Magnetic bead blending device for magnetic control droplet microfluidic system

Abstract

The invention discloses a magnetic bead mixing device for a magnetic control droplet microfluidic system, and relates to the technical field of microfluidics. The device comprises a magnetic control unit and a mechanical motion unit, the magnetic control unit comprises a magnet and a control mechanism which are arranged outside the system, and the mechanical motion unit comprises a mechanism for driving the chip bearing platform to vibrate. The two units work cooperatively, and efficient and uniform mixing of the magnetic beads in a closed cavity of the chip is achieved through the combined action of a magnetic field and mechanical vibration. The magnetic control unit controls magnetic field change, and the mechanical unit preset frequency drives vibration. Through a nonlinear synergistic mechanism, the problem of low uniform mixing efficiency in a laminar environment in a droplet microfluidic system is solved, and the device is simple in structure, easy to integrate and suitable for immunodetection, nucleic acid detection and other scenes needing magnetic bead uniform mixing, and the detection accuracy and the system reliability are improved.

Description

Technical Field

[0001] This invention relates to the field of microfluidics, and more specifically to a magnetic bead mixing device for a magnetically controlled droplet microfluidic system. Background Technology

[0002] Microfluidics is a technology that enables precise manipulation and analysis of minute fluids (such as nanoliter to microliter droplets) within a microchip. It offers advantages such as high portability, strong parallel processing capabilities, and low reagent consumption, making it a crucial platform for integrated and miniaturized biochemical analysis. Droplet-based microfluidics further enhances scalability, programmability, and operational efficiency by independently controlling discrete droplets. Magnetically controlled droplet microfluidics, as a branch of this technology, utilizes an external magnetic field to non-contactly control the collection and transfer of magnetic beads between droplets. For example, in immunoassay, magnetic beads coated with antibodies bind to target antigens to form complexes, and detection is completed through transfer and reaction between different chambers, offering high flexibility and simplicity. The magnetic bead mixing module is a key component of such systems; effective mixing ensures uniform dispersion of the magnetic beads within the droplets, thereby improving detection accuracy.

[0003] However, in the closed chamber of a microfluidic system, due to the low Reynolds number (typically Re < 1), the fluid flow is laminar, and the diffusion process is slow. Without external driving, there is almost no flow inside the droplets, and the magnetic beads tend to remain aggregated, leading to insufficient mixing. Existing mixing methods are divided into passive and active categories: passive mixing relies on the channel geometry to induce mixing, but it is complex to design, inefficient, and unsuitable for closed, discrete droplet microfluidic systems; active mixing utilizes external sources, such as mechanical vibration, acoustic waves, bubble stirring, or magnetic force. Mechanical vibration, if too slow, cannot effectively disperse the magnetic beads within the closed chamber, while high-speed vibration may cause overheating and mechanical wear, affecting instrument lifespan. Acoustic mixing may cause droplet compression, leading to reagent crosstalk and interfering with detection results; bubble stirring requires an additional syringe pump, making the system complex, and the unstable bubble size can affect detection signals (such as photon counting). Magnetic mixing drives the magnetic beads to mix through changes in an external magnetic field, is low-cost, and easy to control, and therefore has attracted widespread attention. However, complex magnet arrays occupy a large space and are difficult to integrate, while simple magnet movements (single-axis movements or combined movements) and the switching on and off of electromagnets cannot achieve uniform dispersion of magnetic beads, resulting in insufficient reaction or incomplete cleaning, ultimately reducing detection sensitivity and accuracy.

[0004] Therefore, the existing technology lacks a simple, efficient and easy-to-integrate magnetic bead mixing device. The existing publicly available technologies cannot achieve rapid and sufficient magnetic bead mixing in a size-limited and pre-sealed droplet microfluidic environment. Summary of the Invention

