Micro-fluidic chip detection structure, micro-fluidic chip and detection method

Abstract

The invention provides a micro-fluidic chip detection structure, a micro-fluidic chip and a detection method, and relates to the technical field of biological fluid detection. According to the micro-fluidic chip detection structure, in the rotating process of a micro-fluidic chip, a to-be-detected sample in a mixing tank flows into a first detection tank pre-filled with a reagent under the action of centrifugal force or capillary force; by means of high-speed rotation of the micro-fluidic chip, a to-be-detected sample and a pre-loaded reagent fully react in the first detection groove. The micro-fluidic chip detection structure can ensure that the sample to be detected and the pre-loaded reagent are fully reacted in the first detection groove and then enter the second detection groove to be subjected to second-step reaction. The method can effectively improve the accuracy of biological detection results in multi-step reactions.

Description

Technical Field

[0001] The present invention relates to the technical field of biological fluid detection, and in particular to a microfluidic chip detection structure, a microfluidic chip and a detection method. Background Art

[0002] Centrifugal microfluidic chips, also known as microfluidic biochemical detection reagent trays, use centrifugation to separate cellular components from biological samples (such as whole blood), measure precise volumes of liquid samples (such as plasma), mix the samples with diluents, and transport the diluted samples through microfluidic channels to pre-loaded detection tanks for optical analysis and detection.

[0003] Some assays require multiple steps. For example, in the detection of creatinine in serum or urine, the first step involves an enzymatic reaction to deplete creatine in the sample, preventing interference with subsequent creatinine detection. After creatine removal, the second step involves a specific enzyme or chemical reagent reacting with creatinine to generate a quantifiable signal (such as color, absorbance, or fluorescence), allowing calculation of creatinine concentration. Creatine removal directly impacts the effectiveness of the second step, the creatinine reaction.

[0004] In the prior art, a variety of solutions have been proposed to address this problem. For example, one solution is to sequentially set a first reaction tank, a buffer tank, and a second reaction tank connected by microchannels in the distal direction of the chip: at low speeds, the liquid first enters the first reaction tank, and a gas-liquid interface is formed at the connection between the microchannel and the buffer tank. The back pressure generated by the interface can prevent the liquid from entering the second reaction tank at low speeds. However, the Rayleigh-Taylor instability gas-liquid interface relied on by this type of solution has obvious defects: on the one hand, the formation and collapse of the interface are directly controlled by the chip speed, and small disturbances on the interface (such as speed fluctuations, flow channel defects, etc.) can easily trigger instability, causing the liquid to flow into the second reaction tank prematurely, disrupting the reaction sequence; on the other hand, in order to maintain the stability of the gas-liquid interface, the first reaction tank cannot be stirred, which can easily cause uneven mixing of the reaction system and insufficient reaction, ultimately affecting the reliability of the test results.

[0005] Therefore, how to reliably ensure that the pre-installed reagents react fully with the sample to be tested before entering the next step of reaction and improving the accuracy of the test results has become a technical problem that needs to be solved urgently by those skilled in the art. Summary of the Invention

[0006] In view of this, one of the objectives of the present invention is to provide a microfluidic chip detection structure to solve the technical problem that the centrifugal detection flow channel used in the prior art cannot fully ensure that the pre-installed reagent reacts fully with the sample to be tested before entering the next step of reaction.

[0007] A second object of the present invention is to provide a microfluidic chip containing a microfluidic chip detection structure.

[0008] A third object of the present invention is to provide a detection method for a microfluidic chip.

[0009] In order to achieve one of the above-mentioned purposes, the present invention provides a microfluidic chip detection structure, comprising at least one microfluidic unit, the microfluidic unit comprising a first detection tank, a first microchannel and a second detection tank connected in sequence, the first detection tank and the second detection tank being arranged at both ends of the first microchannel; a distribution channel is provided in communication with the first detection tank for supplying liquid to the first detection tank; the first microchannel has at least one first elbow, the first elbow faces the rotation center axis, and the distance between the first elbow and the rotation center axis is less than the distance between the distribution channel and the rotation center axis.

[0010] Preferably, the first microchannel is a first U-shaped microchannel, and the first elbow is located on the first U-shaped microchannel.

[0011] Preferably, a ventilation hole is provided on the proximal side of the second detection slot, and the ventilation hole is communicated with the second detection slot.

[0012] Preferably, a mixing groove for introducing liquid into the distribution channel is provided in communication with the distribution channel, and a second microchannel is provided between the mixing groove and the distribution channel; the second microchannel is respectively communicated with the mixing groove and the distribution channel to form a liquid transmission path.

[0013] Preferably, a baffle is provided at the distal bottom of the mixing tank, and the baffle divides the bottom half of the mixing tank into two liquid containing spaces.

[0014] Preferably, the second microchannel, the distribution channel, the first detection tank, the first microchannel and the second detection tank are symmetrically arranged on both sides of the mixing tank.

[0015] Preferably, the mixing tank, the distribution channel, and the first detection tank are arranged telecentrically in sequence, and one end of the distribution channel is connected to the second microchannel.

