Full-automatic high-concentration sample enrichment device and method based on digital micro-fluidic chip

By designing a fully automatic sample high-concentration enrichment device, the liquid mixing system and filling unit are automatically mixed and injected into the microfluidic chip in multiple times, and the magnetic components are used for enrichment, the problem that the microfluidic chip cannot automatically inject the sample and magnetic bead mixture liquid is solved, and the magnetic bead concentration and detection accuracy are improved to meet the high sensitivity detection needs.

CN119666521APending Publication Date: 2025-03-21BEIJING MECHANICAL EQUIP INST
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Patent Information

Application Number
CN202411683465.1
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-22
Publication Date
2025-03-21

AI Technical Summary

Technical Problem

Existing microfluidic chips cannot automatically inject sample solution and magnetic bead mixture, and due to the chip space limitations, the magnetic bead concentration is low, which affects the detection effect.

Method used

A fully automatic sample high-concentration enrichment device is designed, including a liquid mixing system, a filling unit and a microfluidic chip. The sample and magnetic bead solution are mixed through the injection unit, and the microfluidic chip is injected into multiple times using the filling unit. The magnetic beads are adsorbed to the enrichment area with a magnetic element, and a high-concentration magnetic bead solution is obtained through the cleaning solution.

Benefits of technology

Automatic mixing and enrichment of samples and magnetic beads is realized, the concentration of magnetic beads is improved, the experimental process is simplified, the detection accuracy is improved, and the high sensitivity detection needs are met.

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Abstract

The invention discloses a full-automatic high-concentration sample enrichment device and method based on a digital micro-fluidic chip, the device comprises a liquid mixing system, a filling unit and a micro-fluidic chip, the liquid mixing system comprises an injection unit, a liquid storage unit and a liquid mixing cavity, the liquid storage unit, the liquid mixing cavity and the micro-fluidic chip are sequentially connected in series through conduits; the injection unit is used for injecting the sample solution and the magnetic bead solution in the liquid storage unit into the liquid mixing cavity for mixed incubation; the injection unit is used for injecting the incubated magnetic bead sample mixed solution into the micro-fluidic chip; wherein the micro-fluidic chip is used for driving injected mixed liquid to an enrichment area of the micro-fluidic chip, and magnetic beads in the mixed liquid passing through the enrichment area successively are adsorbed and positioned by controlling a magnetic element to move to the enrichment area. The detection precision of the micro-fluidic chip is improved, and the occasion requirements of high-sensitivity detection and analysis are met.
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Description

Technical Field

[0001] The present invention relates to the technical field of biochemical detection, and in particular to a fully automatic sample high-concentration enrichment device and method based on a digital microfluidic chip. Background Art

[0002] Digital microfluidics (DMF) is a droplet processing technology that can manipulate discrete liquids on a plane. The volume of the manipulated droplets is generally in the nL to μL level. Common droplet driving methods mainly include dielectric wetting, thermocapillary, light induction, surface acoustic wave and magnetic force. The DMF technology based on the dielectric wetting effect (Electrowetting on Dielectric, EWOD) is to add an electrical signal to the electrode of the digital microfluidic chip to form an external electric field, so that the contact angle of the droplets on the hydrophobic surface changes to complete the precise manipulation of the droplets, and can realize the driving, fusion, distribution and splitting of the droplets. DMF is widely used in the fields of rapid separation and analysis of life sciences due to its low reagent consumption, short reaction time, high degree of automation and high compatibility. DMF can be coupled with different types of detectors for online analysis. Magnetic beads are superparamagnetic microspheres with tiny particle sizes. They have the characteristics of super strong paramagnetism, small particle size (nm level), and rich surface active genes. Combined with the DMF system, they are widely used in immunoassay, nucleic acid separation and extraction, cell sorting and other fields.

