Magnetic digital microfluidic system and microfluidic method

Abstract

The application discloses a kind of magnetic digital microfluidic system and microfluidic method, the system includes droplet control unit, magnetic core coil array on-off unit, logic control unit and signal detection unit, the droplet control unit includes microfluidic platform and magnetic core coil array, the magnetic core coil array is arranged below microfluidic platform, magnetic core coil array is connected with magnetic core coil array on-off unit, the logic control unit is connected with magnetic core coil array on-off unit, signal detection unit respectively.The application utilizes magnetic core coil array, can directly drive magnetic droplet and non-magnetic droplet in microfluidic platform, and realizes a series of operations such as control, transport, merge, distribution, heating and detection to droplet, can solve the problem that existing magnetic digital microfluidic system can only be limited to drive magnetic droplet, and biological compatibility is poor.

Description

Technical Field

[0001] This invention relates to a microfluidic system, and more particularly to a magnetic digital microfluidic system and microfluidic method, belonging to the field of magnetic digital microfluidic technology. Background Technology

[0002] Digital microfluidic (DMF) chip technology has been favored by many researchers due to its advantages such as strong configurability, ability to process multiple droplets simultaneously and low reagent consumption rate. At the same time, this technology has been widely used in fields such as analytical chemistry, clinical diagnosis, DNA sequencing and environmental monitoring [1].

[0003] Meanwhile, traditional continuous flow microfluidic systems have demonstrated high throughput and powerful fluid handling capabilities [2-4]. However, the operations of defining fluid paths and geometric constraints in microfluidic systems severely limit their adaptability and automation, and the same limitations are imposed on microfluidic systems in large-scale settings.

[0004] To address these limitations, digital microfluidic actuation technology has emerged. Compared to traditional microfluidic chips that require the fabrication of microchannels, digital microfluidic chips have a simpler structure, do not require the fabrication of microchannels and microfluidic power sources, are less prone to sample blockage, contamination, and dead zones, and are easier to integrate on a large scale. The foundation of digital microfluidic chips is digital droplet actuation technology. Droplet actuation technology based on the dielectric wetting effect (EWOD) has become the mainstream technology for driving droplets on chips due to its advantages such as good integration, convenient operation, and less risk of electrode contamination. It can transmit discrete droplets on open surfaces in a programmable manner [5-7]. However, this technology is also limited by the surface charge of the droplets and the fabrication cost of the electrodes (usually disposable). Furthermore, it requires the pre-design of the electrode distribution path, and the droplets can only move along the inherent path of the electrodes. These disadvantages may limit its lifespan and compatibility with other peripheral components, thus affecting its application diversity [8-9].

[0005] Magnetic digital microfluidics refers to digital microfluidics that uses magnetic force to drive and control droplets. Compared to other digital microfluidic platforms, the magnetic droplets used in magnetic digital microfluidics have multiple functions. In addition to serving as driving actuators, they also provide functional solid matrices for molecular targeted binding, thus finding wide application in molecular diagnostics and immunodiagnostics.

[0006] The fundamental principle of magnetic digital microfluidics is the interaction between a magnetic field and a magnetic response structure. Magnetic fields can be broadly classified into permanent magnetic fields and electromagnetic fields. Permanent magnetic fields are widely used in power-free environments, suitable for long-term outdoor biochemical analysis, and possess high magnetic strength and a stronger magnetic force. However, permanent magnets typically require mechanical systems for movement, leading to complex and bulky systems. Electromagnetic fields, on the other hand, are much more flexible than permanent magnetic fields. This is because electromagnets occupy less space, are more flexible in form (e.g., printed circuit copper coils and electromagnetic columns), and the required magnetic field can be flexibly adjusted using current. Their disadvantage is a weaker magnetic field strength, resulting in insufficient driving capability for weakly magnetic droplets. Currently, systems using electromagnetic fields to control magnetic droplets usually require an external static magnetic field to enhance the magnetic force.

[0007] Magnetic response structures can be categorized into magnetic droplets and magnetic substrates. The former can be driven directly by a magnetic field, while the latter is driven by the deformation of the magnetic substrate. Magnetic droplets can be further classified into droplets containing magnetic particles, magnetic fluids, and magnetic liquid marbles. Droplets containing magnetic particles mainly refer to droplets with a certain amount of ferromagnetic or superparamagnetic magnetic beads. The droplets are dragged by the magnetic beads' response to a magnetic field, and the beads also have the function of targeted binding. Magnetic fluids are stable colloidal solutions composed of magnetic solid nanoparticles (usually nano-sized iron oxide or magnetite particles), a base liquid (water or oil), and surfactants. They have functions such as sample transport, actuation, and surface wetting. Magnetic fluids typically have higher magnetic susceptibility and stronger magnetic response, but they also experience greater friction when moving on solid surfaces, and due to biocompatibility issues, they are difficult to possess specific binding capabilities. Magnetic liquid marbles are droplets ranging from hundreds of picoliters to tens of microliters, coated with hydrophobic magnetic powders (such as iron oxide and polyethylene glycol). The magnetic powder on the surface drives the movement of the droplets. A key difference from traditional droplets is that the magnetic powder does not form a plug within the droplet but remains on the surface of the liquid marble. Magnetic liquid marbles exhibit high stability and reduce liquid evaporation, but they present challenges in handling droplet solutions. These droplets are typically contained in hydrophobic coated planes or oil-filled microcavities to prevent particle contamination. The hydrophobic coated planes or oil-based microcavities are usually single-use, thus requiring high cost. Magnetic substrates are flexible hydrophobic substrates capable of magnetic deformation. Flexible substrates are easily deformed to create indentations on their surface. Droplets roll towards the indentation with the lowest potential energy. By deforming and moving the position of the indentation on the flexible substrate, the movement of both magnetic and non-magnetic droplets can be easily controlled, but the fabrication of magnetic substrates is typically complex and expensive.

