WO2021077590A1

WO2021077590A1 - Microfluidic control chip and in vitro detection apparatus

Info

Publication number: WO2021077590A1
Application number: PCT/CN2019/126899
Authority: WO
Inventors: 白孟斌; 万惠芳; 冷杰
Original assignee: 广州万孚生物技术股份有限公司
Priority date: 2019-10-21
Filing date: 2019-12-20
Publication date: 2021-04-29
Also published as: CN112756017A

Abstract

A microfluidic control chip (10) capable of increasing sample processing efficiency and an in vitro detection apparatus comprising said microfluidic control chip (10). The microfluidic control chip (10) is designed with a sampling cavity (11), a first micro flow channel (12), a second micro flow channel (13), a plurality of separating and quantifying units (14), a first capillary flow channel (15), and a first waste liquid cavity (16); after a sample solution is added into the sampling cavity (11), by means of rotation and centrifugation, the sample solution enters a quantifying cavity (142) under the action of centrifugation, and sequentially fills a second waste liquid cavity (143) and the quantifying cavity (142); by means of the centrifugation, solid waste such as blood cells can be centrifugally deposited in the second waste liquid cavity (143) in communication with the quantifying cavity (142), implementing the separation of samples such as whole blood and quantification in the quantifying cavity (142).

Description

Microfluidic chip and in vitro detection device

This application claims the priority of a Chinese patent application filed with the Chinese Patent Office with application number 201911000623.8 on October 21, 2019. The entire content of this application is incorporated into this application by reference.

Technical field

This application relates to the field of in vitro diagnostic technology, for example, to a microfluidic chip and an in vitro detection device.

Background technique

In Vitro Diagnosis (IVD) belongs to the pharmaceutical and biological industry, which refers to taking blood, body fluids, tissues and other samples from the human body, and using in vitro testing reagents, instruments, etc. to test and verify the samples in order to prevent diseases , Diagnosis, treatment testing, late-stage observation, health evaluation, genetic disease prediction, etc. In vitro diagnosis is divided into three categories: biochemical diagnosis, immunodiagnosis and molecular diagnosis according to methodology, as well as point-of-care testing (POCT) differentiated from biochemical, immunological and molecular diagnosis. Dry chemical reaction is a type of biochemical diagnosis, which uses biochemical reagents to react with a specific substrate, and then quantitatively detects the concentration of the target through an instrument to calculate certain biochemical indicators of the human body. Traditional biochemical diagnosis needs to be tested on a large-scale biochemical analyzer, which leads to high reagent consumption and insufficient flexibility. The general dry-type biochemical POCT diagnosis method has a low test throughput, and generally only one or a few tests can be tested at a time. Samples, one or several items. Microfluidics technology (Microfluidics) can integrate basic operation 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, greatly improving the detection efficiency, and at the same time It has the advantages of miniaturization and automation, so it is more and more widely used in the field of POCT.

In the field of biochemical testing, Abaxis of the United States took the lead in the development of microfluidic chips for biochemical testing. Domestic companies such as Tianjin Micronanochip and Chengdu Smart have similar microfluidic chip development. The process of quantification and distribution of whole blood samples with traditional products often requires separation of whole blood and serum quantification. Therefore, multiple centrifugation and quantification are required, which makes the sample processing time longer and leads to detection time. Too extended.

Summary of the invention

The embodiments of the present application provide a microfluidic chip capable of improving sample processing efficiency and an in vitro detection device containing the microfluidic chip.

A microfluidic chip has 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 A sample hole, the sample loading cavity is communicated with the second microchannel through the first microchannel; the microfluidic chip has a center of rotation, and the second microchannel is arranged around the center of rotation The first waste liquid cavity communicates with the outlet end of the second micro-channel through the first capillary channel; there are multiple separation and quantitative units, and each of the separation and quantitative units includes a third micro-channel A flow channel, a quantitative cavity and a second waste liquid cavity, the quantitative cavity is in communication with the second micro flow channel through the third micro flow channel, and the second waste liquid cavity is connected to the quantitative cavity Body is connected, a plurality of the separation and quantification units are distributed around the second micro flow channel on the inner side of the second micro flow channel; the first capillary flow channel is self-contained on the inner side of the second micro flow channel After the second micro-channel is connected, it extends in a direction close to the rotation center, and after being bent, it extends in a direction away from the rotation center to communicate with the first waste liquid cavity; the third micro-channel is from After being connected with the second micro flow channel, it extends in a direction close to the rotation center to communicate with the quantitative cavity; the connection position of the quantitative cavity and the third micro flow channel is about a distance from the rotation center The distance is not less than the distance between the bending apex position of the first capillary flow channel and the rotation center, and the second waste liquid cavity is farther from the rotation center than the quantitative cavity.

