Hybrid digital microfluidic system

Abstract

The invention relates to the technical field of digital microfluidics, and discloses a hybrid digital microfluidics system which comprises an upper computer, a power supply, a main control unit, a programmable voltage source, a multi-way switch, a digital microfluidics chip and a micro piezoelectric pump, the upper computer is used for generating an activation signal and a liquid drop pumping signal; the main control unit is used for responding to the activation signal and activating the electrode array corresponding to the activation signal; the micro piezoelectric pump is used for responding to a liquid drop pumping signal and enabling liquid drops to flow into the digital micro-fluidic chip through the microneedle and to be adsorbed on the activated electrode array. According to the invention, the speed of an experiment and a production process is increased through an automation technology, meanwhile, errors caused by manual operation are reduced, the consistency of operation and the repeatability of a result are ensured, and the effect of liquid drop pumping in digital microfluidics is improved.

Description

Technical Field

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

[0002] Digital microfluidics (DMF) is an emerging technology that uses electric fields to control the movement, separation, mixing and reaction of droplets at the micrometer scale. It achieves the processing and analysis of tiny droplets by precisely manipulating liquids on micrometer-scale chips. Digital microfluidics is efficient, flexible and programmable, and is suitable for many fields such as biomedicine, chemical analysis and environmental monitoring. The core principle of digital microfluidics is the electrowetting effect, which changes the surface tension between droplets and the chip surface by applying voltage, thereby controlling the morphology and movement of droplets. On a typical digital microfluidic chip, electrodes are arranged on the chip substrate, and droplets are suspended on the hydrophobic surface. By applying voltage to different electrodes, droplets can move along the electrodes, achieving precise manipulation of droplets.

[0003] Traditional microfluidics, also known as microfluidics or lab-on-a-chip technology, is a science and technology that precisely controls and manipulates fluids at the micrometer scale. This technology uses microchannels (tens to hundreds of micrometers in size) to process or manipulate tiny fluids, and involves multiple disciplines such as chemistry, fluid physics, microelectronics, new materials, biology, and biomedical engineering.

[0004] Current digital microfluidics usually uses manual sample injection, which is usually slow and time-consuming, especially when a large number of samples need to be processed. Summary of the invention

[0005] Based on this, it is necessary to address the technical problem of low microfluidic injection efficiency in the prior art, and propose a hybrid digital microfluidic system, the hybrid digital microfluidic system comprising: a host computer, a power supply, a main control unit, a programmable voltage source and a multi-way switch, a digital microfluidic chip, and a micro piezoelectric pump, wherein the output end of the host computer is respectively connected to the input end of the main control unit and the input end of the micro piezoelectric pump, the output end of the main control unit is respectively connected to the programmable voltage source and the input end of the multi-way switch, the output end of the programmable voltage source is connected to another input end of the multi-way switch, the output end of the multi-way switch is connected to the digital microfluidic chip, the infusion end of the micro piezoelectric pump is connected to the injection hole of the digital microfluidic chip through a microneedle, the programmable voltage source is used to provide voltage to the multi-way switch, the multi-way switch is used to control the gating of electrodes in the digital microfluidic chip, and the power supply is used to power the main control unit, the micro piezoelectric pump and the programmable voltage source;

[0006] The host computer is used to generate an activation signal based on the activation sequence of the electrodes in the digital microfluidic chip, and to generate a droplet pumping signal based on the moving path and pumping time of the droplet;

[0007] The main control unit is used to respond to the activation signal and activate the electrode array corresponding to the activation signal in the digital microfluidic chip through the multi-way switch;

[0008] The micro piezoelectric pump is used to respond to a droplet pumping signal and perform droplet pumping based on the moving path and pumping time of the droplets. The droplets flow into the digital microfluidic chip through the microneedles and are adsorbed on the activated electrode array.

