A portable particle and droplet manipulation microfluidic device and its operation method and application

Abstract

A portable microfluidic device for particle and droplet manipulation, its operating method, and its application relate to the technical field of microfluidic detection equipment. The present invention utilizes a thermal field as a method for particle and droplet manipulation, disclosing a portable microfluidic device for particle thermal enrichment, thermal migration, and droplet thermal release. This device integrates an information processing module, an electrical signal output module, a small electron microscope module, and a microfluidic chip, combining portability and visualization, enabling experiments to be conducted on particle thermal enrichment, thermal migration, and droplet thermal release manipulation. The present invention provides a portable microfluidic device for particle and droplet manipulation, its operating method, and its application.

Description

Technical Field

[0001] The present invention relates to the technical field of microfluidic detection equipment, and in particular to a portable particle and droplet manipulation microfluidic device, an operation method and an application thereof. Background Art

[0002] Microfluidics primarily studies fluids and particle samples at the micro- and nanoscale, involving multiple disciplines such as mechanics, materials, electronics, biology, and chemistry. Through micro- and nanofabrication techniques, it integrates traditional large-scale laboratory functions onto a chip measuring a few square centimeters. This technology boasts advantages such as high integration, low sample consumption, and high efficiency, and holds important application prospects in areas such as particle material detection, micro- and nano-actuation, cell manipulation, disease diagnosis, and material synthesis. In microfluidics-based applications, samples such as microparticles, cells, and droplets often require multi-step pretreatment, such as enrichment, migration, transport, and controlled release. Therefore, research into convenient, efficient, highly integrated, and easily visualized particle and droplet manipulation technologies is of great significance.

[0003] Attracted by the broad prospects of microfluidics, a range of particle and droplet manipulation methods based on fluid dynamics, electric fields, magnetic fields, optical fields, and acoustic waves have been developed. While these methods hold great promise, they also have limitations that restrict their further application and promotion. For example, passive methods utilizing fluid forces lack flexibility in particle and droplet manipulation; acoustic and optical manipulation methods rely on precision instruments to generate sound waves or light, while electric and magnetic methods place high demands on sample characteristics. Furthermore, these manipulation methods primarily enable the manipulation of particles and samples at room temperature; a large number of applications, such as PCR reactions and the identification of reducing sugars, require heating conditions to trigger.

[0004] In response to the limitations of conventional particle and droplet manipulation methods, thermal field-based manipulation methods have been proposed and applied. They have simple manipulation principles (including particle thermophoresis, thermal buoyancy convection, and thermal capillary convection), non-contact manipulation, low requirements for the physical and chemical properties of solutions and samples (such as conductivity, dielectric properties, and magnetism, etc.), and can also trigger heating synthesis reactions, so they have good application prospects. However, the current thermal field-based particle and droplet manipulation chips often have relatively simple functions and cannot complete multiple functions such as particle enrichment, migration, and droplet release on a single chip. In addition, existing research often requires the use of large-scale professional equipment such as signal generators, computers, and microscopes, and cannot be used for analysis and detection in general outdoor occasions. This greatly reduces the portability of microfluidic devices and limits their application in areas such as instant diagnosis.

[0005] With the development of communication technology and smart phones, traditional large-scale experimental equipment has begun to develop in the direction of intelligence and miniaturization, which has reduced experimental costs and increased flexibility, and gradually broken through the bottlenecks of poor portability and lack of visualization capabilities of equipment. Summary of the Invention

[0006] The purpose of the present invention is to solve the above technical problems and to provide a portable particle and droplet manipulation microfluidic device and its operation method and application.

[0007] A portable particle and droplet manipulation microfluidic device, the portable particle and droplet manipulation microfluidic device includes a circuit board 24, a small electron microscope module and a microfluidic chip 4, the circuit board 24 includes an information processing module 303, an electrical signal output module 301 and a step-down voltage stabilization module 305, and the circuit board 24 is arranged at the bottom of the portable microfluidic device; the information processing module 303 includes a single-chip microcomputer 304, and the electrical signal output module 301 includes five groups of microelectrode drive circuits 302, and the microelectrode drive circuits 302 are composed of a drive chip, an LED indicator 6 and a wire; the signal output end of the single-chip microcomputer 304 is electrically connected to the chip of each group of microelectrode drive circuits 302 through a wire, and the five chips are electrically connected to the chip of each group of microelectrode drive circuits 302. The signal output end is electrically connected to the enrichment electrode 201, transport electrode a202, transport electrode b203, transport electrode c204 and transport electrode d205 on the ITO conductive glass 10 in sequence through wires, and the five LED indicator lights 6 are electrically connected to the output ends of the five driver chips in sequence through wires; the step-down and voltage stabilization module 305 stabilizes the 12V DC power input of the power supply to power the electrical signal output module 301; and at the same time converts it into a 3.3V voltage to power the CMOS camera 22 and the single-chip microcomputer 304; the small electron microscope module includes a CMOS camera 22 and a magnifying lens 15; the microfluidic chip 4 is composed of an ITO conductive glass 10, a PMMA channel 11, a PDMS cover plate 12 and a thin glass sheet 13;

[0008] The portable particle and droplet manipulation microfluidic device is provided with a housing 8 on the outside, and a top cover 7 is provided on the upper portion of the housing 8; a cylindrical clamp 16 is fixedly connected to the housing 8 via a connecting arm 21; a CMOS camera 22 is fixedly connected to the bottom of the clamp 16, and a magnifying lens 15 is provided directly above the CMOS camera 22; the clamp 16 is wrapped around the outside of the CMOS camera 22 and the magnifying lens 15;