An in vitro detection device includes the microfluidic chip described in any one of the above embodiments and a detection mechanism, the detection mechanism is in communication with a quantitative cavity, and the detection mechanism is configured to detect a sample in the quantitative cavity.

Description of the drawings

Figure 1, Figure 2 and Figure 3 are schematic diagrams of the front, back, and side structures of a microfluidic chip according to an embodiment of the application, respectively.

Figure 4-1, Figure 4-2, Figure 4-3, Figure 4-4 are schematic diagrams of the separation and quantification flow of the sample solution by the microfluidic chip shown in Figure 1, Figure 4-3-1, Figure 4-3 -2 is a partial enlarged schematic diagram.

Figure 5-1 and Figure 5-2 are respectively a schematic diagram of the detection process of the microfluidic chip shown in Figure 1, and Figure 5-1-1 is a partial enlarged schematic diagram.

Description of reference signs:

10: microfluidic chip, 101: center of rotation, 102: mounting part, 103: chip body, 104: transparent cover film, 11: sample cavity, 111: sample hole, 112: first vent, 12: First micro flow channel, 13: Second micro flow channel, 14: Separation and quantitative unit, 141: Third micro flow channel, 142: Quantitative cavity, 143: Second waste liquid cavity, 144: Outlet micro flow channel , 145: permeation hole, 146: sixth micro channel, 147: seventh micro channel, 148: second capillary channel, 148a, 148b and 148c are different positions on the second capillary channel, 149: eighth micro channel Flow channel, 15: the first capillary channel, 15a, 15b and 15c are different positions on the first capillary channel, 16: the first waste liquid cavity, 17: the fourth micro channel, 18, the fifth micro channel , 181: second vent, 19: ventilated micro-channel, 191: third vent, 20: installation groove.

Detailed ways

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field of this application. The terminology used in the specification of the application herein is only for the purpose of describing specific embodiments, and is not intended to limit the application. The term "and/or" as used herein includes any and all combinations of one or more related listed items.

1 and FIG. 2, an embodiment of the present application provides a microfluidic chip 10, which has a sample loading cavity 11, a first micro flow channel 12, a second micro flow channel 13, a separation and quantification unit 14, The first capillary flow channel 15 and the first waste liquid cavity 16.

The sample loading cavity 11 has a sample loading hole 111. The sample solution can be added into the sample adding cavity 11 from the sample adding hole 111. The sample application cavity 11 communicates with the second micro flow channel 13 through the first micro flow channel 12. The microfluidic chip 10 has a rotation center 101. When rotating and centrifuging, the microfluidic chip 10 rotates with the rotation center 101 as the center of the circle. The second micro flow channel 13 is arranged around the center of rotation 101. The first waste liquid cavity 16 communicates with the liquid outlet end of the second micro flow channel 13 through the first capillary flow channel 15.

There are multiple separation and quantitative units 14. Each separation and quantitative unit 14 includes a third micro flow channel 141, a quantitative cavity 142 and a second waste liquid cavity 143. Wherein, the quantitative cavity 142 communicates with the second micro channel 13 through the third micro channel 141, and the second waste liquid cavity 143 communicates with the quantitative cavity 142. The multiple separation and quantitative units 14 are distributed around the second micro flow channel 13 inside the second micro flow channel 13. Optionally, a plurality of separation and quantitative units 14 are evenly spaced and distributed around the second micro flow channel 13.

The "surround" described herein may be a closed ring or not, for example, it may be surrounded in a fan shape with an angle greater than 180°.