[0009] The hybrid digital microfluidic system proposed by the present invention includes a host computer, a power supply, a main control unit, a programmable voltage source and a multi-way switch, a digital microfluidic chip, and a micro piezoelectric pump; the host computer is used to generate an activation signal based on the activation sequence of the electrodes in the digital microfluidic chip, and generate a droplet pumping signal based on the moving path and pumping time of the droplet; the main control unit is used to respond to the activation signal, and activate the electrode array corresponding to the activation signal in the digital microfluidic chip through the multi-way switch; the micro piezoelectric pump is used to respond to the droplet pumping signal, and perform droplet pumping based on the moving path and pumping time of the droplet, and the droplet flows into the digital microfluidic chip through a microneedle and adsorbs on the activated electrode array. The present invention improves the speed of the experiment and production process through automation technology, while reducing the errors caused by human operation, ensuring the consistency of operation and the repeatability of the results. It also helps to reduce the labor cost and sample reagent consumption of the laboratory, improve data processing capabilities, and can meet the needs of high-throughput experiments. In addition, the integration of the hybrid digital microfluidic system allows it to work in conjunction with other automated equipment to form an efficient automated production line, improving the efficiency of droplet pumping in digital microfluidics. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0011] in:

[0012] Figure 1 A schematic diagram of the structure of a hybrid digital microfluidic system in one embodiment;

[0013] Figure 2 A schematic diagram of the structure of a digital microfluidic chip of a hybrid digital microfluidic system in one embodiment;

[0014] Figure 3 A schematic diagram of a droplet pumping of a data processing device in one embodiment;

[0015] Figure 4 FIG. 4 is another schematic diagram of droplet pumping of a data processing device in an embodiment. DETAILED DESCRIPTION

[0016] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by technicians in the technical field of the present application; the terms used in the specification of the application herein are only for the purpose of describing specific embodiments and are not intended to limit the present application; the terms "including" and "having" and any variations thereof in the specification and claims of the present application and the above-mentioned drawings are intended to cover non-exclusive inclusions. The terms "first", "second", etc. in the specification and claims of the present application or the above-mentioned drawings are used to distinguish different objects, not to describe a specific order.

[0017] Reference to "embodiments" herein means that a particular feature, structure, or characteristic described in conjunction with the embodiments may be included in at least one embodiment of the present application. The appearance of the phrase in various locations in the specification does not necessarily refer to the same embodiment, nor is it an independent or alternative embodiment that is mutually exclusive with other embodiments. It is explicitly and implicitly understood by those skilled in the art that the embodiments described herein may be combined with other embodiments.

[0018] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. 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.

[0019] refer to Figure 1 The hybrid digital microfluidic system includes: a host computer, a power supply, a main control unit, a programmable voltage source and a multi-way switch, a digital microfluidic chip, and a micro piezoelectric pump, wherein the output end of the host computer is respectively connected to the input end of the main control unit and the input end of the micro piezoelectric pump, the output end of the main control unit is respectively connected to the programmable voltage source and the input end of the multi-way switch, the output end of the programmable voltage source is connected to another input end of the multi-way switch, the output end of the multi-way switch is connected to the digital microfluidic chip, the infusion end of the micro piezoelectric pump is connected to the injection hole of the digital microfluidic chip through a microneedle, the programmable voltage source is used to provide voltage to the multi-way switch, the multi-way switch is used to control the gating of electrodes in the digital microfluidic chip, and the power supply is used to power the main control unit, the micro piezoelectric pump and the programmable voltage source;

[0020] The host computer is used to generate an activation signal based on the activation sequence of the electrodes in the digital microfluidic chip, and to generate a droplet pumping signal based on the movement path and pumping time of the droplets; the main control unit is used to respond to the activation signal and activate the electrode array corresponding to the activation signal in the digital microfluidic chip through the multi-way switch; the micro piezoelectric pump is used to respond to the droplet pumping signal and pump the droplets based on the movement path and pumping time of the droplets, and the droplets flow into the digital microfluidic chip through the microneedles and are adsorbed on the activated electrode array.

