Digital micro-flow control device and operation method

Abstract

The invention provides a digital micro-control flow device and an operation method, and belongs to the technical field of digital micro-control flow. The digital micro-control flow device comprises a chip, a detection system and a control system, the chip comprises an electrode array layer, and a liquid drop operation area is arranged on the electrode array layer; the detection system comprises a plurality of LED lamps, the number of the LED lamps is the same as that of the electrodes in the liquid drop operation area, and the LED lamps are in one-to-one correspondence with the electrodes in the liquid drop operation area; the control system is connected with the detection system or the chip, when the control system is connected with the detection system, on / off of each LED lamp can be controlled, and when the control system is connected with the chip, the control system can control the liquid drop operation area so as to realize movement of liquid drops and capture of single cells. The detection system is added, the control system is detected through the detection system before use, problems are clearly found, and the monitoring and design difficulty is reduced.

Description

Technical Field

[0001] The present invention belongs to the technical field of digital microfluidics, and particularly relates to a digital microfluidic device and an operation method thereof. Background Art

[0002] Single-cell analysis is an analytical method for studying the composition and morphology of substances in cells at the single-cell level. It circumvents the limitation of observing cell individuals in large colonies to obtain their average values, and can have a more in-depth and clear understanding of the differences between cells, so as to master more comprehensive and accurate cell information.

[0003] In order to obtain single cells, currently used devices include digital microfluidic devices. Existing digital microfluidic devices include a chip and a control system, and an electrode array is provided in the chip. When performing single-cell capture, a droplet containing cells is dropped on the electrode array, and the control system controls the operation of the electrode array. Based on the principle of dielectric wetting, the contact angle of the droplet will change under the action of an electric field. Through this method, operations such as droplet generation, splitting, merging, and movement can be achieved.

[0004] The control logic in each digital microfluidic device is designed according to the layout requirements of the corresponding electrode array. At the same time, due to the transformation of the corresponding relationship between the gold finger and the electrode region of the digital microfluidic chip, and between the electrode region of the digital microfluidic chip and the digital microfluidic droplet operation region, it is very complex to implement multi-droplet manipulation by serial-to-parallel conversion. When initially designing and building a digital microfluidic device, the design of the chip is not perfect. If a failure occurs, it is impossible to accurately locate the failure point, and the operation difficulty is high. Summary of the Invention

[0005] In view of this, the present invention provides a digital microfluidic device and an operation method thereof, which adds a detection system. Before use, the detection system is used to detect the control system, clarify the source of the problem, reduce the monitoring difficulty, improve the development efficiency of digital microfluidic operations, and reduce the development cost.

[0006] To achieve the above object, the present invention adopts the following technical solutions: On the one hand, the present invention provides a digital microfluidic device, including a chip, a detection system, and a control system. The chip includes an electrode array layer, and a droplet operation area is provided on the electrode array layer; the detection system includes a plurality of LED lights, and the number of the plurality of LED lights is the same as the number of electrodes in the droplet operation area and corresponds one by one; the control system is connected to the detection system or the chip. When connected to the detection system, it can control the on / off of each LED light. When connected to the chip, it can control the droplet operation area to realize the movement of droplets and the capture of single cells.

[0007] Preferably, each LED lamp is connected with a step-down module.

[0008] Preferably, the step-down module includes a CL520 chip.

[0009] Preferably, the detection system includes a first pin area; When the control system is connected to the detection system, the control system is connected to the first pin area through a gold finger or a flexible cable to achieve the electrical connection between the control system and the multiple LED lamps.

[0010] Preferably, the control system includes a logic control module, and the logic control module includes a serial communication interface and a controller. The serial communication interface can realize communication with a host computer.

[0011] Preferably, the control system further includes a boost module and a serial-to-parallel conversion module. The boost module is connected to the logic control module. The serial-to-parallel conversion module is connected to the boost module and the controller. The serial-to-parallel conversion module is connected to the boost module for inputting power. The serial-to-parallel conversion module is connected to the controller to achieve the output of DC and square wave signals. The output end of the serial-to-parallel conversion module is connected to the first pin area.