In this embodiment, the first capillary flow channel 15 is connected to the second micro flow channel 13 in the inner side of the second micro flow channel 13 in a direction approaching the rotation center 101 (may be a direction gradually approaching the rotation center 101, For example, it may be, but not limited to, extend and bend in a direction away from the rotation center 101 (may be each gradually away from the rotation center 101, for example, but not limited to a diameter away from the rotation center 101). It extends toward) to communicate with the first waste liquid cavity 16. The third micro flow channel 141 is located inside the second micro flow channel 13, and the third micro flow channel 141 extends in a direction close to the rotation center 101 after being connected to the second micro flow channel 13 to communicate with the quantitative cavity 142.

In this embodiment, the distance between the connection position of the quantitative cavity 142 and the third micro flow channel 141 from the rotation center 101 is greater than or equal to the distance between the bending apex position of the first capillary flow channel 15 and the rotation center 101, and the second waste The liquid cavity 143 is farther away from the rotation center 101 than the quantitative cavity 142.

By designing the microfluidic chip 10 with the above-mentioned structure, the sample solution can be separated and quantified in 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 unit The throughput of the test.

In one example, the sample addition cavity 11 is arranged around the center of rotation 101, one end is provided with a sample addition hole 111, and the other end is connected to the first micro flow channel 12, and optionally, the sample addition cavity 11 is provided with its own sample addition The hole 111 gradually widens from one end to the other end, so that the added sample solution can flow smoothly to the first micro-channel 12. Further, the end of the sample adding cavity 11 connected with the first micro flow channel 12 extends in a direction away from the rotation center 101, and is connected to the first micro flow channel 12 at the bottom, so that the sample solution can be introduced into the first micro flow channel during centrifugation. Road 12.

In some embodiments, the sample adding cavity 11 is further provided with a first vent 112 at one end connected to the first microfluidic channel 12. The first vent 112 is larger than the one between the sample loading cavity 11 and the first microfluidic channel 12. The connection position is closer to the center of rotation 101. By providing the first vent hole 112, when the sample solution is added to the sample adding cavity 11, the gas can be led out in time to facilitate the addition of the sample solution.

In an example, one end of the second micro flow channel 13 is connected to the first micro flow channel 12 and extends around the center of rotation 101 to the other end to be connected to the first capillary flow channel 15.

In an example, the microfluidic chip 10 further includes a fourth microfluidic channel 17. The first capillary flow channel 15 is connected to the second micro flow channel 13 through the fourth micro flow channel 17, and the fourth micro flow channel 17 is connected to the second micro flow channel 13 and extends in a direction close to the rotation center 101 to be connected to the first micro flow channel. The capillary flow channel 15 is connected.

In an example, the microfluidic chip 10 further includes a fifth microfluidic channel 18. One end of the fifth microfluidic channel 18 is connected to the first waste liquid cavity 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 cavity 16. Optionally, the fifth micro channel 18 extends in a direction close to the rotation center 101 after being connected to the first waste liquid cavity 16.

In the example shown in the figure, the first waste liquid cavity 16 is arranged around the center of rotation 101 on the outside of the second micro flow channel 13, and the volume of the entire first waste liquid cavity 16 is ensured to be large enough to fully contain the excess sample solution. . Optionally, the radial dimension of a section of the fifth micro flow channel 18 connected to the first waste liquid cavity 16 is larger than that of the section close to the second vent 181 to prevent liquid from entering the fifth micro flow channel The fifth micro-channel 18 is blocked in the middle of 18 and the ventilation is not timely.

In an example, each separation and quantification unit 14 further includes a sixth micro flow channel 146. The quantitative cavity 142 communicates with the third micro flow channel 141 through the sixth micro flow channel 146.

The connection position of the sixth micro flow channel 146 and the third micro flow channel 141 is closer to the rotation center 101 than the quantitative cavity 142. The distance between the connection position of the sixth micro flow channel 146 and the third micro flow channel 141 from the rotation center 101 is greater than or equal to the distance between the bending apex position of the first capillary flow channel 15 and the rotation center 101.