[0016] Preferably, the first detection slot, the first microchannel and the second detection slot are symmetrically arranged on both sides of the distribution channel.

[0017] Preferably, the distribution channel is arranged on the distal side of the first detection tank, and the proximal side of the distribution channel is connected to the first detection tank through a third microchannel; the third microchannel has at least one third elbow, the third elbow faces the rotation center axis, and the distance between the third elbow and the rotation center axis is greater than the distance between the first elbow and the rotation center axis.

[0018] Preferably, it also includes a fourth microfluidic channel and a waste liquid tank connected to the distribution channel, the fourth microfluidic channel is a fourth U-shaped microfluidic channel, and the fourth microfluidic channel has at least one fourth elbow, the fourth elbow faces the rotation center axis, the distance between the fourth elbow and the rotation center axis is smaller than the distance between the third elbow and the rotation center axis, and the distance between the fourth elbow and the rotation center axis is greater than the distance between the first elbow and the rotation center axis.

[0019] In order to achieve the second objective above, the present invention provides a microfluidic chip, comprising a microfluidic substrate, on which is provided at least one microfluidic chip detection structure as described in any one of the above items.

[0020] In order to achieve the third objective above, the present invention provides a detection method of the microfluidic chip as described above, comprising the following steps: (1) Control the chip to rotate at high speed. Under the action of centrifugal force, the sample enters the distribution channel and flows into the first detection tank through the distribution flow channel. Keep the chip oscillating at high speed so that the sample can fully react in the first detection tank. (2) Reduce the chip rotation speed to a low speed or stop, wait for the sample in the first detection tank to fill the first microfluidic channel, and then control the chip to rotate at a high speed so that the sample enters the second detection tank from the first microfluidic channel; (3) Keep the chip oscillating at high speed to ensure that the sample reacts fully in the second detection tank; (4) Perform optical inspection of the sample.

[0021] The microfluidic chip detection structure provided by the present invention has the following technical effects: When the microfluidic chip detection structure of the present invention rotates with the chip, under the action of centrifugal force, the sample to be tested in the mixing tank will flow into the first detection tank pre-loaded with reagents. Thanks to the high-speed oscillation of the chip, the sample to be tested and the pre-loaded reagent can be fully mixed and reacted in the first detection tank. At the same time, since the first elbow of the first microchannel is higher than the distribution channel, although the sample to be tested can flow into the straight end part of the first microchannel, it cannot cross the first elbow. This design ensures that the sample to be tested and the pre-loaded reagent fully react in the first detection tank, and prevents the sample from flowing into the second detection tank through the first microchannel in advance. After the reaction in the first detection tank is complete, the sample is controlled to enter the second detection tank, thereby effectively improving the accuracy of the test results. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0023] Figure 1 1 is a schematic diagram of the three-dimensional structure of a substrate of a microfluidic chip according to Example 1 of the present invention; Figure 2 yes Figure 1 A top view of the middle substrate; Figure 3 yes Figure 2 Schematic diagram of the enlarged structure at A in the middle; Figure 4 1 is a schematic diagram of the three-dimensional structure of a substrate of a microfluidic chip according to Example 2 of the present invention; Figure 5 yes Figure 1 A top view of the middle substrate; Figure 6 yes Figure 5 Schematic diagram of the enlarged structure at B in the middle; Figure 7 1 is a schematic structural diagram of a substrate of a microfluidic chip according to Example 2 of the present invention; Figure 8 1 is a schematic structural diagram of a substrate of a microfluidic chip according to Example 3 of the present invention; Figure 9 yes Figure 8 A first state diagram of the microfluidic chip detection structure on the middle substrate; Figure 10 yes Figure 8 A second state diagram of the microfluidic chip detection structure on the middle substrate; Figure 11 yes Figure 8 The third state diagram of the microfluidic chip detection structure on the middle substrate; Figure 12 This is a centrifuge motor speed control diagram for the microfluidic chip detection method according to Example 4 of the present invention.

[0024] in, Figures 1-12 : 100, microfluidic chip detection structure; 101, microfluidic unit; 1011, first microfluidic channel; 1011a, first elbow; 1012, first detection tank; 1013, second detection tank; 102, mixing tank; 1021, baffle; 103, second microfluidic channel; 1031, second elbow; 104, distribution channel; 105, overflow structure; 1051, waste liquid channel; 1052, waste liquid tank; 106, vent; 1061, first vent; 107, third microfluidic channel; 1071, third elbow; 108, fourth microfluidic channel; 1081, fourth elbow; 200. Microfluidic chip. DETAILED DESCRIPTION

[0025] To make the objectives, technical solutions, and advantages of the present invention more apparent, the technical solutions of the present invention will be described in detail below. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other implementations obtained by those of ordinary skill in the art without inventive effort are within the scope of protection of the present invention.

[0026] It should be noted that the test sample of the present invention can be a blood sample or a variety of other biological fluids, such as urine, sputum, semen, saliva, lens fluid, cerebrospinal fluid, spinal fluid, and amniotic fluid. Other testable fluids include tissue culture medium, food, and industrial chemicals.