[0009] The portable microfluidic device is provided with a tray 2 on the top, and an ITO conductive glass 10 is provided on the upper surface of the tray 2. The upper surface of the ITO conductive glass 10 is processed with microelectrodes. The microelectrodes are composed of an enrichment electrode 201, a transport electrode a202, a transport electrode b203, a transport electrode c204, and a transport electrode d205. The enrichment electrode 201 is arranged at the center of the microelectrode, and the transport electrodes a202, b203, c204, and d205 are respectively arranged inside the four sides of the rectangular cavity inside the PMMA channel 11; a thin glass sheet 13 is provided on the upper surface of the microelectrode, and a PMMA channel 11 is provided on the upper surface of the thin glass sheet 13. The PMMA channel 11 is a hollow rectangular structure with through holes on the upper surface; a PDMS cover plate 12 is provided on the PMMA channel 11;

[0010] One side of the tray 2 is fixedly connected to the upper end of a connector provided with a slide groove, and the connector is slidably connected to the guide rail 9; the other side of the tray 2 is fixedly connected to the nut 17 through the connector, and the nut 17 is threadedly connected to the lead screw 18, and the guide rail 9 and the lead screw 18 are arranged parallel to each other;

[0011] A dip switch 1 is provided on the upper cover 7, and the dip switch 1 is electrically connected to the positive input terminals of the enrichment electrode 201, transport electrode a202, transport electrode b203, transport electrode c204 and transport electrode d205 respectively through wires; a rocker switch 25 is provided on the side of the shell 8, and the rocker switch 25 is electrically connected to the power supply through a wire, and the power supply is electrically connected to the circuit board 24, and after being processed by the step-down and voltage stabilization module 305, it is electrically connected to the electrical signal output module 301, the LED indicator 6 and the CMOS camera 22 respectively.

[0012] A method for operating a portable particle and droplet manipulation microfluidic device, wherein the operation of the portable particle and droplet manipulation microfluidic device can achieve particle enrichment, directional transport, flexible manipulation, and controlled release of double-emulsion droplets;

[0013] The specific steps for achieving particle enrichment are as follows: an integer DC voltage in the range of 1 to 7 V is inputted to both ends of the enrichment electrode 201, which releases Joule heat under the action of its own internal resistance, causing the buffer solution to heat up locally and triggering thermal buoyancy convection, which drags the particles to the enrichment electrode area for enrichment;

[0014] The specific steps for achieving directional particle transport are as follows: an integer DC voltage in the range of 1 to 8 V is applied to the right and upper transport electrodes, respectively. Under the action of thermal buoyancy convection caused by uneven heating, the particles in the buffer solution are pulled toward the upper right side.

[0015] The specific steps for achieving flexible particle manipulation are as follows: according to the actual required particle motion trajectory, the microcontroller 304 sequentially controls the start and stop of the transport electrode a202, the transport electrode b203, the transport electrode c204 and the transport electrode d205 to achieve the particle movement along the predetermined trajectory;

[0016] The specific steps for achieving controlled release of double-emulsion droplets are as follows: single-core and double-core double-emulsion droplets are respectively introduced into the PMMA channel 11 of the microfluidic chip 4, and the enrichment electrode 201 is driven with an integer DC voltage in the range of 3 to 7 V to cause uneven heating of the buffer solution to induce thermal buoyancy capillary convection, while at the same time causing the overall temperature of the buffer solution to rise, causing instability in the water-oil interface of the double-emulsion droplet, and finally rupturing the oil shell to release the droplet core.

[0017] The invention discloses an application of a portable particle and droplet manipulation microfluidic device, and the application of the portable particle and droplet manipulation microfluidic device in particle thermal enrichment, thermal migration and double emulsion droplet thermal release.

[0018] Beneficial effects of the present invention:

[0019] The present invention uses thermal field as a method of manipulating particles and droplets, and discloses a portable microfluidic device for particle thermal enrichment, thermal migration and droplet thermal release. This type of device integrates an information processing module, an electrical signal output module, a small electron microscope module and a microfluidic chip, and has the two major characteristics of portability and visualization, enabling it to have the conditions for conducting particle thermal enrichment, thermal migration and droplet thermal release manipulation experiments.

[0020] The present invention provides a portable microfluidic device for particle thermal enrichment, thermal migration and thermal release of double emulsion droplets, which has broad prospects in particle sample analysis and detection, microrobot driving, cargo transportation and controlled release.

[0021] The present invention can obtain a portable particle and droplet manipulation microfluidic device and an operation method and application thereof. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is a three-dimensional side view of the portable particle and droplet manipulation microfluidic device of the present invention, 1 represents the DIP switch, 2 represents the tray, 3 represents the pressing plate, 4 represents the microfluidic chip, 5 represents the glass sheet, 6 represents the LED indicator, 7 represents the upper cover, and 8 represents the housing;

[0023] Figure 2 for Figure 1 Actual image of the portable microfluidic device for particle and droplet manipulation;

[0024] Figure 3Figure 9 is a three-dimensional cross-sectional view of the portable particle and droplet manipulation microfluidic device of the present invention. 9 represents a guide rail, 10 represents ITO conductive glass, 11 represents a PMMA channel, 12 represents a PDMS cover plate, 13 represents a thin glass sheet, 14 represents an LED fill light, 15 represents a magnifying lens, 16 represents a fixture, 17 represents a nut, 18 represents a lead screw, 19 represents a bearing, 20 represents a knob, 21 represents a connecting arm, 22 represents a CMOS camera, 23 represents a conductive copper column, 24 represents a circuit board, and 25 represents a rocker switch.

