An apparatus for assisted droplet generation and method of use

Abstract

The application discloses a device and a use method for assisting droplet generation, wherein one way of the output end of a gas storage unit is connected to a pressure applying device, and the other way is connected to external atmosphere, gas is delivered into a droplet generation unit through the pressure applying device, and an airtight connection can be formed between the pressure applying device and the droplet generation unit, pressure construction and droplet preparation process can realize full-process automation, in the process of use, firstly, the gas pressure of the gas storage unit is increased to a preset value greater than a target value, then the pressure increasing of the gas storage unit is stopped, then the gas storage unit is gradually exhausted to the atmosphere through control, so that the gas pressure in the gas storage unit gradually decreases, the influence of the rapid flow of gas on the accuracy of real-time gas pressure detection in the pressure feedback control process can be effectively avoided, the accuracy and stability of providing the positive pressure of the target value of the gas pressure to the droplet generation unit are improved, and the reliability of the droplet generation unit in completing the droplet preparation of a specific volume of dispersed phase reagent at a specific time under a specific pressure is ensured.

Description

A device for assisting droplet generation and its usage method Technical Field

[0001] This invention belongs to the field of droplet microfluidics technology, and relates to a device and method for assisting droplet generation. Background Technology

[0002] Droplet microfluidics offers advantages such as automation, ease of integration, and high throughput, leading to its widespread application in fields such as biomedicine, materials science, and chemical analysis. Microdroplets typically consist of an immiscible continuous phase and a dispersed reagent phase. The dispersed phase is divided into monodisperse microdroplets with volumes ranging from nanoliters to superliters by utilizing the interactions between the two fluid phases, such as flow shear forces and interfacial tension.

[0003] Commonly used liquid drive sources include peristaltic pumps, syringe pumps, and pressure pumps. Peristaltic pumps are rarely used in precision experiments due to excessive flow pulsation. Syringe pumps rely on stepper motors to drive the syringe to complete the liquid drive. However, the equilibrium time for stable fluid flow is relatively long, and the periodic vibrations generated by the rotation of the stepper motor during operation are transmitted to the fluid through the syringe piston, causing periodic changes in the fluid velocity, which is not conducive to the precise drive control of droplet microfluidics.

[0004] However, conventional pressure pumps rely on feedback control of pumps and valves by pressure controllers to achieve real-time air pressure regulation, which requires high precision control of the control system and increases the cost of the instrument. Meanwhile, while commercially available microfluidic precision controllers / pressure pumps can provide fast and stable pressure output, most require external pressure or air sources, resulting in large device size, high instrument price, and the need to design and manufacture airtight devices to work with droplet generation chips. These methods cannot meet the requirements for low-cost, integrated, and automated droplet generation. Summary of the Invention

[0005] The purpose of this invention is to solve the problems in the prior art where existing chips require external pressure or gas sources to generate droplets, resulting in large device size, low accuracy of external gas sources during driving, which is not conducive to the precise driving control of droplet microfluidics. At the same time, external instruments can only provide pressure output ports and cannot provide airtight devices for use with droplet generation chips, resulting in low reliability of droplet generation. The invention provides a device and method for assisting droplet generation.

[0006] To achieve the above objectives, the present invention employs the following technical solution:

[0007] A device for assisting droplet generation includes a gas storage unit, the gas storage unit having two outputs, one connected to a pressurizing device and the other connected to the external atmosphere;

[0008] The output end of the pressure application device is used to connect to the droplet generation unit;

[0009] The gas storage unit is connected to the gas pressure detection unit, which is used to monitor the real-time gas pressure in the gas storage unit. The gas pressure detection unit is connected to the control unit.

[0010] The gas storage unit includes a gas storage cylinder, which is connected to a gas pump, and the gas pump is connected to a control unit.

[0011] A further improvement of the present invention is that:

[0012] The air pump and the air storage cylinder are connected by a first air pipe, and a valve is installed on the first air pipe. The valve is a one-way valve.

[0013] The gas cylinder is connected to a pressure application device via a second gas pipe, and a first solenoid valve is installed on the second gas pipe.

[0014] The gas cylinder is connected to the atmosphere via a third gas pipe, and a second solenoid valve is installed on the third gas pipe;

[0015] Both the first solenoid valve and the second solenoid valve are connected to the control unit.

[0016] A flow-resistance tube is provided on the second trachea, and the diameter of the flow-resistance tube is smaller than the diameter of the second trachea.

[0017] The pressurizing device includes a mounting plate, the lower end of which is connected to a flow divider plate. A corresponding flow divider hole is formed on the flow divider plate, and the output end of the gas storage unit is connected to the flow divider hole.

[0018] The pressure application device also includes a motion component connected to the mounting plate, which is used to move the mounting plate up and down.

[0019] An elastic component is provided on the motion component. The elastic component includes a connector that connects to the motion component. A guide rod is provided inside the connector. The upper end of the guide rod is connected to the upper end face inside the connector, and the lower end of the guide rod is connected to the lower end face inside the connector.