[0012] Preferably, the chip includes an upper plate and a lower plate. The upper plate is sequentially stacked with an upper hydrophobic layer, a grounding layer, and an upper plate base layer from bottom to top. The upper plate is provided with through holes. The lower plate is electrically connected to the upper plate. The distance between the lower plate and the upper plate is controlled by a distance control structure. The lower plate is sequentially stacked with a lower plate base layer, an electrode array layer, a dielectric layer, and a lower hydrophobic layer from bottom to top. Among them, the droplet operation area is located on the electrode array layer, and the through holes are correspondingly arranged with the droplet operation area.

[0013] Preferably, the droplet operation area includes a plurality of droplet operation units. Each unit includes a droplet generation area, a cell sorting area, a target cell collection area, and a waste liquid collection area. The droplet generation area, the target cell collection area, and the waste liquid collection area are all connected to the cell sorting area; and / or, The electrode array layer further includes a second pin area and a grounding area. The grounding area is connected to the grounding layer through a conductive structure. When the control system is connected to the chip, the second pin area and the control system are connected through a gold finger or a flexible cable structure.

[0014] Preferably, the distance control structure is a microsphere, and the diameter of the microsphere is 100-500 μm.

[0015] On the other hand, the present invention provides an operation method of the digital microfluidic device as described above, including the following steps: S1. Design a driver program for driving the electrodes in the electrode array layer according to the experimental procedure; S2. Connect the control system with the designed driver program to the detection system, and detect whether the control system can control the on / off of multiple LED lights. If not, it proves that there is a problem with the driver program and needs to be corrected; if so, it proves that the driver program is okay; S3. After proving that the driver program is okay through step S2, connect the control system to the chip.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: By introducing a detection system and using LED lights as a feedback mechanism, the present invention solves the difficulties in fault diagnosis of existing digital microfluidic control devices. By improving the system operability, fault troubleshooting efficiency, accuracy and stability, the accuracy and reliability of digital microfluidic control devices in single-cell capture and droplet operation are significantly improved. This improvement not only enhances the user experience of experimental operators, but also provides a more efficient means for equipment maintenance and fault troubleshooting. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is a schematic cross-sectional view of a chip provided by an embodiment of the present invention; Figure 2 It is a schematic structural view of an electrode array layer provided by an embodiment of the present invention; Figure 3 It is a schematic structural view of a detection system provided by an embodiment of the present invention; Figure 4 It is a schematic structural view of a control system provided by an embodiment of the present invention.

[0018] Reference numerals: chip 1, upper electrode plate 11, upper hydrophobic layer 111, grounding layer 112, upper electrode plate base layer 113, through hole 114, lower electrode plate 12, lower electrode plate base layer 121, electrode array layer 122, droplet operation area 1221, droplet generation area a, cell sorting area b, target cell collection area c, waste liquid collection area d, second pin area 1222, grounding area 1223, dielectric layer 123, lower hydrophobic layer 124, pitch control structure 13, conductive structure 14, detection system 2, LED light 21, step-down module 22, first pin area 23, control system 3, logic control module 31, serial communication interface 311, controller 312, boost module 32, serial-to-parallel conversion module 33. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0019] The following further describes the present invention in detail with reference to specific embodiments, so that those skilled in the art can understand the present invention more clearly.

[0020] Single-cell analysis is an analytical method for studying the composition and morphology of substances in cells at the single-cell level. It circumvents the limitations of observing individual cells in a large community to obtain their average values, enabling a deeper and clearer understanding of the differences between cells, thereby obtaining more comprehensive and accurate cell information. To obtain single cells, currently used devices include digital microfluidic devices. Existing digital microfluidic devices include a chip 1 and a control system 3, and an electrode array is provided in the chip 1. When performing single-cell capture, a droplet containing cells is dropped onto the electrode array, and the control system 3 controls the operation of the electrode array. Based on the principle of dielectric wetting, the contact angle of the droplet will change under the action of an electric field. Through this method, operations such as droplet generation, splitting, merging, and movement can be achieved. The control system 3 in each digital microfluidic device is designed according to the layout requirements of the corresponding electrode array. When the digital microfluidic device is used for the first time, if a failure occurs, it is difficult to determine whether the problem lies in the control system 3 or the chip 1, and the monitoring difficulty is high.