[0005] The purpose of this invention is to provide a magnetic bead mixing device for a magnetically controlled droplet microfluidic system, which overcomes the shortcomings of the prior art. Through the synergistic effect of the magnetic control unit and the mechanical motion unit, combined with the dynamic changes of the magnetic field and the internal flow of the droplet, the device achieves efficient dispersion of magnetic beads. It has the characteristics of simple structure, high efficiency and easy integration, and can achieve rapid and thorough magnetic bead mixing in a closed microfluidic chamber environment.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A magnetic bead mixing device for a magnetron-controlled droplet microfluidic system, the system comprising a chip and a chip carrier platform for carrying the chip, the device being used to perform a magnetic bead mixing operation on the chip, comprising: The magnetic control unit includes a magnet disposed outside the system and a magnet control mechanism for controlling the change of magnetic field, used to apply a magnetic field to the magnetic beads in the droplets during the mixing process; The mechanical motion unit includes a drive mechanism for driving the chip carrier platform to generate mechanical vibrations; The magnetic control unit and the mechanical motion unit are configured to work together to achieve the mixing of magnetic beads in the closed cavity of the chip through the combined effect of the magnetic field change and mechanical vibration.

[0007] Furthermore, the magnet control mechanism is configured to control the distance between the lower surface of the magnet and the upper surface of the chip to be 1-20 mm.

[0008] Furthermore, the driving mechanism is a motor, configured to drive the chip carrier platform to generate reciprocating vibration at a frequency of 5-30Hz, the reciprocating vibration including linear vibration, oscillation, eccentric vibration or micro-amplitude periodic motion.

[0009] Furthermore, the mechanical motion unit also includes a traction mechanism connecting the drive mechanism and the chip carrier platform, the traction mechanism including a traction crossbar, a transmission shaft and a connecting frame.

[0010] Furthermore, the magnet is a ring magnet, a monolithic magnet, a spliced ​​magnet, or an electromagnet.

[0011] Furthermore, the magnet control mechanism is configured to control the magnet to remain fixed or move along a preset single axis of motion during the mixing process.

[0012] Furthermore, the magnet control mechanism is configured to generate a magnetic field during the mixing process and to release the magnetic field before and after mixing.

[0013] Another object of the present invention is to provide the use of the magnetic bead mixing device for a magnetically controlled droplet microfluidic system in the detection of immunoreactions involving magnetic beads.

[0014] Another object of the present invention is to provide the use of the magnetic bead mixing device for a magnetically controlled droplet microfluidic system in the detection of nucleic acid reactions involving magnetic beads.

[0015] Another object of the present invention is to provide the use of the magnetic bead mixing device for a magnetically controlled droplet microfluidic system in a droplet microfluidic system that requires magnetic bead mixing or cleaning.

[0016] The magnetic bead mixing device for a magnetron-controlled droplet microfluidic system provided by this invention has the following significant advantages compared with the prior art: 1. Significantly Improved Mixing Efficiency. Traditional mixing methods struggle to break the aggregation of magnetic beads in a microfluidic laminar flow environment. This invention, however, combines dynamic changes in the magnetic field with chip mechanical vibration to create a non-steady magnetic field and fluid coupling in time and space, promoting rapid and uniform dispersion of the magnetic beads. Experimental verification shows that using the device of this invention significantly improves the uniformity of magnetic bead dispersion within the droplet, with its grayscale distribution variation coefficient being far lower than that of single magnetic or vibration mixing methods. This demonstrates that the synergistic effect effectively overcomes laminar flow limitations, improving mixing speed and uniformity.

[0017] 2. Enhanced Detection Accuracy and Reliability. In biochemical detection applications (such as chemiluminescence immunoassay), insufficient mixing of magnetic beads can easily lead to unbound reagent residues, affecting detection results. The device of this invention ensures thorough cleaning through efficient mixing. For example, in negative sample testing, after multiple rounds of cleaning, the luminescence signal value is stable and close to the background noise level. Different detection systems show good consistency, effectively avoiding the risk of false positives and significantly improving the accuracy and repeatability of detection data.

[0018] 3. Simplified system structure and convenient integration. This invention uses an external magnet and a standard motor drive, eliminating the need for complex magnet arrays or additional fluid control equipment, thus reducing system complexity and manufacturing costs. The overall structure of the device is compact and easily modularized for integration into existing microfluidic platforms, while avoiding overheating or mechanical wear caused by high-speed vibration, extending the instrument's lifespan.

[0019] 4. Wide operability and applicability. By adjusting parameters such as the distance between the magnet and the chip surface and the vibration frequency, this invention can be adapted to microfluidic chips of different sizes and various types of magnetic beads, exhibiting high flexibility and adjustability. This method is not only applicable to immunoassay and nucleic acid detection, but can also be extended to other droplet microfluidic scenarios requiring magnetic bead mixing or cleaning, demonstrating significant potential for widespread application.