[0003] In the existing microfluidic chip technology, there are some key technical bottlenecks that affect its application in the fields of biomedicine, chemical analysis, etc. First, microfluidic chips are usually unable to automatically inject sample solutions and magnetic bead mixtures, which means that when conducting experiments, the mixing process of samples and magnetic beads usually requires manual operation. This not only increases the complexity of the experiment, but also the injection amount is limited to manual operation, which will also result in errors, thus affecting the subsequent experimental results.

[0004] In addition, due to the size and space limitations of the microfluidic chip, especially when designing a more compact microchannel system, the space in the chip can only carry a limited amount of liquid. Since the sample magnetic bead mixture injected into the chip includes not only magnetic beads that adsorb the sample, but also free substances and waste liquid that are useless for biochemical detection. These useless substances in the mixture will take up space in the chip, resulting in a low concentration of magnetic beads in the mixture injected into the chip. Due to the small size of the magnetic beads and their strong affinity on the surface, the enrichment process usually requires a higher concentration of magnetic beads. However, the enrichment concentration of magnetic beads in the microfluidic chip is low, which limits its effect in specific applications, especially in situations where high-density magnetic beads are required for high-sensitivity detection and analysis.

[0005] Therefore, how to solve the technical difficulties of microfluidic chips in automatically injecting sample and magnetic bead mixture, and how to overcome the chip space limitations and increase the concentration of magnetic beads for efficient enrichment have become important directions for the development of microfluidic technology. Summary of the invention

[0006] In view of the problems existing in the prior art, the object of the present invention is to provide a fully automatic sample high-concentration enrichment device and method that can realize automatic injection of samples in a biochemical reaction process and improve the sample enrichment flux on a digital microfluidic chip.

[0007] To achieve the above-mentioned purpose, the first aspect of the present invention provides a fully automatic sample high-concentration enrichment device based on a digital microfluidic chip, comprising a liquid mixing system, a filling unit and a microfluidic chip, wherein the liquid mixing system comprises an injection unit, a liquid storage unit and a liquid mixing chamber, wherein the liquid storage unit, the liquid mixing chamber and the microfluidic chip are sequentially connected in series through a catheter; the injection unit is used to inject the sample solution and the magnetic bead solution in the liquid storage unit into the liquid mixing chamber for mixed incubation; the filling unit is used to inject the incubated magnetic bead sample mixed solution into the microfluidic chip; wherein the sample magnetic bead mixed solution is temporarily stored in the liquid mixing chamber, and the temporarily stored sample magnetic bead mixed solution is successively injected into the microfluidic chip through the filling unit, the microfluidic chip drives the injected mixed solution to the enrichment area of ​​the microfluidic chip, and the magnetic beads in the mixed solution are adsorbed and positioned in the enrichment area by controlling the magnetic element to move to the enrichment area, and a high-concentration magnetic bead solution is obtained by injecting a cleaning solution into the microfluidic chip and mixing with the magnetic beads.

[0008] Furthermore, the injection unit includes a first injection pump, a second injection pump and a third injection pump, and the liquid storage unit includes a first liquid storage chamber, a second liquid storage chamber and a third liquid storage chamber, the first liquid storage chamber is connected to the injection port of the microfluidic chip through a catheter, and the first injection pump is used to inject the cleaning liquid in the first liquid storage chamber into the microfluidic chip; the second liquid storage chamber is connected to the first injection port of the mixing liquid chamber through a catheter, and the second injection pump is used to inject the magnetic bead solution in the second liquid storage chamber into the mixing liquid chamber; the third liquid storage chamber is connected to the second injection port of the mixing liquid chamber through a catheter, and the third injection pump is used to inject the sample solution in the third liquid storage chamber into the mixing liquid chamber.

[0009] Furthermore, the first injection port is arranged at the top of the liquid mixing chamber, and the second injection port is arranged at the bottom of the liquid mixing chamber.

[0010] Furthermore, the filling unit is a micro peristaltic pump, and the micro peristaltic pump is connected to the discharge port of the mixing chamber and the sample injection port of the microfluidic chip through pipelines.

