Chip detachable press-fit liquid drop microfluidic production equipment

Abstract

The invention discloses chip detachable press-fit liquid drop microfluidic production equipment. The production equipment comprises a chip press-fit module, a continuous liquid inlet module and a microsphere detection module, the chip press-fit module comprises a chip assembly, a lever and a press-fit air cylinder, the chip assembly comprises a cover plate, a micro-fluidic chip and a bottom plate which are stacked from top to bottom, a channel is formed in the micro-fluidic chip, one end of the lever is connected with the press-fit air cylinder, and the other end of the lever applies pressure to the chip assembly through a pressing assembly so as to seal the micro-fluidic chip; the continuous liquid inlet module comprises a liquid inlet tank and a liquid supplementing tank, the liquid inlet tank is connected with a liquid inlet of the chip assembly through a liquid outlet pipeline, the liquid supplementing tank is connected with the liquid inlet tank through a liquid supplementing pipeline, and a check valve is arranged on the liquid supplementing pipeline; and the microsphere detection module is used for detecting the particle size of microspheres contained in the solution discharged from the liquid outlet of the chip assembly. According to the equipment, the micro-fluidic chip can be detached, the continuous production of liquid drop micro-fluidic can be realized, and the liquid drop on-line detection function is realized at the same time.

Description

Technical Field

[0001] This invention relates to the field of droplet microfluidics, specifically to a chip-detachable press-fit droplet microfluidic production equipment. Background Technology

[0002] Microfluidics refers to a technology that manipulates fluids at the micrometer scale. This technology can miniaturize the basic functions of chemical and biological laboratories onto a chip of just a few square centimeters, hence the name "lab-on-a-chip." Droplet microfluidics, as an important branch of microfluidic chip research, has been developed in recent years based on traditional continuous flow microfluidic systems. Droplet microfluidics technology has wide applications in biomedicine. For example, by precisely manipulating microdroplets in a reaction, it is possible to reduce the consumption of reaction reagents and improve reagent utilization.

[0003] Currently, droplet microfluidic control ball devices use bonded chips. These microfluidic chips cannot be disassembled, and once the channels are blocked by solidified polymers or other substances, it is difficult to clean the bonded chip, rendering the entire chip unusable. Furthermore, existing microfluidic control ball devices require manually adjustable CCD cameras for observing the microfluidic chip channels, which becomes extremely cumbersome as the number of channels increases. Current microfluidic control ball devices lack integrated pressure control systems, requiring external air compressors and pressure control systems, resulting in low integration. After scaling up production, multi-channel chip microsphere production requires large amounts of external and internal phase solutions (especially the external phase solution). If the solution in the container is depleted, production must be stopped and replenished before resuming. Restarting after a shutdown requires cleaning the chips and tubing (polymers in the solution easily solidify and block channels). This not only prevents continuous production but also consumes significant time, manpower, and resources, greatly reducing production efficiency. Furthermore, restarting and debugging the chips also requires considerable time. As the output of the channel increases, the frequency of detecting the microsphere size also increases, which inadvertently increases the complexity of the workload.

[0004] Therefore, in the scaled-up production of droplet microfluidics, it is necessary to develop a multi-functional integrated droplet microfluidic production equipment that features detachable chips, high throughput, continuous operation, and intelligent operation to overcome the shortcomings of scaled-up microfluidic production. Summary of the Invention

[0005] The purpose of this invention is to address the aforementioned problems of current droplet microfluidic production equipment by providing a chip-detachable pressing droplet microfluidic production equipment. This equipment not only enables the detachable microfluidic chip but also allows for continuous production of droplet microfluidics, while simultaneously enabling online observation of droplet generation and online detection of microspheres.

[0006] This invention is achieved through the following technical solution: This invention provides a chip-removable, press-fit microfluidic production device, comprising a chip pressing module, a continuous liquid feeding module, and a microsphere detection module. The chip pressing module includes a chip assembly, a lever, and a pressing cylinder. The chip assembly includes a cover plate, a microfluidic chip, and a base plate stacked from top to bottom. Channels are formed on the microfluidic chip. One end of the lever is connected to the output end of the pressing cylinder, and the other end applies pressure to the chip assembly via a pressing component to achieve sealing of the microfluidic chip. The continuous liquid feeding module includes an inlet tank and a replenishment tank. The inlet tank is connected to the inlet of the chip assembly via an outlet pipe, and the replenishment tank is connected to the inlet tank via a replenishment pipe equipped with a check valve. The microsphere detection module is used to detect the particle size of the microspheres contained in the solution discharged from the outlet of the chip assembly.