[0027] Taking a blood sample as an example, the microfluidic chip testing process is as follows: a whole blood sample is added to the sample loading tank, centrifuged to separate plasma and blood cells, and the plasma flows through microchannels into a mixing tank. The diluent flows through another set of channels into the mixing tank, where the two are oscillated and mixed to form a blood sample. The microfluidic chip then controls the speed of the blood sample, allowing it to flow through microchannels into the microfluidic unit. There, the blood sample undergoes a first reaction with the reagent in the first detection tank within the microfluidic unit. After the reaction is complete, the blood sample enters the second detection tank for a second reaction, followed by optical detection to obtain biomarker data.

[0028] In the prior art, there is a defect that the reagent enters the next reaction before the previous reaction is fully carried out, resulting in inaccurate detection results.

[0029] Therefore, if Figure 1-11 As shown, the present invention provides a microfluidic chip 200, which includes a substrate, and a microfluidic chip detection structure 100 is disposed on the upper surface of the substrate. Typically, a membrane or plate structure is disposed on the upper surface of the substrate, at least on the upper surface of the microfluidic chip detection structure 100, to form a detection functional area together with the microfluidic chip detection structure 100. The microfluidic chip 200 is a centrifugal microfluidic chip, typically designed in a disc shape. During the rotation of the microfluidic chip 200, the sample to be tested flows from the proximal side to the distal side within the microfluidic chip detection structure 100 under the action of centrifugal force.

[0030] For ease of description, the terms "proximal" and "distal" in this specification refer to the distance from the chip's rotational axis. In the following embodiments of the present invention, reference is made to the description of gravity, using the terms "up," "down," "high," and "low" depending on the distance from the rotational axis. For example, "downward" refers to movement in the same direction as the centrifugal force, toward the distal side, while "upward" refers to movement in the opposite direction of the centrifugal force, toward the proximal side. "Above" refers to movement closer to the rotational axis, and "below" refers to movement farther from the rotational axis.

[0031] The microfluidic chip detection structure of the present invention includes a mixing tank 102, a distribution channel 104 and a microfluidic unit 101. The microfluidic unit 101 includes multiple mixing tanks 102 and 101 through the distribution channel 104. That is, the mixing tank 102 provides the microfluidic unit 101 with samples to be detected through the distribution channel 104.

[0032] In detail, the microfluidic unit 101 includes a first detection tank 1012, a first microchannel 1011 and a second detection tank 1013 which are sequentially connected away from the rotation center axis. The first detection tank 1012 and the second detection tank 1013 are arranged at both ends of the first microchannel 1011 and are connected to the first microchannel 1011, wherein the two ends of the first microchannel 1011 are respectively connected to the distal side of the first detection tank 1012 and the proximal side of the second detection tank 1013.

[0033] The first microchannel 1011 has at least one first elbow 1011a, which faces the central axis of rotation. The distance between the first elbow 1011a and the central axis of rotation should be smaller than the distance between the distribution channel 104 and the central axis of rotation.

[0034] The principle is as follows: When the microfluidic chip starts rotating, the sample to be tested (hereinafter referred to as liquid) enters the distribution channel from the mixing tank and then enters the first detection tank under the action of centrifugal force. Since the first microchannel is connected to the first detection tank, the liquid also enters the first microchannel at the same time. Referring to the principle of communicating vessels, under high-speed centrifugation, the centrifugal force is greater than or equal to the capillary force. The liquid level entering the first microchannel cannot break through the apex of the first elbow, forming a "shut-off valve" at the first elbow of the first microchannel. This "shut-off valve" prevents the liquid from flowing into the second detection tank prematurely, effectively ensuring the full response of the first detection tank.

[0035] When the reaction in the first detection tank is completed, the chip rotation speed is reduced or stopped. At this time, the capillary action in the first microchannel dominates - the liquid climbs along the straight end of the first microchannel toward the first elbow driven by the capillary force. When the centrifugal force is less than the capillary force, the liquid continues to rise and fills the first elbow of the first microchannel until the entire first microchannel is filled with liquid. Then, the chip rotation speed is increased again, and the liquid in the first microchannel flows into the second detection tank under the action of centrifugal force, and reacts with the pre-installed reagent in the tank. Since the liquid in the first microchannel is connected to the liquid in the first detection tank, under the continuous centrifugal force, the liquid in the first detection tank will also flow into the second detection tank, ensuring that the reaction system is completely transferred.

[0036] When operated at an appropriate centrifugal speed, this structure can ensure that the liquid reacts fully in the first detection tank, and can also prevent the liquid from entering the second detection tank and reacting prematurely with the pre-installed reagent in the second detection tank.

[0037] It should be noted that the first microchannel 1011 of the present invention is preferably a first U-shaped microchannel, and the first elbow 1011a is located at the elbow of the first U-shaped microchannel. It can also be a V-shaped channel, and the first elbow 1011a is located at the tip of the first V-shaped microchannel.

[0038] In addition, Figure 1-11 As shown, in order to ensure that the liquid flows smoothly to the first detection tank 1012 and the second detection tank 1013 , a vent hole 106 is provided on the proximal side of the second detection tank 1013 , and the vent hole 106 is communicated with the second detection tank 1013 .