[0011] Furthermore, the liquid mixing chamber is also provided with a heating unit for controlling the incubation temperature of the sample and the magnetic beads.

[0012] Furthermore, quick-release connectors are provided at the catheter connection of the first liquid storage chamber, the catheter connection of the second liquid storage chamber, and the catheter connection of the third liquid storage chamber.

[0013] Furthermore, the microfluidic chip comprises a sample injection port and a cleaning liquid injection port, the first liquid storage chamber is connected to the cleaning liquid injection port via a catheter, and the mixing liquid chamber is connected to the sample injection port via a catheter.

[0014] Furthermore, the microfluidic chip also includes a control unit, the magnetic element, the enrichment area and the waste liquid area, the waste liquid area is provided with a water absorbing material, and the control unit is used to control the movement position of the droplets in the microfluidic chip and the movement position of the magnetic element.

[0015] The second aspect of the present invention provides a fully automatic sample high concentration enrichment method based on a digital microfluidic chip, using the above-mentioned fully automatic sample high concentration enrichment device to perform enrichment operations, the method comprising the following steps:

[0016] Injecting the sample solution and the magnetic bead solution into the mixing chamber through the injection unit for mixed incubation;

[0017] The incubated magnetic bead sample mixture is completely injected into the microfluidic chip in multiple times through the injection unit;

[0018] After controlling the magnetic element to move to the enrichment area, the mixed solution injected each time is driven to the enrichment area of ​​the microfluidic chip through the microfluidic chip;

[0019] After the magnetic element is controlled to move out of the enrichment area, a cleaning solution is injected into the microfluidic chip to mix with the high-density magnetic beads in the enrichment area to obtain a high-concentration magnetic bead solution.

[0020] Furthermore, it also includes:

[0021] The non-enriched solution is moved to the water absorbing material area of ​​the microfluidic chip by a control unit;

[0022] The high-concentration magnetic bead solution is moved to the recovery area or the detection area of ​​the microfluidic chip by a control unit.

[0023] The present invention temporarily stores a magnetic bead sample mixture in a mixing chamber and utilizes the continuous driving characteristics of an injection unit and a filling unit, so that the sample magnetic bead mixture solution can be injected into a digital microfluidic chip in multiple times, and the magnetic beads in the mixture injected each time are adsorbed and positioned in an enrichment area in cooperation with a magnetic element, and a magnetic bead solution carrying a high-concentration sample is obtained by injecting a cleaning solution into the microfluidic chip and mixing it with the magnetic beads, thereby improving the detection accuracy of the microfluidic chip and meeting the needs of high-sensitivity detection and analysis occasions. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. 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 creative work.

[0025] Figure 1 A schematic diagram of a fully automatic sample high concentration enrichment device based on a digital microfluidic chip according to an embodiment of the present invention;

[0026] Figure 2 The present invention is a flowchart of a fully automatic high-concentration sample enrichment method based on a digital microfluidic chip according to an embodiment of the present invention. DETAILED DESCRIPTION

[0027] In order to make the objectives, technical solutions and advantages of the present invention more clear, the embodiments of the present invention will be further described in detail below with reference to the accompanying drawings.