[0007] As a further embodiment of the present invention, the lever has a force application point, a resistance point, and a fulcrum. The force application point is connected to a pressing cylinder, the resistance point is connected to a pressing assembly, and the distance between the force application point and the fulcrum is greater than the distance between the resistance point and the fulcrum.

[0008] As a further embodiment of the present invention, the pressing assembly includes a pressing plate and a pressing rod. One end of the pressing rod is fixedly connected to the pressing plate, and the other end is connected to a lever. After the pressing cylinder pushes the lever to move, the pressing plate applies a pressing force to the cover plate.

[0009] As a further embodiment of the present invention, the microfluidic chip is an open chip rather than a bonded chip. The channel on the chip has a flow channel, an external phase inlet, an internal phase inlet, a shearing port, and an outlet. The flow channel is located on the upper surface of the microfluidic chip. The external phase inlet and the internal phase inlet are connected to an inlet tank to allow liquid to enter the flow channel. The external phase liquid and the internal phase liquid flow into the shearing port, where they are sheared to form microspheres, and then flow to the outlet.

[0010] As a further embodiment of the present invention, the top of the liquid inlet tank and the liquid replenishment tank are respectively provided with air inlet pipes. The air inlet pipe on the liquid inlet tank is used to adjust the air pressure inside the tank to control the liquid output of the liquid outlet pipe, and the air inlet pipe on the liquid replenishment tank is used to adjust the air pressure inside the tank to control the liquid output of the liquid replenishment pipe.

[0011] As a further aspect of the present invention, the diameter of the replenishment pipeline is greater than or equal to the diameter of the outlet pipeline, and the air pressure provided by the air inlet pipeline on the replenishment tank is 20%-100% greater than the air pressure provided by the air inlet pipeline on the inlet tank.

[0012] As a further embodiment of the present invention, both the inlet tank and the replenishment tank are equipped with a liquid level detector and a safety valve. The liquid level detector is used to detect the liquid level in the tank to provide feedback on whether liquid needs to be replenished into the tank. The safety valve is used to control the pressure in the tank to prevent it from exceeding the limit.

[0013] As a further embodiment of the present invention, the microsphere detection module includes a high-speed camera, a detection chipset, and a light source. The detection chipset includes a detection chip and a chip fixture. The detection chip is disposed in the chip fixture and has a channel. The chip fixture has a solution inlet and a solution outlet, as well as observation ports located on the upper and lower sides of the detection chip. The high-speed camera and the light source are respectively located above and below the two observation ports to capture the morphology of the microspheres in the detection chip channel.

[0014] As a further aspect of the present invention, the detection chip is made of a transparent material, and the internal channel size of the detection chip is larger than the microsphere diameter but smaller than the sum of the diameters of two microspheres.

[0015] As a further aspect of the present invention, it also includes an observation system for observing the channels of a microfluidic chip. The observation system includes a CCD camera and an XYZ three-axis platform. The CCD camera is connected to the XYZ three-axis platform to observe each chip channel through the observation port.

[0016] Compared with the prior art, the present invention has the following advantages and beneficial effects: The chip assembly in this invention includes a cover plate, a microfluidic chip, and a base plate stacked from top to bottom. The microfluidic chip is sealed using a lever-pressing method, allowing for disassembly and cleaning, which extends its service life. The combination of a pressing cylinder and lever structure prevents instability during pressing. Since the continuous liquid inlet module includes an inlet tank and a replenishment tank, liquid can be added to the inlet tank when the level is low, enabling continuous production of droplet microfluidics and significantly improving pellet production efficiency. An observation port and CCD camera above the microfluidic chip allow for real-time monitoring of each channel's operation. Furthermore, a microsphere detection module enables online detection of the microsphere size in the solution exiting the chip assembly, improving microsphere detection efficiency. Attached Figure Description

[0017] To more clearly illustrate the technical solutions of the exemplary embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly described below. It should be understood that the following drawings only show some embodiments of the present invention and should not be considered as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort. In the drawings: Figure 1 This is a schematic diagram of the pressing and sealing part of the chip detachable pressing droplet microfluidic production equipment of the present invention; Figure 2 This is a schematic diagram of the lever in this invention; Figure 3This is a schematic diagram of the single-channel microfluidic chip in this invention; Figure 4 This is a schematic diagram of the continuous liquid feeding module in this invention; Figure 5 This is a schematic diagram of the microsphere detection module in this invention; Figure 6 This is a schematic diagram of the detection chipset in the present invention.