[0039] When the liquid flows in the first microchannel 1011 , it has to resist the gas pressure in the pipeline. The vent holes 106 are provided to discharge the gas from the pipeline and the reagent tank, so that the liquid can smoothly enter the first detection tank 1012 and the second detection tank 1013 .

[0040] Specifically, during the centrifugation process, when the liquid enters the second detection tank 1013 from the first detection tank 1012 through the first microchannel 1011, the vents 106 allow the gas in the tank to be discharged outward along with the liquid, avoiding the formation of a closed air cavity that hinders the flow of liquid.

[0041] Under the guidance of the principles of the present invention, the present microfluidic unit can be further arranged behind the second detection tank as needed. For example, a third and fourth reagent tanks can be arranged behind the second detection tank through a microchannel with an elbow to meet the needs of more steps of reaction.

[0042] Based on the structure of the above-mentioned microfluidic unit, the detection structure of the microfluidic chip of the present invention is described in detail below in conjunction with specific embodiments 1-4.

[0043] Example 1: This embodiment provides a microfluidic chip detection structure 100, such as Figure 1-3 As shown, this embodiment includes a mixing tank 102, a second microchannel 103 and a microfluidic unit 101 arranged in sequence away from the central axis of rotation. The second microchannel 103 and the microfluidic unit 101 are symmetrically arranged on both sides of the mixing tank 102. The proximal end of the second microchannel 103 is connected to the distal side of the mixing tank 102, and the distal end of the second microchannel 103 is connected to the corresponding microfluidic unit 101.

[0044] The second microchannel 103 of this embodiment is preferably a second U-shaped microchannel, and the second microchannel 103 has a second elbow 1031. The second elbow 1031 is located at the end of the second U-shaped microchannel, and the second elbow 1031 faces the central axis of rotation. The distance between the second elbow 1031 and the central axis of rotation is smaller than the distance between the liquid surface formed in the mixing tank under the action of centrifugation and the central axis of rotation, that is, the second elbow 1031 is closer to the central axis of rotation relative to the liquid surface of the mixing tank.

[0045] Since the liquid level in the mixing tank is higher than that in the first detection tank, the liquid will flow toward the first detection tank under the action of centrifugal force and react with the pre-installed reagent in the first detection tank.

[0046] like Figure 3 As shown, an overflow structure 105 is provided at the end of the distribution channel 104. Overflow structure 105 is used to collect excess liquid after filling the first detection tank 1012. Specifically, overflow structure 105 includes a waste liquid tank 1052 and a waste liquid channel 1051 connected to waste liquid tank 1052. Waste liquid channel 1051 is provided at the end of the distribution channel 104 and extends away from the central axis of rotation. Waste liquid tank 1052 is provided at the distal end of waste liquid channel 1051. To allow excess liquid to flow smoothly into waste liquid tank 1052, a vent 106 is provided proximal to the end of the distribution channel, which is connected to waste liquid channel 1051.

[0047] In this embodiment, the distribution channel is located between the second microchannel 103 and the first detection tank. The length can be designed based on actual product requirements. In this embodiment, a relatively short distribution channel 104 is designed, preferably in a short arc shape. However, it is understood that its position is at least higher than the waste liquid channel 1051. Under the action of centrifugal force, the liquid flowing out of the mixing tank 102 passes through the second microchannel 103 and the distribution channel 104 and enters the first detection tank 1012. When the first detection tank 1012 is full, the excess liquid will flow into the waste liquid tank 1052 through the waste liquid channel 1051.

[0048] In this embodiment, the two microfluidic units are disposed on both sides of the mixing tank, and the distribution channels are physically isolated, which fundamentally solves the problem of reagent cross-contamination between the microfluidic units during the liquid distribution process.

[0049] It should be noted that, in this embodiment, excess liquid will not enter the second detection tank 1013 through the first microchannel 1011, because the first elbow 1011a is higher than the distribution channel 104. At this time, the liquid level in the first microchannel 1011 will not be higher than the distribution channel 104. When the excess liquid can flow away through the waste liquid channel 1051, the liquid level in the first microchannel 1011 will not continue to rise, the first microchannel 1011 will not be filled, and the liquid that has entered the first detection tank 1012 will be retained in the first detection tank 1012 to react.

[0050] Continue to see Figure 3As shown, a baffle 1021 is provided at the distal bottom of the mixing tank 102. This baffle 1021 has a convex structure, separating the lower and middle portions of the mixing tank 102 into two spaces. The baffle 1021 functions to stir the liquid during high-speed oscillation. Furthermore, when the liquid level in the mixing tank 102 drops to the baffle 1021, the baffle 1021 located in the middle distributes the liquid evenly. Microfluidic units 101 with the same detection capacity on both sides receive the same amount of liquid, thus preventing inadequate reactions caused by insufficient liquid in one detection tank.

[0051] It is easy to understand that if the detection capacity of the microfluidic units 101 on both sides of the distribution channel is different, that is, the capacity of the first detection tank is different, the position of the baffle 1021 can be designed according to the needs of the two microfluidic units 101 so that the space capacity on the left and right sides of the baffle matches the capacity of the two first detection tanks.