[0028] like Figure 1As shown, the fully automatic sample high-concentration enrichment device based on the digital microfluidic chip of the present invention comprises a liquid mixing system 1, a filling unit 2 and a microfluidic chip 3, wherein the liquid mixing system 1 comprises an injection unit, a liquid storage unit and a liquid mixing chamber 11, wherein the liquid storage unit, the liquid mixing chamber 11 and the microfluidic chip 3 are sequentially connected in series through a conduit; the injection unit is used to inject the sample solution and the magnetic bead solution in the liquid storage unit into the liquid mixing chamber 11 for mixed incubation; the injection unit can quantitatively control the volume of the sample solution and the magnetic bead solution in the liquid mixing chamber, and the liquid mixing chamber 11 can be configured with a larger volume to achieve the purpose of temporarily storing a large volume of sample solution and magnetic bead solution. After the sample solution and the magnetic bead solution in the liquid mixing chamber 11 are fully mixed for a period of time, the sample will be captured and adsorbed by the magnetic beads, and the sample magnetic bead mixed solution after incubation will be temporarily stored in the liquid mixing chamber 11. Since the volume of the mixed solution temporarily stored in the liquid mixing chamber 11 is large, if all of it is injected into the microfluidic chip 3 at one time, it will exceed the carrying and processing load of the microfluidic chip. The present invention injects the temporarily stored sample magnetic bead mixture into the microfluidic chip successively through the filling unit 2, and the microfluidic chip 3 drives the injected mixture to the enrichment area 31 of the microfluidic chip 3, and controls the magnetic element 4 to move to the enrichment area 31, so as to adsorb and position the magnetic beads in the mixture passing through the enrichment area 31 successively, and obtains a high-concentration magnetic bead solution by injecting a cleaning solution into the microfluidic chip 3 and mixing it with the magnetic beads.

[0029] The present invention connects the mixing system, the filling unit and the microfluidic chip in series in a specific manner to achieve automatic quantitative access to the sample magnetic bead mixture into the microfluidic chip. The entire experimental process does not require manual operation, which simplifies the experimental process, improves efficiency, and has a higher injection volume accuracy, ensuring the accuracy of subsequent experimental results. In addition, the magnetic bead sample mixture is temporarily stored in the mixing chamber and the continuous driving characteristics of the injection unit and the filling unit are utilized, so that the sample magnetic bead mixed solution can be successively injected into the digital microfluidic chip, and the magnetic beads in the mixed solution that passes through the enrichment zone successively are adsorbed and positioned in cooperation with the magnetic element, and a high-concentration magnetic bead solution is obtained by injecting a cleaning solution into the microfluidic chip and mixing it with the magnetic beads. In this way, fully automated high-concentration enrichment is achieved from a large volume of mixed solution to a final high-concentration small volume mixed solution, improving the detection accuracy of the microfluidic chip and meeting the needs of high-sensitivity detection and analysis.

[0030] In one embodiment of the present invention, the injection unit includes a first injection pump 5, a second injection pump 6 and a third injection pump 7, and the liquid storage unit includes a first liquid storage chamber 8, a second liquid storage chamber 9 and a third liquid storage chamber 10. The first liquid storage chamber 8 is connected to the injection port of the microfluidic chip 3 through a catheter, and the first injection pump 5 is used to inject the cleaning solution in the first liquid storage chamber 8 into the microfluidic chip 3; the second liquid storage chamber 9 is connected to the first injection port of the mixing chamber 11 through a catheter, and the second injection pump 6 is used to inject the magnetic bead solution in the second liquid storage chamber 9 into the mixing chamber 11; the third liquid storage chamber 10 is connected to the second injection port of the mixing chamber 11 through a catheter, and the third injection pump 7 is used to inject the sample solution in the third liquid storage chamber 10 into the mixing chamber 11. In this embodiment, the independently configured first injection pump, second injection pump and third injection pump can be used to individually perform quantitative control on the cleaning solution injected into the microfluidic chip and the sample solution and magnetic bead solution injected into the mixing chamber, so that the subsequent experimental operation is more flexible and meets the needs of different biochemical experiments.

[0031] In one embodiment of the present invention, the catheter connection of the first liquid storage chamber 8, the catheter connection of the second liquid storage chamber 9 and the catheter connection of the third liquid storage chamber 10 are provided with quick-release connectors, for example, Luer connectors commonly used in biochemical experiments are used. By providing quick-release connectors, different types of cleaning solutions, magnetic bead solutions and sample solutions can be easily replaced to meet the needs of different biochemical experiments.