In some embodiments, the microfluidic chip 10 further includes a gas-permeable microfluidic channel 19. The air-permeable micro flow channel 19 communicates with the sixth micro flow channel 146 of each quantitative cavity 142. A third air hole 191 is provided on the air-permeable micro flow channel 19. The air-permeable micro flow channel 19 is closer to the rotation center 101 than the connection position of the sixth micro flow channel 146 and the third micro flow channel 141.

In the example shown in the figure, the gas-permeable micro flow channel 19 is annularly arranged on the inner side of the plurality of separation and quantitative units 14 around the rotation center 101. Optionally, there are multiple third vent holes 191, and the multiple third vent holes 191 are distributed around the breathable micro-channel 19. By arranging a plurality of ventilation holes 191 to cooperate with a plurality of separation and quantitative units 14, the air in each separation and quantitative unit 14 can be discharged in time, which facilitates the introduction of the sample solution.

In the illustrated example, one end of the sixth micro flow channel 146 is connected to the gas-permeable micro flow channel 19, the other end is connected to the quantitative cavity 142, and the third micro flow channel 141 is connected to the middle of the sixth micro flow channel 146. The "middle" mentioned 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, and optionally a non-end position.

In an example, each separation and quantification unit 14 further includes a seventh micro flow channel 147. The second waste liquid cavity 143 communicates with the quantitative cavity 142 through the seventh micro flow channel 147. The liquid outlet micro channel 144 is connected to the seventh micro channel 147.

In an example, the separation and quantification unit 14 further includes a liquid outlet microchannel 144. One end of the liquid outlet microchannel 144 communicates with 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 exuded through the penetration hole 145.

In some embodiments, the liquid outlet microchannel 144 includes a second capillary channel 148. One end of the second capillary channel 148 communicates with the seventh micro channel 147, and the other end is provided with a permeation hole 145. In this example, the second capillary channel 148 is connected to the seventh micro channel 147 and extends in a direction close to the rotation center 101, and after bending, it extends in a direction away from the rotation center 101, and the quantitative cavity 142 and the third The distance between the connection position of the micro flow channel 141 and the rotation center 101 is greater than the distance between the bending apex position of the second capillary channel 148 and the rotation center 101, and the distance between the bending apex 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 flow channel 148 and the rotation center 101. In this way, during centrifugation, the sample solution after the impurities are separated flows along the second capillary flow channel 148, but because the centrifugal force is greater than the hair suction force, the sample solution will not flow to the bending apex position of the second capillary flow channel 148. Therefore, the second capillary flow channel 148 can function as a valve and achieve a closed effect when the sample solution is separated and quantified.

In an example, the liquid outlet microchannel 144 further includes an eighth microchannel 149. The eighth micro flow channel 149 is connected to the middle of the seventh micro flow channel 147, and the second capillary flow channel 148 communicates with the seventh micro flow channel 147 through the eighth micro flow channel 149.

The middle part of the microfluidic chip 10 is also provided with a mounting part 102. The center of the mounting portion 102 is the rotation center 101 of the microfluidic chip 10.

The capillary flow channel described herein is a flow channel structure having a smaller size (e.g., width and/or depth) than the micro flow channel. In an example, the first capillary flow channel 15 and the second capillary flow channel 148 are V-shaped, and the bent portion thereof is close to the rotation center 101. Optionally, 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 It is 0.2mm～0.5mm, and the depth is 0.2mm～0.5mm. When the width of the first capillary channel 15 and the second capillary channel 148 is 0.1mm～0.2mm, and the depth is 0.1mm～0.2mm, no surface treatment is required. When the first capillary channel 15 and the second capillary channel 148 are When the width is 0.2mm-0.5mm, and the depth is 0.2mm-0.5mm, the flow channels of the first capillary flow channel 15 and the second capillary flow channel 148 may preferably be surface-treated with PEG4000. Optionally, the width of the first capillary flow channel 15 and the second capillary flow channel 148 is 0.2 mm, and the depth is also 0.2 mm. After the first capillary flow channel 15 and the second capillary flow channel 148 enter the sample solution, the sample solution can flow to the other end of the sample solution by capillary action. Optionally, the first capillary flow channel 15 and the second capillary flow channel 148 have different sizes in different sections, for example, the width of the first capillary flow channel 15 and the second capillary flow channel 148 at the bending part is 0.2 mm, The depth is also 0.2mm, the width of other parts is 0.5mm, and the depth is also 0.2mm, in order to facilitate the flow of liquid and the formation of siphon and capillary action locally.