[0020] In summary, this invention achieves efficient magnetic bead mixing with a simple structure, improving detection performance while maintaining system stability and economy, and providing reliable support for the development of magnetron-controlled droplet microfluidics. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of the device structure of the present invention; Figure 2 These are schematic diagrams of magnetic force distribution corresponding to different magnet structures in embodiments of the present invention, wherein (a) is a schematic diagram of the distribution of the magnitude of the magnetic force on the magnetic beads within the droplet under the action of the annular magnet, (b) is a schematic diagram of the distribution of the direction of the magnetic force on the magnetic beads within the droplet under the action of the annular magnet, (c) is a schematic diagram of the distribution of the magnitude of the magnetic force on the magnetic beads within the droplet under the action of the integral magnet, (d) is a schematic diagram of the distribution of the direction of the magnetic force on the magnetic beads within the droplet under the action of the integral magnet, (e) is a schematic diagram of the distribution of the magnitude of the magnetic force on the magnetic beads within the droplet under the action of the spliced ​​magnet, and (f) is a schematic diagram of the distribution of the direction of the magnetic force on the magnetic beads within the droplet under the action of the spliced ​​magnet. Figure 3 These are top views of droplets before and after mixing using different mixing methods in embodiments of the present invention, wherein (a) is an image before mixing, (b) is an image after mixing using the device of the present invention, (c) is an image after mixing by magnetic force only, and (d) is an image after mixing by vibration only. Figure 4 This is a schematic diagram showing the luminescence values ​​of the substrate and negative samples of cardiac troponin I (cTnI) and myoglobin (Myo) as measured in an embodiment of the present invention. In the picture: 1-Chip carrier platform, 2-Chip, 3-Magnet, 4-Traction crossbar, 5-Drive shaft, 6-Connecting frame. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.

[0023] This embodiment provides a magnetic bead mixing device for a magnetically controlled droplet microfluidic system. The system includes a chip 2 and a chip carrier platform 1 that carries the chip 2. The device is used to perform magnetic bead mixing operations on the chip 2.

[0024] The magneto-controlled droplet microfluidic system is an advanced biochemical analysis platform that uses a magnetic field to manipulate the transfer and reaction of magnetic beads between droplets in different reaction chambers, achieving automated detection. The magnetic beads simultaneously serve as a transfer, specific binding, and mixing medium for the reaction system. The system mainly includes components such as a microfluidic chip, a mechanical control module, a temperature control module, and an optical detection module, forming a complete analytical system. The magnetic bead mixing device of this invention, as a key functional module of the system, achieves seamless integration through an innovative modular design.

[0025] like Figure 1 As shown, the device of this invention comprises two core components: a magnetic control unit and a mechanical motion unit. The magnetic control unit includes a magnet 3 disposed externally to the system and a magnet control mechanism for controlling changes in the magnetic field, used to apply a magnetic field to the magnetic beads in the droplets during the mixing process. The mechanical motion unit includes a drive mechanism for driving the chip-supporting platform 1 to generate mechanical vibrations. The magnetic control unit and the mechanical motion unit are configured to work collaboratively, achieving mixing of the magnetic beads within the enclosed cavity of the chip 2 through the combined effects of magnetic field changes and mechanical vibrations.

[0026] In terms of integrated design, the device connects to the main system via a standardized interface, and magnet 3 is placed in an adjustable position outside the system, maintaining the system's compactness while significantly improving detection performance through a collaborative mixing mechanism. This integrated design fully considers multiple requirements such as system compatibility, ease of operation, and long-term stability.