[0020] A spring and a fixing block are sequentially sleeved on the outer side of the guide rod from top to bottom. The upper end of the spring is connected to the upper end face inside the connector, and the lower end is connected to the fixing block.

[0021] The fixing block is connected to the mounting plate.

[0022] It also includes a position determination unit, which is connected to the control unit;

[0023] The position determination unit includes a position detection optical coupler and a light-shielding plate;

[0024] The position detection optical coupler is spaced apart and disposed on one side of the motion component, and the height of the position detection optical coupler is corresponding to the height of the droplet generation unit;

[0025] The light-shielding plate is mounted on the connector. When the light-shielding plate moves to a position corresponding to the detection optocoupler, the position detection optocoupler and the light-shielding plate work together to generate a signal, which is then transmitted to the control unit.

[0026] A method of using an apparatus for assisting droplet generation includes the following steps:

[0027] The gas storage unit is pre-filled with gas to bring the gas pressure in the gas storage unit to a preset value. Specifically, when it is necessary to generate droplets, the control unit controls the air pump to input gas into the gas storage bottle. At the same time, the control unit controls the motion component to drive the flow divider to the target position and form an airtight connection with the droplet generation unit to realize the automatic control of the device.

[0028] When the gas pressure inside the gas storage unit reaches the preset value, the gas storage unit first exhausts gas into the atmosphere through one of the pipelines until the gas pressure inside the gas storage unit reaches the target value.

[0029] The gas storage unit inputs gas to the pressurizing device through another pipeline. The pressurizing device applies positive pressure to the droplet generating unit, and droplets are generated inside the droplet generating unit.

[0030] When droplet generation ends, the control unit closes the first solenoid valve and opens the second solenoid valve to quickly release the pressure in the gas storage cylinder and pressurizing device to the atmosphere.

[0031] Further improvements to this method are as follows:

[0032] When the gas storage unit vents gas into the atmosphere, it includes the following steps:

[0033] The control unit controls the gas storage unit to exhaust gas into the atmosphere, so that the preset value in the gas storage unit drops to the first value;

[0034] When the air pressure drops to the first value, the control unit reduces the exhaust speed of the gas storage unit or the duration of each exhaust until the air pressure inside the gas storage unit reaches the target value, at which point it stops exhausting into the atmosphere.

[0035] The first value is greater than the target value.

[0036] Compared with the prior art, the present invention has the following beneficial effects:

[0037] This invention discloses a device for assisting droplet generation. The output end of the gas storage unit includes two paths: one connected to a pressurizing device and the other connected to the external atmosphere. The pressurizing device delivers gas to the droplet generation unit, and an airtight connection is formed between the pressurizing device and the droplet generation unit. The pressure building and droplet preparation process can be fully automated. The other path connects to the atmosphere. During use, the gas pressure of the gas storage unit is first increased to a preset value greater than the target value. Then, after stopping the pressurization of the gas storage unit, the gas storage unit is controlled to exhaust gas into the atmosphere sequentially, so that the gas pressure inside the gas storage unit gradually decreases. During this process, the gas pressure detection unit monitors the internal gas pressure in real time. The gas pressure in the gas storage unit is detected and compared with the target value between each exhaust operation until the gas pressure in the gas storage unit reaches the target value. This method can effectively avoid the influence of rapid gas flow on the accuracy of real-time gas pressure detection during pressure feedback control, improve the accuracy and stability of providing positive pressure of the target value to the droplet generation unit, and ensure the reliability of the droplet generation unit in preparing droplets of a specific volume of dispersed phase reagent at a specific pressure and in a specific time. Meanwhile, by changing the pressure feedback control logic, the precision control requirements for pumps, valves, and control units can be reduced, effectively lowering the cost of the instrument system.

[0038] Furthermore, in this invention, an air pump provides air pressure to the gas storage cylinder, which can provide more stable and accurate fluid drive without directly contacting the driven fluid, thus improving the stability and reliability of the droplet microfluidic system.

[0039] Furthermore, in this invention, the flow divider design can split the gas input from the gas storage cylinder into one or more flow dividers, thereby allowing these multiple flow dividers to act on the dispersed phase reagents in multiple droplet generation chips in the droplet generation unit, enabling the simultaneous preparation of multiple sets of droplets. This achieves integrated, high-throughput, fully automated in-tube droplet preparation, with advantages such as simple operation and control, flexible droplet generation throughput, low cost, and small size and weight.

[0040] Furthermore, in this invention, the pressure application device also includes a motion component, which drives the flow divider plate to move up and down via the mounting plate, facilitating the picking up and placing of the droplet generation unit below during operation, and also facilitating the overall position control of the pressure application device.

[0041] Furthermore, in this invention, an elastic component is provided on the moving component. In the elastic component, when the diverter plate comes into contact with the droplet generating unit below, during the downward movement of the diverter plate, the fixed block is squeezed by the force, compressing the spring upward. The spring's rebound action is transmitted to the diverter plate, converting the mechanical pressure of the diverter plate on the droplet generating unit into an elastic force. This ensures a seal while preventing the mechanical pressure from directly acting on the droplet generating unit, which could easily cause structural damage.

