Digital microfluidic system

Abstract

The invention provides a digital micro-fluidic system, and relates to the technical field of micro-fluidic systems. The digital micro-fluidic system provided by the invention comprises a micro-fluidic chip, and liquid drops are moved, combined and split in the horizontal direction through voltage difference; the heating plate is positioned at the bottom of the micro-fluidic chip and is used for heating the micro-fluidic chip; the magnetic control module is positioned at the bottom of the heating plate and is used for adsorbing magnetic beads on the micro-fluidic chip so as to purify liquid drops; the micro-fluidic chip is provided with a plurality of parallel channels arranged in the first direction, a plurality of electrode units used for bearing liquid drops are arranged in the parallel channels in an array mode, and the corresponding electrode units in the parallel channels are connected in parallel and electrically connected with the control circuit. The problems that the practical application of DMF is limited due to the fact that the flux of an existing passive matrix DMF is too small, the electrode driving force of an active matrix DMF is small, cost is high and the like can be solved, accurate synchronous control over multiple groups of liquid drops is achieved, and a new solution is provided for large-scale low-cost digital micro-fluidic application.

Description

Technical Field

[0001] The present invention relates to the technical field of microfluidic systems, and in particular to a digital microfluidic system. Background Art

[0002] Traditional microfluidic technology builds micro-channels, micro-pumps, valves or micro-mixers and other micro-nano devices on the chip, introduces microfluids into the closed flow channel and controls and operates them, thereby completing the entire experimental process. Common microfluidic driving methods include pressure drive and electroosmotic drive. However, most traditional microfluidics rely on pumps, valves and other configurations, which makes the chip structure and equipment complex, has high requirements for operators, restricts integration flexibility, and the channel is prone to dead volume, causing cross contamination. Digital microfluidics (DMF) technology is a new droplet manipulation technology that independently manipulates discrete droplets. The size of the manipulated droplets is generally in the microliter to picoliter range, and the degree of automation is high, avoiding the problems of dead volume and cross contamination.

[0003] Traditional passive matrix digital microfluidics requires a one-to-one correspondence between pins and control units, which limits the large-scale construction of droplet microreactors and their applications in the field of omics; the latest active matrix digital microfluidics technology uses thin film transistor (TFT) elements to control large-scale unit arrays. This technology has been widely used in liquid crystal flat panel displays and has high reliability and maturity. Although it can achieve complex operations of large-scale droplets, the driving voltage of a single electrode is limited by the withstand voltage of the thin film transistor, and the driving force is limited. If a larger driving force is required, multiple electrodes need to be driven together. In addition, the cost of the DMF chip made by this technology is relatively high. Therefore, a solution is urgently needed to improve the above problems. Summary of the invention

[0004] The purpose of the present invention is to provide a digital microfluidic system.

[0005] A digital microfluidic system provided by the present invention comprises: a microfluidic chip, which moves, merges and splits droplets in a horizontal direction through a voltage difference; a heating plate, which is located at the bottom of the microfluidic chip and is used to heat the microfluidic chip; a magnetic control module, which is located at the bottom of the heating plate and adsorbs magnetic beads on the microfluidic chip to purify the droplets; the microfluidic chip has a plurality of parallel channels arranged along a first direction, and a plurality of electrode units for carrying droplets are arrayed in the parallel channels, and the corresponding electrode units in the plurality of parallel channels are connected in parallel to each other and electrically connected to a control circuit.

[0006] The digital microfluidic system provided by the present invention can realize accurate synchronous movement of multiple groups of droplets by connecting electrode units in different parallel channels in parallel in the microfluidic chip, thereby realizing large-scale and low-cost digital microfluidic operation. In addition, the magnetic beads commonly used in biological applications can be adsorbed by the magnetic control module, thereby purifying the droplets on the microfluidic chip.

[0007] Optionally, the array in the parallel channel is provided with K rows and N columns of electrode units, wherein K and N are both positive integers and K is greater than or equal to 3; M parallel channels are provided on the microfluidic chip, and the first direction is the column direction of the parallel channels, and M×K×N electrode units are provided on the microfluidic chip, wherein M is a positive integer greater than or equal to 2.

[0008] Optionally, the microfluidic chip includes a substrate electrically connected to the control circuit, a plurality of electrode unit arrays are arranged on top of the substrate and electrically connected to the substrate, and the corresponding electrode units in the plurality of parallel channels are connected in parallel to each other through the substrate.