[0052] Example 2: This embodiment also provides a microfluidic chip detection structure 100, such as Figure 4-7 As shown, this embodiment also includes two microfluidic units 101. Specifically, the mixing tank 102, the second microfluidic channel 103, the distribution channel 104 and the microfluidic unit 101 are arranged in sequence away from the central axis of rotation, wherein the liquid inlet of the second microfluidic channel 103 is connected to the distal side of the mixing tank 102, and the liquid outlet is connected to the distribution channel 104. A microfluidic unit 101 is respectively arranged at both ends of the distribution channel 104, that is, the liquid in the mixing tank 102 first flows into the second microfluidic channel 103, then flows into the distribution channel 104, and then enters the two microfluidic units 101.

[0053] Similar to Example 1, the second microchannel 103 of this embodiment is preferably a second U-shaped microchannel, and the second microchannel 103 has a second elbow 1031, which is located at the end of the second U-shaped microchannel, and the second elbow 1031 faces the center axis of rotation, and the distance between the second elbow 1031 and the center axis of rotation is smaller than the distance between the liquid surface formed in the mixing tank 102 under the action of centrifugation and the center axis of rotation, that is, the second elbow 1031 is closer to the center axis of rotation relative to the liquid surface of the mixing tank 102.

[0054] In this embodiment, the distribution channel 104 is preferably an elongated arc-shaped structure, and the distance between the distribution channel 104 and the central axis of rotation gradually increases along the direction of liquid flow. That is, the distribution channel 104 gradually moves away from the central axis of rotation from the liquid inlet end. This ensures that the direction of liquid flow is aligned with the direction of centrifugal force, allowing the liquid to flow more smoothly into the detection unit.

[0055] The distribution channel 104 is connected to the first detection tank through a connecting pipe, and the liquid in the second microchannel 103 enters from the distribution channel 104 and enters the two microfluidic units 101 through the distribution channel. Among them, the second microchannel 103 can be connected to the distribution channel 104 at the middle position of the distribution channel 104, such as Figure 7 As shown, they can also be connected at one end of the distribution channel 104, as shown in FIG. Figure 6 shown.

[0056] The cross-sectional area of the distribution channel 104 is preferably larger than the cross-sectional area of the second microchannel 103 .

[0057] like Figure 6 As shown, when the second microchannel is connected to one end of the distribution channel, the distribution channel is connected to the first detection tank through a connecting pipe. The first detection tank closer to the connection point will be filled first. At this time, if you want the first detection tanks of the same volume to be filled at the same time, the cross-sectional area of the connecting pipe closer to the second channel should be designed to be smaller than the cross-sectional area of the connecting pipe farther away, so as to control the speed at which the liquid enters the closer first detection tank to be smaller than the farther first detection tank, so that the first detection tanks at both ends of the distribution channel are filled at the same time, reducing the risk of crosstalk between the liquids of the two first detection tanks. Alternatively, the cross-sectional area of the two connecting pipes is the same, and two first detection tanks with different volumes are designed. The relationship between the detection tank volume ratio and the length, cross-sectional area, and liquid flow rate of the distribution channel is reasonably designed so that the first detection tank farther away from the second microchannel can be filled first or both detection tanks can be filled at the same time, avoiding the problem of cross-contamination of reagents in the two first detection tanks.

[0058] like Figure 7 As shown, when the second microchannel and the distribution channel meet at the center, liquid flows from the junction to both sides, with the distribution channels moving away from the central axis of rotation along the direction of liquid flow. The cross-sectional area of the distribution channel at the same location on both sides of the junction is as similar as possible to allow liquid to enter both first detection reservoirs simultaneously. This minimizes cross-contamination of reagents in the first detection reservoirs on both sides.

[0059] like Figure 6 As shown, in order to prevent liquid from overflowing from the first detection tank 1012 , an overflow structure 105 is provided at one end of the distribution channel 104 away from the second microchannel 103 . The overflow structure 105 is used to collect excess liquid after the first detection tank 1012 is filled.

[0060] Specifically, the overflow structure 105 includes a waste liquid tank 1052 and a waste liquid channel 1051 connected to the waste liquid tank 1052. The waste liquid channel 1051 is arranged at the end of the distribution channel 104 and extends away from the rotation center axis. The waste liquid tank 1052 is arranged at the end of the waste liquid channel 1051.

[0061] Under the action of centrifugal force, the liquid flowing out of the mixing tank 102 enters the distribution channel through the second microchannel 103 and then enters the first detection tank 1012. When the first detection tank 1012 is filled, the excess liquid will flow into the waste liquid tank 1052 through the waste liquid channel 1051.

[0062] Continue to see Figure 6 As shown, in order to allow excess liquid to smoothly enter the waste liquid tank 1052 , a vent hole 106 is provided on the proximal side of the end of the distribution channel, and the vent hole 106 is communicated with the waste liquid channel 1051 .

[0063] Figure 7 In the embodiment, overflow structures 105 are provided at both ends of the distribution channel 104.

