A microfluidic distribution chip

Abstract

The present invention relates to a microfluidic distribution chip, comprising a sample addition hole, a sample inlet pipe, a distribution chamber, an exhaust pipe, a sample outlet pipe, an exhaust hole and a bypass pipe connected in sequence. The bypass pipe connects the sample inlet pipe and the sample outlet pipe, and is used to allow the fluid sample added through the sample addition hole to flow to the sample outlet pipe via the bypass pipe after filling the distribution chamber. The direction of the fluid can be controlled by limiting the cross-sectional area or depth of each pipe and cavity. The microfluidic distribution chip provided by the present invention has a simple structure, is easy to manufacture and easy to use. While realizing automatic sample distribution, it can ensure the purity of the sample, thereby completing multi-index parallel detection of the sample.

Description

Technical Field

[0001] The invention relates to a microfluidic distribution chip, belonging to the technical field of microfluidics. Background Art

[0002] In the fields of medicine, biology, chemistry, etc., it is often necessary to use a sample to perform multiple tests and operations, which requires the use of sample distribution technology. Existing sample distribution technology usually requires using a pipette to draw samples multiple times, and then respectively injecting them into different reaction tanks or reaction tubes. This method is easy to introduce impurities during the distribution process, causing pollution; at the same time, in order to reduce the impact of sample volatilization, the volume of the distributed single system cannot be too small. Microfluidic technology uses microfluidic chips as carriers, combines with disciplines such as chemistry and biology, and realizes the analysis and detection process in a miniaturized, integrated and automated manner on the platform. Microfluidic technology makes it possible to automatically transport and distribute fluids. The invention patent with the authorization publication number CN102671729B discloses a microfluidic chip for multi-index biochemical detection, in which reaction pools are connected in parallel or in parallel, and pneumatic microvalves are used to achieve isolation between reaction chambers. However, during the continuous flow of samples, cross-contamination between reaction pools at different positions may be caused, which is not conducive to the accurate analysis of the reaction results. The invention patent with the authorization publication number CN110075935B discloses a multi-index detection microfluidic cartridge and application method. This method is based on sample distribution using a rotary valve. When the rotary valve is turned to different gears, a syringe pump is used to drive the sample so that the sample can enter different reaction chambers. However, this method has a complex structure, high cost, and is subject to space constraints, and the number of achievable distributions is limited. Summary of the Invention

[0003] The present invention provides a microfluidic distribution chip with a simple structure, convenient production and easy use. While realizing the automatic distribution of samples, it can ensure the purity of the samples, thereby completing the multi-index parallel detection of the samples.

[0004] The technical solution of the present invention to solve the above technical problems is as follows:

[0005] A microfluidic distribution chip comprises a sample addition hole, a sample inlet pipe, a distribution chamber, an exhaust pipe, a sample outlet pipe, an exhaust hole and a bypass pipe connected in sequence. The bypass pipe connects the sample inlet pipe and the sample outlet pipe and is used to allow the fluid added through the sample addition hole to flow to the sample outlet pipe through the bypass pipe after filling the distribution chamber.

[0006] As a preferred solution, the cross-sectional areas of the distribution chamber, the sampling pipe, the bypass pipe, and the exhaust pipe decrease in sequence.

[0007] As a preferred embodiment, the microfluidic distribution chip further includes an interface valve disposed between the exhaust conduit and the sample outlet conduit. The interface valve is provided at least once and is configured to provide auxiliary isolation for fluid passing through the exhaust conduit. Furthermore, the sample inlet conduit, distribution chamber, and exhaust conduit have the same depth, with the interface valve, bypass conduit, and inlet conduit having decreasing depths.

[0008] As a preferred solution, the microfluidic distribution chip includes a chip body and a cover plate connected to the top of the chip body, the distribution chamber is arranged on the chip body, and the sample addition hole, sample inlet pipe, exhaust pipe, sample outlet pipe, exhaust hole and bypass pipe are arranged on the cover plate.

[0009] As a preferred embodiment, the microfluidic distribution chip includes a chip body and a cover plate connected to the top of the chip body. The distribution chamber, sample addition hole, injection pipe, exhaust pipe, sample outlet pipe, exhaust hole and bypass pipe are all arranged on the chip body. The microfluidic distribution chip also includes a transition pipe arranged between the injection pipe and the distribution chamber.