[0009] Optionally, the microfluidic chip also includes an upper electrode plate arranged on the top of the substrate, and the bottom of the upper electrode plate and the top of the substrate constitute a closed microfluidic space, and the microfluidic space is used to enhance the power of the droplets to move, merge and split in the horizontal direction; the upper electrode plate is an ITO conductive glass with a conductive medium layer at the bottom.

[0010] Optionally, the microfluidic chip also includes a hydrophobic film covering the surface of the substrate, and the electrode unit is located between the substrate and the hydrophobic film, and the hydrophobic film is used to reduce the horizontal movement resistance of the droplets and increase the contact angle of the droplets; the hydrophobic film is an insulating dielectric film that has been hydrophobically treated.

[0011] Optionally, the top area of ​​the substrate is divided into a fluid control area and a liquid storage area, a plurality of electrode unit arrays are arranged in the fluid control area, the substrate is provided with a temporary storage electrode located in the liquid storage area for temporarily storing the reaction liquid, and the substrate is provided with a connecting electrode located between the temporary storage electrode and at least one of the parallel channels; the temporary storage electrode and the connecting electrode are electrically connected to the control circuit through the substrate.

[0012] Optionally, the heating plate is in contact with the bottom of the microfluidic chip, and the heating plate includes a plurality of heating units arranged along a first direction and connected to a control circuit, and the heating units are arranged corresponding to electrode units of the microfluidic chip in the first direction; the plurality of heating units in the heating plate are arranged along a second direction, and the second direction is orthogonal to the first direction in a horizontal direction.

[0013] Optionally, the microfluidic chip is synchronously lifted and lowered with the heating plate and is arranged on the top of the magnetic control module, and the magnetic control module includes a magnetic attraction member, a clamping member and a slide arranged along a first direction, the magnetic attraction member is detachably arranged on the clamping member, and the clamping member is slidably arranged on the slide along a second direction, and the second direction is orthogonal to the first direction in the horizontal direction.

[0014] Optionally, it also includes an adjusting device and a monitoring device both electrically connected to the control circuit, the adjusting device is used to adjust the lifting and lowering of the microfluidic chip and the heating plate, and the monitoring device is located on the top of the microfluidic chip and is used to monitor the movement state of droplets on the microfluidic chip. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 A schematic diagram of the overall structure of a digital microfluidic system provided by an embodiment of the present invention; Figure 2 A schematic diagram of the motion state of the microfluidic chip provided in an embodiment of the present invention when performing droplet movement; Figure 3 This is a schematic diagram of the structure of an electrode unit on a microfluidic chip in an embodiment of the present invention; Figure 4 A schematic diagram of the motion state of the microfluidic chip provided in an embodiment of the present invention when performing droplet movement; Figure 5 A schematic diagram of the motion state of the microfluidic chip provided in an embodiment of the present invention when droplet merging is performed; Figure 6 A schematic diagram of the motion state of the microfluidic chip provided in an embodiment of the present invention when performing droplet splitting; Figure 7 A schematic diagram of the structure of the microfluidic chip and the upper electrode plate provided in an embodiment of the present invention after being combined; Figure 8 A schematic diagram of the motion state of the microfluidic chip provided in an embodiment of the present invention when collecting droplets; Fig. 9 A schematic diagram of the motion state of the microfluidic chip provided in an embodiment of the present invention when performing droplet distribution; Fig.10 This is a schematic diagram of the structure of the heating unit on the heating plate, which is highlighted in an embodiment of the present invention; Fig.11 A schematic structural diagram of a magnetron module provided in an embodiment of the present invention.

[0016] Description of reference numerals: 1. Microfluidic chip; 2. Heating plate; 21. Heating unit; 22. Heating interface; 3. Magnetron module; 31. Magnetic element; 32. Clamping element; 33. Slide; 331. Horizontal ball screw; 332. Optical axis; 333. Stepper motor; 4. Control circuit; 5. Parallel channel; 6. Electrode unit; 7. First direction; 8. Substrate; 9. Chip interface; 10. Upper electrode; 11. Conductive copper foil; 12. Hydrophobic membrane; 13. Fluid control area; 14. Liquid storage area; 15. Temporary storage electrode; 16. Connecting electrode; 17. MOS tube; 18. Adjustment device; 181. Vertical ball screw; 19. Monitoring device; 191. Bright field camera; 192. Fluorescence observation camera; 193. Excitation light source. DETAILED DESCRIPTION

[0017] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention. Unless otherwise defined, the technical terms or scientific terms used herein should be understood by people with general skills in the field to which the present invention belongs. "Including" and similar words used in this article mean that the elements or objects appearing before the word include the elements or objects listed after the word and their equivalents, without excluding other elements or objects.