[0064] It should be noted that, in this embodiment, excess liquid will not enter the second detection tank 1013 through the first microchannel 1011, because the distance between the first elbow 1011a of the first microchannel 1011 and the central axis of rotation is smaller than the distance between the distribution channel and the central axis of rotation. Therefore, the liquid level in the first microchannel 1011 will not be higher than the first elbow 1011a, and the first microchannel 1011 will not be filled.

[0065] Example 3: This embodiment also provides a microfluidic chip detection structure 100, such as Figure 8-11 As shown, this embodiment includes three microfluidic units 101, a mixing tank 102, a distribution channel 104 and a second microfluidic channel 103. The second microfluidic channel 103 is connected to the mixing tank 102 and the distribution channel 104 at the same time, that is, the liquid in the mixing tank 102 first flows into the second microfluidic channel 103, and then flows into the distribution channel 104. Three microfluidic units 101 are arranged in sequence on the proximal side of the distribution channel 104 along the direction of liquid flow.

[0066] It should be noted that the number of the microfluidic units 101 in this embodiment is not limited to three, but may be multiple.

[0067] The second microchannel 103 of this embodiment can be a straight channel or a curved channel, preferably a second U-shaped microchannel. The second microchannel 103 has a second elbow 1031, which is located at the end of the second U-shaped microchannel. The second elbow 1031 faces the center axis of rotation, and the distance between the second elbow 1031 and the center axis of rotation is less than the distance between the liquid surface of the mixing tank and the center axis of rotation, that is, the second elbow 1031 is closer to the center axis of rotation relative to the liquid surface of the mixing tank.

[0068] See also Figures 8-11As shown, the distribution channel 104 is arranged in an arc shape near the edge of the microfluidic chip 200. One end of the distribution channel 104 is connected to the second microchannel 103 and is the end where the liquid flows in. The other end of the distribution channel 104 is provided with a waste liquid tank 1052. Considering the smooth flow of liquid during centrifugal operation, for example, to ensure that the liquid in the distribution channel is drained smoothly after the first detection tank is filled, the distribution channel can be gradually moved away from the central axis of rotation along the direction of liquid flow.

[0069] Since the distance between the liquid surface in the mixing tank and the central axis of rotation is smaller than the distance between the distribution channel 104 and the central axis of rotation, the liquid will flow toward the distribution channel 104 under the action of centrifugal force.

[0070] In this embodiment, a third microchannel 107 is further provided between the distribution channel 104 and the first detection tank 1012. The third microchannel 107 is located on the proximal side of the distribution channel 104. In this embodiment, three third microchannels 107 are included. The three third microchannels 107 are all connected to the distribution channel 104, and the three third microchannels 107 are all connected to the three microfluidic units 101.

[0071] The third microchannel 107 is preferably a U-shaped microchannel, and has a third elbow 1071 on the third microchannel 107. The third elbow 1071 faces the central axis of rotation. The distance between the third elbow 1071 and the central axis of rotation should be greater than the distance between the liquid surface of the mixing tank and the central axis of rotation, so as to ensure that the liquid in the mixing tank can enter the first detection tank.

[0072] When the microfluidic chip 200 rotates, the diluted sample enters the distribution channel 104 under the action of centrifugal force and fills the distribution channel 104, the third microchannel 107 and the first detection tank 1012. The sample reacts with the pre-installed reagent in the first detection tank 1012.

[0073] like Figure 8 As shown, a waste liquid tank 1052 is provided at the end of the distribution channel 104 for collecting excess liquid.

[0074] A fourth microchannel 108 is provided between the waste liquid tank 1052 and the distribution channel 104 . The fourth microchannel 108 is preferably a fourth U-shaped microchannel. The fourth microchannel 108 has a fourth elbow 1081 , which faces the central axis of rotation.

[0075] In order to ensure that the blood sample fully fills the first detection tank and achieves the technical effect of the present invention, the distance between the fourth elbow and the center axis of rotation is less than the distance between the third elbow and the center axis of rotation, and the distance between the fourth elbow and the center axis of rotation is greater than the distance between the first elbow and the center axis of rotation. Under the action of centrifugal force, the distribution channel begins to be filled. Referring to the principle of communicating vessels, the liquid will enter the third microchannel and the fourth microchannel. Since the liquid in the mixing tank continuously enters the third microchannel and the fourth microchannel, the liquid level therein rises until it reaches the top of the third microchannel elbow, and the liquid enters the first detection tank. At this time, since the fourth microchannel elbow is higher than the third microchannel elbow, the liquid will preferentially fill the first detection tank.

[0076] When the first detection tank is filled, the liquid level will continue to rise along the first microchannel and also along the fourth microchannel. However, since the apex of the first microchannel elbow is higher than the apex of the fourth microchannel, the liquid will not cross the first microchannel elbow. When the liquid reaches the elbow of the fourth microchannel, the fourth microchannel is filled. As the chip rotates, all liquid in the microfluidic chip except the first detection tank flows into the waste liquid tank. By rationally designing the size of each channel and the distribution channel structure, while ensuring that each microfluidic unit is filled and emptied synchronously, the liquid isolation between each unit can be precisely controlled, minimizing cross-contamination between units and ensuring detection reliability.