[0042] Furthermore, in this invention, the position determination unit can promptly determine whether the pressure device has reached the designated position, facilitating the timely execution of subsequent operation steps, achieving automated operation, and simplifying the overall operation of the system.

[0043] Furthermore, in this invention, a chip detection unit is provided on the base. When the droplet generating unit is placed on the base, the droplet generating unit will exert pressure on the spring pin at the lower end. After the spring pin senses this, it transmits the signal to the control unit through the wire, so as to know in time that the droplet generating unit has been in place, so as to facilitate the timely execution of subsequent operation steps, realize automated operation, and facilitate the overall operation of the system.

[0044] This invention discloses a method for using a device to assist in droplet generation. Droplet generation is achieved through pressure build-up. In this pressure build-up process, the gas pressure in the gas storage unit is first increased to a preset value greater than the target value. After stopping the pressurization of the gas storage unit, the gas storage unit is then controlled to gradually release gas into the atmosphere, causing the gas pressure inside the unit to gradually decrease. During this process, a gas pressure detection unit monitors the internal gas pressure in real time, detecting the gas pressure in the gas storage unit and comparing it with the target value between each gas release operation until the gas pressure in the gas storage unit reaches the target value. This method effectively avoids the impact of rapid gas flow on the accuracy of real-time gas pressure detection during pressure feedback control, improving the accuracy and stability of providing the droplet generation unit with a positive pressure equal to the target value. This ensures the reliability of the droplet generation unit in preparing droplets of a specific volume of dispersed phase reagent at a specific pressure and within a specific time. Simultaneously, by modifying the pressure feedback control logic, the precision control requirements for pumps, valves, and control units can be reduced, effectively lowering the cost of the instrument system. Attached Figure Description

[0045] To more clearly illustrate the technical solutions of the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0046] Figure 1 is a first perspective view of the device of the present invention;

[0047] Figure 2 is a second perspective view of the device of the present invention;

[0048] Figure 3 is a third perspective view of the device of the present invention;

[0049] Figure 4 is a schematic diagram of the structure of the motion component of the device of the present invention when it moves to the target position;

[0050] Figure 5 is a three-dimensional structural schematic diagram of the droplet generation unit of the device of the present invention;

[0051] Figure 6 is an exploded view of the droplet generation unit of the present invention;

[0052] Figure 7 is a bottom view of the base according to an embodiment of the present invention;

[0053] Figure 8 is a cross-sectional view of the base of the present invention corresponding to the droplet generation unit;

[0054] Figure 9 is a schematic diagram of the control principle of the control unit of the present invention;

[0055] Figure 10 is a schematic diagram of the real-time gas pressure change in the gas storage cylinder of the present invention over time;

[0056] Figure 11 is a schematic diagram of the gas path of the droplet generation auxiliary device of the present invention.

[0057] in:

[0058] 11-Air pump; 12-Air cylinder; 13-Air pressure detection unit; 14-Control unit; 15-First air pipe; 16-Valve; 17-Second air pipe; 18-Third air pipe; 19-First solenoid valve; 20-Second solenoid valve; 21-Mounting plate; 22-Diverter plate; 23-Partition plate; 24-Position judgment unit; 241-Position detection optocoupler; 242-Light shield; 26-Spring; 27-Guide rod; 28-Fixing block; 29-Connector; 30-Base; 31-Chip detection unit; 311-Spring pin; 312-Wire;

[0059] 32-Alarm unit; 33-Fixed base; 34-Elastic sealing gasket; 35-Droplet generation chip; 36-PCR tube; 37-Support component. Detailed Implementation

[0060] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The components of the embodiments of the present invention described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0061] Therefore, the following detailed description of the embodiments of the invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the invention without inventive effort are within the scope of protection of the invention.

[0062] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0063] In the description of the embodiments of the present invention, it should be noted that if terms such as "upper," "lower," "horizontal," or "inner" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship commonly used when the product of the invention is in use, they are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of the present invention. Furthermore, terms such as "first" and "second" are only used to distinguish descriptions and should not be construed as indicating or implying relative importance.

[0064] Furthermore, the use of the term "horizontal" does not imply that the component must be absolutely horizontal, but rather that it can be slightly tilted. For example, "horizontal" simply means that its direction is more horizontal than "vertical," and does not mean that the structure must be completely horizontal, but can be slightly tilted.

[0065] In the description of the embodiments of the present invention, it should also be noted that, unless otherwise explicitly specified and limited, the terms "set," "install," "connect," and "link" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; 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; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in the present invention according to the specific circumstances.

[0066] The present invention will now be described in further detail with reference to the accompanying drawings:

[0067] Referring to Figures 1 to 11, an embodiment of the present invention discloses a device for assisting droplet generation, comprising:

[0068] The gas storage unit has two outputs, one connected to a pressurizing device and the other connected to the outside atmosphere; the output of the pressurizing device is connected to a droplet generating unit; the gas storage unit is connected to a pressure detection unit 13, which is used to monitor the real-time pressure inside the gas storage unit; the pressure detection unit 13 is connected to a control unit 14, which is also connected to the gas storage unit.

