the capillary channel, and PEG4000 is an inert substance in the reaction system and generally does not react with the sample and the detection reagent, and thus does not affect the detection result.

[0067] like Figure 3 As shown in FIG. 1 , in a specific example, the microfluidic chip 10 includes a chip body 103 and a transparent cover film 104 covering the chip body 103. The chip body 103 and the transparent cover film 104 cooperate to form various cavity structures and flow channel structures. Specifically, the grooves of each cavity structure and flow channel structure are pre-formed on the chip body 103, such as Figure 2 As shown, each hole opens on the back side of the chip body 103, while the grooves of each cavity structure and flow channel structure open on the front side of the chip body 103. Subsequently, the cavity structure and flow channel structure are packaged by covering and sealing on the front side of the chip body 11 with a transparent cover film 12 to form a complete cavity structure and flow channel structure.

[0068] The transparent cover film 104 can be, but is not limited to, a transparent tape or a transparent pressure-sensitive adhesive, etc., which cooperates with the chip body 103 to form the entire microfluidic chip 10. The assembly is simple, and there is no need to use complex and expensive ultrasonic welding technology. Direct bonding is sufficient, which can significantly reduce the production cost. It is understandable that in other specific examples, the microfluidic chip 10 can also be formed by welding using a relatively expensive ultrasonic welding technology, or integrally formed using 3D printing technology.

[0069] The present invention further provides an in vitro detection device, which includes the above-mentioned microfluidic chip 10 and a detection mechanism. The detection mechanism is connected to the quantitative cavity 142, for example, it can be connected to the quantitative cavity 142 through but not limited to the permeation hole 145. The detection mechanism is used to detect the sample in the quantitative cavity 142.

[0070] In a specific example, the detection mechanism is a dry chemical test paper. More specifically, the dry chemical test paper may include a support layer and a reaction indicator layer and a diffusion layer stacked in sequence on the support layer, the reaction indicator layer contains a reaction reagent and an indicator reagent that can react with the target substance in the sample to be tested, and the diffusion layer faces the permeation hole 145 through the injection port. It can be understood that in other specific examples, the detection mechanism is not limited to dry chemical test paper, and can also be various other test strips or reactors.

[0071] In a specific example, if Figure 2 As shown, the microfluidic chip 10 is provided with mounting grooves 20 around the permeation holes 145 of each separation and quantitative unit 14 , and the detection mechanism is embedded in each mounting groove 20 .

[0072] The microfluidic chip 10 can separate and quantify impurities in the sample solution through one centrifugation, such as separating blood cells and serum (plasma) of a whole blood sample and quantifying serum, and can realize synchronous loading and testing of different separation and quantification units 14 through the valve action of the second capillary flow channel 148. Therefore, the in vitro detection device using the microfluidic chip 10 can detect different indicators of the sample or repeatedly detect the same indicator by one loading. Each separation and quantification unit 14 is arranged around the rotation center 101, with a high degree of integration. The consistency, accuracy and reliability of the test results can be improved by using the in vitro detection device.

[0073] Specifically, Figure 1 Taking the specific microfluidic chip 10 as an example, when separating impurities in a sample solution and quantifying a solution to be tested, the process may refer to but is not limited to the following:

[0074] like Figure 4-1As shown, a certain amount of sample solution is added to the sample loading chamber 11 from the sample loading hole 111, and the air in the sample loading chamber 11 can be discharged from the first air hole 112. After adding the sample solution, the microfluidic chip 10 is installed in an instrument with a rotating centrifugal function through its mounting portion 102, and the instrument is turned on to centrifuge the microfluidic chip 10 at a speed not limited to 4000-6000 rpm.

[0075] like Figure 4-2 As shown, under the action of centrifugal force, the sample solution starts to flow from one end of the sample loading chamber 11 to the other end, and enters the annular second microchannel 13 through the first microchannel 12 .

[0076] like Figure 4-3 As shown, as the sample solution continues to flow in, the sample solution sequentially enters the third microchannel 141, the sixth microchannel 146, the quantitative cavity 142, the seventh microchannel 147, the second waste liquid cavity 143, the eighth microchannel 149 and the second capillary channel 148 of the separation and quantitative unit 14. These channels and cavities form a communicating vessel structure, and the air in the original channels and cavities is discharged from the third vent hole 191 of the vent microchannel 19. Figure 4-3-1 As shown, when the sample solution fills the quantitative cavity 142 and reaches the junction of the third microchannel 141 and the sixth microchannel 146, the sample solution also enters the second capillary channel 148 through the eighth microchannel 149 and flows in the second capillary channel 148. Under the action of rapid centrifugation, the centrifugal force is greater than the capillary force. When the sample solution flows in the second capillary channel 148 to the position 148a flush with the connection between the third microchannel 141 and the sixth microchannel 146, It stops flowing because the distance between the bending portion 148b of the second capillary channel 143 and the rotation center 101 is closer than the distance between the connection portion between the third microchannel 141 and the sixth microchannel 146 and the rotation center 101. Therefore, the sample solution will not rise to the bending portion 148b of the second capillary channel 143, nor will it form a siphon effect in the second capillary channel 143 and flow out from the permeation hole 145 after passing through the section 148c. At this point, the quantification of the sample solution is completed.