[0077] In addition, to ensure that the first detection tank can be fully filled, the cross-sectional area or diameter of the fourth microfluidic channel 108 is generally not larger than the second microfluidic channel 103, the distribution channel 104 or the third microfluidic channel 107, or the cross-sectional area or diameter of the fourth microfluidic channel 108 is at least the same as that of the second microfluidic channel. In a preferred embodiment, the cross-sectional area size relationship of each channel is: distribution channel>third microfluidic channel>second microfluidic channel≥fourth microfluidic channel, wherein the cross-sectional area of the distribution channel is at least twice the cross-sectional area of the third microfluidic channel. For example, when the channel has a rectangular cross-section, the cross-sectional area of the second microfluidic channel is 0.15mm*0.2mm, the cross-sectional area of the third microfluidic channel is 0.15mm*0.5mm, the cross-sectional area of the distribution channel is 0.3mm*0.5mm, and the cross-sectional area of the waste liquid channel is 0.15mm*0.2mm.

[0078] like Figure 9 and Figure 10 As shown, the microfluidic chip 200 continues to rotate, and the liquid continues to flow into the waste liquid tank 1052 from the distribution channel.

[0079] In this embodiment, the third microchannel is configured in a U-shape, and the third elbow 1071 is positioned close to the central axis of rotation. Thus, when the distribution channel is emptied, the liquid in the connection portion between the third microchannel and the distribution channel (between the distribution channel and the third elbow) will flow back into the distribution channel, but the reaction liquid in the first detection tank 1012 will not flow away. In one embodiment, the third microchannel 107 is a U-shaped channel with an angled shape consisting of three relatively straight channels, such as Figure 8 As shown, the third elbow 1071 is one of the bends in this type of U-shaped flow channel. After the first detection tank is filled, the fluid is discharged from the distribution channel to the waste liquid tank, and the liquid in the third microchannel 107 is "disconnected" from the third elbow 1071, making it easier for the liquid to be discharged from this type of U-shaped flow channel.

[0080] like Figure 11 As shown, after the distribution channel is emptied and all first detection tanks 1012 are filled and fully reacted, the chip rotation speed is reduced. The liquid in the first microchannel 1011 flows to the first elbow 1011a under the action of capillary force, filling the first microchannel 1011. High-speed centrifugation is then started, allowing the liquid to enter the second detection tank 1013 under the action of centrifugal force.

[0081] In this embodiment, a first air vent 1061 is provided in communication with the first detection tank 1012 and is disposed proximal to the first detection tank 1012. When the reaction in the first detection tank 1012 is completed and the distribution channel 104 and the third microfluidic channel 107 are partially emptied, the chip rotation speed is reduced or stopped, and the liquid fills the first microfluidic channel 1011. The rotation speed is then increased to allow the liquid in the first detection tank 1012 and the first microfluidic channel 1011 to enter the second detection tank. During this process, if there is an incompletely emptied liquid column in the third microfluidic channel or other channels connected to the third microfluidic channel, it may affect the liquid from filling the first microfluidic channel. The function of the first air vent 1061 is to balance the air pressure between the first detection tank and the second detection tank, so that the liquid can smoothly fill the first microfluidic channel by capillary action.

[0082] It should be noted that, in this embodiment, the third elbows 1071 of the three third microchannels 107 are at the same distance from the central axis of rotation, so that the liquid levels in all the third microchannels 107 reach the third elbows 1071 at the same time, the liquid enters the first detection tank 1012 at the same time, and the reactions in all the first detection tanks proceed at the same time.

[0083] Example 4: This embodiment provides a detection method for a microfluidic chip, comprising the following steps: Step 1: Perform routine operations such as sample addition and separation. The separated sample and diluent flow into the mixing tank of the microfluidic chip. The centrifuge is controlled to rotate at high speed to mix the sample and diluent in the mixing tank. The motor speed of the high-speed oscillation is varied between 3000-5000 rpm for 15 seconds. Step 2: After the sample is mixed, control the centrifuge motor speed and rotate the chip at a low speed or stop. Figure 12 As shown, the liquid sample enters the second microchannel. Since the cross-sectional area of the distribution channel is larger than that of the second microchannel, when the sample reaches the distribution channel, the capillary force weakens and the sample is blocked at the junction of the second microchannel and the distribution channel. Step 3: After the sample fills the second microchannel, the centrifuge motor is controlled to rotate at high speed, such as Figure 12 As shown, the rotation speed is 5000 rpm. Under the action of centrifugal force, the sample enters the distribution channel and flows into the first detection tank through the third microchannel. After high-speed rotation for 30 seconds, the motor speed is oscillated at a high speed between 3000-5000 rpm for 15 seconds to allow the sample to fully react. When performing some test items, the sample reacts in the first detection tank, and the sample in the first detection tank can be monitored or detected by optical or other means. Step 4: Reduce the chip speed to a low speed of 0-300 rpm and wait for the sample to enter the first microchannel. After the sample fills the first microchannel, control the centrifuge to increase the speed and rotate at high speed for 30 seconds to allow the sample to enter the second detection tank from the first microchannel; Step 5: Maintain high-speed oscillation of the motor between 3000-5000 rpm to allow the sample to fully react in the second detection tank; Step 6: Control the motor speed to be constant at about 1200 rpm and perform optical detection of the sample.