[0069] Referring to Figures 1 and 2, in a further embodiment of this invention, the specific structure of the gas storage unit is as follows:

[0070] It includes a gas cylinder 12, which is connected to an air pump 11, and the air pump 11 is connected to a control unit 14. Specifically, the air pump 11 and the gas cylinder 12 are connected through a first air pipe 15, and a valve 16 is provided on the first air pipe 15.

[0071] Referring to Figure 11, furthermore, valve 16 is a one-way valve to ensure that there is one-way communication between air pump 11 and gas storage cylinder 12, that is, gas can only be input from air pump 11 to gas storage cylinder 12, preventing gas pressure leakage in gas storage cylinder 12 after air pump 11 stops working.

[0072] Furthermore, the air pump 11 is a miniature diaphragm pump.

[0073] Furthermore, the gas cylinder 12 is connected to a pressure device via a second gas pipe 17, on which a first solenoid valve 19 is provided. Meanwhile, the gas cylinder 12 is connected to the atmosphere via a third gas pipe 18, on which a second solenoid valve 20 is provided. Both the first solenoid valve 19 and the second solenoid valve 20 are connected to the control unit 14.

[0074] Furthermore, in this embodiment, a flow-resistance air tube is provided on the second air tube 17. The diameter of the flow-resistance air tube is smaller than the diameter of the second air tube 17. Through the design of the flow-resistance air tube, it plays the role of sharing the pressure difference.

[0075] When the pressure in the gas storage cylinder 12 is built up (especially when the target value is reached), the pressure detection unit 13 measures the internal pressure and feeds the measured pressure back to the control unit 14. Since the pressure value detected by the pressure detection unit 13 itself has a certain error compared to the actual value, in this embodiment, the pressure detection unit 13 can be a sensor. Because the sensor itself experiences fluctuations in voltage signal transmission, the detected pressure will have an error of ±0.1 kPa, resulting in an error between the actual pressure value and the target value. By using the pressure distribution through the flow-resistance gas tube, the pressure error is reduced, minimizing the impact of pressure fluctuations on the pressure applied to the droplet generation unit. This ensures the accurate and reliable preparation of droplets of a specific volume of dispersed phase reagent at a specific pressure and time, reducing the requirements for system pressure control accuracy.

[0076] Furthermore, in this embodiment, the specific diameter of the flow-resistance tube is not a limiting condition of the present invention. In practical applications, it can be set according to the specific application scenario. The smaller the diameter of the flow-resistance tube, the greater the relative partial pressure, and the more accurately the pressure device applies positive pressure to the droplet generation unit to the target value.

[0077] Furthermore, in this embodiment, the first solenoid valve 19 is a three-way valve, with one end connected to the gas cylinder 12, one end connected to the pressurizing device, and the other end connected to the atmosphere. The control unit 14 controls the opening and closing of the gas path between the gas cylinder 12 and the pressurizing device by switching the first solenoid valve 19 on and off. When the three-way valve is not powered, the pressurizing device is connected to the atmosphere and there is no pressure; when powered, the pressurizing device connects to the gas cylinder 12 and begins to provide pressure.

[0078] The second solenoid valve 20 is a proportional valve, and when it is working:

[0079] When the second solenoid valve 20 is a proportional valve, the speed at which the gas cylinder 12 discharges gas to the atmosphere each time is adjusted by controlling the proportional valve, so as to slowly reduce the gas pressure in the gas cylinder 12 from the preset value to the target value, thereby ensuring the accuracy of the gas pressure in the gas cylinder 12.

[0080] When the second solenoid valve 20 is a common solenoid valve, the opening time of the solenoid valve can be adjusted to slowly reduce the gas pressure in the gas storage cylinder 12 from the preset value to the target value, thereby ensuring the accuracy of the gas pressure in the gas storage cylinder 12.

[0081] Referring to Figures 2 to 4, in a further embodiment of this invention, the specific structure of the pressure application device is as follows:

[0082] It includes a mounting plate 21, with a flow divider plate 22 connected to the lower end of the mounting plate 21. The flow divider plate 22 is provided with at least one flow divider hole. The end of the second gas pipe 17 away from the gas storage cylinder 12 is connected to the flow divider hole. The flow divider plate 22 is provided with a flow divider pipe inside. The flow divider pipe divides the gas from the second gas pipe 17 into at least one flow divider gas. Each flow divider gas corresponds to one flow divider hole.

[0083] Furthermore, the mounting plate 21 is connected to a motion component, which specifically includes a motor. The motor drives the slider to move, and the slider causes the mounting plate 21 and the diverter plate 22 to move up and down. The motor is connected to the control unit 14.