[0025] Figure 4 for Figure 3 In the physical diagram of the circuit board, 301 represents the micro-electrode driving module, 302 represents the micro-electrode driving circuit, 303 represents the information processing module, 304 represents the single-chip microcomputer, and 305 represents the buck-stabilizing module;

[0026] Figure 5 Schematic diagram of the microfluidic chip structure, 201 represents the enrichment electrode, 202 represents the transport electrode a, 203 represents the transport electrode b, 204 represents the transport electrode c, and 205 represents the transport electrode d;

[0027] Figure 6 Provide a connection diagram for each functional module;

[0028] Figure 7 This is the general logic flow chart of the experimental platform;

[0029] Figure 8 The dimensions and assembly diagram of each part of the chip;

[0030] Figure 9 Schematic diagram of the chip for single emulsion droplet generation;

[0031] Figure 10 Generate a schematic for the double-emulsion droplet chip;

[0032] Figure 11 For particle enrichment experiments;

[0033] Figure 12 For particle migration experiments;

[0034] Figure 13 The particles migrate along a specific trajectory;

[0035] Figure 14 This is the heat release experiment of a single-core double emulsion droplet;

[0036] Figure 15 This is the heat release experiment of double-core double emulsion droplets. DETAILED DESCRIPTION

[0037] Specific embodiment 1: This embodiment is a portable particle and droplet manipulation microfluidic device, the portable particle and droplet manipulation microfluidic device includes a circuit board 24, a small electron microscope module and a microfluidic chip 4, the circuit board 24 includes an information processing module 303, an electrical signal output module 301 and a step-down voltage stabilization module 305, and the circuit board 24 is arranged at the bottom of the portable microfluidic device; the information processing module 303 includes a single-chip microcomputer 304, the electrical signal output module 301 includes five groups of microelectrode drive circuits 302, the microelectrode drive circuit 302 consists of a drive chip, an LED indicator 6 and a wire; the signal output end of the single-chip microcomputer 304 is electrically connected to the chip of each group of microelectrode drive circuits 302 through a wire. The signal output ends of the five chips are electrically connected to the enrichment electrode 201, transport electrode a202, transport electrode b203, transport electrode c204 and transport electrode d205 on the ITO conductive glass 10 in sequence through wires, and the five LED indicator lights 6 are electrically connected to the output ends of the five driver chips in sequence through wires; the step-down and voltage stabilization module 305 stabilizes the 12V DC power input of the power supply to power the electrical signal output module 301; and at the same time converts it into a 3.3V voltage to power the CMOS camera 22 and the single-chip microcomputer 304; the small electron microscope module includes a CMOS camera 22 and a magnifying lens 15; the microfluidic chip 4 is composed of an ITO conductive glass 10, a PMMA channel 11, a PDMS cover plate 12 and a thin glass sheet 13;

[0038] The portable particle and droplet manipulation microfluidic device is provided with a housing 8 on the outside, and a top cover 7 is provided on the upper portion of the housing 8; a cylindrical clamp 16 is fixedly connected to the housing 8 via a connecting arm 21; a CMOS camera 22 is fixedly connected to the bottom of the clamp 16, and a magnifying lens 15 is provided directly above the CMOS camera 22; the clamp 16 is wrapped around the outside of the CMOS camera 22 and the magnifying lens 15;

[0039] The portable microfluidic device is provided with a tray 2 on the top, and an ITO conductive glass 10 is provided on the upper surface of the tray 2. The upper surface of the ITO conductive glass 10 is processed with microelectrodes. The microelectrodes are composed of an enrichment electrode 201, a transport electrode a202, a transport electrode b203, a transport electrode c204, and a transport electrode d205. The enrichment electrode 201 is arranged at the center of the microelectrode, and the transport electrodes a202, b203, c204, and d205 are respectively arranged inside the four sides of the rectangular cavity inside the PMMA channel 11; a thin glass sheet 13 is provided on the upper surface of the microelectrode, and a PMMA channel 11 is provided on the upper surface of the thin glass sheet 13. The PMMA channel 11 is a hollow rectangular structure with through holes on the upper surface; a PDMS cover plate 12 is provided on the PMMA channel 11;

[0040] One side of the tray 2 is fixedly connected to the upper end of a connector provided with a slide groove, and the connector is slidably connected to the guide rail 9; the other side of the tray 2 is fixedly connected to the nut 17 through the connector, and the nut 17 is threadedly connected to the lead screw 18, and the guide rail 9 and the lead screw 18 are arranged parallel to each other;

[0041] A dip switch 1 is provided on the upper cover 7, and the dip switch 1 is electrically connected to the positive input terminals of the enrichment electrode 201, transport electrode a202, transport electrode b203, transport electrode c204 and transport electrode d205 respectively through wires; a rocker switch 25 is provided on the side of the shell 8, and the rocker switch 25 is electrically connected to the power supply through a wire, and the power supply is electrically connected to the circuit board 24, and after being processed by the step-down and voltage stabilization module 305, it is electrically connected to the electrical signal output module 301, the LED indicator 6 and the CMOS camera 22 respectively.