[0018] The present invention provides a digital microfluidic system. Figure 1 , including: a microfluidic chip 1, which moves, merges and splits droplets in the horizontal direction through voltage difference; a heating plate 2, which is located at the bottom of the microfluidic chip 1 and is used to heat the microfluidic chip 1; a magnetic control module 3, which is located at the bottom of the heating plate 2 and adsorbs magnetic beads on the microfluidic chip 1 to purify the droplets.

[0019] In fact, a control circuit 4 is also provided at the bottom of the digital microfluidic chip 1, and the microfluidic chip 1, the heating plate 2, the magnetic control module 3 and the control circuit 4 are all electrically connected. In addition, the microfluidic chip 1, the heating plate 2 and the magnetic control module 3 can be individually controlled by the control circuit 4, so that they can be applied to different working scenarios. For example, in the face of chemical trace reactions and analysis, the microfluidic chip 1 can be controlled to move droplets to achieve chemical reactions and analysis, and the microfluidic chip 1 can be heated by the heating plate 2 to provide a temperature environment. In the face of biological applications, the magnetic beads in the droplets can be adsorbed by the magnetic control module 3, and then the droplets can be purified after the microfluidic chip 1 is used to move the droplets.

[0020] Specifically, see Figure 1 , Figure 2 and Figure 3 The microfluidic chip 1 has a plurality of parallel channels 5 arranged along a first direction 7, and a plurality of electrode units 6 for carrying droplets are arranged in an array in the parallel channels 5, and the corresponding electrode units 6 in the plurality of parallel channels 5 are connected in parallel to each other and electrically connected to the control circuit 4. In fact, when the droplet control of the microfluidic chip 1 is performed, since the corresponding electrode units 6 in the plurality of parallel channels 5 are arranged in parallel, the movement of the droplets on the plurality of parallel channels 5 can be achieved by a single voltage control.

[0021] In some embodiments, when performing droplet control on the microfluidic chip 1, the synchronous movement of droplets on multiple parallel channels 5 can be controlled, and the transfer movement of droplets between adjacent parallel channels 5 can also be controlled. For example, droplets can be moved sequentially from the first parallel channel 5 to the last parallel channel 5.

[0022] In some embodiments, see Figure 2 and Figure 3 , K rows and N columns of electrode units 6 are arranged in an array in the parallel channel 5, wherein K and N are both positive integers and K is greater than or equal to 3. In fact, by arranging multiple electrode units 6 on the parallel channel 5, a large flux application can be achieved on the same parallel channel 5, and at the same time, the electrode units 6 in the parallel channel 5 are greater than or equal to 3 rows, which is conducive to isolating mutual interference when the droplets move.

[0023] In fact, see Figure 2 and Figure 4 When the droplet is moving, for example, when the droplet is in the first row and first column of the parallel channel 5 and needs to be moved to the first row and second column of the parallel channel 5, a bias voltage can be applied to the first row and second column of the parallel channel 5, so that the shape of the droplet can be changed and move toward the electrode unit 6 in the first row and second column, and by repeating the above operation, the droplet can be moved in the row direction in the parallel channel 5. Similarly, when the droplet needs to be moved in the column direction, a bias voltage can be applied to the electrode unit 6 adjacent to the direction of movement.

[0024] In fact, see Figure 5 When merging droplets, for example, when droplets are in the first row and first column and the first row and third column of the parallel channel 5, and two droplets need to be merged in the first row and second column, a bias voltage can be applied to the first row and second column of the parallel channel 5, so that the droplets in the first row and first column and the first row and third column move closer to the electrode unit 6 in the first row and second column and merge. Similarly, when droplets at other positions need to be merged, a bias voltage can be applied to the electrode unit 6 between the two droplets to be merged, so that the positions of the two droplets can be brought closer to each other and the merging operation can be completed.

[0025] In fact, see Figure 6 When splitting droplets, for example, when a droplet is in the first row and second column of the parallel channel 5 and needs to be split into the first row and first column and the first row and third column, bias voltages can be applied to the first row and first column and the first row and third column of the parallel channel 5, respectively, so that the droplet in the first row and second column splits to both sides. Similarly, when droplet splitting is required, bias voltages can be applied to both sides (upper and lower sides, left and right sides) of the droplet to be split, so that the droplet splits to both sides.