[0018] The attached diagram shows the markings and corresponding component names: Compression cylinder 1-1, lever 1-2, pressing assembly 1-3, chip assembly 1-4, XYZ three-axis platform 1-5, pressure control system 1-6, micro air pump 1-7, observation system 1-8, observation port 1-9, external phase inlet 3-1, internal phase inlet 3-2, shearing port 3-3, outlet 3-4, inlet tank 4-1, outlet pipeline 4-2, air inlet pipeline 4-3, safety valve 4-4, level detector 4-5, upper limit monitor Measurement point 4-6, lower limit monitoring point 4-7, cover 4-8, replenishment pipeline 4-9, check valve 4-10, air inlet pipeline 4-11, liquid level detector 4-12, upper limit monitoring point 4-13, lower limit monitoring point 4-14, cover 4-15, replenishment tank 4-16, high-speed camera 5-1, detection chip set 5-2, light source 5-3, solution inlet 5-4, observation port 5-5, solution outlet 5-6, detection chip 5-7. Detailed Implementation

[0019] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the embodiments and accompanying drawings. The illustrative embodiments and descriptions of the present invention are only used to explain the present invention and are not intended to limit the present invention.

[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains; the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the application; the terms “comprising” and “having”, and any variations thereof, in the specification, claims, and foregoing description of the drawings are intended to cover non-exclusive inclusion.

[0021] In the description of the embodiments of this application, technical terms such as "first" and "second" are used only to distinguish different objects and should not be construed as indicating or implying relative importance or implicitly indicating the number, specific order, or primary and secondary relationship of the indicated technical features.

[0022] In this document, the term "embodiment" means that a particular feature, structure, or characteristic described in connection with an embodiment may be included in at least one embodiment of this application. The appearance of this phrase in various places throughout the specification does not necessarily refer to the same embodiment, nor is it a separate or alternative embodiment mutually exclusive with other embodiments. It will be explicitly and implicitly understood by those skilled in the art that the embodiments described herein can be combined with other embodiments.

[0023] In the description of the embodiments in this application, the term "and / or" is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent three cases: A exists, A and B exist simultaneously, and B exists. In addition, the character " / " in this document generally indicates that the related objects before and after it have an "or" relationship.

[0024] In the embodiments of this application, the same reference numerals denote the same components, and for the sake of brevity, detailed descriptions of the same components are omitted in different embodiments. It should be understood that the thickness, length, width, and other dimensions of various components in the embodiments of this application shown in the accompanying drawings, as well as the overall thickness, length, width, and other dimensions of the integrated device, are merely illustrative and should not constitute any limitation on this application.

[0025] In the description of the embodiments of this application, the term "multiple" refers to two or more (including two), similarly, "multiple sets" refers to two or more (including two sets), and "multiple pieces" refers to two or more (including two pieces), unless otherwise explicitly specified.

[0026] In the description of the embodiments of this application, the technical terms "center," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," "counterclockwise," "axial," "radial," and "circumferential" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing the embodiments of this application and simplifying the description, and are not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the embodiments of this application.

[0027] In the description of the embodiments of this application, unless otherwise expressly specified and limited, technical terms such as "installation," "connection," "joining," and "fixing" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components. For those skilled in the art, the specific meaning of the above terms in the embodiments of this application can be understood according to the specific circumstances.

[0028] Please refer to Figures 1 to 6 This application provides a chip-removable, press-fit droplet microfluidic production device, including a chip pressing module, a continuous liquid feeding module, and a microsphere detection module. The chip pressing module includes a chip assembly 1-4, a lever 1-2, and a pressing cylinder 1-1. The chip assembly 1-4 includes a cover plate, a microfluidic chip, and a base plate stacked from top to bottom. Channels are formed on the microfluidic chip. One end of the lever 1-2 is connected to the output end of the pressing cylinder 1-1, and the other end is connected to the pressing assembly 1-1. 3. Pressure is applied to the chip assembly 1-4 to achieve sealing of the microfluidic chip; the continuous liquid feeding module includes a liquid feeding tank 4-1 and a liquid replenishment tank 4-16. The liquid feeding tank 4-1 is connected to the liquid inlet of the chip assembly 1-4 through a liquid outlet pipe 4-2. The liquid replenishment tank 4-16 is connected to the liquid feeding tank 4-1 through a liquid replenishment pipe 4-9, and a check valve 4-10 is provided on the liquid replenishment pipe 4-9; the microsphere detection module is used to detect the particle size of the microspheres contained in the solution discharged from the liquid outlet of the chip assembly 1-4.