[0008] From the above situation, it can be concluded that, regarding magnetic fields, while permanent magnets can generate strong magnetic fields and have a strong ability to drive magnetic droplets, they require an additional mechanical movement system to control them. Electromagnets, while flexible and controllable, have weaker magnetic fields and usually require an external static magnetic field to drive magnetic droplets. Regarding droplets, most existing magnetic digital microfluidic systems can only manipulate magnetic droplets. Although magnetic beads have the advantage of specific binding, many magnetic fluids lack good biocompatibility, limiting the downstream applications of magnetic digital microfluidics. Furthermore, the cost of magnetic substrates capable of manipulating non-magnetic droplets is much higher than that of planar or oil-based microcavities with hydrophobic coatings, which is not conducive to applications such as real-time diagnostics in different environments.

[0009] The references mentioned above are as follows:

[0010] [1]SAMIEI E,TABRIZIAN M,HOORFAR M.Areview of digital microfluidics asportable platforms for lab-on-a-chip application[J].Lab on a Chip,2016,16(13):2376-2396.

[0011] [2]M.Antfolk, T.Laurell, Continuous flow microfluidic separation and processing of rare cells and bioparticles found in blood–Areview.Anal.Chim.Acta 965,9-35(2017).

[0012] [3] M.Karle, SKVashist, R.Zengerle, F.von Stetten, Microfluidicsolutions enabling continuous processing and monitoring of biological samples:Areview.Anal.Chim.Acta929,1-22(2016).

[0013] [4] D. Di Carlo, D. Irimia, R. G. Tompkins, M. Toner, Continuous inertial focusing, ordering, and separation of particles in microchannels. Proc. Natl. Acad. Sci. U.S.A. 104, 18892 - 18897 (2007).

[0014] [5] M. Abdelgawad, A. R. Wheeler, The digital revolution: A new paradigm for microfluidics. Adv. Mater. 21, 920 - 925 (2009).

[0015] [6] M. G. Pollack, R. B. Fair, A. D. Shenderov, Electrowetting - based actuation of liquid droplets for microfluidic applications. Appl. Phys. Lett. 77, 1725 (2000).

[0016] [7] K. Choi, A. H. C. Ng, R. Fobel, A. R. Wheeler, Digital Microfluidics. Annu. Rev. Anal. Chem. 5, 413 - 440 (2012).

[0017] [8] M. Mibus, G. Zangari, Performance and reliability of electrowetting - on - dielectric (EWOD) systems based on tantalum oxide. ACS Appl. Mater. Interfaces 9, 42278 - 42286 (2017).

[0018] [9] Y. Zhang, N. - T. Nguyen, Magnetic digital microfluidics - A review. LabChip 17, 994 - 1008 (2017). Summary of the Invention

[0019] The purpose of this invention is to solve the problems of existing magnetic digital microfluidic systems being limited to driving magnetic droplets and having poor biocompatibility. This invention provides a magnetic digital microfluidic system that utilizes a magnetic core coil array to directly drive magnetic and non-magnetic droplets in a microfluidic platform and achieve a series of operations such as droplet control, transport, merging, distribution, heating, and detection.

[0020] Another objective of this invention is to provide a magnetic digital microfluidic method.

[0021] The objective of this invention can be achieved by adopting the following technical solutions:

[0022] A magnetic digital microfluidic system includes a droplet manipulation unit, a magnetic core coil array switching unit, a logic control unit, and a signal detection unit. The droplet manipulation unit includes a microfluidic platform and a magnetic core coil array. The magnetic core coil array is disposed below the microfluidic platform and is connected to the magnetic core coil array switching unit. The logic control unit is connected to both the magnetic core coil array switching unit and the signal detection unit.

[0023] Furthermore, the droplet manipulation unit also includes a magnetic core coil array heat dissipation structure, which is stacked and nested on the outer contour of the magnetic core coil array.

[0024] Furthermore, the microfluidic platform has a three-layer sandwich structure, including an upper substrate, a microchannel layer, and a lower substrate arranged sequentially from top to bottom;

[0025] The upper substrate includes a dielectric inlet, a dielectric outlet, and a sample inlet. The dielectric inlet and dielectric outlet are located around the magnetic core coil array, and the sample inlet is located above the magnetic core coil array.

[0026] The microchannel layer includes microcavities and microchannel structures, which are located directly above the magnetic core coil array. The area covered by the microcavities and microchannel structures is larger than the cross-section of the magnetic core coil array. The microcavities and microchannel structures are separated from the magnetic core coil array by a lower substrate. The microcavities and microchannel structures are respectively connected to the medium inlet, the medium outlet, and the sample inlet.

[0027] Furthermore, the microchamber and microchannel structure includes a droplet basic functional area, a droplet heating functional area, and a droplet detection functional area. The control area of ​​the magnetic core coil array covers the droplet basic functional area, the droplet heating functional area, and the droplet detection functional area. The droplet basic functional area is connected to the sample inlet. The basic functions of the droplet in the droplet basic functional area include droplet transport, merging, and distribution. The signal detection unit is arranged above the droplet detection functional area.

[0028] Furthermore, the microfluidic platform is a single-layer hydrophobic platform structure.

[0029] Furthermore, the magnetic core coil array includes multiple magnetic core coils, which can be arranged into any array shape. Each magnetic core coil includes a magnetic core and an electromagnetic coil, with the electromagnetic coil tightly wound around the magnetic core.

[0030] Furthermore, it also includes a human-computer interaction unit, which is connected to the logic control unit.

