Three-dimensional microfluidic control hazard detection chip

Abstract

This system enables rapid and simultaneous detection of multiple hazards within a single detection technology framework, maximizing sample utilization efficiency and ensuring the accuracy of detection results. [Solution] Disclosed is a detection chip for three-dimensional microfluidic control hazards, comprising at least one microfluidic control chip body and one detection reaction base. The microfluidic control chip body is columnar and includes a magnet rod housing hole, a spiral passage, a liquid inlet chamber, a waste liquid chamber, a detection reaction base positioning port, a liquid outlet, a first intake passage and a second intake passage, and one removable magnet rod is placed in the magnet rod housing hole. The detection reaction base is removable and provided in the detection reaction base positioning port at the bottom of the microfluidic control chip body, and the detection reaction base and the detection reaction base positioning port are sealed together. The present invention proposes a detection chip for three-dimensional microfluidic control hazards that can integrate uniform mixing, magnetic separation, purification, and one-step multiple detection.

Description

Technical Field

[0001] The present invention relates to the field of microfluidic control technology, and particularly to a detection chip for hazard factors combined with three-dimensional microfluidic control.

Background Art

[0002] Currently, biological hazard factors, chemical hazard factors, etc. have become key items attracting global attention. The health problems, product quality problems, and agricultural production problems caused by them have a profound impact on the safety of human life and have brought unpredictable economic losses. Regarding the detection of various hazard factors, various detection technologies and equipment have been developed, and this field mainly focuses on nucleic acid detection, immunoassay, electrochemical detection, and spectral detection technology systems. Based on these technologies, researchers have developed numerous detection devices. For example, fluorescence quantitative PCR instruments, microplate readers, electrochemical workstations, Raman detectors, etc. The application of these machines has played an active role in the research and prevention of hazard factors, but there are still problems such as complex operation, high cost of equipment, the need for multiple machines for testing, the possibility of false negatives and missed inspections. Especially for the detection of unknown samples, in many cases, it is necessary to use a combination of multiple types of technologies and equipment. Quickly and simultaneously detecting multiple types of hazard factors within the same detection technology system, maximizing the use efficiency of samples, and ensuring the accuracy of detection results are urgent issues to be solved.

[0003] Detection methods based on microfluidic control technology have characteristics such as anti-pollution, integration, low cost, fast analysis speed, and the ability to detect in parallel, and are an ideal strategy for realizing high-throughput and multi-target detection. However, the currently mainstream planar microfluidic control chips have problems such as limitations in drive control, insufficient expandable space, and difficulty in modular integration, resulting in limitations in their usage functions and usage scenarios.

Summary of the Invention

[0004] To solve the above problems, the present invention proposes a detection chip for three-dimensional microfluidic control hazards that can detect and integrate multiple targets simultaneously in a single step, including uniform mixing, magnetic separation, and purification.

[0005] To solve the above problems, the present invention employs the following technical solutions. The three-dimensional microfluidic control hazard detection chip includes at least one microfluidic control chip body and one detection reaction base. The microfluidic control chip body is columnar, and the following are installed inside the microfluidic control chip body. A magnet rod housing hole is provided, the magnet rod housing hole is installed vertically and has an open top, and a removable magnet rod is installed inside the magnet rod housing hole. A spiral passage is provided, the spiral passage is installed surrounding the lower part of the magnet rod housing hole, and the central axis of the spiral passage coincides with the central axis of the magnet rod housing hole. A liquid inlet chamber, the top of which is open, and the bottom of which communicates with the upper end of a spiral passage. A waste liquid chamber is provided, and the waste liquid chamber is connected to the lower end of the spiral passage. A detection reaction base positioning port is located at the bottom of the microfluidic control chip body. A liquid outlet is provided, the liquid outlet being located at the inner top of the detection reaction base positioning port, and the liquid outlet communicating with the lower end of the spiral passage. The first intake passage has one end that communicates with the outer wall of the microfluidic control chip body and the other end that communicates with the waste liquid chamber. A second intake passage, one end of which communicates with the outer wall of the microfluidic control chip body, and the other end of which communicates with the inner top of the detection reaction base positioning port. The detection reaction base is removably installed in a detection reaction base positioning port at the bottom of the microfluidic control chip body, and the detection reaction base and the detection reaction base positioning port are sealed and coupled together.