[0021] To solve the above technical problems, the present invention combines Figures 1-4 to provide a digital microfluidic device, including a chip 1, a detection system 2, and a control system 3. The chip 1 includes an electrode array layer 122, and a droplet operation area 1221 is provided on the electrode array layer 122; the detection system 2 includes a plurality of LED lights 21, the number of the plurality of LED lights 21 is the same as the number of electrodes in the droplet operation area 1221, and they are in one-to-one correspondence; the control system 3 is connected to the detection system 2 or the chip 1. When connected to the detection system 2, it can control the on / off of each LED light 21. When connected to the chip 1, it can control the droplet operation area 1221 to realize droplet movement and single-cell capture.

[0022] In the above technical solution, the electrode array layer 122 included in the chip 1 realizes droplet operation through electric field control. The strength, direction, etc. of the electric field can be adjusted by precisely controlling the electrode array. The generation, splitting, merging, and movement of droplets are realized by the electrode array of the chip 1 through the action of the electric field. Each electrode is independently controllable, so that the size, shape, and movement trajectory of the droplets can be flexibly controlled. In the application of single-cell capture and sorting, the precise control of the electrode array is crucial for successfully capturing target cells. The core of the detection system 2 is the multiple LED lights 21. Each LED light 21 corresponds to an electrode array on the chip 1 one by one, and the on / off state of the LED light 21 reflects the control status of the control system 3. Through the feedback of the LED light 21, the operator can timely detect the abnormalities of the device and take corresponding measures, thereby improving the stability of the device and the efficiency of troubleshooting. The control system 3 is the "brain" of the entire device. When the control system 3 is connected to the detection system 2, the system will adjust the on / off state of each LED light 21 according to the experimental requirements, thereby realizing the detection of the control system 3. When the control system 3 is connected to the chip 1 and controls the electrode array, operations such as droplet generation, movement, splitting, and merging can be realized, ensuring that single cells can be accurately captured and sorted.

[0023] The present invention solves the difficulties in fault diagnosis of existing digital microfluidic devices by introducing a detection system 2 with the LED lights 21 as the feedback mechanism. By improving the system operability, troubleshooting efficiency, accuracy, and stability, the accuracy and reliability of the digital microfluidic device in single-cell capture and droplet operation are significantly improved. This improvement not only enhances the use experience of experimental operators but also provides a more efficient means for device maintenance and troubleshooting.

[0024] Furthermore, each LED light 21 is connected to a step-down module 22. Each LED light 21 is connected to an external power supply through a step-down module 22. The main function of the step-down module 22 is to reduce the high voltage of the external power supply to the low voltage suitable for the operation of the LED light 21. In addition, the step-down module 22 also has the function of adjustable output voltage, so that it can be precisely adjusted according to the working characteristics of different LED lights 21 (such as different working voltages, power requirements, etc.) to ensure that the LED light 21 can operate in the optimal working state, thereby improving the performance and efficiency of the overall device. In some embodiments, the step-down module 22 includes a CL520 chip to realize the control experiment of the LED light 21 with a voltage range of 4.5 - 90V.

[0025] Further, the detection system 2 includes a first pin area 23; when the control system 3 is connected to the detection system 2, the control system 3 and the first pin area 23 are connected by a gold finger or a flexible cable to achieve the electrical connection between the control system 3 and the multiple LED lights 21. The connection methods of the gold finger or the flexible cable include but are not limited to: electrical contact, welding, plugging and unplugging connection, etc., so as to achieve the electrical connection between the control system 3 and the multiple LED lights 21.

[0026] These different connection methods provide higher flexibility to meet different application scenarios and design requirements. By providing multiple connection methods, the adaptability and maintainability of the system in actual use are ensured.

[0027] Further, the control system 3 includes a logic control module 31, and the logic control module 31 includes a serial communication interface 311 and a controller 312. The serial communication interface 311 can realize communication with the host computer. In some embodiments, the controller 312 uses an STM32F103ZET6 single chip to achieve logic control through its rich interfaces.