[0031] Another objective of this invention can be achieved by adopting the following technical solution:

[0032] A microfluidic method, implemented based on the aforementioned magnetic digital microfluidic system, the method comprising:

[0033] Droplets are injected into a microfluidic platform, and a magnetic field is generated by controlling the magnetic core coil array through a magnetic core coil array switching unit to drive the movement of the droplets in the microfluidic platform.

[0034] When the signal detection unit detects a change in the droplet's signal, it feeds the signal change back to the logic control unit, which then activates the next stage of the droplet manipulation path based on the signal change. The logic control unit then controls the switching on and off of each magnetic core coil in the magnetic core coil array through the magnetic core coil array switching unit to generate the corresponding magnetic field.

[0035] Furthermore, the microfluidic platform has a three-layer sandwich structure;

[0036] The process of injecting droplets into a microfluidic platform and controlling the magnetic core coil array to generate a magnetic field through a magnetic core coil array switching unit to drive the movement of the droplets in the microfluidic platform specifically includes:

[0037] If the manipulated droplet is a magnetic droplet, a non-magnetic liquid medium is filled into the microchannel layer of the microfluidic platform. This non-magnetic liquid medium and the magnetic droplet are immiscible. The magnetic droplet is injected from the sample inlet of the microfluidic platform. The magnetic core coil below the magnetic droplet is energized by the magnetic core coil array on / off unit. A magnetic field is generated above the magnetic core of the magnetic core coil through electromagnetic induction, attracting and fixing the magnetic droplet above the magnetic core of the magnetic core coil. The magnetic core coil is de-energized by the magnetic core coil array on / off unit, and the adjacent magnetic core coils are energized. The magnetic droplet is attracted and moves to the top of the adjacent magnetic core coil, thus realizing the motion manipulation of the magnetic droplet.

[0038] If the manipulated droplet is a non-magnetic droplet, a magnetic liquid medium is filled into the microchannel layer of the microfluidic platform. This magnetic liquid medium is immiscible with the non-magnetic droplet. The non-magnetic droplet is injected from the sample inlet of the microfluidic platform. The magnetic core coil below the non-magnetic droplet is energized by the magnetic core coil array switching unit. A magnetic field is generated above the magnetic core of the magnetic core coil through electromagnetic induction. This magnetic field attracts the magnetic liquid medium around the non-magnetic droplet, thereby generating a squeezing and repulsive force on the non-magnetic droplet. This causes the non-magnetic droplet to move to the top of the adjacent unenergized magnetic core coil, thus realizing the motion manipulation of the non-magnetic droplet.

[0039] Furthermore, the microfluidic platform is a single-layer hydrophobic platform structure;

[0040] The process of injecting droplets into a microfluidic platform and controlling the magnetic core coil array to generate a magnetic field through a magnetic core coil array switching unit to drive the movement of the droplets in the microfluidic platform specifically includes:

[0041] A magnetic droplet is injected into a microfluidic platform above a magnetic core coil array. The magnetic core coil below the magnetic droplet is energized by the magnetic core coil array on / off unit. A magnetic field is generated above the magnetic core of the magnetic core coil through electromagnetic induction, attracting and fixing the magnetic droplet above the magnetic core of the magnetic core coil. The magnetic core coil is de-energized by the magnetic core coil array on / off unit, and the adjacent magnetic core coil is energized. The magnetic droplet is attracted and moves to the top of the adjacent magnetic core coil, thus realizing the motion manipulation of the magnetic droplet.

[0042] The present invention has the following advantages over the prior art:

[0043] This invention utilizes the electromagnetic field generated by a simple magnetic core coil array to manipulate magnetic or non-magnetic droplets, or simultaneously. For non-magnetic droplets, it can also achieve three-dimensional manipulation. Furthermore, the microfluidic platform in this invention is an open platform that does not require complex microchannel structures, PCB (printed circuit board) circuits, or electrodes. It is highly scalable, with extremely low manufacturing and replacement costs. The magnetic core coil array can simultaneously control up to 500 droplets, greatly improving droplet manipulation efficiency. Attached Figure Description

[0044] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0045] Figure 1This is a schematic diagram of the magnetic digital microfluidic system according to Embodiment 1 of the present invention.

[0046] Figure 2 This is a schematic diagram of the droplet manipulation unit structure in Embodiment 1 of the present invention.

[0047] Figure 3 This is a front view structural diagram of the droplet manipulation unit in Embodiment 1 of the present invention.

[0048] Figure 4 for Figure 3 AA cross-section view.

[0049] Figure 5 This is a front view structural diagram of the droplet manipulation unit with magnetic core coil array according to Embodiment 1 of the present invention.

[0050] Figure 6 This is a side view of the droplet manipulation unit of the magnetic core coil array according to Embodiment 1 of the present invention.

[0051] Figure 7 This is a top view of the droplet manipulation unit according to Embodiment 1 of the present invention.

[0052] Figure 8 This is a schematic diagram of the microfluidic platform structure in Embodiment 1 of the present invention.

[0053] Figure 9 This is a schematic diagram of the functional partitions of the microfluidic platform in Embodiment 1 of the present invention.

[0054] Figure 10 This is a schematic diagram of the magnetic core coil array structure of Embodiment 1 of the present invention.

[0055] Figure 11 This is a schematic diagram of the heat dissipation structure of the magnetic core coil array in Embodiment 1 of the present invention.

[0056] Figure 12 This is a basic schematic diagram of the magnetic droplet motion principle in Embodiment 1 of the present invention.

[0057] Figure 13 This is a basic schematic diagram of the motion principle of nonmagnetic droplets in Embodiment 1 of the present invention.

[0058] Figure 14 This is a schematic diagram of horizontal droplet transport in Embodiment 1 of the present invention.

[0059] Figures 15a-15c This is a schematic diagram of horizontal droplet distribution and merging in Embodiment 1 of the present invention.

[0060] Figures 16a-16c This is a schematic diagram of another horizontal droplet distribution and merging in Embodiment 1 of the present invention.