[0006] Preferably, the spiral passage has a conical spiral shape with a large upper opening and a small lower opening.

[0007] Preferably, the liquid outlet has a nozzle structure that protrudes downward.

[0008] Preferably, the detection reaction base consists of a sealed base and a detection array chip. The upper part of the sealed base is cylindrical, a sealed coil is installed in the outer ring direction of the cylindrical structure, and the detection reaction base positioning port is cylindrical and is sealedly coupled to the upper part of the sealed base. A groove for positioning the detection array chip is provided at the top of the sealed base, the detection array chip is placed in the groove for positioning the detection array chip, a reagent storage tank is provided at the top of the detection array chip, and the liquid outlet is located above the reagent storage tank at the top of the detection array chip.

[0009] Preferably, a plurality of independently distributed recessed single-target detection microgrooves are provided on the inner bottom of the detection array chip, the detection array chip has a recessed shape, an open top, relatively high sides, and can contain the liquid to be measured inside.

[0010] Preferably, the bottom of the liquid inlet chamber is funnel-shaped.

[0011] Preferably, the microfluidic control chip body further includes a waste liquid chamber cap, the inside of which communicates with the waste liquid chamber and the outside of which is sealed by the waste liquid chamber cap.

[0012] Preferably, the front side of the waste liquid chamber cap has a lateral cylindrical shape, a sealing ring is provided in the outer ring direction of the cylindrical structure, and the waste liquid chamber cap is sealed and connected to the waste liquid outlet by the sealing ring.

[0013] The present invention has the following beneficial effects. 1. By installing a spiral passage inside and moving a mixture containing a sample awaiting detection and magnetic beads surface-modified with a probe / antibody (hereinafter referred to as modified magnetic beads) spirally downwards through the spiral passage, the modified magnetic beads and the target awaiting detection can be sufficiently and uniformly mixed and brought into contact within the relatively long spiral passage under conditions where spiral centrifugal force, gravity, and magnetic force continuously fluctuate, thereby effectively improving the capture rate by the magnetic beads. 2. The spiral passage is set in a conical spiral shape with a large upper opening and a small lower opening. The upper spiral passage is relatively far from the magnetic rod, and the magnetism is relatively weak, ensuring the fluidity of the mixed liquid, and the magnetic beads are not concentrated and do not block the passage. As the distance from the magnetic rod decreases, the magnetism becomes stronger, and the magnetic beads are gradually attracted to the inner wall of the spiral passage. The lower spiral passage is relatively close to the magnetic rod, and the magnetism is relatively strong, so magnetic beads that are not attracted to the inner wall of the spiral passage flow through the spiral passage into the waste liquid chamber, preventing missed inspections of targets awaiting detection. 3. The magnetic rod is designed to be removable. After removing the magnetic rod, the magnetic beads adsorbed to the inner wall of the spiral passage are eluted with the elution solution and dropped onto the detection array chip on the detection reaction base to perform a specificity recognition reaction. All concave single-target detection microgrooves are immersed in the detection waiting liquid, and the detection waiting targets bound to the modified magnetic beads bind specifically to the detection probe / antigen in the concave single-target detection microgrooves with equal probability. After being held at a constant temperature for a certain period of time while being shaken, the detection array chip is removed, and the unbound magnetic beads are washed on a washing plate. After drying, high-resolution images are captured, and the detection results are determined by image recognition. 4. Each concave single-target detection microgroove can be coated with various detection probes / antibodies based on detection requirements, enabling simultaneous detection of various types of hazards. Furthermore, spatial coating by the detection array chip ensures accurate identification, eliminating the need for complex operations such as multiple fluorescent labels. 5. The microfluidic control chip allows for high-efficiency magnetic separation and direct dropping of the concentrated and purified sample onto the detection array chip, covering all concave single-target detection microgrooves. This ensures that all pending target magnetic bead composites come into contact with the coated detection probe / antibody within the detection microgrooves with equal probability. This enables multi-target detection in a single step without the need for liquid-liquid or liquid-flow separation of the sample, reducing the likelihood of missed detections and false negatives. [Brief explanation of the drawing]