[0021] Among them, reference Figure 2 The digital microfluidic chip consists of a top plate, a bottom plate and a flexible printed circuit (FPC). The top plate is a glass substrate with an indium tin oxide (ITO) coating, and the bottom plate contains a series of driving electrodes. The electrode surface is covered with a 300nm silicon nitride film (SiNx) as a dielectric layer. The ITO glass and the electrode array substrate are bonded, and the electrode surface is coated with AF Teflon material to meet the hydrophobic requirements, so as to accurately control the movement of droplets and realize efficient digital microfluidic control of complex biological experiments.

[0022] As an example, refer to Figure 3 , Figure 4 First, activate electrode 1 and start pumping liquid to fill the position of electrode 1. After the liquid fills electrode 1, stop pumping and disconnect electrode 1, then activate electrode 2 to move the droplet to electrode 2. By activating the electrodes in sequence and cycling this operation, continuous automatic injection of droplets can be achieved, effectively controlling the transmission and positioning of liquids in the microfluidic system.

[0023] In general, the hybrid digital microfluidic system design of the present invention provides a high-performance, high-flexibility and high-precision microfluidic solution by combining advanced control strategies, precise voltage drive circuits and efficient automatic sample injection devices. The system has broad application prospects in the fields of chemical analysis, biological detection, drug screening, etc.

[0024] As an example, the control software of the host computer can use QT Creator to develop an interface program based on C++ language. Through the software interface, the user can set the volume, flow rate and time of the pumped reagent and other parameters to accurately control the experimental process. This software control method not only improves the convenience and accuracy of operation, but also reduces human errors and improves the repeatability of the experiment. The main control unit uses the STM32H743VI H6 chip to process the control signal, and the programmable voltage source uses the combination of MAX1771 and digital potentiometer MCP41100-I / SN to provide a stable voltage output. The multi-way switch uses the HV582 analog switch to control the selection of row and column electrodes. The micro piezoelectric pump can use the TTP Ventus piezoelectric micro pump, which is an advanced fluid drive device that uses the deformation of piezoelectric materials to achieve fluid pumping. When AC power is applied to both ends of the piezoelectric vibrator, the piezoelectric vibrator will bend and deform, thereby changing the volume of the pump chamber to achieve liquid suction and discharge. This pumping method has the advantages of no pollution, no dead volume, and easy control, which is very suitable for precise fluid control in microfluidic systems.

[0025] In one embodiment, the hybrid digital microfluidic system includes a microneedle fixing device made of PDMS material, the microneedle fixing device is provided with a penetrating fixing hole, the diameter of the fixing hole is designed based on the diameter of the microneedle, the microneedle fixing device is bonded to the digital microfluidic chip, the fixing hole of the microneedle fixing device is aligned with the injection hole of the digital microfluidic chip, one end of the microneedle is inserted into the fixing hole, and the other end of the microneedle is connected to the infusion end of the micro piezoelectric pump.

[0026] In this embodiment, PDMS (polydimethylsiloxane) material is used to make a microneedle fixture, and the PDMS material has transparency, biocompatibility and excellent sealing performance. The production process of the microneedle fixture includes mixing the prepolymer and the curing agent in a ratio of 10: 1 and stirring them fully, then degassing under a vacuum environment, and then slowly pouring them into a mold and curing them at 60-80 ° C for 1-2 hours. After curing, carefully demould to obtain a molded microneedle fixture, and use a puncher to punch holes in the microneedle fixture to integrate microneedles. The punched microneedle fixture is plasma treated by plasma enhanced chemical vapor deposition (PLAMSA) technology. The treatment method is to place the microneedle fixture in a vacuum chamber, pass oxygen and excite plasma at low power, and treat the surface for 30 seconds to enhance its hydrophilicity and activity. The surface of the treated microneedle fixture can be quickly bonded to glass to ensure sealing and stability. During the bonding process, the punched holes need to be aligned with the injection holes of the digital microfluidic chip as a channel for automatic injection of droplets. During the operation of the system, the electrode near the injection hole is first selected and activated in the host computer, and then the micro piezoelectric pump is started to pump droplets. The droplets flow into the digital microfluidic chip through the microneedle and adsorb on the activated electrode.