[0029] The chip assembly in this application includes a cover plate, a microfluidic chip, and a base plate stacked from top to bottom. When in use, the chip assembly is placed on the device for positioning, and downward pressure is applied to the chip assembly by using a lever pressing method to achieve sealing of the upper and lower sides of the microfluidic chip. The pressing sealing method makes the microfluidic chip removable and cleanable, which helps to extend its service life. This solves the problems of current bonded chips, such as the inability to be disassembled and cleaned, short lifespan, and limited material selection.

[0030] Meanwhile, by using a pressing cylinder in conjunction with a lever structure and a pressing component to apply pressure to the chip assembly, the microfluidic chip is sealed. Compared with using multiple cylinders for pressing and sealing, the pressing and sealing method in this application has a simple structure, occupies less space, and can avoid the phenomenon of unstable pressing.

[0031] It should be noted that if multiple cylinders are used for pressing and sealing, from a structural perspective, multiple cylinders take up a lot of space, and there are also more wiring and pipelines. From a consistency perspective, it is also difficult for multiple cylinders to maintain the same speed, moving up and down simultaneously. When the cylinder speeds are inconsistent, jamming can occur during pressing. As production scales up, more cylinders will be needed, and ensuring consistency will become even more difficult.

[0032] The continuous liquid feeding module in this application includes a liquid feeding tank and a liquid replenishment tank. When the liquid level in the feeding tank is low, the replenishment tank can promptly replenish the liquid, ensuring a constant liquid supply. This eliminates the need for equipment shutdown for replenishment, enabling continuous production of droplet microfluidics and significantly improving pellet production efficiency. Simultaneously, by incorporating a microsphere detection module, the particle size of microspheres in the solution exiting the chip assembly can be detected online, thereby improving microsphere detection efficiency and reducing personnel workload.

[0033] This application employs an open-structure chip assembly and replaces traditional bonded chips with a lever-based compression seal, enabling chip detachability. Secondly, this compression seal method is compatible with chips ranging from a single chip to hundreds or thousands of channels, achieving high-throughput pellet production. A continuous liquid inlet module is introduced at the liquid inlet end of the equipment to achieve continuous pellet production. A microsphere detection module is introduced at the liquid outlet end to achieve automated detection of microspheres and feedback signals, realizing the intelligentization of the entire pellet production system.

[0034] Specifically, such as Figure 1 As shown, the chip pressing module in this application includes a pressing cylinder 1-1, a lever 1-2, a pressing component 1-3, and a chip assembly 1-4. The pressing cylinder 1-1 moves upward, and the force is amplified and transmitted to the pressing component 1-3 through the lever 1-2. Finally, the pressing component 1-3 applies the force to the chip assembly 1-4 to achieve chip sealing.

[0035] According to some embodiments of this application, the lever 1-2 has a force application point, a resistance point, and a fulcrum. The force application point is connected to the pressing cylinder 1-1, the resistance point is connected to the pressing assembly 1-3, and the distance between the force application point and the fulcrum is greater than the distance between the resistance point and the fulcrum.

[0036] By using a single pressing cylinder and leveraging the principle to amplify the force of the pressing cylinder several times, multiple cylinders are reduced to one while ensuring that the pressing pressure remains unchanged. This solves the problem of consistent cylinder action and also reduces wiring and air paths, making it applicable to the scale-up production of microfluidic technology.

[0037] The principle of lever amplification in this application is as follows: Figure 2 As shown, the lever has three points of application: the force application point, the resistance point, and the fulcrum. The distance between the force application point and the fulcrum is L1, and the distance between the resistance point and the fulcrum is L2. The force application point is connected to the pressing cylinder 1-1, and the resistance point is connected to the pressing assembly 1-3. The ratio of L1 to L2 is the force amplification factor. Currently, the production equipment has L1 = 200 mm and L2 = 50 mm. The ratio of L1 to L2 is 4, so the force acting on the pressing assembly 1-3 through the lever 1-2 is 4 times the output force of the pressing cylinder 1-1.