[0084] Furthermore, the slider is connected to the mounting plate 21 via an elastic component, the structure of which is as follows:

[0085] The connector 29 is a "U"-shaped structure. A guide rod 27 is installed inside the connector 29. The upper end of the guide rod 27 connects to the upper surface inside the connector 29, and the lower end of the guide rod 27 connects to the lower surface inside the connector 29. A spring 26 and a fixing block 28 are sequentially fitted onto the outer side of the guide rod 27 from top to bottom. The upper end of the spring 26 connects to the upper surface inside the connector 29, and the lower end connects to the fixing block 28. The fixing block 28 connects to the mounting plate 21. During operation:

[0086] The slider in the motion assembly drives the connector 29 to move, and the diverter 22 contacts the droplet generating unit. Then, referring to Figure 4, the motion assembly continues to move to the target position. During this process, the diverter 22 is supported by the droplet generating unit. As the connector 29 continues to move downward with the slider, the fixing block 28 will squeeze the spring 26 upward under pressure. The spring 26 will generate a downward reaction force. By adjusting the elastic force, the clamping force applied to the droplet generating unit is changed. When the diverter 22 applies positive pressure to the droplet generating unit, the mechanical pressure of the diverter 22 on the droplet generating unit is converted into an elastic force. This ensures a seal while avoiding direct mechanical pressure on the droplet generating unit, which could easily cause structural damage.

[0087] Furthermore, in this embodiment, in the initial state (before the moving component starts moving), the spring 26 is in a compressed state. By compressing the spring, it has a certain preload, which ensures the stability of the elastic component. At the same time, it ensures that when the moving component continues to move to the target position, the diverter plate 22 has sufficient clamping force on the droplet generating unit. The sealing connection between the diverter plate 22 and the droplet generating unit does not require high clamping force. Due to the presence of the spring preload, the flexibility of the target position of the position detection optocoupler 241 is high, thereby reducing the positioning requirements of the moving component.

[0088] Furthermore, in this embodiment, the fixing block 28 and the mounting plate 21 are integrally formed.

[0089] Furthermore, in this embodiment, the flow divider 22 is made by 3D printing and is made of photosensitive resin material.

[0090] Furthermore, in this embodiment, the diverter plate 22 is manufactured by machining and is made of aluminum alloy.

[0091] Furthermore, in this embodiment, the function of the motion component is to drive the mounting plate 21 to move in a straight line, so as to drive the diverter plate 22 to the location of the droplet generating unit and form a sealed connection with the droplet generating unit, thereby enabling the diverter plate 22 to apply positive pressure to the droplet generating unit.

[0092] Furthermore, in this embodiment, the motion component is connected to the control unit 14. The principle of the motion component is: through the control of the control unit 14, the rotation of the motor is converted into linear motion.

[0093] When the moving component reaches the target position, the control unit 14 begins to control the gas storage bottle 12 to input gas into the diverter plate 22; before the moving component reaches the target position, the diverter plate 22 has already contacted the droplet generating unit; and as the moving component continues to move to the target position, the diverter plate 22 squeezes the droplet generating unit, so that the diverter plate 22 and the droplet generating unit form a tight sealing connection.

[0094] During the process of the moving part reaching the target position, the diverter plate 22 moves from away from the droplet generating unit to gradually approach the droplet generating unit, until it comes into contact with the droplet generating unit. Finally, it applies a certain amount of pressure to the droplet generating unit (the specific amount of pressure is not a limiting condition of the present invention; in practical applications, the pressure can be controlled according to the droplet generating unit's ability to withstand the pressure and the elastic coefficient of the subsequent spring 26, etc.), causing the droplet generating unit to undergo a certain deformation (specifically, the diverter plate causes a certain structure in the droplet generating unit to deform; such as the "elastic sealing gasket 34" described below), thereby forming a sealed connection between the diverter plate 22 and the droplet generating unit (i.e., the diverter plate 22 can press the elastic sealing gasket 34 tightly).

[0095] Furthermore, this device also includes a position determination unit 24, the specific structure of which is as follows:

[0096] The position determination unit 24 is connected to the control unit 14. The control unit 14 and the position determination unit 24 determine whether the moving component has reached the target position. When the moving component reaches the target position, the control unit 14 controls the gas storage cylinder 12 to input gas into the pressurizing device.

[0097] Specifically, it includes a position detection optocoupler 241, which is mounted on the partition 23 and connected to the control unit 14. The position detection optocoupler 241 is located at the target position. A light-shielding plate 242 is mounted on the pressure application device, which can be mounted on the slider or on the connector 29. The light-shielding plate 242 can move vertically with the movement of the moving components. When the light-shielding plate 242 moves to the position of the position detection optocoupler 241 (i.e., the target position, see Figure 4), the position detection optocoupler 241 generates a control signal and feeds the control signal back to the control unit 14, so that the control unit 14 starts to control the gas storage cylinder 12 to input gas into the pressure application device according to the control signal (at this time, the real-time gas pressure reaches the target value).

[0098] Furthermore, the device also includes a position limiting unit, the structure of which includes:

[0099] The position detection optical coupler 251 is disposed on the partition 23 and is connected to the control unit 14. The position detection optical coupler 251 is located above the position detection optical coupler 241. The position detection optical coupler 251, the control unit 14 and the aforementioned light shield 242 are used to make the diverter 22 be in a limited position.

[0100] In this embodiment, the position defined by the position limiting unit is located above the target position. The design of this limiting position is to facilitate the installation of the droplet generating unit. Specifically, by raising the flow divider 22 to place the droplet generating unit below the flow divider 22, the flow divider 22 is then moved to the target position.