[0028] Further, the control system 3 further includes a boost module 32 and a serial-to-parallel conversion module 33. The boost module 32 is connected to the logic control module 31, the serial-to-parallel conversion module 33 is connected to the boost module 32 and the controller 312. The serial-to-parallel conversion module 33 is connected to the boost module 32 for inputting power, and the serial-to-parallel conversion module 33 is connected to the controller 312 to achieve the output of DC and square wave signals. The output end of the serial-to-parallel conversion module 33 is connected to the first pin area 23. The boost module 32 is connected to the serial-to-parallel conversion module 33 and provides power input with a voltage range of 55 - 300V. The controller 312 converts the drive control of the electrode into a serial signal of a corresponding format and transmits it to the serial-to-parallel conversion module 33; in some embodiments, the serial-to-parallel conversion module 33 uses an HV507 low-voltage serial to high-voltage parallel converter, which can support 64 high-voltage push-pull outputs with a maximum of 300V, is connected to the controller 312, and can achieve the output of DC or square wave signals under the control of the controller 312. The output end of the serial-to-parallel conversion module 33 is connected to the chip 1 or the detection system 2 by a gold finger or a flexible cable, and the control of a larger electrode array can be achieved through a multi-connected serial-to-parallel structure.

[0029] In some embodiments, the chip 1 includes an upper electrode plate 11 and a lower electrode plate 12. The upper electrode plate 11 is successively stacked with an upper hydrophobic layer 111, a grounding layer 112, and an upper electrode plate base layer 113 from bottom to top. A through hole 114 is provided through the upper electrode plate 11; the lower electrode plate 12 is electrically connected to the upper electrode plate 11, and the distance between the lower electrode plate 12 and the upper electrode plate 11 is controlled by a distance control structure 13. The lower electrode plate 12 is successively stacked with a lower electrode plate base layer 121, an electrode array layer 122, a dielectric layer 123, and a lower hydrophobic layer 124 from bottom to top. Among them, the droplet operation area 1221 is located on the electrode array layer 122, and the through hole 114 is correspondingly arranged with the droplet operation area 1221.

[0030] In the above technical solution, in some embodiments, the electrode array is processed by laser etching, which is convenient for integration with a microscope to realize cell observation; in some embodiments, the minimum square electrode in the droplet operation area 1221 is 0.8 mm * 0.8 mm, and the distance between the electrodes is 0.03 μm. Both the electrode array layer 122 and the grounding layer 112 are transparent conductive materials, such as indium tin oxide conductive thin film, carbon nanotube transparent conductive thin film, graphene transparent conductive thin film, etc.; the thicknesses of the electrode array layer 122 and the grounding layer 112 are 20 - 200 nm. In some embodiments, the upper hydrophobic layer 111 and the lower hydrophobic layer 124 are made of hydrophobic materials, which can provide a large initial contact angle, such as Teflon, Cytop, or PFC; the thicknesses of the upper hydrophobic layer 111 and the lower hydrophobic layer 124 are 10 - 50 nm; the dielectric layer 123 is a material with good dielectric properties, which can achieve better dielectric characteristics and a large breakdown voltage, such as silicon nitride, silicon dioxide, parylene C, organic polymer materials, etc.; the thickness of the dielectric layer 123 is 0.1 - 50 μm. In some embodiments, the size of the lower electrode plate 12 is 41 mm * 41 mm, which is convenient for realizing the connection with the gold finger structure. In some embodiments, the conductive structure 14 is a compressible conductive sponge or a bent wire to realize the connection between the upper electrode plate 11 and the lower electrode plate 12.

[0031] In some embodiments, the droplet operation area 1221 includes a plurality of droplet operation units, and each unit includes a droplet generation area a, a cell sorting area b, a target cell collection area c, and a waste liquid collection area d. The droplet generation area a, the target cell collection area c, and the waste liquid collection area d are all connected to the cell sorting area b. The droplet generation area a is composed of a plurality of large electrodes, which can meet the requirements of multiple single-cell analyses for one sample injection.

[0032] In some embodiments, the electrode array layer 122 further includes a second pin region 1222 and a grounding region 1223. The grounding region 1223 is connected to the grounding layer 112 through a conductive structure 14. When the control system 3 is connected to the chip 1, the second pin region 1222 and the control system 3 are connected through a gold finger or a flexible cable. In some embodiments, the second pin region 1222 is composed of 50 electrodes with a pitch of 0.8 mm, which facilitates the interconnection with the gold finger.

[0033] Further, the pitch control structure 13 is a microsphere, and the diameter of the microsphere is 100 - 500 μm. The combination of the microsphere and the photo-curable adhesive can more precisely control the gap between the upper electrode plate 11 and the lower electrode plate 12.