[0061] Figures 17a-17cThis is a schematic diagram of the motion control of a non-magnetic droplet in the vertical direction according to Embodiment 1 of the present invention.

[0062] Among them, 1-droplet manipulation unit, 2-microfluidic platform, 3-magnetic core coil array, 4-magnetic core coil array heat dissipation structure, 5-magnetic core coil array control connection line, 6-magnetic core coil array on / off unit, 7-magnetic core coil power connection line, 8-coil power supply, 9-signal detection unit, 10-signal feedback transmission line, 11-logic control unit, 12-magnetic core coil on / off control line, 13-logic control unit power supply and transmission line, 14-human-machine interaction unit, 15-upper substrate, 16-microchannel layer, 17-lower substrate, 18-medium inlet, 19-medium outlet, 20-sample inlet, 21-microchamber and microchannel structure, 22-magnetic core, 23-electromagnetic coil, 24-droplet basic functional area, 25-droplet heating functional area, 26-droplet detection functional area, 27-magnetic droplet, 28-non-magnetic droplet, 29-groove structure. Detailed Implementation

[0063] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0064] Example 1:

[0065] like Figure 1 and Figure 2As shown, this embodiment provides a magnetic digital microfluidic system. The system includes a droplet manipulation unit 1, a magnetic core coil array switching unit 6, a logic control unit 11, a signal detection unit 9, and a coil power supply 8. The droplet manipulation unit 1 includes a microfluidic platform 2 and a magnetic core coil array 3. The microfluidic platform is used to carry magnetic or non-magnetic droplets and perform various manipulations of the droplets. The droplets include water-based and oil-based droplets. The magnetic core coil array 3 is located below the microfluidic platform 2 and is used to generate a magnetic field to drive the droplet movement. The magnetic core coil array 3 is connected to the magnetic core coil array switching unit 6. Specifically, each magnetic core coil in the magnetic core coil array 3 is connected to one end of the magnetic core coil array switching unit 6 through a magnetic core coil array control connection line 5, so that the switching of each magnetic core coil can be controlled by the magnetic core coil array. The switching unit 6 is controlled independently. The other end of the magnetic core coil array switching unit 6 is connected to the magnetic core coil power supply line 7 and the coil power supply 8. The current adjustment range of the coil power supply 8 is 0-400A, which can drive up to 200 magnetic core coils at the same time. The logic control unit 11 is connected to the magnetic core coil array switching unit 6 and the signal detection unit 9 respectively. Specifically, the switching point and duration of the magnetic core coil array switching unit 6 are controlled by the logic control unit 11. The magnetic core coil array switching unit 6 and the logic control unit 11 are connected through the magnetic core coil switching control line 12. At the same time, the logic control unit 11 is connected to the signal detection unit 9 through the signal transmission line 10. The magnetic core coil array switching unit 6 is a relay switch array or a field effect transistor array, and the logic control unit 11 is a microcontroller such as a single-chip microcontroller.

[0066] Furthermore, in this embodiment, the signal detection unit 9 is arranged above the microfluidic platform 2. Depending on different application requirements, a color detector, a fluorescence detector, or a thermal infrared detector can be used. After detecting the signal change of the droplet, the signal change is fed back to the logic control unit 11. Then, the next stage of the droplet manipulation path is automatically activated according to the signal change, and the magnetic core coil on / off program is controlled by the logic control unit 11, so that the magnetic core coil array on / off unit 6 performs the corresponding magnetic core coil on / off operation.

[0067] Furthermore, the magnetic digital microfluidic system of this embodiment also includes a human-machine interaction unit 14, which is connected to the logic control unit 11. Specifically, the human-machine interaction unit 14 and the logic control unit 11 are connected through the logic control unit power supply and transmission line 13. After the signal detection unit 9 feeds back the signal change to the logic control unit 11, it can be collected and displayed through the human-machine interaction unit 14. The interactive software in the human-machine interaction unit 14 can customize the coil array arrangement and coil on / off control process. The adjustment parameters include the coil array arrangement, coil selection, energizing duration, current magnitude, and energizing switching time. It also has a photoelectric detection signal acquisition program and a feedback control program. Through this software, multiple control processes can be customized, and the logic control unit 11 can automatically execute the coil on / off program according to the defined process.

[0068] like Figures 2-8 As shown, the microfluidic platform 2 in the droplet manipulation unit 1 is a three-layer sandwich structure, which includes an upper substrate 15, a microchannel layer 16, and a lower substrate 17 arranged sequentially from top to bottom. The upper substrate includes a medium inlet 18, a medium outlet 19, and a sample inlet 20. The medium inlet 18 and the medium outlet 19 are located on the periphery of the magnetic core coil array 3 (i.e., there is no magnetic core coil below them), and the sample inlet 20 is located above the magnetic core coil array 3. The microchannel layer 16 includes microcavities and microchannel structures 21. The microcavities and microchannel structures 21 are located directly above the magnetic core coil array 3. The area covered by the microcavities and microchannel structures 21 is larger than the cross-section of the magnetic core coil array 3. The microcavities and microchannel structures 21 are separated from the magnetic core coil array 3 by the lower substrate 17. The microcavities and microchannel structures 21 are connected to the medium inlet 18, the medium outlet 19, and the sample inlet 20, respectively.

[0069] Furthermore, the microchamber and microchannel structure 21 can be divided into different functional areas according to application requirements, such as... Figure 9 As shown, for example, there are droplet basic functional areas 24, droplet heating functional areas 25, and droplet detection functional areas 26. Each functional area can be freely defined according to the arrangement shape of the magnetic core coil array 3 and the application requirements. The droplet basic functional area 24 is connected to the sample inlet 20. The basic functions of the droplet basic functional area 24 include droplet transport, merging, and distribution. In the droplet heating functional area 25, the heating temperature range of the droplet is 0℃-99℃.