[0038] For chips with more than 100 channels, larger chips require greater force during compression sealing. This force can be increased by changing the distance between levers L1 and L2. For example, if the distance between L1 and L2 is changed to 240 mm and the distance between L2 is changed to 40 mm, with the ratio of L1 to L2 being 6, then the force acting on the pressing component through the lever will be 6 times the output force of the pressing cylinder 1-1.

[0039] According to some embodiments of this application, the pressing assembly 1-3 includes a pressing plate and a pressing rod. One end of the pressing rod is fixedly connected to the pressing plate, and the other end is connected to the lever 1-2. After the pressing cylinder 1-1 pushes the lever 1-2 to move, the pressing plate applies a pressing force to the cover plate.

[0040] According to some embodiments of this application, the channel on the microfluidic chip has a flow channel, an external phase inlet 3-1, an internal phase inlet 3-2, a shearing port 3-3, and an outlet 3-4. The flow channel is located on the upper surface of the microfluidic chip. The external phase inlet 3-1 and the internal phase inlet 3-2 are connected to the inlet tank 4-1 to allow liquid to enter the flow channel. The external phase liquid and the internal phase liquid flow into the shearing port 3-3 for shearing to form microspheres and then flow to the outlet 3-4.

[0041] This application uses a detachable microfluidic chip, with chip types including cross-shaped shear ports, Y-shaped shear ports, and T-shaped shear ports, etc. Figure 3 As shown, the chip eliminates the traditional bonding method and adopts a pressure sealing method. The chip has an external phase inlet 3-1 and an internal phase inlet 3-2. The external phase and the internal phase enter the flow channel from the bottom through the circular hole, and then flow into the shearing port 3-3 for shearing. The resulting microspheres flow out through the liquid outlet 3-4.

[0042] The aforementioned microfluidic chip, along with its cover plate and base plate, is placed into the chip assembly 1-4 positions of the pressing section of the equipment. The chip is then sealed by pressing down with the pressing assembly 1-3. This pressing and sealing process allows the chip to be disassembled and cleaned at any time, preventing chip channel blockage and damage. Furthermore, this chip can be arranged in an array from a single chip to hundreds or thousands of chips. By using a pressing method instead of a bonding method, the misalignment problem that is common in multi-channel bonding is avoided. This not only enables the microfluidic chip to be disassembled but also greatly increases the production capacity of microfluidic droplets and reduces the difficulty of chip processing.

[0043] It should be noted that the microfluidic chip in this application can form chip channels on the upper and lower surfaces of a substrate made of materials such as aluminum alloy, stainless steel, polymethyl methacrylate, polyether ether ketone, polydiethyl terephthalate, cyclic olefin copolymer, and glass through processes such as etching, machining, or injection molding. Then, a pressing structure is used to seal the upper and lower sides of the chip by using a cover plate and a base plate.

[0044] According to some embodiments of this application, the tops of the inlet tank and the replenishment tank are respectively provided with air inlet pipes. The air inlet pipe on the inlet tank is used to regulate the air pressure inside the tank to control the liquid output of the outlet pipe, and the air inlet pipe on the replenishment tank is used to regulate the air pressure inside the tank to control the liquid output of the replenishment pipe. With the above design, air can be supplied to the replenishment tank via the air inlet pipe to pressurize it, thereby controlling the liquid in the tank to flow to the inlet tank through the replenishment pipe. Similarly, air can be supplied to the inlet tank via another air inlet pipe to pressurize it, thereby controlling the liquid in the tank to flow to the chip assembly through the outlet pipe. Since a check valve is provided on the replenishment pipe, liquid backflow can be prevented.

[0045] According to some embodiments of this application, the diameter of the replenishment pipeline is greater than or equal to the diameter of the outlet pipeline, and the air pressure provided by the air inlet pipeline on the replenishment tank is 20%-100% greater than the air pressure provided by the air inlet pipeline on the inlet tank. Through the above design, the replenishment rate of the inlet tank can be greater than the outlet rate, thereby causing the liquid level in the inlet tank to rise.

[0046] According to some embodiments of this application, both the inlet tank and the replenishment tank are equipped with a liquid level detector and a safety valve. The liquid level detector is used to detect the liquid level in the tank to provide feedback on whether liquid needs to be replenished into the tank. The safety valve is used to control the pressure in the tank to prevent it from exceeding the limit.

[0047] The liquid level detector on the inlet tank of this application is used to monitor the liquid level in the tank. When the liquid level reaches the lower limit, the liquid level detector transmits a signal to the PLC. The PLC controls the proportional valve to open the air supply to pressurize the replenishment tank and deliver the liquid in the replenishment tank to the inlet tank. When the liquid level detector detects that the solution in the tank has reached the upper limit, it transmits a signal to the PLC. At this time, the PLC controls the proportional valve to stop the air supply, which stops the replenishment.