[0042] Specific embodiment 2: The difference between this embodiment and specific embodiment 1 is that the ITO conductive glass 10, micro-electrodes, PMMA channels 11, PDMS cover plate 12 and thin glass sheet 13 are all fixed to the upper surface of the tray 2 by a pressing sheet 3.

[0043] The other steps are the same as those in the first embodiment.

[0044] Specific embodiment three: This embodiment differs from specific embodiment one or two in that: a glass sheet 5 is provided on the upper cover 7 , and the glass sheet 5 is provided directly above the microfluidic chip 4 .

[0045] The other steps are the same as those in the first or second embodiment.

[0046] Specific embodiment four: The difference between this embodiment and specific embodiments one to three is that five LED indicator lights 6 are provided on the upper cover 7, which are electrically connected to the enrichment electrode 201, transport electrode a202, transport electrode b203, transport electrode c204 and transport electrode d205 through wires.

[0047] The other steps are the same as those in Specific Embodiments 1 to 3.

[0048] Specific embodiment five: The difference between this embodiment and any one of specific embodiments one to four is that the small electron microscope module also includes an LED fill light 14, and the LED fill light 14 is arranged directly above the magnifying lens 15. The LED fill light 14 and the CMOS camera 22 are both electrically connected to the 3.3V power supply output by the step-down and voltage stabilization module 305 through a conductive copper column 23.

[0049] The other steps are the same as those in Specific Embodiments 1 to 4.

[0050] Specific embodiment 6: This embodiment differs from specific embodiments 1 to 5 in that a bearing 19 is provided in the axial direction of the nut 17 .

[0051] The other steps are the same as those in Specific Embodiments 1 to 5.

[0052] Specific embodiment seven: The difference between this embodiment and specific embodiments one to six is ​​that a knob 20 is provided at the tail of the lead screw 18 .

[0053] The other steps are the same as those in Specific Embodiments 1 to 6.

[0054] Specific embodiment eight: This embodiment provides a method for operating a portable microfluidic device, wherein the operation of the portable microfluidic device can achieve particle enrichment, directional transport, flexible manipulation, and controlled release of double emulsion droplets;

[0055] The specific steps for achieving particle enrichment are as follows: an integer DC voltage in the range of 1 to 7 V is inputted to both ends of the enrichment electrode 201, which releases different degrees of Joule heat under the action of its own internal resistance, causing the buffer solution to locally heat up and trigger thermal buoyancy convection, dragging the particles at different speeds in the enrichment electrode area to complete enrichment;

[0056] The specific steps for achieving directional particle transport are as follows: an integer DC voltage in the range of 1 to 8 V is applied to the right and upper transport electrodes, respectively. Under the action of thermal buoyancy convection caused by uneven heating, the particles in the pulling buffer move toward the upper right side at different speeds;

[0057] The overall experimental results show that the greater the direct current input at both ends of the enrichment electrode 201, the more intense the induced thermal buoyancy convection, and thus the faster the particle movement speed.

[0058] The specific steps to achieve flexible control of particles are as follows: according to the actual required particle motion trajectory, the single-chip microcomputer 304 controls the start and stop of the transport electrode a202, the transport electrode b203, the transport electrode c204 and the transport electrode d205 in sequence to realize the movement of the particles along the predetermined trajectory; if the particles need to move along a rectangular trajectory, the transport electrodes need to be controlled to start and stop in the order of left, bottom, right and top to realize the rectangular trajectory movement of the particles; if the particles need to move along a T-shaped trajectory, the transport electrodes need to be controlled to start and stop in the order of right, left and bottom, where the electrode start time for pulling the particles to the left should be half the electrode start time for pulling the particles to the right, so that the particles can move along a T-shaped trajectory.

[0059] The specific steps for achieving controlled release of double-emulsion droplets are as follows: single-core and double-core double-emulsion droplets are respectively introduced into the PMMA channel 11 of the microfluidic chip 4, and the enrichment electrode 201 is driven with an integer DC voltage in the range of 3 to 7 V to cause uneven heating of the buffer solution to induce thermal buoyancy capillary convection, while at the same time causing the overall temperature of the buffer solution to rise, causing instability in the water-oil interface of the double-emulsion droplet, and finally rupturing the oil shell to release the droplet core.

[0060] Specific embodiment 9: The difference between this embodiment and specific embodiment 8 is that when achieving particle enrichment, directional transport and flexible manipulation, the particles use solidified water-in-oil single emulsion droplets with photocurable oil as the inner phase, and use Figure 9 The glass capillary chip shown in the figure is generated in the following specific steps: the inner diameter of the tapered tip of the incident tube inside the chip is 40 μm, the inner diameter of the tapered tip of the collecting tube is 90 μm, and the linear distance between the two tube openings is 50 μm; the external phase solution is a 5 wt% polyvinyl alcohol aqueous solution, and the internal phase is a mixed solution of 98 wt% 1,6-hexanediol diacrylate and 2 wt% 2-hydroxy-2-methyl-1-phenyl-1-propanone. The volume flow rate of the internal phase is Qo = 8 mL / h, and the volume flow rate of the external phase is Qi = 0.2 mL / h. The oil-in-water single emulsion droplets generated in the glass capillary chip are cured by ultraviolet light to form solid particles with an average size of 35 μm.