[0070] Furthermore, the thickness of the lower substrate 17 is 0.1mm-2mm, and the thickness of the microchannel layer 16, i.e., the height of the microchamber and microchannel structure 21, is 0.05mm-10mm; the control area of ​​the magnetic core coil array 3 can cover all functional areas in the microchamber and microchannel structure 21, i.e., the control area of ​​the magnetic core coil array 3 can cover the droplet basic functional area 24, the droplet heating functional area 25, and the droplet detection functional area 26, so that there is a magnetic core coil below the sample inlet 20; the number of sample inlets 20 The number of microchannels ranges from 1 to 500; the microcavities and microchannel structures 21 of the microchannel layer 16 are processed by laser cutting, mechanical cutting and drilling, etc.; the upper substrate 15 is made of transparent plastic film, acrylic sheet, glass sheet, etc., and the lower substrate 17 and the microcavities and microchannel structures 21 are made of transparent or opaque plastic film, acrylic sheet, glass sheet, ceramic sheet, polydimethylsiloxane (PDMS), etc.; the different layers of the microfluidic platform 2 are sealed by adhesive, hot pressing, bonding or clamping.

[0071] The structure of magnetic core coil array 3 is as follows Figure 10 As shown, it includes multiple magnetic core coils, each magnetic core coil including a magnetic core 22 and an electromagnetic coil 23. The electromagnetic coil 23 is made of wire wound around the magnetic core 22.

[0072] Furthermore, the number of magnetic core coils can be 1-10000, and they can be arranged in any shape, such as a 10×10 array, or other arbitrary shapes; the magnetic core 22 can be a cylindrical body with an arbitrary cross-section (e.g., a circular, rectangular, or triangular cross-section). In this embodiment, the magnetic core 22 is cylindrical. Figure 10 As shown), the length is 1mm-200mm, and the cross-sectional area is 0.1mm². 2 -20mm 2 The magnetic core is made of a high-permeability alloy, such as permalloy, silicon steel, or ferrite. The core can be a single piece or composed of stacked sheet-like structures. As will be readily understood by those skilled in the art, besides a cylindrical shape, the magnetic core 22 can also be an "I"-shaped structure, thicker at both ends and thinner in the middle. The electromagnetic coil 23 is wound within the cylindrical section of this "I"-shaped structure, which has a length of 1mm-200mm and a cross-sectional area of ​​0.1mm². 2 -20mm 2 The length at both ends is 0.1-5mm, and the cross-sectional area is 0.2mm². 2 -40mm 2 The diameter of the wire used to wind the electromagnetic coil 23 is 0.02mm-5mm. The wire is tightly wound on the magnetic core column to form a solenoid electromagnetic coil. The number of winding layers of the solenoid is 1-500. The wire is made of conductive materials such as copper, aluminum, and silver, and the surface is coated with insulating varnish.

[0073] like Figure 11 As shown, the droplet manipulation unit 1 in this embodiment also includes a magnetic core coil array heat dissipation structure 4. The magnetic core coil array heat dissipation structure 4 is a heat sink structure customized according to the shape of the magnetic core coil array 3. The magnetic core coil array heat dissipation structure 4 is stacked and nested on the outer contour of the magnetic core coil array 3. In addition to heat dissipation, it also serves to fix the magnetic core coil.

[0074] Furthermore, the heat dissipation structure 4 of the magnetic core coil array is made of materials with high thermal conductivity and non-magnetic properties, such as alumina, aluminum nitride, graphite, thermally conductive silicone, and sapphire / ruby glass. Each piece of the heat dissipation structure 4 of the magnetic core coil array is processed into a shape that can wrap around the magnetic core coil array 3 by laser cutting and other methods, and is stacked and nested on the outer contour of the magnetic core coil array 3. It plays a role in heat dissipation and fixation of the magnetic core coil array 3.

[0075] In this embodiment, the basic functional area 24 of the droplet can control the transport, merging, and distribution of magnetic and non-magnetic droplets in the horizontal direction, as well as the three-dimensional motion control in the vertical direction.

[0076] When manipulating magnetic droplets, a non-magnetic liquid medium is first filled into the microcavity and microchannel structure 21 through the medium inlet 18. This non-magnetic liquid medium and the magnetic droplet are immiscible. Examples include the magnetic droplet being a water-based magnetic fluid, a magnetic salt solution, or an aqueous solution containing magnetic beads, and the non-magnetic liquid medium being an oil-based mineral oil, or the magnetic droplet being an oil-based sample solution and the non-magnetic liquid medium being water-based pure water. Then, the magnetic droplet is dropped into the microcavity and microchannel structure 21 through the sample inlet 20. At this point, the magnetic droplet will be positioned above the magnetic core coil. The basic principle of the magnetic droplet's motion is as follows: Figure 12 As shown, when the magnetic core coil below the magnetic droplet is energized, a magnetic field is generated above the magnetic core of the coil through electromagnetic induction, attracting and fixing the magnetic droplet above the magnetic core of the coil. Then, when the magnetic core coil is de-energized and the adjacent magnetic core coil is energized, the magnetic droplet will be attracted and move to the top of the adjacent magnetic core coil. That is, the magnetic droplet is attracted by the magnetophoresis effect. By controlling the on and off sequence of the magnetic core coil below to generate changes in the magnetic field, the magnetic droplet can be attracted to move along a predetermined path, thus realizing the motion control of the magnetic droplet.