[0027] The magnetocontrol unit uses a magnet 3 to apply a magnetic field to the magnetic beads in the droplet. In a preferred embodiment, the magnet 3 is a toroidal magnet (outer diameter 15mm, inner diameter 6mm, thickness 5mm). This size has been verified through magnetic field simulation and experiments, ensuring magnetic field strength while avoiding edge effects. The magnet material is preferably neodymium iron boron (N52 grade), with a remanent magnetic induction of 1.4T, exhibiting good temperature stability and long-term magnetic retention. The magnet control mechanism uses a precision stepper motor, driven by a ball screw, achieving a positioning accuracy of ±0.1mm. It can precisely control the distance between the lower surface of the magnet 3 and the upper surface of the chip 2 from 1-50mm, with 1-20mm being the optimized range. Figure 2A schematic diagram of the magnetic force distribution corresponding to different magnet structures in embodiments of the present invention is shown (total magnetic beads are 1 μg). The arrows are used only to indicate the direction of the magnetic force and do not represent the magnitude of the magnetic force. The working distance between the magnet 3 and the chip 2 can be adjusted according to the magnet structure used. When using the above-mentioned ring magnet, 12 mm is the optimal working point; when using a monolithic magnet, 6 mm is the optimal working point; and when using a spliced ​​magnet, 3-4 mm is the optimal working point. The magnet control mechanism is configured to control the magnet 3 to remain fixed or move along a preset single motion axis during the mixing process. When the magnetic beads are transferred to a new chamber, the magnet control mechanism drives the magnet 3 to move to the optimal working distance directly above the surface of the chamber to perform the mixing operation.

[0028] Different magnet structures produce different magnetic field distributions, thus affecting the mixing effect. For example... Figure 2 (a) and Figure 2 As shown in (b), the ring magnet generates a relatively uniform magnetic force distribution within the droplet: in the lower region of the droplet, the magnetic force is predominantly vertical, while in the upper region, the magnetic force exhibits multiple oblique directions, meaning the horizontal and vertical force components are similar. Therefore, magnetic beads at different locations are more likely to detach from their aggregated state and disperse in different directions. Figure 2 (c)- Figure 2 (f) shows that the spliced ​​magnet and the integral magnet exhibit significant differences in magnetic force distribution within the droplet range. The magnetic force is generally directed vertically, with a relatively weak horizontal component, making it easier for the aggregated magnetic beads to move vertically and difficult to disperse completely. Based on these differences, a ring magnet, as a preferred magnet structure, is more conducive to achieving excellent magnetic bead dispersion. Both spliced ​​and integral magnets can achieve the magnetic bead mixing function in the device described in this invention. Furthermore, magnet 3 also includes an electromagnet implementation. This electromagnet comprises an iron core and an excitation coil, and is controlled by a programmable current source to generate an adjustable magnetic field of 0.1-2.0T. Compared to permanent magnets, the electromagnet solution has the advantage of precisely adjustable magnetic field parameters.

[0029] The key to the magnet control mechanism lies in the precise start and stop control of the magnetic field. It is configured to generate a magnetic field during the mixing process and to release the magnetic field before and after mixing. In the magnetic bead mixing operation, the magnetic field effect is strictly limited to the mixing stage: before mixing, magnet 3 is in a non-working state (e.g., the electromagnet current is 0 or the distance between permanent magnets is ≥80mm) to ensure that the initial state of the magnetic beads is not disturbed; within 0.5 seconds after mixing starts, the magnetic field is rapidly established to the working intensity and works in conjunction with mechanical vibration; within 1 second after mixing ends, the magnetic field is completely released (residual magnetic field <1mT), creating an interference-free environment for subsequent transfer and testing operations.

[0030] The core of the mechanical motion unit is the drive mechanism, which uses a motor (such as a servo motor) with a rated power of 3W and a rated torque of 30g·cm. Precise speed and position control is achieved through a PID controller. The motor is configured to drive the chip-supporting platform 1 to generate reciprocating vibrations at a frequency of 5-30Hz (preferably 14Hz). These reciprocating vibrations include linear vibrations, oscillations, eccentric vibrations, or micro-amplitude periodic movements. The vibration parameters are optimized using a frequency response function to ensure operation near the resonant frequency for maximum energy transfer efficiency. The traction mechanism includes a traction crossbar 4, a drive shaft 5, and a connecting frame 6. The traction crossbar 4 is made of nylon, while the drive shaft 5 and the connecting frame 6 are made of aluminum alloy.