[0027] In this embodiment, polydimethylsiloxane (PDMS) is bonded to the digital microfluidic chip, and microneedles are integrated into the PDMS, which can effectively introduce external reagents into the chip. The microneedles directly deliver the reagents to the designated location of the chip without manual operation. This automatic injection method is achieved through a piezoelectric pump, a device that can accurately control the volume and flow rate of the fluid. It can generate pressure in response to electrical signals, thereby pushing the reagents through the microneedles into the chip.

[0028] In one embodiment, the microneedle adopts an L-shaped steel needle capillary structure. In this embodiment, the microneedle adopting the L-shaped steel needle capillary structure has good biocompatibility and sufficient mechanical strength. The microneedle needs to be directly inserted into the hole of the microneedle fixture to ensure the sealing and stability of the combination. The piezoelectric pump accurately controls the flow of liquid, and the liquid is automatically injected into the chip through the microneedle to achieve accurate reagent delivery, which significantly improves the efficiency and repeatability of the experiment.

[0029] In one embodiment, the manufacturing process of the microneedle fixing device made of PDMS material includes:

[0030] Step A: mixing the prepolymer and the curing agent in a ratio of 10:1 and stirring thoroughly to obtain a mixture;

[0031] Step B: degassing the mixture under vacuum, pouring it into a mold and curing it at 60-80° C. for 1-2 hours. After curing, demolding the mixture to obtain a microneedle fixing device;

[0032] Step C: using a puncher to punch holes through the microneedle fixing device to form fixing holes;

[0033] Step D: The microneedle fixture after the holes are penetrated is plasma treated by plasma enhanced chemical vapor deposition technology to obtain a microneedle fixture made of PDMS material.

[0034] It should be noted that the hybrid digital microfluidic system proposed in the present invention shows significant innovation and advantages in automatic injection, integration, droplet manipulation accuracy, automation and integration: Automatic injection: The system uses TTP Ventus piezoelectric micropump to realize automatic injection of reagents, thereby improving the efficiency and accuracy of the operation and reducing human errors, which is crucial to improving the repeatability and reliability of microfluidic experiments. Integration: Through the carefully designed microneedle fixture made of PDMS material and PLAMSA bonding technology, the system ensures the sealing and stability of the microfluidic chip. The introduction of microneedles further enhances the integration of the system, making it possible to accurately inject and manipulate droplets. Accuracy of droplet manipulation: The core of the system is the ability to accurately control the generation, movement and other microfluidic operations of droplets. This involves a series of innovative engineering technologies and methods, including precise fluid dynamics design and control systems, which ensure the high accuracy of droplet manipulation. Automation and integration: The entire system shows a high degree of automation and integration, and the seamless connection with the host computer software allows users to easily set and adjust experimental parameters and achieve complete control over the experimental process. This highly integrated design not only improves the efficiency of the experiment, but also makes the system more user-friendly. In summary, the hybrid digital microfluidic system of the present invention provides an efficient, precise and user-friendly microfluidic solution through automated sample injection, precise droplet manipulation and highly integrated design, which is suitable for a wide range of application fields, including biomedical research, drug development and chemical analysis.

[0035] The hybrid digital microfluidic system proposed in the present invention has the following advantages, which improves efficiency and accuracy: the micro piezoelectric pump can quickly and accurately complete the addition of samples, saving the time and labor costs of the laboratory, and at the same time improving the accuracy and repeatability of the experiment. Reduce sample and reagent consumption: DMF technology can accurately control the volume of droplets, reduce the consumption of samples and reagents, and is conducive to cost saving. Minimize cross contamination: Automatic injection can effectively prevent cross contamination between droplets and ensure the accuracy of experimental results. High throughput capability: DMF technology has the characteristics of high throughput and can process multiple droplets at the same time, thereby improving experimental efficiency. Easy to integrate and automate: The system proposed in the present invention is easy to use with other laboratory equipment, thereby achieving full integration, which is convenient for realizing miniaturized and integrated analysis systems. Flexibility and versatility: The micro piezoelectric pump can perform different sample addition methods according to experimental requirements, such as quantitative sample addition, fixed-point sample addition, continuous sample addition, etc., to meet the requirements of different experiments. Easy to operate: It is equipped with a friendly operating interface and software, making it easy to operate and manage. High reliability: The system proposed in the present invention adopts high-quality materials and technologies, has high reliability and stability, and can work stably for a long time. Reduce human errors: Automated operations reduce interference from human operations and improve the accuracy and repeatability of experiments.