[0084] In the description of the present invention, it should be noted that, unless otherwise specified, "plurality" means two or more; the terms "upper," "lower," "left," "right," "inner," "outer," "front end," "rear end," "head," "tail," etc., indicating directions or positional relationships, are based on the directions or positional relationships shown in the accompanying drawings and are intended only to facilitate the description of the present invention and simplify the description. They do not indicate or imply that the devices or components referred to must have a specific direction, be constructed, or operate in a specific direction, and therefore should not be construed as limiting the present invention. Furthermore, the terms "first," "second," "third," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0085] It should also be noted that, in the description of the present invention, unless otherwise expressly specified or limited, the terms "mounted," "connected," and "connected" should be understood broadly. For example, they may refer to fixed, detachable, or integral connections; mechanical or electrical connections; and direct or indirect connections through an intermediary. Those skilled in the art will understand the specific meanings of the above terms in the present invention depending on the specific circumstances.

[0086] The above description is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with this technical field can easily think of changes or replacements within the technical scope disclosed by the present invention, which should be covered by the scope of protection of the present invention.

Claims

1. A microfluidic chip detection structure, characterized in that: The microfluidic unit comprises at least one microfluidic unit, wherein the microfluidic unit comprises a first detection tank, a first microfluidic channel, and a second detection tank connected in sequence, wherein the first detection tank and the second detection tank are arranged at both ends of the first microfluidic channel; A distribution channel is provided in communication with the first detection tank and is used to supply liquid to the first detection tank; The first microchannel has at least one first elbow, the first elbow faces the central axis of rotation, and the distance between the first elbow and the central axis of rotation is smaller than the distance between the distribution channel and the central axis of rotation.

2. The microfluidic chip detection structure according to claim 1, characterized in that: The first microchannel is a first U-shaped microchannel, and the first elbow is located on the first U-shaped microchannel.

3. The microfluidic chip detection structure according to claim 1, characterized in that: A vent hole is provided on the proximal side of the second detection slot, and the vent hole is communicated with the second detection slot.

4. The microfluidic chip detection structure according to claim 1, characterized in that: A mixing groove for introducing liquid into the distribution channel is provided in communication with the distribution channel, and a second microchannel is provided between the mixing groove and the distribution channel; the second microchannel is respectively communicated with the mixing groove and the distribution channel to form a liquid transmission path.

5. The microfluidic chip detection structure according to claim 4, characterized in that: A baffle is provided at the distal bottom of the mixing tank, and the baffle divides the bottom half of the mixing tank into two liquid accommodating spaces.

6. The microfluidic chip detection structure according to claim 5, characterized in that: The second microchannel, the distribution channel, the first detection tank, the first microchannel and the second detection tank are symmetrically arranged on both sides of the mixing tank.

7. The microfluidic chip detection structure according to claim 4, characterized in that: The mixing tank, the distribution channel, and the first detection tank are arranged telecentrically in sequence, and one end of the distribution channel is communicated with the second microchannel.

8. The microfluidic chip detection structure according to claim 7, characterized in that: The first detection slot, the first microchannel, and the second detection slot are symmetrically arranged on both sides of the distribution channel.

9. The microfluidic chip detection structure according to claim 1, characterized in that: The distribution channel is arranged on the distal side of the first detection tank, and the proximal side of the distribution channel is connected to the first detection tank through a third microchannel; the third microchannel has at least one third elbow, the third elbow faces the rotation center axis, and the distance between the third elbow and the rotation center axis is greater than the distance between the first elbow and the rotation center axis.

10. The microfluidic chip detection structure according to claim 9, characterized in that: It also includes a fourth microfluidic channel and a waste liquid tank connected to the distribution channel, the fourth microfluidic channel is a fourth U-shaped microfluidic channel, and the fourth microfluidic channel has at least one fourth elbow, the fourth elbow faces the rotation center axis, the distance between the fourth elbow and the rotation center axis is smaller than the distance between the third elbow and the rotation center axis, and the distance between the fourth elbow and the rotation center axis is greater than the distance between the first elbow and the rotation center axis.

11. A microfluidic chip, characterized in that: It comprises a microfluidic substrate, on which is provided at least one microfluidic chip detection structure according to any one of claims 1 to 10.

12. A detection method for a microfluidic chip according to claim 11, characterized in that: The following steps are involved: (1) Control the chip to rotate at high speed. Under the action of centrifugal force, the sample enters the distribution channel and flows into the first detection tank through the distribution flow channel. Keep the chip oscillating at high speed so that the sample can fully react in the first detection tank. (2) Reduce the chip rotation speed to a low speed or stop, wait for the sample in the first detection tank to fill the first microfluidic channel, and then control the chip to rotate at a high speed so that the sample enters the second detection tank from the first microfluidic channel; (3) Keep the chip oscillating at high speed to ensure that the sample reacts fully in the second detection tank; (4) Perform optical inspection of the sample.

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