[0010] As a preferred solution, the microfluidic distribution chip further comprises an overflow cavity provided between the sample outlet pipe and the exhaust hole, and the overflow cavity is used to store excess fluid sample.

[0011] As a preferred solution, an optical detection sensor is provided at the overflow cavity for detecting the filling amount of the fluid.

[0012] As a preferred solution, the microfluidic distribution chip further includes a filtration unit, which includes a filter membrane disposed below the sample loading hole and a filter cavity disposed below the filter membrane, the filter membrane is at least one layer, and the filter cavity is connected to the sample feeding pipe.

[0013] As a preferred solution, the distribution chamber is pre-stored with a reaction reagent for reacting with the sample to complete the detection.

[0014] As a preferred solution, the sample inlet pipe, distribution chamber, exhaust pipe, sample outlet pipe and bypass pipe constitute a set of distribution units. Several sets of distribution units can be provided, and adjacent distribution units are connected through the sample outlet pipe of the previous unit and the sample inlet pipe of the next unit.

[0015] The microfluidic distribution chip provided by the present invention has the following beneficial effects:

[0016] (1) It has a simple structure, is easy to manufacture, and is convenient to use. While achieving automated sample distribution, it can ensure the purity of the sample and prevent cross-contamination of fluids between different cavities.

[0017] (2) Through structural optimization and the introduction of interface valves, the microfluidic distribution chip provided by the present invention is also compatible with fluids of different properties, especially effectively improving compatibility with low surface energy samples;

[0018] (3) By introducing the filtration unit, serum separation of whole blood samples can be achieved, thereby enabling the detection of biochemical or immune indicators using serum as a sample;

[0019] (4) It has a wide compatible range for the pressure or flow rate of the driving liquid, thereby completing the parallel detection of multiple indicators of the sample. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a schematic diagram of the overall structure of the microfluidic distribution chip embodiment 1 of the present invention;

[0021] Figure 2 This is a top view of the chip body in Example 1 of the microfluidic distribution chip of the present invention;

[0022] Figure 3 This is a bottom view of the cover plate in Example 1 of the microfluidic distribution chip of the present invention;

[0023] Figure 4 This is an exploded view of Example 1 of the microfluidic distribution chip of the present invention;

[0024] Figure 5 This is a top view of the chip body in Example 2 of the microfluidic distribution chip of the present invention;

[0025] Figure 6 This is a schematic diagram of the overall structure of the microfluidic distribution chip embodiment 2 of the present invention;

[0026] Figure 7 1 is a top view of the chip body in Example 3 of the microfluidic distribution chip of the present invention;

[0027] Figure 8 is the relationship between the driving pressure and the filling time when the sample is water in the present invention;

[0028] Figure 9 is the relationship between the driving pressure and the filling time when the sample is a 50% ethanol aqueous solution in the present invention;

[0029] Figure 10 This is the relationship between the driving pressure and the filling time when the whole blood sample fills the distribution chamber after passing through the filter unit in the present invention.

[0030] In the figure, 1. chip body, 2. cover plate, 11.21.31. distribution chamber, 12.22.32. sample addition hole, 13.23.33. sample injection pipe, 14.24.34. bypass pipe, 15.25.35. exhaust pipe, 16.26.36. interface valve, 17.27.37. sample outlet pipe, 18. overflow chamber, 19.29.39. exhaust hole, 20. transition pipe, 41. filter chamber, 42. filter membrane. DETAILED DESCRIPTION

[0031] The principles and features of the present invention are described below with reference to the accompanying drawings. The embodiments given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0032] Example 1

[0033] See also Figures 1-4 The microfluidic distribution chip provided in this embodiment includes a chip body 1 and a cover plate 2. The chip body 1 and the cover plate 2 can be sealed by double-sided adhesive bonding, hot pressing bonding, ultrasonic welding, laser welding, etc. The chip body 1 is provided with a distribution cavity 11, and the cover plate 2 is provided with a sample addition hole 12, a sample injection pipe 13, a bypass pipe 14, an exhaust pipe 15, a sample output pipe 17, and an exhaust hole 19. The sample addition hole 12, the sample injection pipe 13, the distribution cavity 11, the exhaust pipe 15, the sample output pipe 17, and the exhaust hole 19 are connected in sequence, and the bypass pipe 14 connects the sample injection pipe 13 and the sample output pipe 17.