[0077] When manipulating non-magnetic droplets, a magnetic liquid medium is first injected into the microchamber and microchannel structure 21 through the medium inlet 18. This magnetic liquid medium and non-magnetic droplets are immiscible. Examples of immiscible magnetic liquid media include water-based magnetic fluids, magnetic salt solutions, or aqueous solutions containing magnetic beads, while non-magnetic droplets are oil-based samples such as mineral oil, or oil-based magnetic solutions and water-based pure water or cell culture media. Then, the magnetic droplet is dripped into the microchamber and microchannel structure 21 through the sample inlet 20. At this point, the magnetic droplet will be positioned above the magnetic core coil. The basic principle of the non-magnetic droplet's motion is as follows: Figure 13 As shown, when the magnetic core coil below the magnetic droplet is not energized, there is no magnetic field in the microcavity and microchannel structure 21 above. At this time, the non-magnetic droplet in the magnetic liquid medium will remain at the sample inlet 20 because it is not under any force. When the magnetic core coil below the magnetic droplet is energized, and the magnetic core coil adjacent to it is not energized, a magnetic field can be generated above the magnetic core of the magnetic core coil through electromagnetic induction. This magnetic field can attract the magnetic liquid medium around the non-magnetic droplet, thereby generating a squeezing and repulsive force on the non-magnetic droplet. That is, the negative magnetophoresis effect is used to repel the non-droplet in the magnetic liquid medium, causing the non-magnetic droplet to move to the top of the adjacent non-energized magnetic core coil, thereby realizing the motion control of the non-magnetic droplet. Here, multiple coils around the droplet can be energized at the same time to generate directional repulsive force, and the non-magnetic droplet can be precisely controlled to move in a predetermined direction without magnetic field. In addition, the non-magnetic droplet can also be lifted and lowered in the vertical direction due to the magnetic field repulsive force, thereby realizing the three-dimensional motion control of the non-magnetic droplet.

[0078] A schematic diagram of droplet transport in the horizontal direction is shown below. Figure 14As shown; for better explanation, the magnetic core coils are numbered 1-12. For magnetic droplets, movement is achieved using the attraction of the magnetic field, i.e., magnetophoresis. In the diagram, when magnetic core coil 2 is energized, the magnetic droplet is fixed above magnetic core coil 2 due to the attraction of the magnetic force. When magnetic core coil 2 is deactivated and magnetic core coil 5 is energized, the magnetic force of magnetic core coil 2 disappears, and magnetic core coil 5 will exert an attraction on the magnetic droplet, thereby driving the magnetic droplet to move from above magnetic core coil 2 to above magnetic core coil 5. At this point, the basic transportation of the magnetic droplet is completed. By controlling the energizing sequence and time of the coils, the magnetic droplet can be controlled to move along any path. For non-magnetic droplets, to precisely control their direction of movement, firstly, magnetic core coils 2, 4, and 6 are energized, with the current in coil 2 flowing in the opposite direction to the other two core coils, resulting in opposite magnetic field directions. This creates a groove-shaped magnetic field above the 4-2-6 core coils. The non-magnetic droplet above the 5 core coil will then experience a negative magnetophoretic repulsion force from this magnetic field, causing it to move towards the 8 core coil. Similarly, when the energizers 2, 4, and 6 are de-energized, and the energizers 5, 7, and 9 are energized, the non-magnetic droplet will continue to experience a negative magnetophoretic repulsion force and move towards the 11 core coil. By customizing the energization of the coils, precise transport and control of the non-magnetic droplet can be achieved.

[0079] A schematic diagram of the horizontal distribution and merging of droplets is shown below. Figures 15a-15c , Figures 16a-16c As shown, there are two forms of droplet distribution and merging. The first form is for magnetic droplets. The magnetic core coil below the droplet is de-energized, while the two adjacent magnetic core coils are energized. This splits the magnetic droplet in two, attracting each droplet to the top of its respective magnetic core coil. When merging is needed, the two adjacent magnetic core coils are de-energized, and the middle coil channel is energized. This attracts the two separated magnetic droplets to the middle, achieving droplet merging. Figures 15a-15c As shown; the second form is for magnetic core droplets or non-magnetic droplets. This form requires the use of edge-assisted microstructures, that is, groove structures 29, as shown in the figure, are pre-cut in the microcavities of the microchannel layer 16 and the microchannel structure 21. Using the droplet manipulation method described above, the droplet is moved close to the edge of the groove structure 29, and the droplet can be distributed into the groove structure 29. The volume of the droplet remaining in the groove is determined by the size of the groove. When it is necessary to merge droplets, the droplets are simply driven to the groove structure 29 again, so that the two droplets come into contact and merge, as shown. Figures 16a-16c As shown.

[0080] Because non-magnetic droplets are driven by negative magnetophoretic repulsion, they can also move in the vertical direction, enabling three-dimensional manipulation of the droplets. A schematic diagram of their vertical motion control is shown below. Figures 17a-17c As shown, firstly, the magnetic core coils around the non-magnetic droplet are energized to generate a magnetic field. The negative magnetophoretic repulsive force fixes the non-magnetic droplet above the central magnetic core coil. Then, the central magnetic core coil is energized, and its current is adjusted to always be less than the current of the surrounding coils. That is, the magnetic field generated by the central magnetic core coil is less than the magnetic field generated by the surrounding coils. In this way, the non-magnetic droplet will rise due to the repulsive force of the central coil's magnetic field. At the same time, because the surrounding magnetic field is stronger, the non-magnetic droplet will not move to the surrounding areas. This achieves its vertical movement. Combined with the horizontal movement of the non-magnetic droplet, the magnetic digital microfluidic system of this embodiment can perform three-dimensional motion control of the non-magnetic droplet.

[0081] Furthermore, the volume range of the droplets (including magnetic droplets and non-magnetic droplets) controlled in this embodiment is 1 pL-100 μL, and the droplet movement speed is 1 μm / s-20 mm / s.