[0026] In fact, by applying the movement, merging and splitting operations of the droplets in the parallel channel 5, the droplets can be moved to the specified positions in the parallel channel 5 and react, which facilitates the flexible control of the droplets.

[0027] In some embodiments, see Figures 2 to 6 , M parallel channels 5 are arranged on the microfluidic chip 1, and the first direction 7 is the column direction of the parallel channels 5, so a total of M×K×N electrode units 6 are arranged on the microfluidic chip 1, where M is a positive integer greater than or equal to 2. In fact, by setting M parallel channels 5, the microfluidic system can be used for large channels simultaneously.

[0028] Specifically, participate in Figures 2 to 6 On the microfluidic chip 1, the electrode units 6 in the first row and first column of the first parallel channel 5 to the electrode units 6 in the first row and first column of the Mth parallel channel 5 are connected in parallel. In this way, there is no need to connect each electrode unit 6 to a control line separately, and only K×N control points are needed to realize the parallel control of M×K×N electrode units 6 on the microfluidic chip 1, and the number of control points is independent of the number of parallel channels 5 set on the microfluidic chip 1, which is conducive to increasing the number of parallel channels 5 and providing guarantee for channel expansion of different applications.

[0029] In fact, see Figure 1 and Figure 3 The microfluidic chip 1 includes a substrate 8 electrically connected to the control circuit 4, and a plurality of electrode units 6 are arrayed on the top of the substrate 8. In addition, the corresponding electrode units 6 in the plurality of parallel channels 5 are connected in parallel to each other through the substrate 8, thereby realizing the parallel setting of the plurality of parallel channels 5. Specifically, a chip interface 9 is provided on the microfluidic chip 1, and is electrically connected to the control circuit 4 and transmits signals through the chip interface 9.

[0030] In fact, the substrate 8 of the microfluidic chip 1 can be manufactured by PCB or FPC process, and the size of the electrode unit 6 on the substrate 8 can be 2mm×2mm. In fact, the size of the electrode unit 6 can be adjusted according to the actual application scenario under the condition of satisfying the processing technology.

[0031] In some embodiments, see Figure 3 and Figure 7 The microfluidic chip 1 further includes a hydrophobic film 12 covering the surface of the substrate 8, and the electrode unit 6 is located between the substrate 8 and the hydrophobic film 12, wherein the hydrophobic film 12 is used to reduce the horizontal movement resistance of the droplets and increase the contact angle of the droplets on the substrate 8, thereby facilitating the horizontal movement of the droplets on the substrate 8 of the microfluidic chip 1. Specifically, the hydrophobic film 12 is an insulating dielectric film that has been subjected to a hydrophobic treatment.

[0032] In some embodiments, see Figure 1 and Figure 7 The microfluidic chip 1 also includes an upper electrode plate 10 disposed on the top of the substrate 8, and the bottom of the upper electrode plate 10 and the top of the substrate 8 form a closed microfluidic space, wherein the microfluidic space is used to enhance the power of the droplets to move, merge and split in the horizontal direction. Specifically, the upper electrode plate 10 is an ITO conductive glass with a conductive medium layer at the bottom.

[0033] In fact, the upper electrode plate 10 is made of indium tin oxide (ITO) material and is made into a transparent glass shape, which is conducive to directly observing the movement state and movement position of the droplets on the substrate 8 from the outside, and the bottom of the upper electrode plate 10 is also hydrophobic to facilitate the horizontal movement of the droplets.

[0034] join Figure 7 In addition, a conductive copper foil 11 with a thickness of 50-300 μm is attached to the bottom edge of the upper electrode 10, and the conductive copper foil 11 is grounded, so that when the droplets move in the horizontal direction, the droplets can be driven by the double-layer electrodes of the upper electrode 10 and the microfluidic chip 1, thereby ensuring that the droplets can complete the splitting action. At the same time, the conductive copper foil 11 can also provide a gap between the upper electrode 10 and the microfluidic chip 1, and the volume of the droplets moving on the microfluidic can be adjusted by adjusting the thickness of the conductive copper foil 11. In fact, the volume of a single droplet moving on the microfluidic chip 1 is related to the length and width of the electrode unit 6 and the spacing between the microfluidic chip 1 and the upper electrode 10.

[0035] In some embodiments, see Figure 3 The top of the substrate 8 can be divided into a flow control area 13 and a liquid storage area 14, and a plurality of electrode units 6 are arranged in an array in the flow control area 13 of the substrate 8, and the droplets are moved, split and merged in the horizontal direction in the flow control area 13, and a temporary storage electrode 15 for temporarily storing the reaction liquid is arranged in the liquid storage area 14 of the substrate 8, and a large number of droplets can be collected and temporarily stored through the temporary storage electrode 15.