[0014] [Figure 1] This is a schematic diagram of the present invention. [Figure 2] This is a perspective view of the present invention. [Figure 3] This is an exploded view of the present invention. [Figure 4] This is an exploded view of the present invention from a different angle. [Figure 5] This is a perspective view of the disassembled state of the present invention. [Figure 6] This is a perspective view of the disassembled state of the present invention from a different angle. [Figure 7] This is a plan view of the microfluidic control chip body of the present invention. [Figure 8] This is a cross-sectional view in the direction AA in Figure 7. [Modes for carrying out the invention]

[0015] The present invention will be further described below in conjunction with the attached drawings and specific implementation plans. The present invention relates to a three-dimensional microfluidic control hazard detection chip, which, as shown in Figures 1 to 8, comprises at least one microfluidic control chip body 1 and one detection reaction base 2, wherein the microfluidic control chip body 1 is columnar in shape and comprises the following within the microfluidic control chip body 1. A magnet rod housing hole 3 is provided, which is installed vertically and has an open top, and a removable magnet rod 4 is installed inside the magnet rod housing hole 3. A spiral passage 5, which is installed to surround the lower part of the magnet bar accommodating hole 3, and the central axis of the spiral passage 5 coincides with the central axis of the magnet bar accommodating hole 3. The spiral passage 5 presents a conical spiral shape with a large upper opening and a small lower opening. A liquid inlet chamber 6, the top of which is open, the bottom of the liquid inlet chamber 6 presents a funnel shape, and the bottom communicates with the upper end of the spiral passage 5. A waste liquid chamber 7, which communicates with the lower end of the spiral passage 5, and the communication port between the spiral passage 5 and the waste liquid chamber 7 is located at the top of the waste liquid chamber 7. A detection reaction base positioning port 8, which is located at the bottom of the microfluidic control chip body 1. A liquid discharge port 9, which is located at the inner top of the detection reaction base positioning port 8, and the liquid discharge port 9 communicates with the lower end of the spiral passage 5. The liquid discharge port 9 has a nozzle structure protruding downward. A first intake passage 10, one end of which communicates with the outer wall of the microfluidic control chip body 1, the other end communicates with the waste liquid chamber 7, and the communication port between the first intake passage 10 and the waste liquid chamber 7 is located at the top of the waste liquid chamber 7. A second intake passage 11, one end of which communicates with the outer wall of the microfluidic control chip body 1, and the other end communicates with the inner top of the detection reaction base positioning port 8. The detection reaction base 2 is removably installed in the detection reaction base positioning port 8 at the bottom of the microfluidic control chip body 1, and a sealed connection is formed between the detection reaction base 2 and the detection reaction base positioning port 8.

[0016] The detection reaction base 2 consists of a sealed base 201 and a detection array chip 202. The upper part of the sealed base 201 is cylindrical, and a sealed coil is installed in the outer ring direction of the cylindrical structure. The detection reaction base positioning port 8 is cylindrical and is sealedly coupled to the upper part of the sealed base 201. A detection array chip positioning groove 203 is provided at the top of the sealed base 201, and the detection array chip 202 is placed within the detection array chip positioning groove 203. A reagent storage tank is provided at the top of the detection array chip 202, and 16 independently distributed 4x4 array-type concave single-target detection microgrooves 204 are provided at the inner bottom of the reagent storage tank of the detection array chip 202. The liquid outlet 9 is located above the reagent storage tank at the top of the detection array chip 202. The detection reaction base 2 is designed with two parts, the sealed base 201 and the detection array chip 202, so that the sealed base 201 is not contaminated by contact with reagents, can be reused, and improves the environmental protection of the product.

[0017] The present invention further includes a waste liquid chamber cap 12, and a microfluidic control chip body 1 is provided with a waste liquid outlet 13, the inside of which communicates with a waste liquid chamber 17, and the outside of which is sealed by the waste liquid chamber cap 12. The front side of the waste liquid chamber cap 12 has a lateral cylindrical shape, and a sealing ring is provided in the outer ring direction of the cylindrical structure, and the waste liquid chamber cap 12 is sealed and coupled to the waste liquid outlet 13 by the sealing ring.