The PEG4000 surface treatment can be, but is not limited to, adding a 1wt% PEG4000 solution to the capillary flow channel and forming it after natural drying. PEG4000 surface treatment is beneficial to increase the capillary force of the capillary flow channel, and PEG4000 is an inert substance in the reaction system, and generally does not react with samples and detection reagents, so it will not affect the test results.

As shown in FIG. 3, in an 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. Exemplarily, the grooves of each cavity structure and flow channel structure are pre-formed on the chip body 103, as shown in FIG. 2, each hole is opened on the back of the chip body 103, and each cavity structure and flow channel The groove of the structure is opened on the front surface of the chip body 103, and subsequently covered by a transparent cover film 104 and sealed on the front surface of the chip body 103 to complete the packaging of the cavity structure and the flow channel structure, forming a complete cavity structure and Runner structure.

The transparent cover film 104 can be, but is not limited to, a transparent tape or a transparent pressure-sensitive adhesive film, etc., which cooperates with the chip body 103 to form the entire microfluidic chip 10, which is simple to assemble and does not need to use complex and expensive ultrasonic welding technology. Yes, the production cost can be significantly reduced. It can be understood that, in other examples, the microfluidic chip 10 may also be formed by welding with a relatively high-cost ultrasonic welding technology, or be integrally formed with a 3D printing technology.

The application also provides an in vitro detection device, which includes the above-mentioned microfluidic chip 10 and a detection mechanism. The detection mechanism communicates with the quantitative cavity 142, for example, but not limited to, communicates with the quantitative cavity 142 through the permeation hole 145. The detection mechanism is configured to detect the sample in the quantitative cavity 142.

In one example, the detection mechanism is a dry chemical test paper. Exemplarily, the dry chemical test paper may include a support layer and a reaction indicator layer and a diffusion layer sequentially stacked on the support layer. The reaction indicator layer contains a reaction reagent and an indicator reagent capable of reacting with the target substance in the sample to be tested. The layer faces the permeation hole 145 through the injection port. It can be understood that, in other examples, the detection mechanism is not limited to dry chemical test paper, and may also be various other test paper strips or reactors.

In an example, as shown in FIG. 2, the microfluidic chip 10 is provided with installation grooves 20 around the permeation holes 145 of each separation and quantitative unit 14, and the detection mechanism is embedded in each installation groove 20.

The microfluidic chip 10 can realize the separation and quantification of impurities in the sample solution by one centrifugation, such as the separation and quantification of blood cells and serum (plasma) of a whole blood sample, and the valve function of the second capillary flow channel 148 , To achieve simultaneous sample loading detection of different separation and quantification units 14. Therefore, the in vitro detection device using the microfluidic chip 10 can realize the detection of different indexes of the sample or the repeated detection of the same index by loading the sample at one time. Each separation and quantification unit 14 is arranged around the center of rotation 101 and has a high degree of integration. By using the in vitro detection device, the consistency, accuracy and reliability of the detection result can be improved.

In some embodiments, taking the microfluidic chip 10 shown in FIG. 1 as an example, when separating impurities in a sample solution and quantifying a solution to be tested, the process can refer to but is not limited to the following:

As shown in FIG. 4-1, a certain amount of sample solution is added into the sample adding cavity 11 from the sample adding hole 111, and the air in the sample adding cavity 11 can be discharged from the first vent hole 112. After the sample solution is added, the microfluidic chip 10 is installed in an instrument with a rotating centrifugal function through its mounting part 102, the instrument is turned on, and the microfluidic chip 10 is centrifuged at a speed not limited to 4000-6000 rpm.

As shown in Figure 4-2, 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 .