[0032] In one embodiment of the present invention, an injection port for the magnetic bead solution is set at the top of the mixing chamber 11, and an injection port for the sample solution is set at the bottom of the mixing chamber 11 to prevent the catheter for the sample solution from contaminating the remaining magnetic bead solution and affecting the detection accuracy of subsequent experiments after replacing the sample solution.

[0033] In one embodiment of the present invention, the filling unit 2 is a micro peristaltic pump, and the micro peristaltic pump is connected to the discharge port of the mixing liquid chamber 11 and the sample injection port of the microfluidic chip 3 through pipelines. A trace amount of sample magnetic bead solution can be injected into the microfluidic chip for enrichment operation through the micro peristaltic pump. The flow rate of the micro peristaltic pump pumped into the microfluidic chip can be set as needed. It is preferred to adapt the driving flow rate of the micro peristaltic pump to the droplet driving speed and magnetic element displacement control of the microfluidic chip, and reserve a buffer time for the enrichment operation of the enrichment area of ​​the microfluidic chip, so as to ensure that the micro peristaltic pump can continuously inject a small amount of mixed liquid in the mixing liquid chamber into the microfluidic chip until all the mixed liquid is injected and the high-density magnetic beads are adsorbed and positioned in the enrichment area. It should be noted that the control method of the micro peristaltic pump is not limited to this. It can also inject trace amounts of mixed liquid into the microfluidic chip in batches and in a quantitative manner. After the droplet drive and magnetic element control operations of the microfluidic chip are completed, the micro peristaltic pump is started to perform the next mixed liquid filling operation until all the mixed liquid in the mixing chamber is injected into the chip.

[0034] In one embodiment of the present invention, a heating unit for controlling the incubation temperature of the sample and the magnetic beads is also provided on the mixing chamber 11. The temperature in the mixing chamber can be controlled at the optimal temperature for incubating the sample and the magnetic beads through the heating unit, thereby accelerating the incubation speed of the sample and the magnetic beads and improving the efficiency of the entire experiment.

[0035] In one embodiment of the present invention, the microfluidic chip 3 includes a sample injection port 32 and a cleaning solution injection port 33, the first liquid storage chamber 8 is connected to the cleaning solution injection port 33 through a conduit, and the mixing solution chamber 11 is connected to the sample injection port 32 through a conduit. The cleaning solution and the mixed solution are injected into the chip through different injection ports to avoid contamination and affect the detection results of subsequent replacement of the sample solution.

[0036] In one embodiment of the present invention, the microfluidic chip 3 further includes a control unit 34, the magnetic element 4, the enrichment area 31 and the waste liquid area, the waste liquid area is provided with a water absorbing material 35, and the control unit 34 is used to control the movement position of the droplets in the microfluidic chip 3 and the movement position of the magnetic element 4. The control unit 34 can drive and control the mixed liquid injected into the chip to move to the enrichment area, the waste liquid area or the recovery area according to experimental needs, and can control the magnetic element 4 to move to the enrichment area or move out of the enrichment area.

[0037] like Figure 2 As shown, the second aspect of the present invention provides a fully automatic sample high concentration enrichment method based on a digital microfluidic chip, using the above-mentioned fully automatic sample high concentration enrichment device to perform enrichment operations, the method comprising the following steps:

[0038] Step S210: injecting the sample solution and the magnetic bead solution into the mixing chamber through the injection unit for mixing and incubation;

[0039] Step S220: injecting the incubated magnetic bead sample mixture into the microfluidic chip completely in multiple times through the filling unit;

[0040] Step S230: After controlling the magnetic element to move to the enrichment area, the mixed solution injected each time is driven to the enrichment area of ​​the microfluidic chip through the microfluidic chip;

[0041] Step S240: After the magnetic element is controlled to move out of the enrichment area, a cleaning solution is injected into the microfluidic chip to mix with the high-density magnetic beads in the enrichment area to obtain a high-concentration magnetic bead solution.