[0101] In this embodiment, the position limiting unit (in conjunction with the light-shielding plate 242) has the same structure and working principle as the position determination unit 24.

[0102] Referring to Figures 5 and 6, the specific structure of the droplet generation unit is further as follows:

[0103] It includes a fixing base 33, a PCR tube 36 is placed on the upper end of the fixing base 33, a droplet generating chip 35 is placed inside the PCR tube 36, an elastic sealing gasket 34 is provided above the PCR tube 36, and an air inlet is opened on the elastic sealing gasket 34, the air inlet is connected to the pressure application device and the droplet generating chip 35.

[0104] Furthermore, it also includes a base 30:

[0105] The partition 23 is located on the base 30, and the moving component is located on the side wall of the partition 23. The base 30 is used to support the bottom of the entire device. The chip detection unit 31 is set on the fixed base 30. The specific structure of the chip detection unit 31 is as follows:

[0106] Referring to Figure 7, the device includes two spring pins 311, each corresponding to a wire 312. The base 30 has two first mounting holes 38. The spring pin 311 is disposed in one of the first mounting holes 38. One end of the spring pin 311 is connected to one end of the wire 312, and the other end of the wire 312 is connected to the control unit 14.

[0107] It is necessary to ensure that at least the part of the droplet generating unit that contacts the spring needle 311 is made of conductive material, while the part of the base 30 where the spring needle 311 is mounted is made of insulating material.

[0108] Referring to Figure 8, the base 30 is provided with a second mounting hole 39, and an insulating plate 40 is provided inside the second mounting hole 39. Both first mounting holes 38 are provided on the insulating plate 40.

[0109] Specifically, before the droplet generating unit is placed on the base 30, the upper end of the spring pin 311 extends beyond the upper surface of the base 30. When the droplet generating unit is placed on the base 30, the lower end of the droplet generating unit contacts the spring pin 311 and exerts a certain pressure on the spring pin 311, thereby achieving circuit conduction. Furthermore, based on whether the circuit is conducting, it is possible to determine whether the droplet generating unit exists; specifically, if the circuit is conducting, the droplet generating unit exists; if the circuit is not conducting, the droplet generating unit does not exist.

[0110] Specifically, during droplet preparation, a fixing seat 33 is placed on a base 30, and the lower end of the fixing seat 33 contacts a spring pin 311. The fixing seat 33 has at least one fixing hole (taking Figures 5 and 6 as examples, the fixing seat 33 has two rows of fixing holes arranged side by side, each row including eight fixing holes, that is, the droplet generation system can simultaneously achieve 16-throughput droplet generation). A PCR tube 36 is correspondingly placed inside the fixing hole. A droplet generation chip 35 is correspondingly placed inside the PCR tube 36, wherein the PCR tube 36 stores continuous phase reagents; the droplet generation chip 35 stores dispersed phase reagents; an elastic sealing pad 34 is placed above the droplet generation chip 35, and the elastic sealing pad 34 has at least one air inlet, the air inlet corresponding to the droplet generation chip, and each air inlet corresponding to each flow hole of the flow divider 22.

[0111] Furthermore, the elastic sealing gasket 34 is connected to the fixed seat 33 via the support member 37, and under pressure, the diverter plate 22 and the elastic sealing gasket 34 are in close contact.

[0112] Furthermore, the mounting base 33 is made of conductive material, specifically, it can be made of 304 stainless steel.

[0113] Furthermore, a conductive block is provided at the bottom of the fixing base 33 so that the conductive block contacts the spring pin 311. The conductive block can be made of 304 stainless steel.

[0114] During operation, the control unit 14 controls the pressure application device to apply positive pressure to the dispersed phase reagent to generate droplets in the PCR tube 36. Specifically, the lower end face of the flow divider 22 contacts and squeezes the upper surface of the elastic sealing pad 34, and the gas in the gas storage bottle 12 is introduced into the droplet generation chip 35 through the flow divider hole of the flow divider 22, so as to pressurize the dispersed phase reagent.

[0115] Before the moving component reaches the target position, the diverter plate 22 has already contacted the elastic sealing gasket 34. As the slider continues to move to the target position, the diverter plate 22 squeezes the elastic sealing gasket 34, so that a tight sealing connection is formed between the diverter plate 22 and the elastic sealing gasket 34.

[0116] By applying positive pressure to the dispersed phase reagent in the droplet generation chip 35, droplets are generated in the PCR tube 36. The specific principle of the chip can be found in the chip structure principle disclosed in application number 201811430323.9. This system, combined with the chip, controls the flow divider and droplet generation unit to form an airtight connection through the motion component. The pressure construction and droplet preparation process can be fully automated. The flow divider design can split the gas input from the gas storage bottle into multiple (at least one) flow gases, which then act on the dispersed phase reagent in multiple droplet generation chips in the droplet generation unit, thereby achieving the simultaneous preparation of multiple sets of droplets. This enables integrated, high-throughput, fully automated in-tube droplet preparation, with advantages such as simple operation and control, flexible droplet generation throughput, low cost, and small size and weight.