[0048] It should be noted that the liquid level detectors mentioned above can be of different types (ultrasonic, infrared, etc.); the PLC controller may not directly control the proportional valve, but may act on the solenoid valve in the gas circuit to realize the gas delivery.

[0049] Specifically, such as Figure 4As shown, the continuous liquid feeding module in this application includes an inlet tank 4-1 and a replenishment tank 4-16. The inlet tank 4-1 has a cover 4-8 connected to its top, and the cover 4-8 is connected to an outlet pipe 4-2, an air inlet pipe 4-3, a level detector 4-5, and a safety valve 4-4. The level detector 4-5 has an upper limit monitoring point 4-6 and a lower limit monitoring point 4-7. Similarly, the replenishment tank 4-16 has a cover 4-15 connected to its top, and the cover 4-15 is connected to an air inlet pipe 4-11, a safety valve 4-4, and a level detector 4-12. The level detector 4-12 has an upper limit monitoring point 4-13 and a lower limit monitoring point 4-14. The inlet tank 4-1 and the replenishment tank 4-16 are connected via a replenishment pipe 4-9 and a check valve 4-10.

[0050] The cover 4-8 is fixed above the inlet tank 4-1 by a flange. The outlet pipe 4-2 extends to the bottom of the inlet tank to drain all the liquid in the tank. The air inlet pipe 4-3 can penetrate the cover 4-8 to avoid contact with the liquid. The lower limit monitoring point 4-7 of the liquid level detector 4-7 is 10CM away from the bottom of the tank to prevent all the liquid in the tank from being drained and unable to be replenished in time. The upper limit monitoring point 4-6 is 5CM away from the top to prevent the liquid from contacting the cover.

[0051] The air inlet pipe 4-3 is connected to the connection port of the pressure control system 1-6. The liquid output is controlled by adjusting the air pressure. The liquid level detector 4-5 is connected to the PLC. The cover 4-15 is fixed above the replenishment tank 4-16 by a flange. The air inlet pipe 4-11 is connected to the pressure control system 1-6. The liquid level detector 4-12 is connected to the PLC system.

[0052] When the liquid level in the inlet tank 4-1 is at the upper or lower limit, the PLC output signal controls the pressure control system connected to the air inlet pipe 4-11 to open or close automatically to achieve automatic liquid replenishment. A check valve 4-10 is connected to the replenishment pipe 4-9 to prevent backflow of liquid in the inlet tank 4-1; the replenishment pipe 4-9 is connected to the bottom of the replenishment tank 4-16. The diameter of the replenishment pipe 4-9 is greater than or equal to that of the outlet pipe 4-2, and the air pressure provided by the air inlet pipe 4-11 is 20-100% greater than the air pressure provided by the air inlet pipe 4-3.

[0053] When the liquid in the replenishment tank 4-16 is consumed to the lower limit, the PLC receives a signal and issues an alarm indicating that the liquid level in the replenishment tank is insufficient. This allows the replenishment tank 4-16 to be opened in time for manual replenishment, while the inlet tank 4-1 is working normally at this time.

[0054] To achieve longer droplet production times, replenishment tanks are added to both the internal and external phase feed tanks. A 2L 4% polylactic acid solution (4g of polylactic acid added to 100mL of dichloromethane, stirred and dissolved for 4 hours) is used as the internal phase, and a 10L 1% PVA solution is used as the external phase. On the droplet microfluidic device, the pressures of the internal and external phase feed tanks are set to 15 / 25 kPa, respectively, and the pressure parameters of the proportional valves of the internal and external phase replenishment tanks are set to 20 / 30 kPa. When the solution in the internal and external phase feed tanks drops to the lower limit, the internal and external phase replenishment tanks automatically start to replenish the solution, achieving continuous production with a production time >24 hours.

[0055] It should be noted that multiple droplet microfluidic devices may be started simultaneously during production. If each device is matched with an internal / external phase inlet tank or replenishment tank, it will not only occupy space but also require more materials and equipment. Multiple liquid lines can be connected to the droplet microfluidic device from an internal / external phase tank at the same time, and only one liquid supply device is needed to supply multiple devices.