[0031] The key to this invention lies in the discovery of a nonlinear synergistic effect between magnetic control and mechanical vibration. This synergy is not a simple superposition, but is achieved through a unique spatiotemporal coupling mechanism, specifically manifested as follows: When magnet 3 remains in a fixed position, the synergistic effect is achieved through the following mechanism: the stationary magnet 3 forms a stable magnetic field distribution in space, generating a magnetic field gradient. The magnetic force experienced by the magnetic bead in this gradient field is along the direction of the magnetic field intensity gradient, and its magnitude is related to the magnetic properties, volume, and magnetic field gradient of the magnetic bead. Simultaneously, mechanical vibration induces fluid motion inside the droplet, generating a dynamic velocity field. Due to the reciprocating vibration of chip 2 driven by the homogenizing module (i.e., the mechanical motion unit and chip carrier platform 1), the relative position of the magnetic bead inside the droplet and the fixed magnet 3 continuously changes, causing the magnitude and direction of the magnetic force experienced by the magnetic bead to continuously change, thereby helping to break up aggregation and promote dispersion. This fluid motion interacts with the changing magnetic field, generating additional magnetic migration force. The combination of "dynamic magnetic field constraint and dynamic fluid disturbance" produces a directional diffusion effect in a low Reynolds number laminar flow environment, with a diffusion efficiency significantly higher than that of pure Brownian motion.

[0032] The synergistic effect is further enhanced when magnet 3 moves in a single direction. An optimal matching relationship exists between the magnet's velocity and the mechanical vibration frequency; when the velocity and frequency reach a specific ratio, the system enters a resonant state, producing the best synergistic effect. This multi-scale coupling causes the magnetic bead's trajectory to exhibit chaotic characteristics, making the system sensitive to initial conditions and further improving mixing efficiency.

[0033] The following details the specific workflow of the magnetic bead mixing device, and verifies the mixing effect through microscopic observation and quantitative analysis.

[0034] (1) Work process After the magnetic bead is transferred to the new chamber, the device operates according to optimized parameters: the ring magnet 3 is controlled to move to a position 12mm directly above the upper surface of the chip 2; the mixing motor rotates at a speed of 14 revolutions per second, driving the chip 2 to vibrate repeatedly through the traction bar 4; the magnetic bead is driven to move in all directions through the dynamic changes in the relative position of the magnetic field and the microflow inside the droplet; after mixing for 20 seconds, the magnetic bead is rapidly and uniformly dispersed inside the droplet; after mixing is completed, the magnet 3 is quickly removed to avoid affecting the subsequent operation of the magnetic bead.

[0035] (2) Verification of mixing effect The mixing process was observed and recorded using a microscope. Figure 3 These are top views of the droplets before and after mixing using different mixing methods. Among them, (a) is the image before mixing, (b) is the image after mixing using the device described in this invention, (c) is the image after mixing by magnetic force only, and (d) is the image after mixing by vibration only. Figure 3 (a) The magnetic beads are shown to be clustered in short lines before mixing. After mixing for 20 seconds using the device described in this invention, as shown... Figure 3 As shown in (b), the magnetic beads are uniformly dispersed throughout the droplet. Quantitative analysis shows that the average gray value of the 30 sampling points is 162.52, with a coefficient of variation of only 2.96%, proving that the dispersion is good.

[0036] (3) Verification of the necessity of collaboration Comparative experiments fully demonstrate the necessity of synergistic effects: magnetic mixing alone ( Figure 3 (c) Makes the magnetic beads spherically dispersed but not uniformly distributed; only vibration mixing ( Figure 3 (d) It has almost no dispersing effect on the aggregated magnetic beads. This indicates that neither magnetic force nor vibration alone can achieve effective mixing, while the present invention produces a significant enhancing effect through synergistic action.

[0037] This embodiment provides the application of a magnetic bead mixing device for a magnetically controlled droplet microfluidic system in the detection of immunoassays involving magnetic beads. During chemiluminescent immunoassay, antibodies coated with magnetic beads capture the analyte antigen in the sample through antigen-antibody specific binding, forming a magnetic immune complex. After a washing step removes unbound free enzyme-labeled antibodies and impurities from the sample, the complex reacts with the substrate in a chemiluminescent reaction. The content of the analyte antigen in the sample is calculated based on the luminescence signal value. It is worth noting that after antigen-antibody binding, some unbound enzyme-labeled antibodies may be encapsulated by the magnetic bead clusters and carried into subsequent droplets. Incomplete washing will cause the detection results to deviate from the true value, or even produce false positives, seriously affecting the accuracy of the detection. Therefore, the performance of the mixing device needs to be evaluated through washing effect verification.