[0036] In fact, the size of the temporary storage electrode 15 on the substrate 8 is larger than the size of the electrode unit 6, so that more reaction liquid can be temporarily stored at the temporary storage electrode 15. In addition, the substrate 8 is provided with a connecting electrode 16 between the temporary storage electrode 15 and at least one parallel channel 5, so the microfluidic chip 1 can use the connecting electrode 16 as a transition to split the reaction liquid temporarily stored in the reaction liquid into droplets and move them to the connecting electrode 16, and then move them to the electrode unit 6 of the parallel channel 5.

[0037] In fact, a plurality of temporary electrodes 15 are provided on the substrate 8, and the plurality of temporary electrodes 15 can be connected to the same parallel channel 5, that is, the plurality of temporary electrodes 15 are on the side of the parallel channel 5 at the end of the first direction 7 and are evenly arranged along the row direction of the parallel channel 5, or the plurality of temporary electrodes 15 are respectively connected to the plurality of parallel channels 5 accordingly.

[0038] In fact, the temporary electrode 15 and the connecting electrode 16 on the substrate 8 are electrically connected to the control circuit 4 respectively, so that the temporary electrode 15 and the connecting electrode 16 can be controlled separately. In addition, when multiple temporary electrodes 15 are arranged on the substrate 8, the multiple temporary electrodes 15 are electrically connected to the control circuit 4 independently.

[0039] In some embodiments, see Figure 8 When the temporary electrode 15 is used to collect the droplets, for example, when the droplets in the first row and the first column of the M parallel channels 5 need to be merged onto the temporary electrode 15 located below the parallel channels 5, the bias voltage can be cyclically applied to the first column of the second row and the first column of the third row in sequence, so that the droplets in the first row move to the third row, and a bias voltage is applied to the connecting electrode 16, so that the droplets in the first column of the third row of the Mth parallel channel 5 move to the connecting electrode 16, and then a bias voltage is applied to the temporary electrode 15, so that the droplets on the connecting electrode 16 move to the temporary electrode 15. After the cycle is performed, the droplets in the first column of the M parallel channels 5 can be all collected on the temporary electrode 15.

[0040] In some embodiments, see Fig. 9 When the temporary electrodes 15 are used to distribute the droplets, after the reaction liquid is pre-stored on the first column of the temporary electrodes 15, a bias voltage is applied to the first column of the connecting electrodes 16, so that a part of the reaction liquid moves to the connecting electrodes 16 to form droplets, and then a bias voltage is applied to the first column of the third row of the parallel channel 5, so that the droplets enter the parallel channel 5, and the cycle is repeated so that the first droplet enters the first parallel channel 5.

[0041] In fact, the heating plate 2 fits the bottom of the microfluidic chip 1, so that the droplets on the microfluidic chip 1 can be evenly heated. Fig.10The heating plate 2 includes a plurality of heating units 21 arranged along a first direction 7 and independently connected to the control circuit 4, and the heating units 21 are arranged corresponding to the electrode units 6 of the microfluidic chip 1 in the first direction 7, and the plurality of heating units 21 are arranged on the heating plate 2 along a second direction of the microfluidic chip 1, and the second direction is orthogonal to the first direction 7 in the horizontal direction, and the second direction is the row direction of the parallel channel 5.

[0042] In fact, the heating plate 2 can be made by PCB or FPC process, and multiple groups of heating units 21 are arranged on it along the second direction, and specifically, the heating units 21 can be electric thermal resistance wires. Furthermore, a heat-conducting material, such as heat-conducting silica gel, can be coated at the joint between the heating plate 2 and the microfluidic chip 1 to facilitate the connection stability between the heating plate 2 and the microfluidic chip 1 and improve the heat conduction efficiency.

[0043] In fact, when setting the heating units 21 on the heating plate 2, multiple heating units 21 can be evenly spaced at the bottom of the microfluidic chip 1. For example, the heating units 21 can be set at positions corresponding to the electrode units 6 in the second column, the fifth column, the eighth column, etc., to avoid temperature interference between the multiple heating units 21, resulting in heating of the electrode units 6 that do not need to be heated. Specifically, when multiple heating units 21 are set, the number of interval columns of the electrode units 6 can be calculated and set according to actual needs.