[0042] In one embodiment of the present invention, the method further includes:

[0043] The non-enriched solution is moved to the water absorbing material area of ​​the microfluidic chip by a control unit;

[0044] The high-concentration magnetic bead solution is moved to the recovery area or the detection area of ​​the microfluidic chip by a control unit.

[0045] In order to make the objectives, technical solutions and advantages of the present invention more clear, the embodiments of the present invention are described in further detail below.

[0046] For the immunoassay process, the double antibody sandwich method is used, with magnetic beads as solid phase carriers. The capture antibody is modified onto the magnetic beads through the reaction of avidin and biotin to prepare an immune capture magnetic bead solution, and the detection antibody is modified onto the surface of the fluorescent microspheres to prepare fluorescent detection microspheres. The sample to be tested and the fluorescent detection microspheres are prepared into a sample solution. This method can complete the process of magnetic separation and cleaning of magnetic beads. The second and third injection pumps are controlled to inject 1980μL of sample solution and 20μL of magnetic bead solution into the mixing chamber respectively. The temperature of the mixing chamber is controlled at 37°C (optimal reaction temperature). The mixed solution is placed in a 37°C environment. After the sample solution and the magnetic bead solution are incubated after repeated pumping and pushing by the third injection pump for 30 minutes, the micro peristaltic pump is controlled to drive the 2mL solution in the mixing chamber to the sample injection port of the digital microfluidic chip. At the same time, the magnet of the magnetic absorption system is controlled to move to the mixing and enrichment area. The main control system drives the droplets in the chip to flow directly under the magnet. The waste liquid is absorbed by the water-absorbing material, and the magnetic beads are adsorbed to "one point" to complete the magnetic separation. Process: The main control system drives the droplets in the chip to flow through the magnetic beads enriched into a "point". After multiple cycles of movement, all the magnetic beads in the mixed liquid in the mixed liquid chamber are adsorbed and positioned on the magnet. The magnetic suction system is controlled to move the magnet away from the enrichment area on the chip surface. The first injection pump is controlled to inject 20μL of cleaning solution into the chip cleaning solution injection port to mix the magnetic beads with the cleaning solution. The waste liquid flows into the water-absorbing material. After 2-3 adsorption-cleaning operations, a high-concentration magnetic bead sample mixed solution is obtained. In this way, fully automated high-concentration enrichment is achieved from a large volume of mixed solution to a final high-concentration small volume mixed solution. Similar methods can be used to efficiently purify nucleic acids.

[0047] In summary, the present invention temporarily stores the magnetic bead sample mixture in a mixing chamber and utilizes the continuous driving characteristics of the injection unit and the filling unit, so that the sample magnetic bead mixture solution can be injected into the digital microfluidic chip in multiple times, and the magnetic beads in the mixture injected each time are adsorbed and positioned in the enrichment area with the help of magnetic elements, and a magnetic bead solution carrying a high-concentration sample is obtained by injecting a cleaning solution into the microfluidic chip to mix with the magnetic beads, thereby improving the detection accuracy of the microfluidic chip and meeting the needs of high-sensitivity detection and analysis.

[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 principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A fully automatic sample high concentration enrichment device based on a digital microfluidic chip, characterized in that: The invention comprises a liquid mixing system, a filling unit and a microfluidic chip, wherein the liquid mixing system comprises an injection unit, a liquid storage unit and a liquid mixing chamber, wherein the liquid storage unit, the liquid mixing chamber and the microfluidic chip are connected in series in sequence through a catheter; the injection unit is used to inject the sample solution and the magnetic bead solution in the liquid storage unit into the liquid mixing chamber for mixed incubation; the filling unit is used to inject the incubated magnetic bead sample mixed solution into the microfluidic chip; wherein the sample magnetic bead mixed solution is temporarily stored in the liquid mixing chamber, and the temporarily stored sample magnetic bead mixed solution is successively injected into the microfluidic chip through the filling unit, the microfluidic chip drives the injected mixed solution to the enrichment area of ​​the microfluidic chip, controls the magnetic element to move to the enrichment area, adsorbs and positions the magnetic beads in the mixed solution in the enrichment area, and injects a cleaning solution into the microfluidic chip to mix with the magnetic beads to obtain a high-concentration magnetic bead solution.