As shown in Figure 4-3, as the sample solution continues to flow in, the sample solution sequentially enters the third micro-channel 141, the sixth micro-channel 146, the quantitative cavity 142, and the seventh micro-channel 147 of the separation and quantitative unit 14 In the second waste liquid cavity 143, the eighth micro channel 149 and the second capillary channel 148, these channels and the cavity constitute the structure of the communicating device, and the air in the original channel and the cavity is self-permeable micro channel The third ventilation hole 191 of 19 is discharged. As shown in Figure 4-3-1, when the sample solution fills the quantitative cavity 142 to the junction of the third microchannel 141 and the sixth microchannel 146, the sample solution also enters the second through the eighth microchannel 149. In the second capillary channel 148 and flow in the second capillary channel 148, under the action of rapid centrifugation, the centrifugal force is greater than the hair suction force. When the sample solution flows in the second capillary channel 148 to the third micro channel 141 and When the connection part of the sixth micro channel 146 is flush with the position 148a, the flow is no longer. Because the distance between the bending part 148b of the second capillary channel 148 and the rotation center 101 is longer than that of the third micro channel 141 and the sixth micro channel 141 The distance between the connection part of the flow channel 146 and the rotation center 101 is close, therefore, the sample solution will not rise to the bending part 148b of the second capillary flow channel 148, nor will it cause a siphon effect in the second capillary flow channel 148 to pass through After section 148c, it flows out from the permeation hole 145. At this point, the quantification of the sample solution is completed.

As shown in Figure 4-3-2, at the same time, the sample solution enters the first capillary channel 15 through the second microchannel 13 and the fourth microchannel 17, and the sample solution continues to advance after passing through the 15a section. The distance between the bent apex of a capillary channel 15 and the center of rotation 101 is the same as the distance between the connection part of the third micro channel 141 and the sixth micro channel 146 and the center of rotation 101, so the sample solution can reach the highest point 15b As shown in Figure 4-3, 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, and the excess sample solution is continuously discharged to the first waste In the liquid chamber 16, this can improve the accuracy of quantification and avoid cross-contamination of the sample solution.

As shown in Figure 4-4, continue centrifugal rotation, under the action of centrifugal force, the fixed impurities (such as blood cells of a whole blood sample) in the quantitative cavity 142 can be separated from the liquid, and the fixed impurities finally enter the second waste liquid chamber In the body 143, the impurities in the sample solution and the solution to be tested are separated in this way.

The microfluidic chip 10 requires only one centrifugal operation in the separation of impurities in the sample solution from the solution to be tested and the quantification of the solution to be tested. The valve function of the second capillary channel 148 is used in the separation and quantification of the sample solution. At this time, the sample solution can be closed in the quantitative cavity 142 and the second waste liquid cavity 143 without flowing out.

When testing, you can refer to but not limited to the following process:

As shown in Figure 5-1, Figure 5-2 and Figure 5-1-1, when the quantification 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 is constantly under the action of gross suction. Go forward and pass the highest point 148b into the 148c section of the second capillary channel 148, and finally reach the permeation hole 145. At this time, you can turn on low-speed centrifugation, such as rotating at 1000-2500 rpm, under the action of siphon, and with centrifugation, the solution to be tested quantitatively in the quantitative cavity 142 continuously leaks out into the detection mechanism through the permeation hole 145 to proceed. The biochemical reaction is tested.

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 water-soluble membrane or valve and other delayed opening mechanisms, making the sampling and detection process more stable and reliable. At the same time, the chip assembly process is simplified, which helps reduce production costs.

The above microfluidic chip is designed by designing a sample addition cavity, a first microfluidic channel, a second microfluidic channel, a plurality of separation and quantitative units, a first capillary channel and a first waste liquid cavity, wherein the first microfluidic channel , The second micro flow channel, the third micro flow channel and the first capillary flow channel of each separation and quantitative unit constitute the structure of the communicating device. After adding the sample solution to the sample loading chamber, by rotating and centrifuging, the sample solution enters the second micro flow channel through the first micro flow channel, and splits into the third micro flow of each separation and quantification unit in the second micro flow channel. In this way, the sample solution will enter the quantitative cavity under the action of centrifugation, and fill the second waste liquid cavity and the quantitative cavity in turn. Through centrifugation, solid wastes such as blood cells can be centrifuged and deposited to the second fluid chamber connected to the quantitative cavity. In the second waste liquid chamber, the separation of whole blood and other samples and the quantification in the quantitative chamber are realized. The excess sample solution enters the first capillary flow channel through the second micro flow channel. The distance between the connection position of the third microchannel and the center of rotation of the microfluidic chip is equal to the distance between the bending apex of the first capillary channel and the center of rotation, so that when the sample solution reaches the bending apex of the first microchannel The time will continue to advance, and under the action of centrifugal force, a siphon effect is formed, and the excess sample solution is introduced into the first waste liquid chamber.