[0082] In addition, the magnetic digital microfluidic system of this embodiment can simultaneously manipulate magnetic droplets and non-magnetic droplets. When the magnetic susceptibility of the magnetic liquid medium (which is immiscible with the droplets) is between that of the magnetic droplets and non-magnetic droplets, that is, the magnetic susceptibility of the magnetic liquid medium is greater than that of the non-magnetic droplets but less than that of the magnetic droplets, the magnetic droplets will be subjected to magnetophoresis and move towards the magnetic field under the action of the magnetic field, while the non-magnetic droplets will be subjected to negative magnetophoresis and move away from the magnetic field. First, the magnetic liquid medium is filled into the microcavity and microchannel structure 21 through the medium inlet 18. Then, the magnetic droplets and non-magnetic droplets are dripped into the microcavity and microchannel structure 21 from the sample inlet 20. Finally, by adopting the above-mentioned scheme for manipulating magnetic droplets and non-magnetic droplets, the simultaneous manipulation of magnetic droplets and non-magnetic droplets can be achieved.

[0083] In the droplet heating functional area 25, the magnetic digital microfluidic system of this embodiment can heat the droplet according to the temperature required for droplet manipulation or reaction. The heating temperature range of the droplet is 0℃-99℃. This droplet heating functional area 25 can be used for various chemical reactions or biological reactions such as nucleic acid amplification. First, the droplet is transported to the droplet heating functional area 25 through the system's transport function. Then, the magnetic core coil below this functional area is energized. At this time, both the electromagnetic coil 23 and the magnetic core 22 will generate heat, and the heating amplitude and rate increase with the increase of current. Finally, the heat is conducted through the lower substrate 17 to the microcavity in the droplet heating functional area 25, heating the droplet in the microcavity. The heating temperature and duration can be controlled by the current magnitude and energizing time, and the temperature range of the droplet can be controlled within 0℃-99℃.

[0084] Above the droplet detection functional area 26, a signal detection unit 9 is arranged. This signal detection unit 9 is a sensor used to detect the state of the droplet, such as a color sensor for detecting changes in droplet color, a fluorescence sensor for detecting changes in droplet fluorescence, or an infrared sensor for detecting changes in droplet temperature. When the droplet is used for the detection of specific markers, it can be co-incubated with a specific fluorescent dye for a period of time. The marker will be stained and emit fluorescence, which can then be detected by a fluorescence sensor. When the droplet sample is used for nucleic acid amplification and extraction, the fluorescence, color, or temperature of the sample may change. In this case, the droplet can be detected by a fluorescence sensor, a color sensor, or a thermal infrared sensor. The detection signal can determine the reaction progress or state of the droplet sample, thereby determining the next sample manipulation steps.

[0085] The manipulation of the droplets is achieved through the magnetic field generated by the magnetic core coil array 3 below the microfluidic platform 2, which is generated by the electromagnetic effect of the coils. Firstly, each coil of the magnetic core coil array 3 is connected to a magnetic core coil array switching unit 6. This switching unit 6 can be a control unit such as a switching array or a field-effect transistor. One end of the switching unit 6 is connected to the magnetic core coil array 3 via a magnetic core coil array control connection line, and the other end is connected to the coil power supply 8 via a magnetic core coil power connection line 7. The switching on / off status of each coil, the magnitude and direction of the current, and the logical sequence of switching are controlled by a logic control unit 11. The logic control unit 11 controls the magnetic core coil array via a magnetic core coil switching control line 12. The switching on and off of the disconnection unit 6 controls the switching on and off of each coil in the magnetic core coil array 3 to generate a corresponding magnetic field. The logic control unit 11 is a microcontroller or a programmable integrated chip. In addition, the signal from the signal detection unit 9 will also be fed back to the logic control unit 11 through the signal feedback transmission line 10 for signal acquisition and to determine the next stage of droplet manipulation. Finally, the logic control unit 11 will be connected to the human-machine interaction unit 14 through the logic control unit power supply and transmission line 13 to realize human-machine interaction control in the microcontroller or computer, and realize the custom functions of droplet manipulation path and signal acquisition output.

[0086] The magnetic digital microfluidic system of this embodiment can realize the on / off control of any magnetic core coil in the magnetic core coil array 3, including the individual control of a single magnetic core coil and the simultaneous on / off control of multiple magnetic core coils. The upper limit of simultaneous multi-channel control is the number of magnetic core coils in the magnetic core coil array 3. The current adjustment range of the magnetic core coil is 0.2A-4A, the control mode is constant current mode, and the current direction of each magnetic core coil can be individually adjusted. The energizing duration of the magnetic core coil is adjustable from 0.1s to 2s, and the energizing switching time of the magnetic core coil is 0s-0.1s. The system parameters are controlled by human-machine interaction software. The software can customize the arrangement of the magnetic core coil array 3 and the magnetic core coil on / off control process. The adjustable parameters include the arrangement of the magnetic core coil array 3, magnetic core coil selection, energizing duration, current magnitude, and energizing switching time. It has a detection signal acquisition program and a feedback control program.

[0087] Example 2:

[0088] The magnetic digital microfluidic system in this embodiment also includes a droplet manipulation unit, a magnetic core coil array switching unit, a logic control unit, a signal detection unit, a coil power supply, and a human-machine interaction unit. The droplet manipulation unit also includes a microfluidic platform and a magnetic core coil array. The difference is that the microfluidic platform is a single-layer hydrophobic platform structure, which can only manipulate magnetic droplets. Specifically, the magnetic droplet is dropped into the microfluidic platform above the magnetic core coil array. When the magnetic core coil below the magnetic droplet is energized, a magnetic field is generated above the magnetic core of the magnetic core coil through electromagnetic induction, attracting and fixing the magnetic droplet above the magnetic core of the magnetic core coil. The magnetic core coil is de-energized, and the adjacent magnetic core coil is energized. The magnetic droplet is attracted and moves to the top of the adjacent magnetic core coil, thus realizing the motion control of the magnetic droplet.