[0018] When performing a hazard detection test using the present invention, first, an intake device (cylinder) is connected to the openings of the first intake passage 10 and the second intake passage 11, and a magnetic rod 4 is inserted into the magnetic rod housing hole 3.

[0019] The sample solution and the modified magnetic bead solution (magnetic beads modified with nucleic acid aptamers, probes, antibodies, etc.) are each injected into the liquid inflow chamber 6 to form a mixture. At this time, the modified magnetic beads can specifically bind to the target awaiting detection.

[0020] Then, the intake device on the first intake passage 10 starts intake work, gradually increasing the intake volume and creating negative pressure in the waste liquid chamber 7. The mixed liquid in the liquid inlet chamber 6 is affected by the negative pressure in the waste liquid chamber 7 and gradually passes through the spiral passage 5 into the waste liquid chamber 7. When the mixed liquid passes through the spiral passage 5, initially, the upper part of the spiral passage 5 is relatively far from the magnetic rod 4 and the magnetism is relatively weak, ensuring the fluidity of the mixed liquid, and the modified magnetic beads in the mixed liquid are not concentrated and do not block the passage. At the same time, as the mixed liquid flows through the spiral passage 5, the narrowness of the spiral passage, the long spiral distance, and the continuous changes in spiral centrifugal force, gravity, and magnetic force all act together, further increasing contact between the target awaiting detection and the modified magnetic beads, effectively promoting the capture of the target awaiting detection by the modified magnetic beads. As the mixed liquid continues to flow downwards and the distance between the spiral passage 5 and the magnetic rod decreases, the magnetism becomes stronger, and the modified magnetic beads are gradually attracted to the inner wall of the spiral passage 5. The lower part of the spiral passage 5 is relatively close to the magnetic rod 4 and has relatively strong magnetism, effectively preventing the remaining unattached modified magnetic beads from flowing through the spiral passage 5 and entering the waste liquid chamber 7, thereby improving the recovery rate of magnetic beads and reducing the probability of missed inspections.

[0021] Once the liquid mixture in the liquid inlet chamber 6 and the spiral passage 5 has finished flowing, the modified magnetic beads in the mixture are essentially adsorbed to the inner wall of the spiral passage 5. These modified magnetic beads have already made sufficient contact with the targets awaiting detection, and the surfaces of many of the modified magnetic beads have already captured the targets awaiting detection.

[0022] Subsequently, the passage is cleaned using the eluent to elute substances and other impurities that were not captured by the modified magnetic beads remaining in the spiral passage 5. A sufficient amount of eluent is added to the liquid inlet chamber 6, and the suction device on the first suction passage 10 continues its suction operation, allowing the eluent in the liquid inlet chamber 6 to enter the waste liquid chamber 7 via the spiral passage 5.

[0023] After removing impurities, the intake device on the first intake passage 10 stops working and begins collecting the modified magnetic beads. The magnetic rod 4 is withdrawn from the magnetic rod housing hole 3, and the magnetic beads on the inner wall of the spiral passage 5 lose their magnetic fixation. A sufficient amount of eluent is added again to the liquid inlet chamber 6, and the intake device on the second intake passage 11 starts the intake operation, creating negative pressure in the detection reaction base positioning port 8. The eluent in the liquid inlet chamber 6, under the negative pressure in the detection reaction base positioning port 8, flows together with the modified magnetic beads that have lost their magnetic fixation in the spiral passage 5, and finally flows out from the liquid outlet 9 and drips into the detection array tip 202 below the liquid outlet 9. After the target identification reaction is completed in the detection array tip 202, the detection reaction base 2 is removed, the detection array tip 202 is taken out, the unbound modified magnetic beads are washed with a washing plate, and after drying, high-resolution images are taken, and the detection result is determined by image recognition. [Explanation of symbols]