[0077] like Figure 4-3-2 As shown, at the same time, the sample solution enters the first capillary channel 15 through the second microchannel 13 and the fourth microchannel 17. The sample solution continues to move forward after passing through section 15a. Since the distance between the bending vertex of the first capillary channel 15 and the rotation center 101 is consistent with the distance between the connection part of the third microchannel 141 and the sixth microchannel 146 and the rotation center 101, the sample solution can reach the highest point 15b, as shown in FIG. Figure 4-3As shown, as the sample solution continues to flow, the first capillary channel 15 is filled, and under the action of centrifugal force, a continuous siphon effect is formed to continuously discharge excess sample solution into the first waste liquid chamber 16, which can improve the accuracy of quantification and avoid cross contamination of the sample solution.

[0078] like Figure 4-4 As shown, the centrifugal rotation continues, and under the action of centrifugal force, the fixed impurities (such as blood cells in the whole blood sample) in the quantitative chamber 142 can be separated from the liquid, and the fixed impurities eventually enter the second waste liquid chamber 143, thereby achieving the separation of impurities in the sample solution and the solution to be tested.

[0079] The microfluidic chip 10 only needs one centrifugation operation to separate the impurities in the sample solution from the test solution and to quantify the test solution. Through the valve function of the second capillary channel 148, the sample solution can be closed in the quantification chamber 142 and the second waste liquid chamber 143 during the separation and quantification of the sample solution without flowing out.

[0080] During the test, you can refer to but not limited to the following process:

[0081] like Figure 5-1 , Figure 5-2 and Figure 5-1-1 As shown, after the quantitative determination of the solution to be tested is completed, the centrifugation is stopped, and the solution to be tested in the second capillary flow channel 148 continuously moves forward under the action of the capillary force, and passes through the highest point 148b to enter the 148c section of the second capillary flow channel 148, and finally reaches the permeation hole 145. At this time, a low-speed centrifugation can be started, such as rotating at a speed of 1000-2500 rpm, and under the action of siphon and the centrifugal action, the solution to be tested in the quantitative cavity 142 continuously seeps out through the permeation hole 145 to the detection mechanism for biochemical reaction to be detected.

[0082] The microfluidic chip 10 uses the second capillary channel 148 as a valve to control the contact reaction between the sample and the detection mechanism, which can replace the traditional delayed opening mechanism such as water-soluble membrane or valve, making the sampling detection process more stable and reliable, while simplifying the chip assembly process, which is conducive to reducing production costs.

[0083] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0084] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A microfluidic chip, characterized in that: The microfluidic chip comprises a sample loading chamber, a first microfluidic channel, a second microfluidic channel, a separation and quantitative unit, a first capillary channel and a first waste liquid chamber; the sample loading chamber has a sample loading hole, and the sample loading chamber is connected with the second microfluidic channel through the first microfluidic channel; the microfluidic chip has a rotation center, and the second microfluidic channel is arranged around the rotation center; the first waste liquid chamber is connected with the liquid outlet of the second microfluidic channel through the first capillary channel; there are multiple separation and quantitative units, each of which comprises a third microfluidic channel, a quantitative chamber and a second waste liquid chamber, the quantitative chamber is connected with the second microfluidic channel through the third microfluidic channel, the second waste liquid chamber is connected with the quantitative chamber, and multiple separation and quantitative units are distributed around the second microfluidic channel on the inner side of the second microfluidic channel; The first capillary channel extends from the second microchannel to the direction close to the rotation center on the inner side of the second microchannel and bends to extend away from the rotation center to communicate with the first waste liquid chamber; the third microchannel extends from the second microchannel to the direction close to the rotation center to communicate with the quantitative chamber; The distance between the connection position between the quantitative chamber and the third microfluidic channel and the rotation center is not less than the distance between the bending vertex position of the first capillary channel and the rotation center, and the second waste liquid chamber is farther from the rotation center than the quantitative chamber; The sample loading cavity is arranged around the rotation center, one end of which is provided with the sample loading hole, and the other end is connected to the first microchannel; the sample loading cavity gradually widens from the end of which is provided with the sample loading hole to the other end; The sample loading chamber is further provided with a first vent hole at one end connected to the first microfluidic channel, and the first vent hole is closer to the rotation center than the connection position between the sample loading chamber and the first microfluidic channel.