2. The fully automatic sample high concentration enrichment device according to claim 1, characterized in that: The injection unit includes a first injection pump, a second injection pump and a third injection pump, the liquid storage unit includes a first liquid storage chamber, a second liquid storage chamber and a third liquid storage chamber, the first liquid storage chamber is connected to the injection port of the microfluidic chip through a catheter, and the first injection pump is used to inject the cleaning liquid in the first liquid storage chamber into the microfluidic chip; The second liquid storage chamber is connected to the first injection port of the mixing liquid chamber through a catheter, and the second injection pump is used to inject the magnetic bead solution in the second liquid storage chamber into the mixing liquid chamber; The third liquid storage chamber is connected to the second injection port of the liquid mixing chamber through a catheter, and the third injection pump is used to inject the sample solution in the third liquid storage chamber into the liquid mixing chamber.

3. The fully automatic sample high concentration enrichment device as claimed in claim 2, characterized in that: The first injection port is disposed at the top of the liquid mixing chamber, and the second injection port is disposed at the bottom of the liquid mixing chamber.

4. The fully automatic sample high concentration enrichment device as claimed in claim 2, characterized in that: The filling unit is a micro peristaltic pump, and the micro peristaltic pump is connected to the discharge port of the mixing chamber and the sample injection port of the microfluidic chip through pipelines.

5. The fully automatic sample high concentration enrichment device according to claim 1, characterized in that: The mixing chamber is also provided with a heating unit for controlling the incubation temperature of the sample and the magnetic beads.

6. The fully automatic sample high concentration enrichment device as claimed in claim 2, characterized in that: The catheter connection of the first liquid storage chamber, the catheter connection of the second liquid storage chamber, and the catheter connection of the third liquid storage chamber are provided with quick-release connectors.

7. The fully automatic sample high concentration enrichment device as claimed in claim 2, characterized in that: The microfluidic chip comprises a sample injection port and a cleaning liquid injection port, the first liquid storage chamber is connected to the cleaning liquid injection port through a catheter, and the mixing liquid chamber is connected to the sample injection port through a catheter.

8. The fully automatic sample high concentration enrichment device according to claim 7, characterized in that: The microfluidic chip also includes a control unit, the magnetic element, the enrichment area and the waste liquid area. The waste liquid area is provided with a water absorbing material. The control unit is used to control the moving position of the droplets in the microfluidic chip and the moving position of the magnetic element.

9. A fully automatic sample high concentration enrichment method based on a digital microfluidic chip, characterized in that: The fully automatic sample high concentration enrichment device according to any one of claims 1 to 8 is used to perform an enrichment operation, the method comprising the following steps: Injecting the sample solution and the magnetic bead solution into the mixing chamber through the injection unit for mixed incubation; The incubated magnetic bead sample mixture is completely injected into the microfluidic chip in multiple times through the injection unit; After controlling the magnetic element to move to the enrichment area, the mixed solution injected each time is driven to the enrichment area of ​​the microfluidic chip through the microfluidic chip; After the magnetic element is controlled to move out of the enrichment area, a cleaning solution is injected into the microfluidic chip to mix with the high-density magnetic beads in the enrichment area to obtain a high-concentration magnetic bead solution.

10. The fully automatic sample high concentration enrichment method according to claim 9, characterized in that: Also includes: The non-enriched solution is moved to the water absorbing material area of ​​the microfluidic chip by a control unit; The high-concentration magnetic bead solution is moved to the recovery area or the detection area of ​​the microfluidic chip by a control unit.

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