[0034] The distribution cavity 11 on the chip body 1 and the sample inlet pipe 13, bypass pipe 14, exhaust pipe 15, and sample outlet pipe 17 on the cover plate 2 form a set of distribution units. In actual use, the number of distribution units can be arbitrarily set according to test needs. Adjacent distribution units are connected through the sample outlet pipe 17 of the previous unit and the sample inlet pipe 13 of the next unit.

[0035] In this embodiment, the cross-sectional area of the bypass conduit 14 is smaller than that of the sample inlet conduit 13, and the cross-sectional area of the exhaust conduit 15 is smaller than that of the bypass conduit 14. Specifically, the ratio of the cross-sectional areas of the sample inlet conduit 13, bypass conduit 14, and exhaust conduit 15 can be 10-30:3-7:1. More specifically, the ratio of the cross-sectional areas of the three is 18:6:1. During use, a fluid sample is added through the sample inlet 12, and positive pressure is applied at the sample inlet 12, or negative pressure is applied at the exhaust conduit 19, thereby continuously driving the sample. After passing through the sample inlet conduit 13, the fluid sample can enter two flow paths: the bypass conduit 14 and the distribution chamber 11. The bypass conduit 14 has a smaller cross-sectional area and a greater flow resistance. Therefore, the fluid sample in the sample inlet conduit 13 will preferentially enter the distribution chamber 11. Once the distribution chamber 11 is filled with liquid, it will enter the exhaust conduit 15. Because the cross-sectional area of the exhaust conduit 15 is smaller than that of the bypass conduit 14, the fluid sample will preferentially pass through the bypass conduit 14, flowing from the bypass conduit 14 into the sample outlet conduit 17, and then into the next distribution unit.

[0036] When the fluid sample contains surfactants or organic solvents, capillary forces may still allow the liquid to fill the exhaust pipe 15 despite the small cross-sectional area and high flow resistance of the exhaust pipe 15. To improve the reliability of the structure and prevent cross-contamination between dispensing chambers 11, an interface valve 16 is added to the exhaust pipe 15. Specifically, the interface valve 16 is positioned between the exhaust pipe 15 and the sample outlet pipe 17. The structure is configured to suddenly expand the pipe width, depth, or both. When the fluid sample fills the front section of the exhaust pipe 15 and reaches the interface valve 16, surface tension will block the fluid sample within the pipe and prevent it from entering the interface valve 16. This structure further prevents the fluid sample from passing through the exhaust pipe 15, improving the reliability of the structure and widening the range of fluid driving pressures allowed by the structure. If the fluid sample still has a high flow rate when it reaches the interface valve 16 through the exhaust pipe 15, the interface valve 16 may not be sufficient to block the fluid sample. In this case, the number of interface valves 16 can be increased to further improve the reliability of the structure. When the liquid passes through the bypass pipe 14 and the sample outlet pipe 17 and enters the next parallel distribution unit, a portion of air will remain in the exhaust pipe 15, thereby ensuring that the liquid in the distribution chamber 11 cannot flow out of the chamber during the continuous sample actuation process, thereby preventing cross contamination. By repeating the above distribution process, the fluid sample can enter each distribution chamber 11 on the chip body 1 in turn.

[0037] The microfluidic distribution chip provided by the present invention drives the sample at a constant pressure when the fluid sample is water or an aqueous solution. Figure 8As shown, when the driving pressure is in the range of 50Pa-3000Pa, the structure can achieve stable sample distribution, and the greater the pressure, the shorter the time required to complete the filling. When the driving pressure is lower than 50Pa, it is not enough to drive the fluid flow. When the driving pressure is higher than 3000Pa, the flow speed of the sample is too fast, and when the distribution chamber is not full, there is a probability that the sample will pass through the bypass pipe, causing the distribution structure to fail. When the fluid sample contains low surface energy components such as surfactants or organic solvents, the sample is subjected to greater capillary force in the pipe, which makes it easier for the sample to pass through small structures. Through the optimization of the structure of the present invention and the introduction of the interface valve, the compatibility of the structure with low surface energy samples can be effectively improved. For example, when the sample is a 50% ethanol aqueous solution, such as Figure 9 As shown, the structure can achieve stable sample distribution under a driving pressure of 20Pa-800Pa.