[0061] To achieve controlled release of double-emulsion droplets, single-core and dual-core double-emulsion droplets are generated using a glass capillary chip. The specific steps are as follows: the chip consists of two inlet tubes, a collection tube, and a square tube. The inner phase solution is injected through the inner phase inlet tube and is sheared and dispersed near the tip of the intermediate phase inlet tube. The intermediate phase solution wraps around the inner phase solution and flows out of the intermediate phase inlet tube, where it is sheared by the outer phase solution to generate double emulsion droplets.

[0062] In such Figure 10Inside the glass capillary chip shown, the inner diameter of the tapered tip of the inner phase incident tube is 30 μm, the inner diameter of the tapered tip of the intermediate phase incident tube is 100 μm, the inner diameter of the tapered tip of the collection tube is 350 μm, and the straight-line distance between the intermediate phase incident tube and the collection tube is 60 μm; the inner phase solution is a mixed solution consisting of 1 wt% polyvinyl alcohol, 50 wt% glycerol, and 49 wt% deionized water; the intermediate phase solution is a mixed solution consisting of 97 wt% dimethyl silicone oil and 3 wt% silicone resin RSN-0749; and the outer phase solution is a 5 wt% polyvinyl alcohol aqueous solution.

[0063] When the volume flow rate of the inner phase solution is set to Qo = 2mL / h, the volume flow rate of the intermediate phase solution is Qm = 1mL / h, and the volume flow rate of the external phase solution is Qi = 0.35mL / h, single-core water-in-oil-in-water double emulsion droplets with an outer diameter of 300μm are generated; when the volume flow rate of the inner phase solution is set to Qo = 1mL / h, the volume flow rate of the intermediate phase solution is Qm = 1.5mL / h, and the volume flow rate of the external phase solution is Qi = 0.35mL / h, double-core water-in-oil-in-water double emulsion droplets with an outer diameter of 320μm are generated.

[0064] The other steps are the same as those in the eighth embodiment.

[0065] Specific embodiment ten: This embodiment provides an application of a portable particle and droplet manipulation microfluidic device, and the portable particle and droplet manipulation microfluidic device is used in particle thermal enrichment, thermal migration and double emulsion droplet thermal release.

[0066] The following examples are used to verify the beneficial effects of the present invention:

[0067] Example 1:

[0068] (1) Equipment installation and operation logic:

[0069] This embodiment integrates an information processing module 303, an electrical signal output module 301, a small electron microscope module, and a microfluidic chip 4, making the experimental equipment miniaturized, portable, and simplified, freeing it from the constraints of a laboratory environment. The information processing module 303 is responsible for outputting pulse-width modulation (PWM) waveforms, outputting five independent PWM waveforms through five I / O ports. Simultaneously, an internal timing function controls the start and stop of the five I / O ports according to a specific schedule. The electrical signal output module 301, based on the SI4336 chip, receives the I / O port voltage output from the information processing module 303, amplifies it, and outputs an integer voltage within the range of 3V to 8V in the form of direct current. The small electron microscope module integrates a CMOS camera 22, a magnifying lens 15, and an LED fill light 14. It transmits magnified images to a mobile phone app via Wi-Fi, improving the portability of the experimental equipment and enabling real-time observation.

[0070] This embodiment relates to a portable microfluidic device for thermal accumulation, thermal migration of particles and thermal release of double-emulsion droplets, which has the function of real-time observation of the accumulation, transport and controllable release of particles or droplets under a DC voltage range of 0V to 12V.

[0071] Among them, the information processing module 303 is based on the single-chip microcomputer 304, and the model of the single-chip microcomputer 304 is STM32F103C8T6. Its built-in PWM (pulse width modulation) function can realize adjustable output voltage of the driving circuit by controlling the duty cycle. By driving the five independent I / O ports of the single-chip microcomputer to output PWM signals, the five micro-electrode driving circuits output DC voltages accordingly, thereby realizing control of the enrichment electrode 201, transport electrode a202, transport electrode b203, transport electrode c204 and transport electrode d205. In addition, relying on the timing function of the single-chip microcomputer, the five PWM signals can be controlled to start in a certain regular sequence, thereby completing the sequential start and stop work of the enrichment electrode 201 and the four transport electrodes, and realizing flexible transport of particles or droplets.

[0072] Among them, the electrical signal output module 301 is based on the SI4336 chip, receives the PWM signal from the single-chip microcomputer, and realizes the adjustable 0-12V voltage at the output end under the 12V external power supply; among them, the small electron microscope module integrates the magnifying lens 15, the LED fill light 14, the CMOS camera 22 and the WIFI module. The CMOS camera 22 reads the image magnified by the magnifying lens 15 and transmits it to the mobile phone APP through the WIFI module. The small electron microscope is clamped and wrapped by the clamp 16 as a whole and fixed to the shell 8 by the limit bolt and the tightening bolt.

[0073] The microfluidic chip 4 consists of an indium tin oxide (ITO) conductive glass 10, a PMMA channel 11, a PDMS cover plate 12, and a thin glass sheet 13. The conductive layer of the ITO conductive glass 10 is processed by conventional photolithography into microelectrodes of specific shapes. To isolate the buffer solution from the microelectrodes, a thin glass sheet 13, only 0.1 mm thick, is placed over the photolithographic electrodes. The PMMA channel 11 is a hollow rectangular structure with a through-hole on its top surface. After the buffer solution is dripped into the experiment, the PDMS cover plate 12 can be placed over the channel to prevent bubbles from affecting observation. The PDMS covering the top has the same side length as the PMMA and is slightly thinner. The resulting microelectrodes include a central enrichment electrode 201 and transport electrodes arranged around the periphery.