[0038] (1) Experimental design and reagent preparation First, paraffin oil was injected into all the chip chambers. The following reagent groups were then added to the reaction chambers respectively: cTnI (cardiac troponin I) detection group: 20 μL ALP (alkaline phosphatase) labeled cTnI antibody + 20 μL magnetic bead coated cTnI antibody + 24 μL negative sample (buffer); Myoglobin (myoglobin) detection group: 10μL ALP-labeled Myo antibody + 10μL magnetic bead-coated Myo antibody + 20μL negative sample.

[0039] Three cleaning chambers were set up, each containing 100 μL of cleaning solution; the optical detection chamber contained 40 μL of chemiluminescent substrate APS-5. All reagents and paraffin oil were used to fill the chip chamber system. Negative samples were used in the experiment to replace the real antigen to avoid interference from specific antigen-antibody binding on the evaluation of the cleaning effect.

[0040] (2) Cleaning process and mixing operation Using the mixing method described in this embodiment, after mixing in the reaction chamber for 20 seconds, the magnet 3 was quickly removed to avoid interference with subsequent steps. Then, the mixture was incubated at 37°C for 5 minutes to promote full contact between the reagent and the magnetic beads.

[0041] Magnetic beads were extracted from the reaction droplets using a magnetically controlled process and sequentially transferred to three washing chambers for three rounds of washing. Each washing round involved repeating the mixing method described in the previous example, mixing for 20 seconds to prevent the magnetic beads from carrying unbound enzyme-labeled antibodies.

[0042] The magnetic beads were transferred to the detection chamber containing the chemiluminescent substrate and mixed again for 20 seconds as described in the previous example to ensure sufficient reaction between the beads and the substrate. The chemiluminescence signal was acquired using a photomultiplier tube. By comparing the sample luminescence value with the substrate background signal, the impact of residual free enzyme-labeled antibody after washing on the detection results was evaluated. All experiments were repeated three times.

[0043] (3) Experimental results and analysis Experimental results are as follows Figure 4 As shown, the luminescence values ​​of the substrate and cTnI and Myo negative samples after reaction are displayed, with the error bars representing the standard deviation of three replicate experiments. After three rounds of cleaning, the luminescence values ​​of the negative samples remained stable, with small differences between the replicate groups, and all were close to the background noise level. This indicates that the device described in this invention can achieve effective cleaning in different detection systems, effectively avoiding false positive signals and ensuring the accuracy of chemiluminescent immunoassay results.

[0044] This embodiment provides the application of the magnetic bead mixing device for a magnetically controlled droplet microfluidic system in the detection of nucleic acid reactions involving magnetic beads. This device is suitable for nucleic acid extraction, purification, and detection processes. In DNA / RNA extraction, the device promotes the binding of magnetic beads to nucleic acids through synergistic mixing, improving extraction efficiency; in PCR pretreatment, it achieves uniform mixing of the reaction system, enhancing amplification efficiency.

[0045] This embodiment provides the application of the magnetic bead mixing device for magnetron sputtering microfluidic systems in microfluidic systems requiring magnetic bead mixing or cleaning. This device is suitable for any microfluidic system scenario requiring magnetic bead mixing or cleaning, including: immunoassay (such as chemiluminescence immunoassay), protein analysis, drug screening, etc. Through standardized mixing operations, this device ensures mixing effectiveness in different applications and has good platform adaptability.

[0046] In summary, this invention achieves efficient and stable mixing of magnetic beads within the closed chamber of a microfluidic chip in a short time through the synergistic effect of the magnetic control unit and the mechanical motion unit. The device is simple in structure, easy to operate, and readily integrated. While reducing system costs and mechanical losses, it improves the performance and reliability of biochemical detection systems, providing a practical technical solution for the modular design of magnetically controlled droplet microfluidic instruments.

[0047] Embodiments of the present invention may be provided as methods, systems, or computer program products. Therefore, the present invention may take the form of a completely hardware embodiment, a completely software embodiment, or an embodiment combining software and hardware aspects. Furthermore, the present invention may take the form of a computer program product embodied on one or more computer-usable storage media (including, but not limited to, disk storage, CD-ROM, optical storage, etc.) containing computer-usable program code.