[0117] In this embodiment, an alarm unit 32 is also included. The alarm unit 32 is connected to the control unit 14. When a preset alarm occurs, the control unit 14 controls the alarm unit 32 to issue an alarm indication. After the alarm is triggered, the control unit 14 controls the pressure application device to stop applying positive pressure to the droplet generating unit.

[0118] In this embodiment, the preset alarm conditions include, but are not limited to, any one or a combination of two or more of the following:

[0119] First scenario:

[0120] During the process of the control unit 14 controlling the pressure application device to apply positive pressure to the droplet generation unit, the real-time gas pressure of the gas storage cylinder 12 meets the preset leakage conditions.

[0121] It should be noted that during the pressurization process, there may be air leakage. Specifically, the presence of air leakage can be determined by observing the real-time pressure changes in the gas cylinder 12 (for example, if the real-time pressure drops rapidly, it is considered to be leaking).

[0122] The preset leakage condition is: the real-time air pressure drops, and the rate of drop is greater than the preset pressure change rate.

[0123] It should be noted that the specific value of the preset pressure change rate is not a limiting factor of the present invention. In practical applications, it can be set according to the specific application scenario.

[0124] The second scenario:

[0125] When the control unit 14 controls the pressure application device to start applying positive pressure to the droplet generation unit, the moving component is not in the target position.

[0126] The third scenario:

[0127] When the control unit 14 controls the pressure application device to start applying positive pressure to the droplet generation unit, the real-time gas pressure of the gas storage cylinder 12 has not reached the target value.

[0128] Furthermore, this embodiment also includes a start button, which, when pressed, initiates the automated droplet generation process.

[0129] This embodiment also discloses a method of using a device for assisting droplet generation, including the following steps:

[0130] When droplets need to be generated, the control unit 14 controls the motion component to drive the flow divider 22 to the target position and form an airtight connection with the droplet generation unit. At the same time, the control unit 14 controls the air pump 11 to input gas into the gas storage bottle 12 (as shown by the red curve in Figure 10).

[0131] When the real-time gas pressure in the gas storage cylinder 12 reaches the preset value, the control unit 14 controls the air pump 11 to stop inputting gas into the gas storage cylinder 12 and opens the second solenoid valve 20. The control unit 14 controls the gas storage cylinder 12 to discharge gas into the atmosphere one by one (as shown by the green curve in Figure 10).

[0132] When the real-time gas pressure in the gas storage cylinder 12 reaches the target value, the control unit 14 closes the second solenoid valve 20 and opens the first solenoid valve 19. The control unit 14 controls the gas storage cylinder 12 to input gas into the pressure application device (as shown by the blue curve in Figure 10), so that the pressure application device applies positive pressure to the droplet generating unit, causing the droplet generating unit to generate droplets.

[0133] When droplet generation ends, the control unit 14 closes the first solenoid valve 19 and opens the second solenoid valve 20, quickly releasing the pressure in the gas storage cylinder 12 and the pressurizing device to the atmosphere (as shown by the cyan curve in Figure 10).

[0134] Furthermore, in the above method, the target value is less than the preset value.

[0135] Furthermore, in the above method, the control unit 14 controls the gas storage cylinder 12 to successively discharge gas into the atmosphere, including:

[0136] First stage: Control unit 14 controls gas storage cylinder 12 to discharge gas into the atmosphere, so that the real-time gas pressure drops from the preset value to the first value, which is greater than the target value.

[0137] It should be noted that during the process of reducing the real-time gas pressure in the gas storage cylinder 12 from the preset value to the first value, it can be done by one or more operations. The purpose is to make the real-time gas pressure in the gas storage cylinder 12 drop to the first value quickly, as shown in the first part of the green curve in Figure 10.

[0138] Second stage: Control unit 14 reduces the exhaust speed or the exhaust time of gas cylinder 12 until the real-time gas pressure reaches the target value.

[0139] Specifically, when the second solenoid valve 20 is a proportional valve, the exhaust speed of the gas cylinder 12 can be reduced by adjusting the voltage or current of the proportional valve; if the second solenoid valve 20 is a common solenoid valve, the exhaust time can be reduced by reducing the opening time of the solenoid valve each time.

[0140] It should be noted that the purpose of this stage is to allow the real-time gas pressure in the gas storage cylinder 12 to slowly decrease from the first value to the target value, thereby ensuring the accuracy of the gas pressure in the gas storage cylinder 12, as shown in the latter part of the green curve in Figure 10.

[0141] It should be noted that the specific values ​​of the preset value, the first value, and the target value mentioned above are not intended to limit the present invention. As long as the preset value > the first value > the target value, it is acceptable. In practical applications, the target value can be determined according to the specific application scenario. In particular, the target value can be determined according to the size of the droplet to be generated.

[0142] Furthermore, in this embodiment, the preset value, the first value, and the target value are all ranges, not fixed values. That is, as long as they are near the set pressure value, a certain deviation is allowed, such as a deviation of ±0.1 kPa.