[0038] Furthermore, the microfluidic distribution chip provided in this embodiment also includes a filtration unit, which includes a filter membrane 42 disposed below the sample loading hole 12 and a filter cavity 41 disposed below the filter membrane 42. The filter cavity 41 is connected to the sample inlet pipe 13. The filter membrane 42 is preferably a porous material such as polysulfone (PS), polyarylsulfone (PASF), polyphenylene ether sulfone (PES), polyethylene (PE), and polycarbonate (PC). It can include only one layer of filter membrane, or it can be selected to use a combination of two, three, or more layers of filter membranes depending on the substance to be filtered in the sample. The filter unit can be used directly or after processing, such as coating with antibodies to specific substances. In the field of in vitro diagnosis, serum is often required as a sample for the detection of biochemical or immune indicators. In traditional methods, serum separation from whole blood usually requires large equipment such as centrifuges, which is cumbersome to operate and has high requirements for experimental conditions. In this embodiment, a filtration unit is integrated at the injection end to achieve serum separation of whole blood samples. Since parameters such as blood viscosity and hematocrit vary significantly among different people, the driving pressure required for the blood filtration process also varies greatly. At the same time, there are also certain differences in the components of the serum sample passing through the filter membrane 42. Based on this embodiment, it can be compatible with different sample characteristics and a wide range of driving pressures. Therefore, it is suitable for integrating the blood filtration step to achieve portable detection of serum biochemical indicators. When the sample is blood, the blood sample passing through the sample injection hole 12 is filtered out of blood cells by the filtration unit, and the obtained plasma or serum flows into the injection pipe. Since parameters such as viscosity and hematocrit of different blood samples vary significantly, the driving pressure drop generated after the sample passes through the filter membrane will fluctuate within a wide range, such as Figure 10 As shown, the distribution structure of this embodiment can achieve stable sample distribution under a driving pressure of 2000Pa-4000Pa, and can therefore be well used in conjunction with various filtering and pre-processing modules.

[0039] Preferably, the microfluidic distribution chip provided in this embodiment also includes an overflow chamber 18 arranged between the sample outlet pipe 17 and the exhaust hole 19. When the sample distribution is completed, the fluid sample continues to be driven, and the excess fluid sample and the sample in the sample inlet pipe 13 and the bypass pipe 14 will flow into the overflow chamber 18. Since the flow resistance of the exhaust pipe 15 is relatively large, the liquid in the distribution chamber 11 will remain in place, thereby achieving isolation of the distribution sample. When there are fewer samples, the samples in the sample inlet pipe 13 and the bypass pipe 14 can be used to fill the subsequent distribution chamber 11, thereby achieving high sample utilization. Furthermore, an optical detection sensor can be configured at the overflow chamber 18 to determine whether there is a fluid sample entering the overflow chamber 18 from the transmitted signal, so as to determine whether the filling process is completed and whether the sample volume is sufficient.

[0040] Preferably, freeze-dried or air-dried reagents may be pre-stored in the distribution chamber 11 to react with the sample to complete the corresponding detection function.

[0041] Example 2

[0042] Figure 5 and Figure 6 A second embodiment of the microfluidic chip provided by the present invention is schematically shown. The microfluidic chip provided by the second embodiment has substantially the same structure as the microfluidic chip provided by the first embodiment, wherein structures with similar functions are given similar figure marks. For the sake of brevity, only the distinguishing parts are described in detail here.

[0043] Different from the first embodiment, in the second embodiment, all pipes and cavities are arranged on the chip body 1, that is, the distribution chamber 21, the filter chamber 41, the sample addition hole 22, the sampling pipe 23, the exhaust pipe 25, the sample outlet pipe 27, the exhaust hole 29, the bypass pipe 24 and the interface valve 26 are all arranged on the chip body 1. When the depths of the sampling pipe 23 and the distribution chamber 21 at the same level are different, in order to avoid the sudden change of the pipe depth affecting the distribution of the fluid, a transition pipe 20 is introduced between the sampling pipe 23 and the distribution chamber 21 to make the cross-sectional area of the fluid channel transition smoothly, thereby improving the reliability of the structure.

[0044] Example 3

[0045] Figure 7 The third embodiment of the microfluidic chip provided by the present invention is schematically shown. The microfluidic chip provided by the third embodiment has substantially the same components and connection relationships as the microfluidic chip provided by the first embodiment, wherein structures with similar functions are given similar figure marks. For the sake of brevity, only the distinguishing parts are described in detail here.