[0048] This invention is described with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, special-purpose computer, embedded processor, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, generate instructions for implementing the flowchart illustrations and / or block diagrams. Figure 1 One or more processes and / or boxes Figure 1 A device that provides the functions specified in one or more boxes.

[0049] These computer program instructions may also be stored in a computer-readable storage medium that can direct a computer or other programmable data processing device to function in a particular manner, such that the instructions stored in the computer-readable storage medium produce an article of manufacture including instruction means, which are implemented in a process Figure 1 One or more processes and / or boxes Figure 1 The function specified in one or more boxes.

[0050] These computer program instructions may also be loaded onto a computer or other programmable data processing equipment to cause a series of operational steps to be performed on the computer or other programmable equipment to produce a computer-implemented process, thereby providing instructions that execute on the computer or other programmable equipment for implementing the process. Figure 1 One or more processes and / or boxes Figure 1 The steps of the function specified in one or more boxes.

[0051] Contents not described in detail in this specification are prior art known to those skilled in the art. It is hereby indicated that the above description is intended to help those skilled in the art understand this invention, but does not limit the scope of protection of this invention. Any equivalent substitutions, modifications, improvements, or simplifications of the above descriptions that do not depart from the essential content of this invention fall within the scope of protection of this invention.

Claims

1. A magnetic bead mixing device for a magnetically controlled droplet microfluidic system, the system comprising a chip (2) and a chip carrier platform (1) supporting the chip (2), the device being used to perform magnetic bead mixing operations on the chip (2), characterized in that, include: The magnetic control unit includes a magnet (3) disposed outside the system and a magnet control mechanism for controlling the change of magnetic field, used to apply a magnetic field to the magnetic beads in the droplets during the mixing process; The mechanical motion unit includes a drive mechanism for driving the chip carrier platform (1) to generate mechanical vibration; The magnetic control unit and the mechanical motion unit are configured to work together to achieve the mixing of magnetic beads in the closed cavity of the chip (2) through the combined effect of the magnetic field change and mechanical vibration.

2. The magnetic bead mixing device for a magnetically controlled droplet microfluidic system according to claim 1, characterized in that, The magnet control mechanism is configured to control the distance between the lower surface of the magnet (3) and the upper surface of the chip (2) to be 1-20 mm.

3. The magnetic bead mixing device for a magnetron-controlled droplet microfluidic system according to claim 1, characterized in that, The driving mechanism is a motor, which is configured to drive the chip carrier platform (1) to generate reciprocating vibration at a frequency of 5-30Hz. The reciprocating vibration includes linear vibration, oscillation, eccentric vibration or micro-amplitude periodic motion.

4. The magnetic bead mixing device for a magnetron-controlled droplet microfluidic system according to claim 1, characterized in that, The mechanical motion unit also includes a traction mechanism that connects the drive mechanism and the chip carrier platform (1). The traction mechanism includes a traction crossbar (4), a transmission shaft (5), and a connecting frame (6).

5. The magnetic bead mixing device for a magnetically controlled droplet microfluidic system according to claim 1, characterized in that, The magnet (3) is a ring magnet, a monolithic magnet, a spliced ​​magnet, or an electromagnet.

6. The magnetic bead mixing device for a magnetically controlled droplet microfluidic system according to claim 1, characterized in that, The magnet control mechanism is configured to control the magnet (3) to remain fixed or move along a preset single axis of motion during the mixing process.

7. The magnetic bead mixing device for a magnetically controlled droplet microfluidic system according to claim 1, characterized in that, The magnet control mechanism is configured to generate a magnetic field during the mixing process and to release the magnetic field before and after mixing.

8. The use of the magnetic bead mixing device for a magnetically controlled droplet microfluidic system according to any one of claims 1-7 in the detection of immunoreactions involving magnetic beads.

9. The use of the magnetic bead mixing device for a magnetically controlled droplet microfluidic system according to any one of claims 1-7 in the detection of nucleic acid reactions involving magnetic beads.

10. The use of the magnetic bead mixing device for a magnetically controlled droplet microfluidic system according to any one of claims 1-7 in a droplet microfluidic system requiring magnetic bead mixing or cleaning.

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