[0056] According to some embodiments of this application, the microsphere detection module includes a high-speed camera 5-1, a detection chip group 5-2, and a light source 5-3. The detection chip group 5-2 includes a detection chip 5-7 and a chip fixture. The detection chip is disposed in the chip fixture and has a channel. The chip fixture has a solution inlet and a solution outlet, as well as observation ports located on the upper and lower sides of the detection chip. The high-speed camera and the light source are respectively located above and below the two observation ports to capture the morphology of the microspheres in the channel of the detection chip.

[0057] Specifically, such as Figure 5 As shown, the microsphere detection module in this application includes a high-speed camera 5-1, a detection chipset 5-2, and a light source 5-3. Figure 6 As shown, the detection chipset includes a detection chip 5-7 and a chip fixture. A solution containing microspheres enters the detection chip 5-7 through the solution inlet 5-4. A high-definition camera 5-1 captures images through the observation port 5-5. The solution with the captured images is discharged from the solution outlet 5-6 into a collection tank. Notably, the detection chip 5-7 is made of glass, and the internal channel size is larger than the microsphere diameter but smaller than the sum of the diameters of two microspheres, thus solving the problem of misjudgment caused by microsphere overlap.

[0058] The microsphere detection module in this application includes a high-speed camera, a detection chipset, and a light source. During production, the high-speed camera captures the morphology of the microspheres, and the microsphere size is automatically determined through analysis, outputting analytical conclusions. Specifically, the detection chip is made of a transparent material, such as glass, cyclic olefin copolymers, or PMMA. The internal channel size of the detection chip is larger than the microsphere diameter but smaller than the sum of the diameters of two microspheres, thus resolving the problem of misjudgment caused by microsphere overlap.

[0059] According to some embodiments of this application, an observation system for observing the channels of a microfluidic chip is also included. The observation system 1-8 includes a CCD camera and an XYZ three-axis platform 1-5. The CCD camera is connected to the XYZ three-axis platform to observe each channel through observation ports 1-9. Because the XYZ three-axis platform can move the CCD camera, it is controlled by a PLC and operated via a touchscreen, allowing for rapid observation of each channel of the microfluidic chip. In this application, an observation port is provided on the pressure plate, and a transparent cover plate is used, allowing the channel status of the chip to be observed using the CCD camera.

[0060] Specifically, when observing the flow channels of a microfluidic chip, the XYZ three-axis platform 1-5 uses a PLC to control the motor of each axis to achieve automatic control of the three axes. Through the operation of the touch screen, the observation system 1-8 can quickly observe each flow channel through the observation port 1-9.

[0061] The production equipment in this application integrates an air compressor system, which supplies compressed air to the air storage tank through micro air pumps 1-7. The air storage tank is equipped with a pressure sensor. When the pressure reaches the required value, the pressure sensor will send a signal to the PLC. The PLC controls the start and stop of the micro air pump by controlling the intermediate relay. Thus, an air compressor system with PID control is integrated into the equipment.

[0062] The production equipment in this application integrates a pressure control system 1-6. Different pressure values ​​are output to the PLC via a touch screen. The PLC controls the proportional valve by simulating different voltage values. The proportional valve outputs the corresponding air pressure through different voltage values. The real-time air pressure output by the proportional valve is fed back to the PLC through the simulated voltage. Finally, the real-time air pressure is displayed on the touch screen. Thus, a pressure control system is integrated into the equipment.

[0063] This application achieves a high degree of integration of the production equipment by integrating the pressure control system 1-6 and the micro air pump 1-7 into the production equipment. It should be noted that the continuous liquid feeding module and the microsphere detection module in this application can be arranged separately in... Figure 1 The device shown is located on both the left and right sides, but... Figure 1 The diagram is not shown in the text.

[0064] This application provides a chip-removable, high-throughput, continuous, and intelligent droplet microfluidic device, which not only solves the problems of difficult cleaning, easy clogging, and material limitations of bonded chips, but also enables continuous production through continuous liquid replenishment and sample injection. The use of lever pressing principle eliminates the problem of deviation in the operation of multiple cylinders, and the discovery of online detection function further realizes the intelligence of the device.