[0044] Specifically, when the X-1th column to the X+1th column in the microfluidic chip 1 need to be heated, a heating unit 21 is set at the bottom of the corresponding microfluidic chip 1, and the droplets at the remaining positions are moved to the heated electrode unit 6 through the voltage difference for heating treatment.

[0045] In some embodiments, the heating unit 21 is arranged at the top of the heating plate 2 near the microfluidic chip 1, and a thermistor is arranged at the bottom of the heating plate 2. The thermistor can be used to obtain and adjust the heating degree of the microfluidic chip 1 by the heating unit 21 in real time, thereby facilitating closed-loop control of the temperature of the heating plate 2.

[0046] Specifically, a plurality of MOS tubes 17 are provided on the heating plate 2, and the plurality of MOS tubes 17 correspond to the heating units 21 one by one, so that each heating unit 21 can be individually opened and closed by the MOS tube 17. In addition, a heating interface 22 is provided on the heating plate 2, and the heating interface 22 can be electrically connected to the control circuit 4 and transmit signals, so that each heating unit 21 can be individually controlled by the control circuit 4.

[0047] In some embodiments, see Fig.11The magnetic control module 3 includes a magnetic member 31, a clamping member 32 and a slide 33 arranged along the first direction 7, and the magnetic member 31 is detachably arranged on the clamping member 32, and the clamping member 32 is slidably arranged on the slide 33 along the second direction. Specifically, the slide 33 includes a horizontal ball screw 331, an optical axis 332 and a stepper motor 333, wherein the horizontal ball screw 331 and the optical axis 332 are parallel to the second direction, the clamping member 32 is fixed on the top of the horizontal ball screw 331 and the optical axis 332, and the power output end of the stepper motor 333 is transmission-connected with the horizontal ball screw 331 to drive the horizontal ball screw 331 to rotate.

[0048] In fact, the magnetic member 31 can be a bar magnet. When the magnetic member 31 is demagnetized and its magnetism decreases, it can be removed from the clamping member 32 and replaced, which is conducive to maintaining the stability of the magnetic member 31 and avoiding the adverse effects of the demagnetization of the magnetic member 31. In addition, in order to improve the movement stability of the clamping member 32 on the slide 33, two optical axes 332 can be placed on both sides of the horizontal ball screw 331.

[0049] Specifically, the microfluidic chip 1 and the heating plate 2 are synchronously lifted and lowered on the top of the magnetic control module 3, and an adjustment device 18 is arranged on the peripheral side of the microfluidic chip 1 and the heating plate 2, wherein the adjustment device 18 is used to horizontally adjust and lift the microfluidic chip 1 and the heating plate 2.

[0050] Specifically, the adjusting device 18 includes a plurality of screw nuts, a vertical ball screw 181 and a rotating motor evenly arranged on the sides of the microfluidic chip 1 and the heating plate 2. In fact, the screw nuts are fixedly connected to the sides of the microfluidic chip 1 and the heating plate 2, and the vertical ball screw 181 is rotatably connected to the screw nut and threadedly engaged. The rotating motor is used to rotate the vertical ball screw 181, which is beneficial to the horizontal adjustment and lifting adjustment of the microfluidic chip 1 and the heating plate 2.

[0051] In fact, a power combination of a coupling and a rotating motor is provided at the bottom of the plurality of vertical ball screws 181, and the rotation of the rotating motor drives the coupling to move, thereby driving the rotation of the vertical ball screw 181, and the vertical ball screw 181 converts the rotational motion into linear motion, so that the microfluidic chip 1 and the heating plate 2 can be adjusted in the lifting position. Specifically, the adjustment device 18 includes four vertical ball screws 181, so that the microfluidic chip 1 and the heating plate 2 can be adjusted horizontally and lifted in the direction of the vertical ball screw 181.

[0052] In fact, when biological applications are carried out, the magnetic suction member 31 can be moved to the bottom of the corresponding column electrode unit 6 of the microfluidic chip 1 in advance through the slide 33, and the microfluidic chip 1 and the heating plate 2 can be moved downward toward the magnetic suction member 31 through the adjustment device 18, so that the magnetic suction member 31 can adsorb the magnetic beads on the microfluidic chip 1, and then the target substance can be magnetically fixed. After the adsorption and fixation is completed, the adjustment device 18 can be used to make the microfluidic chip 1 and the heating plate 2 rise away from the magnetic suction member 31, so as to achieve the separation of the magnetic suction member 31, and at the same time, by controlling the distance between the microfluidic chip 1 and the magnetic suction member 31, the magnetic force obtained by the magnetic beads on the microfluidic chip 1 can be controlled.