[0089] In summary, the magnetic digital microfluidic system of the present invention has the following advantages:

[0090] 1) This invention utilizes the electromagnetic field generated by a simple magnetic core coil array to manipulate magnetic and non-magnetic droplets, completely solving the problems of poor biocompatibility and dependence on magnetic beads in magnetic digital microfluidics.

[0091] 2) The microfluidic platform of the present invention does not have a complex microchannel structure or electrodes. The droplet movement path can be customized. It is an open platform with high scalability and can realize various operations such as droplet transport, merging, distribution, heating and detection. It has a wide range of applications in the field of biochemistry.

[0092] 3) The magnetic core coil array in this patent can be reused. The microfluidic platform has only a simple microcavity, no complex PCB circuit, and no electrodes. To meet different application requirements, the microfluidic platform can be replaced at a very low cost.

[0093] The above description is only a preferred embodiment of the present invention, but the implementation of the present invention is not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A microfluidic method, characterized in that, The method includes: Droplets are injected into a microfluidic platform, and a magnetic field is generated by controlling the magnetic core coil array through a magnetic core coil array switching unit to drive the movement of the droplets in the microfluidic platform. When the signal detection unit detects a change in the droplet's signal, it feeds the signal change back to the logic control unit, which then activates the next stage of the droplet manipulation path based on the signal change. The logic control unit then controls the switching on and off of each magnetic core coil in the magnetic core coil array through the magnetic core coil array switching unit to generate the corresponding magnetic field. The microfluidic platform has a three-layer sandwich structure; The process of injecting droplets into the microfluidic platform and controlling the magnetic core coil array to generate a magnetic field through the on / off unit of the magnetic core coil array to drive the movement of the droplets in the microfluidic platform specifically includes: The manipulated droplet is a non-magnetic droplet. A magnetic liquid medium is filled into the microchannel layer of the microfluidic platform. This magnetic liquid medium and the non-magnetic droplet are immiscible. The non-magnetic droplet is injected from the sample inlet of the microfluidic platform. The magnetic core coil below the non-magnetic droplet is energized by the magnetic core coil array switching unit. A magnetic field is generated above the magnetic core of the magnetic core coil through electromagnetic induction. This magnetic field attracts the magnetic liquid medium around the non-magnetic droplet, thereby generating a squeezing and repulsive force on the non-magnetic droplet. This causes the non-magnetic droplet to move to the top of the adjacent unenergized magnetic core coil, thus realizing the motion manipulation of the non-magnetic droplet. First, the magnetic core coils around the non-magnetic droplet are energized to generate a magnetic field. The negative magnetophoretic repulsive force fixes the non-magnetic droplet above the central magnetic core coil. Then, the central magnetic core coil is energized, and its current is adjusted to always be less than that of the surrounding coils. This makes the magnetic field generated by the central magnetic core coil less than that generated by the surrounding coils. The non-magnetic droplet will rise due to the repulsive force of the central coil's magnetic field. At the same time, because the surrounding magnetic field is stronger, the non-magnetic droplet moves in the vertical direction. Combined with the horizontal movement of the non-magnetic droplet, three-dimensional motion control of the non-magnetic droplet is achieved.

2. A magnetic digital microfluidic system, characterized in that, To implement the microfluidic method of claim 1, the system includes a droplet manipulation unit, a magnetic core coil array switching unit, a logic control unit, and a signal detection unit. The droplet manipulation unit includes a microfluidic platform and a magnetic core coil array. The magnetic core coil array is disposed below the microfluidic platform and is connected to the magnetic core coil array switching unit. The logic control unit is connected to both the magnetic core coil array switching unit and the signal detection unit.

3. The magnetic digital microfluidic system according to claim 2, characterized in that, The droplet manipulation unit also includes a magnetic core coil array heat dissipation structure, which is stacked and nested on the outer contour of the magnetic core coil array.

4. The magnetic digital microfluidic system according to claim 2, characterized in that, The microfluidic platform has a three-layer sandwich structure, including an upper substrate, a microchannel layer, and a lower substrate arranged from top to bottom; The upper substrate includes a dielectric inlet, a dielectric outlet, and a sample inlet. The dielectric inlet and dielectric outlet are located around the magnetic core coil array, and the sample inlet is located above the magnetic core coil array. The microchannel layer includes microcavities and microchannel structures, which are located directly above the magnetic core coil array. The area covered by the microcavities and microchannel structures is larger than the cross-section of the magnetic core coil array. The microcavities and microchannel structures are separated from the magnetic core coil array by a lower substrate. The microcavities and microchannel structures are respectively connected to the medium inlet, the medium outlet, and the sample inlet.

5. The magnetic digital microfluidic system according to claim 4, characterized in that, The microchamber and microchannel structure includes a droplet basic functional area, a droplet heating functional area, and a droplet detection functional area. The control area of ​​the magnetic core coil array covers the droplet basic functional area, the droplet heating functional area, and the droplet detection functional area. The droplet basic functional area is connected to the sample inlet. The basic functions of the droplet in the droplet basic functional area include droplet transport, merging, and distribution. The signal detection unit is arranged above the droplet detection functional area.

6. The magnetic digital microfluidic system according to claim 2, characterized in that, The microfluidic platform is a single-layer hydrophobic platform structure.

7. The magnetic digital microfluidic system according to claim 2, characterized in that, The magnetic core coil array includes multiple magnetic core coils, which can be arranged into any array shape. Each magnetic core coil includes a magnetic core and an electromagnetic coil, with the electromagnetic coil tightly wound around the magnetic core.

8. The magnetic digital microfluidic system according to claim 2, characterized in that, It also includes a human-computer interaction unit, which is connected to the logic control unit.

Images