[0065] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A chip-removable, press-fit droplet microfluidic manufacturing device, characterized in that, The system includes a chip pressing module, a continuous liquid feeding module, and a microsphere detection module. The chip pressing module comprises a chip assembly, a lever, and a pressing cylinder. The chip assembly includes a cover plate, a microfluidic chip, and a base plate stacked from top to bottom. Channels are formed on the microfluidic chip. One end of the lever is connected to the output end of the pressing cylinder, and the other end applies pressure to the chip assembly via a pressing component to achieve sealing of the microfluidic chip. The continuous liquid feeding module includes an inlet tank and a replenishment tank. The inlet tank is connected to the inlet of the chip assembly via an outlet pipe, and the replenishment tank is connected to the inlet tank via a replenishment pipe equipped with a check valve. The microsphere detection module is used to detect the particle size of the microspheres contained in the solution discharged from the outlet of the chip assembly.

2. The chip detachable press-fit droplet microfluidic production equipment according to claim 1, characterized in that, The lever has a force application point, a resistance point, and a fulcrum. The force application point is connected to a pressing cylinder, and the resistance point is connected to a pressing assembly. The distance between the force application point and the fulcrum is greater than the distance between the resistance point and the fulcrum.

3. The chip detachable press-fit droplet microfluidic production equipment according to claim 1, characterized in that, The pressing assembly includes a pressing plate and a pressing rod. One end of the pressing rod is fixedly connected to the pressing plate, and the other end is connected to a lever. After the pressing cylinder pushes the lever, the pressing plate applies a pressing force to the cover plate.

4. The chip detachable press-fit droplet microfluidic production equipment according to claim 1, characterized in that, The microfluidic chip is an open chip rather than a bonded chip. The number of channels in the microfluidic chip can be single or dozens to hundreds or thousands of channels formed by array arrangement to achieve mass production. The material of the microfluidic chip includes one of aluminum alloy, stainless steel, polymethyl methacrylate, polyether ether ketone, polydiethyl terephthalate, cyclic olefin copolymer and glass. The channels on the microfluidic chip have a flow channel, an external phase inlet, an internal phase inlet, a shearing port and an outlet. The shearing port includes one or more of a cross shearing port, a Y-shaped shearing port and a T-shaped shearing port. The flow channel is located on the upper surface of the microfluidic chip. The external phase inlet and the internal phase inlet are connected to the inlet tank to allow liquid to enter the flow channel. The external phase liquid and the internal phase liquid flow into the shearing port, where they are sheared to form microspheres and then flow to the outlet.

5. The chip detachable press-fit droplet microfluidic production equipment according to claim 1, characterized in that, The top of the liquid inlet tank and the liquid replenishment tank are respectively equipped with air inlet pipes. The air inlet pipe on the liquid inlet tank is used to adjust the air pressure inside the tank to control the liquid output of the liquid outlet pipe. The air inlet pipe on the liquid replenishment tank is used to adjust the air pressure inside the tank to control the liquid output of the liquid replenishment pipe.

6. The chip detachable press-fit droplet microfluidic production equipment according to claim 5, characterized in that, The diameter of the replenishment pipeline is greater than or equal to the diameter of the outlet pipeline, and the air pressure provided by the air inlet pipeline on the replenishment tank is 20%-100% greater than the air pressure provided by the air inlet pipeline on the inlet tank.

7. The chip detachable press-fit droplet microfluidic production equipment according to claim 5, characterized in that, Both the inlet tank and the replenishment tank are equipped with a liquid level detector and a safety valve. The liquid level detector is used to detect the liquid level in the tank to provide feedback on whether liquid needs to be added to the tank. The safety valve is used to control the pressure in the tank to prevent it from exceeding the limit.

8. The chip detachable press-fit droplet microfluidic production equipment according to claim 1, characterized in that, The microsphere detection module includes a high-speed camera, a detection chipset, and a light source. The detection chipset includes a detection chip and a chip fixture. The detection chip is disposed in the chip fixture and has channels. The chip fixture has a solution inlet and a solution outlet, as well as observation ports located on the upper and lower sides of the detection chip. The detection chip is made of one of glass, cyclic olefin copolymer, and PMMA. The high-speed camera and the light source are located above and below the two observation ports, respectively, to capture the morphology of the microspheres in the channels of the detection chip.

9. The chip detachable press-fit droplet microfluidic production equipment according to claim 8, characterized in that, The detection chip is made of transparent material, and the internal channel size of the detection chip is larger than the microsphere diameter but smaller than the sum of the diameters of two microspheres.

10. The chip detachable press-fit droplet microfluidic production equipment according to claim 1, characterized in that, It also includes an observation system for observing the channels of a microfluidic chip, the observation system comprising a CCD camera and an XYZ three-axis platform, the CCD camera being connected to the XYZ three-axis platform to observe each chip channel through the observation port.

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