[0074] Among them, this embodiment provides a flexible control solution at the software level by using the internal timing function of the information processing module. The start and stop of the five micro-electrode drive circuits can also be manually controlled by the dip switch 1. The micro-electrode drive circuits 1-5 correspond to channels 1-5 of the 6p dip switch respectively.

[0075] In addition, the small electron microscope is fixed on the shell 8, which is inconvenient to adjust. Therefore, in order to meet the imaging requirements, a focusing device consisting of six parts: a tray 2, a guide rail 9, a nut 17, a screw 18, a bearing 19 and a knob 20 is provided. The knob 20 is rotated to drive the nut 17 and the screw 18 to convert the rotational motion into axial motion, and the microfluidic chip 4 is placed on the tray 2 and fixed with the pressing sheet 3 to achieve focusing.

[0076] (2) Design and fabrication of microfluidic chips:

[0077] The key structural parameters of microfluidic chip 4 are as follows: the glass substrate with the electrode structure is 50 mm long, 40 mm wide, and 1.1 mm high. The indium tin oxide film used to make the microheater is 1 μm thick. The thin glass sheet 13, used to isolate the fluid from the microheater, measures 25 mm × 25 mm × 0.1 mm. The PMMA channel cavity is 3 mm wide and 3 mm deep. The PDMS cover is 2 mm thick. Figure 8 .

[0078] The microheater structure was fabricated using a glass sheet with an indium tin oxide film and photoresist AZ4620 based on standard soft lithography technology. The PMMA channel 11 was processed using a CNC machine tool. A 0.1 mm thick thin glass sheet 13 was adhered to the glass substrate using shadowless adhesive. The PMMA channel 11 was adhered to the thin glass sheet 13 using double-sided tape.

[0079] (3) Preparation of particles and droplets:

[0080] In the particle enrichment and directional transport experiments, the particles used were solidified oil-in-water single emulsion droplets with photocurable oil as the inner phase, and thus were generated in one step using a glass capillary chip. Figure 9 As shown, the inner diameter of the tapered tip of the incident tube inside the chip is 40 μm, the inner diameter of the tapered tip of the collecting tube is 90 μm, and the straight-line distance between the two tube openings is 50 μm; the external phase solution is a 5 wt% polyvinyl alcohol aqueous solution, and the internal phase is a mixed solution of 98 wt% 1,6-hexanediol diacrylate (HDDA) and 2 wt% 2-hydroxy-2-methyl-1-phenyl-1-propanone (HMPP). The volume flow rate of the internal phase is Qo = 8 mL / h, and the volume flow rate of the external phase is Qi = 0.2 mL / h. The water-in-oil single emulsion droplets generated by the glass capillary chip are cured by ultraviolet light to generate solid particles with an average size of 35 μm.

[0081] In the double emulsion droplet controlled release experiment, the required droplets also need to be prepared with the help of glass capillary chips, but the chip structure and generation principle are different. Figure 10 As shown, this type of chip consists of two incident tubes, a collecting tube and a square tube. The inner phase solution is injected through the inner phase incident tube and is sheared and discrete near the tip of the intermediate phase incident tube. The intermediate phase solution wraps the inner phase solution and flows out of the intermediate phase incident tube and is sheared by the outer phase solution to generate double emulsion droplets, that is, the double emulsion droplets are generated by a two-step method.

[0082] In such Figure 10 Inside the glass capillary chip shown, the inner diameter of the tapered tip of the inner phase incident tube is 30 μm, the inner diameter of the tapered tip of the intermediate phase incident tube is 100 μm, the inner diameter of the tapered tip of the collection tube is 350 μm, and the straight-line distance between the intermediate phase incident tube and the collection tube is 60 μm. The inner phase solution is a mixed solution consisting of 1 wt% polyvinyl alcohol, 50 wt% glycerol, and 49 wt% deionized water, the intermediate phase solution is a mixed solution consisting of 97 wt% dimethyl silicone oil and 3 wt% RSN-0749, and the outer phase solution is a 5 wt% polyvinyl alcohol aqueous solution.

[0083] When the volume flow rate of the inner phase solution is set to Qo = 2mL / h, the volume flow rate of the intermediate phase solution is Qm = 1mL / h, and the volume flow rate of the external phase solution is Qi = 0.35mL / h, single-core water-in-oil-in-water double emulsion droplets with an outer diameter of 300μm are generated; when the volume flow rate of the inner phase solution is set to Qo = 1mL / h, the volume flow rate of the intermediate phase solution is Qm = 1.5mL / h, and the volume flow rate of the external phase solution is Qi = 0.35mL / h, double-core water-in-oil-in-water double emulsion droplets with an outer diameter of 320μm are generated.

[0084] (4) Particle enrichment and directional transport:

[0085] The experiments completed by this equipment include but are not limited to the following three parts. The first is the particle enrichment experiment, such as Figure 11 As shown, an integer DC voltage in the range of 1 to 7 V is inputted at both ends of the enrichment electrode 201, and Joule heat of varying degrees is released under the action of its own internal resistance, causing the buffer solution to locally heat up and trigger thermal buoyancy convection, dragging the particles to complete enrichment in the enrichment electrode area at different speeds.

[0086] The second is the particle directional transport experiment, such as Figure 12 As shown, an integer DC voltage in the range of 1 to 8 V is applied to both ends of the transport electrodes on the right and upper sides, respectively. Under the action of thermal buoyancy convection caused by uneven heating, the particles in the pulling buffer move toward the upper right side at different speeds.