[0143] The system provided by this invention, during the target pressure construction process, first uses an air pump to raise the gas pressure in the gas storage cylinder to a preset value greater than the target value. Then, after stopping the pressurization of the gas storage cylinder, it controls the gas storage cylinder to gradually release gas into the atmosphere, causing the gas pressure inside the cylinder to gradually decrease. During each gas release operation interval, the gas pressure in the storage cylinder is detected and compared with the target value until the gas pressure in the storage cylinder reaches the target value. This method effectively avoids the impact of rapid gas flow on the accuracy of real-time gas pressure detection during pressure feedback control, improving the accuracy and stability of providing the droplet generation unit with the target positive pressure. This ensures the reliability of the droplet generation unit in preparing droplets of a specific volume of dispersed phase reagent at a specific pressure and within a specific time. Simultaneously, by changing the pressure feedback control logic, the precision control requirements for pumps, valves, and control units can be reduced, effectively lowering the cost of the instrument system.

[0144] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Various modifications and variations can be made to the present invention by those skilled in the art. 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 device for assisting droplet generation, characterized in that, The system includes a gas storage unit, the output of which has two paths: one connected to a pressurizing device and the other connected to the external atmosphere; the output of the pressurizing device is used to connect to a droplet generation unit; the gas storage unit is connected to a pressure detection unit (13), which is used to monitor the real-time pressure inside the gas storage unit, and the pressure detection unit (13) is connected to a control unit (14); the gas storage unit includes a gas storage cylinder (12), which is connected to an air pump (11), and the air pump (11) is connected to the control unit (14); the air pump (11) and the gas storage cylinder (12) are connected by a first air pipe (1... 5) Connecting, a valve (16) is provided on the first air pipe (15), the valve (16) is a one-way valve; the gas storage cylinder (12) is connected to the pressure application device through the second air pipe (17), the second air pipe (17) is provided with a first solenoid valve (19); the gas storage cylinder (12) is connected to the atmosphere through the third air pipe (18), the third air pipe (18) is provided with a second solenoid valve (20); the first solenoid valve (19) and the second solenoid valve (20) are both connected to the control unit (14); a flow resistance air pipe is provided on the second air pipe (17), the diameter of the flow resistance air pipe is smaller than the diameter of the second air pipe (17); A method of using a device for assisting droplet generation includes the following steps: pre-filling a gas storage unit with gas to make the gas pressure in the gas storage unit reach a preset value; when the gas pressure in the gas storage unit reaches the preset value, the gas storage unit first exhausts gas into the atmosphere through one of its pipelines until the gas pressure inside the gas storage unit reaches a target value; the gas storage unit inputs gas into a pressure applying device through another pipeline, and the pressure applying device applies positive pressure to the droplet generation unit, and droplets are generated inside the droplet generation unit; when droplet generation ends, the control unit closes the first solenoid valve and opens the second solenoid valve to release the pressure in the gas storage unit and the pressure applying device into the atmosphere; when the gas storage unit exhausts gas into the atmosphere, the following steps are included: the control unit (14) controls the gas storage unit to exhaust gas into the atmosphere, so that the preset value in the gas storage unit drops to a first value; when the gas pressure drops to the first value, the control unit (14) reduces the exhaust speed of the gas storage unit or the time of each exhaust until the gas pressure inside the gas storage unit reaches the target value, and then stops exhausting gas into the atmosphere; the first value is greater than the target value.

2. The device for assisting droplet generation according to claim 1, characterized in that, The pressurizing device includes a mounting plate (21), the lower end of which is connected to a diversion plate (22). A corresponding diversion hole is opened on the diversion plate (22), and the output end of the gas storage unit is connected to the diversion hole.

3. The device for assisting droplet generation according to claim 2, characterized in that, The pressure application device also includes a motion component connected to the mounting plate (21), which is used to drive the mounting plate (21) to move up and down.

4. The device for assisting droplet generation according to claim 3, characterized in that, The motion component is provided with an elastic component, the elastic component includes a connector (29), the connector (29) is connected to the motion component, the connector (29) is provided with a guide rod (27) inside the connector (29), the upper end of the guide rod (27) is connected to the upper end face inside the connector (29), and the lower end of the guide rod (27) is connected to the lower end face inside the connector (29); a spring (26) and a fixing block (28) are sequentially sleeved on the outside of the guide rod (27) from top to bottom, the upper end of the spring (26) is connected to the upper end face inside the connector (29), and the lower end is connected to the fixing block (28); the fixing block (28) is connected to the mounting plate (21).

5. The device for assisting droplet generation according to claim 4, characterized in that, It also includes a position determination unit (24), which is connected to the control unit (14); the position determination unit includes a position detection optocoupler (241) and a light shield (242); the position detection optocoupler (241) is spaced apart on one side of the moving component, and the height of the position detection optocoupler (241) corresponds to the height of the droplet generation unit; the light shield (242) is disposed on the connector (29), and when the light shield (242) moves to the position corresponding to the position detection optocoupler (241), the position detection optocoupler (241) and the light shield (242) cooperate to generate a signal, and the signal is transmitted to the control unit (14).

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