[0034] The present invention also provides an operation method for the digital microfluidic control device described above, including the following steps: S1. Design a driving program for driving the electrodes in the electrode array layer 122 according to the experimental process; S2. Connect the control system 3 with the designed driving program to the detection system 2, and detect whether the control system 3 can control the on / off of multiple LED lights 21 according to a predetermined logic. If not, it proves that there is a problem with the driving program and needs to be corrected; if so, it proves that the driving program is okay; S3. After proving that the driving program is okay through step S2, connect the control system 3 to the chip 1.

[0035] By introducing a detection system 2 and using the LED lights 21 as a feedback mechanism, the present invention solves the difficulties in fault diagnosis of existing digital microfluidic control devices. By improving the system operability, fault troubleshooting efficiency, accuracy, and stability, the accuracy and reliability of the digital microfluidic control device in single-cell capture and droplet operation are significantly improved. This improvement not only enhances the user experience of experimental operators but also provides a more efficient means for equipment maintenance and troubleshooting.

[0036] In the present invention, if no specific raw materials are described, they are existing substances that can be directly purchased from the market.

[0037] The above are only the preferred embodiments of the present invention and are not intended to limit the protection scope of the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A digital microfluidic device, characterized in that, Comprising: A chip, including an electrode array layer, and a droplet operation area on the electrode array layer; A detection system, including a plurality of LED lights, the number of the plurality of LED lights being the same as the number of electrodes in the droplet operation area and corresponding one by one; A control system, connected to the detection system or the chip. When connected to the detection system, it can control the on / off of each LED light. When connected to the chip, it can control the droplet operation area to realize the movement of droplets and the capture of single cells.

2. The digital microfluidic device according to claim 1, characterized in that Each LED light is connected with a step-down module.

3. The digital microfluidic device according to claim 2, wherein, The step-down module includes a CL520 chip.

4. The digital microfluidic device according to claim 1, wherein The detection system includes a first pin area; When the control system is connected to the detection system, the control system is connected to the first pin area through a gold finger or a cable structure to realize the electrical connection between the control system and the plurality of LED lights.

5. The digital microfluidic device according to claim 4, characterized in that, The control system includes a logic control module, and the logic control module includes a serial communication interface and a controller, and the serial communication interface can realize communication with a host computer.

6. The digital microfluidic device according to claim 5, wherein The control system further includes a boost module and a serial-to-parallel conversion module. The boost module is connected to the logic control module. The serial-to-parallel conversion module is connected to the boost module and the controller. The serial-to-parallel conversion module is connected to the boost module for inputting power. The serial-to-parallel conversion module is connected to the controller to realize the output of DC and square wave signals. The output end of the serial-to-parallel conversion module is connected to the first pin area.

7. The digital microfluidic device according to claim 1, wherein The chip includes: An upper electrode plate, on which an upper hydrophobic layer, a grounding layer, and an upper electrode plate base layer are sequentially stacked from bottom to top. The upper electrode plate is provided with through holes; A lower electrode plate, electrically connected to the upper electrode plate. The distance between the lower electrode plate and the upper electrode plate is controlled by a distance control structure. The lower electrode plate is sequentially stacked with a lower electrode plate base layer, an electrode array layer, a dielectric layer, and a lower hydrophobic layer from bottom to top. Among them, the droplet operation area is located on the electrode array layer, and the through holes are correspondingly arranged with the droplet operation area.

8. The digital microfluidic device according to claim 7, wherein, The droplet operation area includes a plurality of droplet operation units. Each unit includes a droplet generation area, a cell sorting area, a target cell collection area, and a waste liquid collection area. The droplet generation area, the target cell collection area, and the waste liquid collection area are all connected to the cell sorting area; and / or, The electrode array layer further includes a second pin area and a grounding area. The grounding area is connected to the grounding layer through a conductive structure. When the control system is connected to the chip, the second pin area is connected to the control system through a gold finger or a cable.

9. The digital microfluidic device according to claim 7, characterized in that, The distance control structure is a microsphere, and the diameter of the microsphere is 100-500 μm.

10. The operating method of the digital microfluidic device according to any one of claims 1-9, characterized in that, Including the following steps: S1. Design a driving program for driving the electrodes in the electrode array layer according to the experimental process; S2. Connect the control system with the designed driving program to the detection system, and detect whether the control system can control the on / off of a plurality of LED lights. If not, it proves that the driving program has problems and needs to be corrected; If it can, it proves that the driving program has no problems; S3. After proving that the driver is problem-free through step S2, connect the control system to the chip.

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