[0053] In some embodiments, a monitoring device 19 is provided on the top of the microfluidic chip 1, and the monitoring device 19 is electrically connected to the control current and is used to monitor the motion state on the microfluidic chip 1. In fact, the motion state of the droplets on the microfluidic chip 1 on the non-horizontal surface can be known through the monitoring device 19, and then the horizontal position of the microfluidic chip 1 can be adjusted by the adjusting device 18.

[0054] Specifically, the monitoring device 19 includes a bright field camera 191, a fluorescence observation camera 192 and an excitation light source 193, wherein the bright field camera 191 can monitor the movement trajectory of the droplets on the microfluidic chip 1 in real time, and the excitation light source 193 can use a light source that matches the fluorescent marker and be configured with appropriate excitation filters and emission filters to ensure the wavelength separation of the excitation light and the fluorescence signal. In addition, the excitation light intensity and irradiation time of the excitation light source 193 can be adjusted according to the observation results of the fluorescence observation camera 192 to avoid photobleaching and sample damage to the samples in the droplets on the microfluidic chip 1.

[0055] In fact, the control circuit 4 is located at the bottom of the magnetic control module 3, and the microfluidic chip 1, the heating plate 2, the magnetic control module 3, the adjustment device 18 and the monitoring device 19 are all electrically and signal-connected to the control circuit 4. Specifically, the control circuit 4 includes a main control MCU, a DC-DC boost module, a DC-DC buck module, a half-bridge drive module, a high-voltage drive selection module, a multi-channel high-voltage switch module, an LED drive module, a heating plate 2 drive module, and a temperature sampling module.

[0056] Among them, the DC-DC boost module is used to modulate the DC output of the 12V power supply and increase it to an adjustable output voltage of 60-300V by using a current limiting pulse frequency; the DC-DC-step-down module is used to reduce the DC voltage of 12V to 5V and output it; the half-bridge drive module is used to convert the 60-300V adjustable output voltage converted by the DC-DC boost module into a frequency-adjustable positive polarity square wave; the high-voltage drive selection module is used to select DC high voltage or positive polarity square wave as the input signal of the multi-channel high-voltage switch module, and the multi-channel high-voltage switch module, under the control of the main control MCU, outputs multiple high-voltage drive signals to the microfluidic chip 1, thereby realizing the controllable movement, separation and merging of droplets in the horizontal direction on the microfluidic chip 1.

[0057] In addition, the main control MCU can also obtain the moving state of the droplets on the microfluidic chip 1 through the monitoring device 19, and then know whether the microfluidic chip 1 is in a horizontal state. When the microfluidic chip 1 is not in a horizontal state, it can control the adjustment device 18 to adjust the horizontal state of the microfluidic chip 1. At the same time, the active MCU can also use multi-channel PWM signals to control the multiple MOS tubes 17 in the heating plate 2 respectively, and then control the heating position and heating temperature in the heating plate 2 respectively, and use the SPI bus to communicate with the thermistor at the bottom of the heating plate 2, so as to realize PID control of the temperature of the heating plate 2, and avoid the interference of the high-voltage signal on the control circuit 4 on the sampling of the thermistor in the heating plate 2.

[0058] In some embodiments, the workflow of the digital microfluidic system provided by the present invention is: Start the system power switch, the control circuit 4 performs a self-check on the whole system, and turns off the power supply when a fault occurs. Otherwise, the movement state of the droplets on the microfluidic chip 1 is observed by the monitoring device 19. When the microfluidic chip 1 is in a non-horizontal state, the microfluidic chip 1 is adjusted to a horizontal position by the adjusting device 18, and the magnetic control module 3 is in an initial state; When the temperature of the heating plate 2 is adjusted, the temperature value on the microfluidic chip 1 is collected, and the control circuit 4 drives the temperature control circuit to rise until the microfluidic chip 1 reaches the required temperature, and then magnetically fixed or droplet moved; when magnetically fixed, the control circuit 4 uses the magnetic control module 3 to move the magnetic attraction member 31 to the preset target drive in advance, and the microfluidic chip 1 is raised or lowered through the adjustment device 18, thereby realizing the magnetization and demagnetization of the target area on the microfluidic chip 1 by the magnetic attraction member 31; When the droplets on the microfluidic chip 1 need to be moved, the movement of the droplets on the microfluidic chip 1 is analyzed in advance, and the multi-channel high-voltage switch module in the control circuit 4 is used to select the required electrode unit 6 to apply a bias voltage, thereby controlling the movement of the droplets on the microfluidic chip 1; in addition, the motion image of the droplets on the microfluidic chip 1 is collected by the bright field camera 191 in the monitoring device 19, and the fluorescence signal under the fluorescence observation camera 192 is combined to perform a comprehensive analysis of the droplet movement state.