The microfluidic chip only needs one centrifugation after adding the sample solution to separate and quantify the impurities in the sample solution and the target detection solution. There is no need for excessive centrifugation, so the operation is simple, the waiting time is short, and the sample processing The efficiency is significantly improved.

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 with the seventh microchannel, and the other end is provided with a permeation hole. The second capillary channel is free from After the seventh micro-channel is connected, it extends in the direction close to the center of rotation and after bending, it extends in the direction away from the center of rotation, and the distance between the connection position of the quantitative cavity and the third micro-channel from the center of rotation is greater than that of the second capillary channel The distance between the bending apex position and the center of rotation, so that during centrifugation, because the centrifugal force is greater than the capillary suction force, the sample solution will not break through the bending position of the second capillary channel, and the second capillary channel can act as a " The function of the “valve” closes the sample solution in the quantitative chamber without flowing out; after the subsequent centrifugation, the liquid in the second capillary channel moves forward along the second capillary channel under the action of the hair suction force, and the “valve” opens. After the liquid continues to flow to the permeable hole, it can seep out from the permeable hole. Optionally, it can be combined with low-speed centrifugation, under the action of siphon, the liquid continuously seeps from the permeable hole to the detection mechanism to complete the detection of the sample.

The second capillary flow channel is used as a valve to control the contact reaction between the sample and the detection mechanism, which can replace the traditional water-soluble membrane or valve and other delayed opening mechanisms, making the sampling detection process more stable and reliable, and simplifying the chip assembly process. Conducive to reducing production costs.

Claims

A microfluidic chip has 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 A sample hole, the sample loading cavity is communicated with the second microchannel through the first microchannel; the microfluidic chip has a center of rotation, and the second microchannel is arranged around the center of rotation The first waste liquid cavity communicates with the outlet end of the second micro-channel through the first capillary channel; there are multiple separation and quantitative units, and each of the separation and quantitative units includes a third micro-channel A flow channel, a quantitative cavity and a second waste liquid cavity, the quantitative cavity is in communication with the second micro flow channel through the third micro flow channel, and the second waste liquid cavity is connected to the quantitative cavity Body connected, a plurality of the separation and quantitative units are distributed around the second micro flow channel inside the second micro flow channel;

The first capillary flow channel extends in a direction close to the rotation center after being connected to the second micro flow channel on the inner side of the second micro flow channel, and is bent and then extends in a direction away from the rotation center To communicate with the first waste liquid cavity; the third micro-channel extends in a direction close to the rotation center after being connected with the second micro-channel to communicate with the quantitative cavity;

The distance between the connection position of the quantitative cavity and the third micro flow channel and the rotation center is greater than or equal to the distance between the bending vertex position of the first capillary flow channel and the rotation center, and the second The waste liquid cavity is farther from the rotation center than the quantitative cavity.
The microfluidic chip of claim 1, wherein the sample loading cavity is arranged around the center of rotation, one end is provided with the sample loading hole, and the other end is connected to the first microfluidic channel.
The microfluidic chip according to claim 2, wherein the sample loading cavity is further provided with a first vent hole at one end connected to the first micro flow channel, and the first vent hole is larger than the The connection position of the sample cavity and the first micro flow channel is closer to the rotation center.
The microfluidic chip according to claim 1, further comprising a fifth microfluidic channel, one end of the fifth microfluidic channel is connected to the first waste liquid cavity, and the other end has a second vent hole, the The second vent hole is closer to the rotation center than the first waste liquid cavity.
The microfluidic chip of claim 4, wherein the microfluidic chip satisfies at least one of the following:

The first waste liquid cavity is arranged around the center of rotation on the outside of the second micro flow channel;

The radial dimension of a section of the fifth micro flow channel connected to the first waste liquid cavity is larger than the radial dimension of a section close to the second vent hole.
The microfluidic chip according to any one of claims 1 to 5, each of the separation and quantification units further comprises a sixth micro flow channel, and the quantitative cavity passes through the sixth micro flow channel and the third micro flow channel. Micro-channel connection;

The connection position of the sixth micro flow channel and the third micro flow channel is closer to the rotation center than the quantitative cavity; the connection position of the sixth micro flow channel and the third micro flow channel The distance from the rotation center is greater than or equal to the distance between the bending vertex position of the first capillary flow channel and the rotation center.
The microfluidic chip according to claim 6, further comprising a gas-permeable micro-channel, the gas-permeable micro-channel is connected with the sixth micro-channel of each of the quantitative cavities, and the gas-permeable micro-channel is provided with The third ventilation hole;

The gas-permeable micro-channel is closer to the rotation center than the connection position of the sixth micro-channel and the third micro-channel.
The microfluidic chip according to claim 7, wherein the gas-permeable micro-channel is arranged in a ring shape on the inner side of the plurality of separation and quantitative units around the center of rotation, and the third gas-permeable hole has a plurality of The three third air holes are distributed around the air-permeable micro-channels.
The microfluidic chip of claim 7, wherein one end of the sixth microfluidic channel is connected to the gas-permeable microfluidic channel, the other end is connected to the quantitative cavity, and the third microfluidic channel is connected to the gas-permeable microfluidic channel. The middle part of the sixth micro channel is connected.
The microfluidic chip according to any one of claims 1 to 5 and 7 to 9, each of the separation and quantification units further comprises a seventh micro flow channel, and the second waste liquid cavity passes through the seventh micro flow channel. The flow channel communicates with the quantitative cavity.
10. The microfluidic chip according to claim 10, wherein the separation and quantification unit further comprises a liquid discharge microchannel, one end of the liquid discharge microchannel is in communication with the quantitative cavity, and the other end is provided with a permeation hole.
The microfluidic chip of claim 11, wherein 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 said penetration holes;

The second capillary flow channel extends in a direction close to the rotation center after being connected with the seventh micro flow channel, and is bent and then extends in a direction away from the rotation center;

The distance between the connection position of the quantitative cavity and the third micro flow channel and the rotation center is greater than the distance between the bending apex position of the second capillary flow channel and the rotation center, and the first capillary flow The distance between the bending apex position of the channel and the rotation center is greater than the distance between the bending apex position of the second capillary flow channel and the rotation center.
The microfluidic chip according to claim 12, the liquid outlet microchannel further comprises an eighth microchannel, the eighth microchannel is connected to the seventh microchannel, and the second capillary channel The channel communicates with the seventh micro channel through the eighth micro channel.
The microfluidic chip according to any one of claims 1 to 5, 7 to 9 and 11 to 13, wherein the microfluidic chip comprises a chip body and a transparent cover film covering the chip body, The chip body cooperates with the transparent cover film to form each cavity structure and flow channel structure of the microfluidic chip.
The microfluidic chip of claim 14, wherein the transparent cover film is a transparent pressure-sensitive adhesive film.
An in vitro detection device, comprising the microfluidic chip according to any one of claims 1-15 and a detection mechanism, wherein the detection mechanism is in communication with the quantitative cavity, and the detection mechanism is configured to detect the quantitative The sample inside the cavity.
The in vitro testing device according to claim 16, wherein the testing mechanism is a dry chemical test paper.
The in vitro detection device according to claim 17, wherein the dry chemical test paper comprises a support layer and a reaction indicator layer and a diffusion layer stacked on the support layer, and the reaction indicator layer contains The reaction reagent and indicator reagent for the reaction of the target substance in the sample, the diffusion layer faces the permeation hole through the injection port.
The in vitro detection device according to any one of claims 16 to 18, wherein the microfluidic chip is provided with a mounting groove around the permeation hole of each of the separation and quantitative units, and the detection mechanism is embedded in each of the mounting Slot.