[0046] Different from the first embodiment, in the third embodiment, all pipes and cavities are arranged on the chip body 1, that is, the distribution chamber 31, the filter chamber 41, the sample addition hole 32, the sample inlet pipe 33, the exhaust pipe 35, the sample outlet pipe 37, the exhaust hole 39, the bypass pipe 34 and the interface valve 36 are all arranged on the chip body 1. Different from the first and second embodiments in which the flow resistance is controlled by the change of the pipe cross-sectional area, this embodiment realizes the orderly filling of the distribution chamber 31 by utilizing the change of the pipe depth. This embodiment is often suitable for situations when the required distribution sample amount is small, the cross-sectional area of the distribution chamber 31 is smaller than the cross-sectional area of the bypass pipe 34, and the fluid sample distribution cannot be achieved by the flow resistance difference.

[0047] Specifically, the depths of the sampling pipe 33, the distribution chamber 31, and the exhaust pipe 35 are the same, the depth of the bypass pipe 34 is greater than the depth of the sampling pipe 33, the depth of the interface valve 36 is greater than the depth of the bypass pipe 34, and the depth ratio of the interface valve 36, the bypass pipe 34, and the sampling pipe 33 is 4-10:1.5-2.5:1. More specifically, the depth ratio of the three is 5:2:1. Due to the depth mutation between the bypass pipe 34 and the sampling pipe 33, an interface valve effect will be generated at the intersection of the two, which hinders the passage of fluid. However, there is no depth mutation of the interface between the sampling pipe 33 and the distribution chamber 31. Therefore, the fluid sample will first fill the distribution chamber 31. After the distribution chamber 31 is filled, the fluid sample enters the exhaust pipe 35 and contacts the interface valve 36. Since the depth of the interface valve 36 is greater than that of the bypass pipe 34, the effect of hindering the passage of fluid is stronger. Therefore, the fluid sample will stop at the interface valve 36, but enter the sample outlet pipe 37 through the bypass pipe 34 and merge into the next distribution unit, and then repeat this process to achieve sample distribution.

[0048] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A microfluidic distribution chip, comprising a sample addition hole, a sample inlet pipe, a distribution chamber, an exhaust pipe, a sample outlet pipe and an exhaust hole connected in sequence, characterized in that: The invention also includes a bypass pipe, the bypass pipe is connected to the sample inlet pipe and the sample outlet pipe, and is used to allow the fluid added through the sample addition hole to flow to the sample outlet pipe through the bypass pipe after filling the distribution cavity; It also includes an interface valve disposed between the exhaust pipe and the sample outlet pipe, wherein the number of the interface valve is at least one and is used to assist in blocking the fluid passing through the exhaust pipe; The microfluidic distribution chip includes a chip body and a cover plate connected to the chip body. The distribution cavity, sample addition hole, sample injection pipe, exhaust pipe, sample outlet pipe, exhaust hole and bypass pipe are all arranged on the chip body. A transition pipe is connected between the sample injection pipe and the distribution cavity. The depth of the bypass pipe is greater than the depth of the sample injection pipe, and the depth of the interface valve is greater than the depth of the bypass pipe. The sample inlet pipe, distribution chamber, exhaust pipe, sample outlet pipe and bypass pipe constitute a set of distribution units. Several sets of distribution units can be provided. Adjacent distribution units are connected through the sample outlet pipe of the previous unit and the sample inlet pipe of the next unit.

2. The microfluidic distribution chip according to claim 1, characterized in that: The microfluidic distribution chip further comprises an overflow cavity arranged between the sample outlet pipe and the exhaust hole. An optical detection sensor is provided at the overflow cavity for detecting the filling amount of the fluid.

3. The microfluidic distribution chip according to claim 1, characterized in that: The microfluidic distribution chip further comprises a filter unit, which comprises a filter membrane disposed below the sample addition hole and a filter cavity disposed below the filter membrane. The filter membrane is at least one layer, and the filter cavity is connected to the sample introduction pipeline.

4. The microfluidic distribution chip according to any one of claims 1 to 3, characterized in that: The distribution chamber contains pre-stored reaction reagents for reacting with samples to complete detection.

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