[0036] Those skilled in the art can clearly understand that for the convenience and simplicity of description, only the division of the above-mentioned functional units and modules is used as an example. In actual applications, the above-mentioned functions can be distributed and completed by different functional units and modules as needed, that is, the internal structure of the device can be divided into different functional units or modules to complete all or part of the functions described above.

[0037] The embodiments described above are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention, and should all be included in the protection scope of the present invention.

Claims

1. A hybrid digital microfluidic system, characterized in that: The hybrid digital microfluidic system comprises: a host computer, a power supply, a main control unit, a programmable voltage source and a multi-way switch, a digital microfluidic chip, and a micro piezoelectric pump, wherein the output end of the host computer is respectively connected to the input end of the main control unit and the input end of the micro piezoelectric pump, the output end of the main control unit is respectively connected to the programmable voltage source and the input end of the multi-way switch, the output end of the programmable voltage source is connected to another input end of the multi-way switch, the output end of the multi-way switch is connected to the digital microfluidic chip, the infusion end of the micro piezoelectric pump is connected to the injection hole of the digital microfluidic chip through a microneedle, the programmable voltage source is used to provide voltage to the multi-way switch, the multi-way switch is used to control the gating of electrodes in the digital microfluidic chip, and the power supply is used to power the main control unit, the micro piezoelectric pump and the programmable voltage source; The host computer is used to generate an activation signal based on the activation sequence of the electrodes in the digital microfluidic chip, and to generate a droplet pumping signal based on the moving path and pumping time of the droplet; The main control unit is used to respond to the activation signal and activate the electrode array corresponding to the activation signal in the digital microfluidic chip through the multi-way switch; The micro piezoelectric pump is used to respond to a droplet pumping signal and perform droplet pumping based on the moving path and pumping time of the droplets. The droplets flow into the digital microfluidic chip through the microneedles and are adsorbed on the activated electrode array.

2. The hybrid digital microfluidic system according to claim 1, characterized in that: The hybrid digital microfluidic system includes a microneedle fixing device made of PDMS material, the microneedle fixing device is provided with a penetrating fixing hole, the diameter of the fixing hole is designed based on the diameter of the microneedle, the microneedle fixing device is bonded to the digital microfluidic chip, the fixing hole of the microneedle fixing device is aligned with the injection hole of the digital microfluidic chip, one end of the microneedle is inserted into the fixing hole, and the other end of the microneedle is connected to the infusion end of the micro piezoelectric pump.

3. The hybrid digital microfluidic system according to claim 2, characterized in that: The microneedle adopts an L-shaped steel needle capillary structure.

4. The hybrid digital microfluidic system according to claim 3, characterized in that: The manufacturing process of the microneedle fixture made of PDMS material includes: The prepolymer and the curing agent are mixed in a ratio of 10:1 and stirred thoroughly to obtain a mixture; The mixture is degassed under vacuum, poured into a mold and cured at 60-80° C. for 1-2 hours, and after curing, demolded to obtain a microneedle fixing device; Use a hole puncher to punch holes through the microneedle fixture to form fixation holes.

5. The hybrid digital microfluidic system according to claim 4, characterized in that: The microneedle fixing device after the through-holes are subjected to plasma treatment by plasma enhanced chemical vapor deposition technology to obtain a microneedle fixing device made of PDMS material.

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