[0087] Finally, there is the flexible manipulation experiment of particles, such as Figure 13As shown, by setting the start and stop time of each PWM signal in the information processing module 303 of the present invention, flexible control of particles can be achieved.

[0088] If you want to control the movement of particles along a rectangular trajectory, you need to control the transport electrodes to start and stop in the order of left, bottom, right, and top to realize the movement of particles along a rectangular trajectory; if you want to make the particles move along a T-shaped trajectory, you need to control the transport electrodes to start and stop in the order of right, left, and bottom. The start-up time of the electrode that pulls the particles to the left should be half of the start-up time of the electrode that pulls the particles to the right, so that the particles can move along a T-shaped trajectory.

[0089] (5) Controlled release of double emulsion droplets:

[0090] After the above steps to prepare single-core and double-core double-emulsion droplets, Figure 14-15 As shown, single-core and double-core double-emulsion droplets are respectively introduced into the PMMA channel 11 of the microfluidic chip 4, and the enrichment electrode 201 is driven with an integer DC voltage in the range of 3 to 7 V to unevenly heat the buffer solution, triggering thermal buoyancy capillary convection and increasing the overall temperature of the buffer solution, causing instability in the water-oil interface of the double-emulsion droplet, and eventually rupturing the oil shell to release the droplet core.

Claims

1. A portable microfluidic device for particle and droplet manipulation, characterized in that The portable particle and droplet manipulation microfluidic device is used for particle thermal enrichment, thermal migration and double emulsion droplet thermal release; the portable particle and droplet manipulation microfluidic device comprises a circuit board (24), a small electron microscope module and a microfluidic chip (4); the circuit board (24) comprises an information processing module (303), an electric signal output module (301) and a step-down voltage stabilization module (305); the circuit board (24) is arranged at the bottom of the portable microfluidic device; the information processing module (303) comprises a single chip microcomputer (304); the electric signal output module (301) comprises five groups of microelectrode driving circuits (302); the microelectrode driving circuits (302) are composed of a driving chip, an LED indicator light (6) and a wire; the signal output end of the single chip microcomputer (304) is electrically connected to the chip of each group of microelectrode driving circuits (302) through a wire, and the signal output ends of the five chips are sequentially connected to the enrichment electrode (201), the transport electrode a (202), the transport electrode α (203) and the transport electrode β (204) on the ITO conductive glass (10) through a wire. The electrode b (203), the transport electrode c (204) and the transport electrode d (205) are electrically connected to each other, and the five LED indicators (6) are electrically connected to the output terminals of the five driver chips in sequence through wires; the step-down voltage stabilizing module (305) stabilizes the 12V DC power input by the power supply to supply power to the electrical signal output module (301); and at the same time converts it into a 3.3V voltage to supply power to the CMOS camera (22) and the single-chip microcomputer (304); the small electron microscope module includes a CMOS camera (22) and a magnifying glass The microfluidic chip (4) is composed of an ITO conductive glass (10), a PMMA channel (11), a PDMS cover plate (12) and a thin glass sheet (13); The portable microfluidic device is provided with a housing (8) on the outside, and an upper cover (7) is provided on the upper part of the housing (8); a cylindrical clamp (16) is fixedly connected to the housing (8) via a connecting arm (21); a CMOS camera (22) is fixedly connected to the bottom of the clamp (16), and a magnifying lens (15) is provided directly above the CMOS camera (22); the clamp (16) is wrapped around the outside of the CMOS camera (22) and the magnifying lens (15); The portable microfluidic device is provided with a tray (2) on the top, and an ITO conductive glass (10) is provided on the upper surface of the tray (2). The upper surface of the ITO conductive glass (10) is processed with a microelectrode, and the microelectrode consists of an enrichment electrode (201), a transport electrode a (202), a transport electrode b (203), a transport electrode c (204) and a transport electrode d (205). The enrichment electrode (201) is provided at the center of the microelectrode, and the transport electrode a (202), the transport electrode b (203), the transport electrode c (204) and the transport electrode d (205) are respectively provided inside the four sides of the rectangular cavity inside the PMMA channel (11); a thin glass sheet (13) is provided on the upper surface of the microelectrode, and a PMMA channel (11) is provided on the upper surface of the thin glass sheet (13). The PMMA channel (11) is a hollow rectangular structure, and a through hole is provided on the upper surface; a PDMS cover plate (12) is provided on the PMMA channel (11); One side of the tray (2) is fixedly connected to the upper end of a connector provided with a slide groove, and the connector is slidably connected to the guide rail (9); the other side of the tray (2) is fixedly connected to the nut (17) through the connector, and the nut (17) is threadedly connected to the lead screw (18), and the guide rail (9) and the lead screw (18) are arranged in parallel; The upper cover (7) is provided with a dial switch (1), and the dial switch (1) is electrically connected to the positive input terminals of the enrichment electrode (201), the transport electrode a (202), the transport electrode b (203), the transport electrode c (204) and the transport electrode d (205) through wires; the side of the shell (8) is provided with a rocker switch (25), and the rocker switch (25) is electrically connected to the power supply through wires, and the power supply is electrically connected to the circuit board (24), and after being processed by the step-down voltage stabilization module (305), it is electrically connected to the electric signal output module (301), the LED indicator light (6) and the CMOS camera (22).