2. The microfluidic chip according to claim 1, characterized in that: It also includes a fifth microchannel, one end of which is connected to the first waste liquid chamber, and the other end of which has a second air hole, and the second air hole is closer to the rotation center than the first waste liquid chamber.

3. The microfluidic chip according to claim 2, characterized in that: The first waste liquid chamber is arranged outside the second microchannel and around the rotation center; and / or A radial dimension of a section of the fifth microfluidic channel connected to the first waste liquid chamber is greater than a radial dimension of a section close to the second air permeable hole.

4. The microfluidic chip according to any one of claims 1 to 3, characterized in that: Each of the separation and quantitative units further includes a sixth microfluidic channel, and the quantitative cavity is connected to the third microfluidic channel through the sixth microfluidic channel; The connection position between the sixth microfluidic channel and the third microfluidic channel is closer to the rotation center than the quantitative cavity; the distance between the connection position between the sixth microfluidic channel and the third microfluidic channel and the rotation center is not less than the distance between the bending vertex position of the first capillary channel and the rotation center.

5. The microfluidic chip according to claim 4, characterized in that: It also includes a ventilated micro-channel, the ventilated micro-channel is connected to the sixth micro-channel of each quantitative cavity, and the ventilated micro-channel is provided with a third vent hole; The air-permeable microchannel is closer to the rotation center than the connection position between the sixth microchannel and the third microchannel.

6. The microfluidic chip according to claim 5, characterized in that: The air-permeable microchannel is annularly arranged around the rotation center on the inner side of the plurality of separation quantitative units. There are a plurality of third air holes, which are distributed around the air-permeable microchannel.

7. The microfluidic chip according to claim 5, characterized in that: One end of the sixth microfluidic channel is connected to the air-permeable microfluidic channel, and the other end is connected to the quantitative cavity. The third microfluidic channel is connected to the middle of the sixth microfluidic channel.

8. The microfluidic chip according to any one of claims 1 to 3 and 5 to 7, characterized in that: Each of the separation and quantitative units further includes a seventh microfluidic channel, and the second waste liquid chamber is connected to the quantitative chamber via the seventh microfluidic channel.

9. The microfluidic chip according to claim 8, characterized in that: The separation and quantitative unit also includes a liquid outlet microchannel, one end of which is connected to the quantitative cavity, and the other end of which is provided with a permeation hole.

10. The microfluidic chip according to claim 9, characterized in that: The liquid outlet microchannel comprises a second capillary channel, one end of the second capillary channel is connected to the seventh microchannel, and the other end is provided with the permeation hole; The second capillary channel extends toward the direction close to the rotation center after being connected to the seventh microchannel and bends to extend toward the direction away from the rotation center; The distance between the connection position of the quantitative cavity and the third microfluidic channel and the rotation center is greater than the distance between the bending vertex position of the second capillary channel and the rotation center, and the distance between the bending vertex position of the first capillary channel and the rotation center is greater than the distance between the bending vertex position of the second capillary channel and the rotation center.

11. The microfluidic chip according to claim 10, characterized in that: The liquid outlet microfluidic channel further includes an eighth microfluidic channel, the eighth microfluidic channel is connected to the seventh microfluidic channel, and the second capillary channel is connected to the seventh microfluidic channel through the eighth microfluidic channel.

12. The microfluidic chip according to any one of claims 1 to 3, 5 to 7 and 9 to 11, characterized in that: The microfluidic chip comprises a chip body and a transparent cover film covering the chip body, and the chip body and the transparent cover film cooperate to form various cavity structures and flow channel structures of the microfluidic chip.

13. The microfluidic chip according to claim 12, characterized in that: The transparent cover film is a transparent pressure-sensitive adhesive film.

14. An in vitro detection device, characterized in that: It comprises the microfluidic chip and the detection mechanism as described in any one of claims 1 to 13, wherein the detection mechanism is connected to the quantitative cavity, and the detection mechanism is used to detect the sample in the quantitative cavity.

15. The in vitro detection device according to claim 14, characterized in that: The detection mechanism is a dry chemical test paper.

16. The in vitro detection device according to claim 14 or 15, characterized in that: The microfluidic chip is provided with mounting grooves around the permeation holes of each separation and quantitative unit, and the detection mechanism is embedded in each mounting groove.

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