[0059] Although the embodiments of the present invention are described in detail above, it is obvious to those skilled in the art that various modifications and variations can be made to these embodiments. However, it should be understood that such modifications and variations are within the scope and spirit of the present invention as described in the claims. Moreover, the present invention described herein may have other embodiments and may be implemented or realized in a variety of ways.

Claims

1. A digital microfluidic system, characterized in that: include: Microfluidic chips use voltage differences to move, merge, and split droplets horizontally; A heating plate is located at the bottom of the microfluidic chip and is used to heat the microfluidic chip; a magnetic control module is located at the bottom of the heating plate and adsorbs the magnetic beads on the microfluidic chip to purify the droplets; the microfluidic chip has a plurality of parallel channels arranged along a first direction, and a plurality of electrode units for carrying droplets are arrayed in the parallel channels, and the corresponding electrode units in the plurality of parallel channels are connected in parallel to each other and electrically connected to a control circuit.

2. The digital microfluidic system according to claim 1, characterized in that: The array in the parallel channel is provided with K rows and N columns of electrode units, wherein K and N are both positive integers and K is greater than or equal to 3; M parallel channels are provided on the microfluidic chip, and the first direction is the column direction of the parallel channels, and M×K×N electrode units are provided on the microfluidic chip, wherein M is a positive integer greater than or equal to 2.

3. The digital microfluidic system according to claim 1, characterized in that: The microfluidic chip includes a substrate electrically connected to the control circuit, a plurality of electrode unit arrays are arranged on the top of the substrate and electrically connected to the substrate, and the corresponding electrode units in the plurality of parallel channels are connected in parallel with each other through the substrate.

4. The digital microfluidic system according to claim 3, characterized in that: The microfluidic chip also includes an upper electrode plate arranged on the top of the substrate, and the bottom of the upper electrode plate and the top of the substrate form a closed microfluidic space, and the microfluidic space is used to enhance the power of the droplets to move, merge and split in the horizontal direction; the upper electrode plate is ITO conductive glass with a conductive medium layer at the bottom.

5. The digital microfluidic system according to claim 3, characterized in that: The microfluidic chip also includes a hydrophobic film covering the surface of the substrate, and the electrode unit is located between the substrate and the hydrophobic film. The hydrophobic film is used to reduce the horizontal movement resistance of the droplets and increase the contact angle of the droplets. The hydrophobic film is an insulating dielectric film that has been hydrophobically treated.

6. The digital microfluidic system according to claim 3, characterized in that: The top area of ​​the substrate is divided into a fluid control area and a liquid storage area, a plurality of electrode unit arrays are arranged in the fluid control area, the substrate is provided with a temporary storage electrode for temporarily storing the reaction liquid in the liquid storage area, and the substrate is provided with a connecting electrode between the temporary storage electrode and at least one of the parallel channels; the temporary storage electrode and the connecting electrode are electrically connected to the control circuit through the substrate.

7. The digital microfluidic system according to claim 1, characterized in that: The heating plate is fitted with the bottom of the microfluidic chip, and the heating plate includes a plurality of heating units arranged along a first direction and connected to a control circuit, and the heating units are arranged corresponding to the electrode units of the microfluidic chip in the first direction; the plurality of heating units in the heating plate are arranged along a second direction, and the second direction is orthogonal to the first direction in a horizontal direction.

8. The digital microfluidic system according to claim 1, characterized in that: The microfluidic chip is synchronously lifted and lowered with the heating plate and is arranged on the top of the magnetic control module, and the magnetic control module includes a magnetic attraction member, a clamping member and a slide table arranged along a first direction, the magnetic attraction member is detachably arranged on the clamping member, and the clamping member is slidably arranged on the slide table along a second direction, and the second direction is orthogonal to the first direction in the horizontal direction.

9. The digital microfluidic system according to claim 8, characterized in that: It also includes an adjusting device and a monitoring device both connected to the control circuit, wherein the adjusting device is used to adjust the lifting and lowering of the microfluidic chip and the heating plate, and the monitoring device is located on the top of the microfluidic chip and is used to monitor the movement state of the droplets on the microfluidic chip.

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