[0024] 1: Microfluidic control chip body, 2: Detection reaction base, 201: Sealed base, 202: Detection array chip, 203: Detection array chip positioning groove, 204: Concave single target detection microgroove, 3: Magnet rod housing hole, 4: Magnet rod, 5: Helical passage, 6: Liquid inlet chamber, 7: Waste liquid chamber, 8: Detection reaction base positioning port, 9: Liquid outlet, 10: First intake passage, 11: Second intake passage, 12: Waste liquid chamber cap, 13: Waste liquid outlet

Claims

1. A chip for detecting hazards in three-dimensional microfluidic control, It includes at least one microfluidic control chip body (1) and one detection reaction base (2), wherein the microfluidic control chip body (1) is columnar, and the following is installed inside the microfluidic control chip body (1): A magnet rod housing hole (3) is provided, wherein the magnet rod housing hole (3) is installed vertically and has an open top, and a removable magnet rod (4) is installed inside the magnet rod housing hole (3). A spiral passage (5) is installed surrounding the lower part of the magnet rod housing hole (3), and the central axis of the spiral passage (5) coincides with the central axis of the magnet rod housing hole (3). A liquid inlet chamber (6) is provided, the top of which is open and the bottom of which is in communication with the upper end of the spiral passage (5), A waste liquid chamber (7) is connected to the lower end of the spiral passage (5), A detection reaction base positioning port (8) is located at the bottom of the microfluidic control chip body (1). A liquid outlet (9) is located at the inner top of the detection reaction base positioning port (8), and the liquid outlet (9) communicates with the lower end of the spiral passage (5). The first intake passage (10) is such that one end of the first intake passage (10) communicates with the outer wall of the microfluidic control chip body (1), and the other end communicates with the waste liquid chamber (7). The second intake passage (11) is such that one end of the second intake passage (11) communicates with the outer wall of the microfluidic control chip body (1), and the other end communicates with the inner top of the detection reaction base positioning port (8). A detection chip for three-dimensional microfluidic control hazards, characterized in that the detection reaction base (2) is removablely installed in a detection reaction base positioning port (8) at the bottom of the microfluidic control chip body (1), and the detection reaction base (2) and the detection reaction base positioning port (8) are sealed together.

2. The three-dimensional microfluidic control hazard detection chip according to claim 1, characterized in that the helical passage (5) has a conical spiral shape with a large upper opening and a small lower opening.

3. The three-dimensional microfluidic control hazard detection chip according to claim 1, characterized in that the liquid outlet (9) has a nozzle structure that protrudes downward.

4. The detection reaction base (2) is composed of a sealed base (201) and a detection array chip (202), the upper part of the sealed base (201) has a cylindrical structure, a sealing ring is provided in the outer ring direction of the cylindrical structure, the detection reaction base positioning port (8) has a cylindrical shape that is sealedly coupled to the upper part of the sealed base (201), a detection array chip positioning groove (203) is provided at the top of the sealed base (201), the detection array chip (202) is provided in the detection array chip positioning groove (203), a reagent storage tank is provided at the top of the detection array chip (202), and the liquid outlet (9) is located above the reagent storage tank at the top of the detection array chip (202), characterized in that the detection chip for three-dimensional microfluidic control hazards is as described in claim 1 or 3.

5. The detection chip for three-dimensional microfluidic control hazards according to claim 4, characterized in that a plurality of independently distributed concave single-target detection microgrooves (204) in an array-like manner are provided on the inner bottom of the detection array chip (202).

6. The three-dimensional microfluidic control hazard detection chip according to claim 1, characterized in that the bottom of the liquid inflow chamber (6) is funnel-shaped.

7. The three-dimensional microfluidic control hazard detection chip according to claim 1, further comprising a waste liquid chamber cap (12), wherein the microfluidic control chip body (1) is provided with a waste liquid outlet (13), the inside of the waste liquid outlet (13) is in communication with the waste liquid chamber (7), and the outside is sealed by the waste liquid chamber cap (12).

8. The three-dimensional microfluidic control hazard detection chip according to claim 7, characterized in that the front side of the waste liquid chamber cap (12) has a lateral cylindrical structure, a sealing ring is provided in the outer ring direction of the cylindrical structure, and the waste liquid chamber cap (12) is sealed and coupled with the waste liquid outlet (13) by the sealing ring.

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