2. A portable particle and droplet manipulation microfluidic device according to claim 1, characterized in that The ITO conductive glass (10), micro-electrodes, PMMA channels (11), PDMS cover plate (12) and thin glass sheet (13) are all fixed on the upper surface of the tray (2) via a pressing sheet (3).

3. A portable particle and droplet manipulation microfluidic device according to claim 1, characterized in that A glass sheet (5) is provided on the upper cover (7), and the glass sheet (5) is provided directly above the microfluidic chip (4).

4. A portable particle and droplet manipulation microfluidic device according to claim 1, characterized in that The upper cover (7) is provided with five LED indicator lights (6), which are electrically connected to the enrichment electrode (201), the transport electrode a (202), the transport electrode b (203), the transport electrode c (204) and the transport electrode d (205) through wires.

5. A portable particle and droplet manipulation microfluidic device according to claim 1, characterized in that A bearing (19) is provided in the axial direction of the nut (17).

6. A portable particle and droplet manipulation microfluidic device according to claim 1, characterized in that The tail of the lead screw (18) is provided with a knob (20).

7. A method for operating a portable particle and droplet manipulation microfluidic device according to any one of claims 1 to 6, characterized in that The operation of the portable microfluidic device enables particle enrichment, directional transport, flexible manipulation, and controlled release of double emulsion droplets; The specific steps for achieving particle enrichment are as follows: an integer DC voltage in the range of 1 to 7 V is inputted at both ends of the enrichment electrode (201), and Joule heat is released under the action of its own internal resistance, causing the buffer solution to locally heat up and induce thermal buoyancy convection, dragging the particles to the enrichment electrode area to complete enrichment; The specific steps for achieving directional particle transport are as follows: an integer DC voltage in the range of 1 to 8 V is applied to the right and upper transport electrodes, respectively. Under the action of thermal buoyancy convection caused by uneven heating, the particles in the buffer solution are pulled toward the upper right side. The specific steps for realizing flexible particle control are as follows: according to the actual required particle motion trajectory, the start and stop of the transport electrode a (202), the transport electrode b (203), the transport electrode c (204) and the transport electrode d (205) are controlled in sequence by the single chip microcomputer (304) to realize the movement of the particle along the predetermined trajectory; The specific steps for achieving controlled release of double emulsion droplets are as follows: single-core and double-core double emulsion droplets are introduced into the PMMA channel (11) of the microfluidic chip (4) respectively, and the enrichment electrode (201) is driven with an integer DC voltage in the range of 3~7V to cause uneven heating of the buffer solution to induce thermal buoyancy capillary convection, while at the same time causing the overall temperature of the buffer solution to rise, causing instability of the water-oil interface of the double emulsion droplet, and finally the oil shell ruptures to release the droplet core; To achieve particle enrichment, directional transport, and flexible manipulation, the particles were solidified using water-in-oil single emulsion droplets with a photocurable oil as the internal phase, and were generated using a glass capillary chip. The specific steps are as follows: the inner diameter of the tapered tip of the incident tube inside the chip is 40 μm, the inner diameter of the tapered tip of the collection tube is 90 μm, and the straight-line distance between the two tube openings is 50 μm; the external phase solution is a 5 wt% polyvinyl alcohol aqueous solution, and the internal phase is a mixed solution of 98 wt% 1,6-hexanediol diacrylate and 2 wt% 2-hydroxy-2-methyl-1-phenyl-1-propanone. The volume flow rate of the internal phase is Qo = 8 mL / h, and the volume flow rate of the external phase is Qi = 0.2 mL / h. The water-in-oil single emulsion droplets generated on the glass capillary chip are cured by ultraviolet light to form solid particles with an average size of 35 μm. To achieve controlled release of double-emulsion droplets, single-core and dual-core double-emulsion droplets are generated using a glass capillary chip. The specific steps are as follows: the chip consists of two inlet tubes, a collection tube, and a square tube. The inner phase solution is injected through the inner phase inlet tube and is sheared and dispersed near the tip of the intermediate phase inlet tube. The intermediate phase solution wraps around the inner phase solution and flows out of the intermediate phase inlet tube, where it is sheared by the outer phase solution to generate double emulsion droplets. Inside the glass capillary chip, the inner diameter of the tapered tip of the inner phase incident tube is 30 μm, the inner diameter of the tapered tip of the intermediate phase incident tube is 100 μm, the inner diameter of the tapered tip of the collection tube is 350 μm, and the straight-line distance between the intermediate phase incident tube and the collection tube is 60 μm; the inner phase solution is a mixed solution composed of 1 wt% polyvinyl alcohol, 50 wt% glycerol, and 49 wt% deionized water, the intermediate phase solution is a mixed solution composed of 97 wt% dimethyl silicone oil and 3 wt% silicone resin RSN-0749, and the outer phase solution is a 5 wt% polyvinyl alcohol aqueous solution; When the volume flow rate of the inner phase solution is set to Qo=2 mL / h, the volume flow rate of the intermediate phase solution is Qm=1 mL / h, and the volume flow rate of the external phase solution is Qi=0.35 mL / h, single-core water-in-oil-in-water double emulsion droplets with an outer diameter of 300 μm are generated; when the volume flow rate of the inner phase solution is set to Qo=1 mL / h, the volume flow rate of the intermediate phase solution is Qm=1.5 mL / h, and the volume flow rate of the external phase solution is Qi=0.35 mL / h, double-core water-in-oil-in-water double emulsion droplets with an outer diameter of 320 μm are generated.

Images