Motion control mechanism microdroplet generation device

Abstract

To provide a liquid discharge pipette tip capable of accurately controlling volume of a generated fine droplet, and a fine droplet generation device including the liquid discharge pipette tip.SOLUTION: A liquid discharge pipette tip includes a needle shaft 113 having a hollow cavity and an outlet end 112 disposed at one end of the needle shaft 113, where an enclosing angle between a normal line of an end surface of the outlet end 112 and an extending direction of the needle shaft 113 is greater than 0° and less than or equal to 90°. Preferably, the liquid dispensing pipette tip has a straight tube shape, and the outlet end 112 of the liquid dispensing pipette tip has an obliquely cut structure.SELECTED DRAWING: Figure 18

Description

Technical Field

[0001] This application claims priority from Chinese Patent Applications No. 201810070377.2, filed on January 24, 2018, entitled "Digital PCR Quantitative Detection Method", and No. 201810884995.0, filed on August 6, 2018, entitled "Fluid Driving Mechanism and Fluid Driving Method", and incorporates all of them herein by reference.

[0002] This application relates to the technical field of metering and dispensing of trace liquids, and particularly relates to a motion control mechanism, a liquid ejection pipette tip, a micro-droplet generation device and generation method, a fluid driving mechanism and fluid driving method, a micro-droplet generation method, and a surface treatment method for a liquid ejection pipette tip.

Background Art

[0003] Currently, in application fields such as medical clinical examinations, nano-material manufacturing, food and environmental inspections, and biochemical analysis, precise operations on trace liquids are widely required. One of the core technologies for operating trace liquids is to divide micro-liter-level liquids into a micro reaction system with a volume of nano-liters and even pico-liters. One of the main technical fields related to the generation of a micro reaction system is to generate emulsified micro-droplets. In recent years, various micro-droplet generation technologies, such as membrane emulsification methods, spray emulsification methods, micro-fluidic control chip methods, and liquid ejection pipette tip injection / atomization methods, have been described in the literature. Among them, the liquid ejection pipette tip injection / atomization method, as the latest micro-droplet generation technology, has an excellent application prospect in terms of the generation of micro-droplets and the reduction of costs as consumables.

[0004] Conventional liquid dispensing pipette tips are generally straight. When a liquid dispensing pipette tip moves rapidly towards one end near its outlet in its direction of extension, it can destroy the generated microdroplets. To maintain the integrity of the generated microdroplets, it is necessary to reduce the vibration frequency of the liquid dispensing pipette tip, which results in a decrease in the rate at which microdroplets are generated. When using the liquid dispensing pipette tip injection / injection method, the outlet end of the liquid dispensing pipette tip experiences opposing motion with the oil phase composition due to the interlocking motion control mechanism. Conventional motion control mechanisms cannot precisely control the opposing motion between the outlet end of the liquid dispensing pipette tip and the oil phase composition when in use, resulting in poor uniformity in the volume of the generated microdroplets. In the process of generating microdroplets, the flow velocity of the discharged liquid becomes unstable and uncontrollable because the outlet end of the liquid dispensing pipette tip is in motion. The generated microdroplets exhibit randomness in their volume. Conventional liquid dispensing pipette tip injection / injection methods require the pipette tip to undergo shear motion above and below the liquid surface to generate microdroplets. However, this method can lead to the formation of unstable standing waves, potentially destabilizing the microdroplet generation process. The surface properties of the liquid dispensing pipette tip are a crucial factor influencing microdroplet generation. Conventional liquid dispensing pipette tips generally have cross-sectional dimensions at the micron level. Furthermore, conventional surface treatment methods, while used for relatively large components, are not easily applicable to the relatively small liquid dispensing pipette tips. [Overview of the project]

[0005] In view of this, the liquid dispensing pipette tip provided in this application is a liquid dispensing pipette tip for generating microdroplets, comprising a needle shaft having a hollow cavity and an outlet end positioned at one end of the needle shaft, wherein the angle between the normal to the end face of the outlet end of the liquid dispensing pipette tip and the extending direction of the needle shaft is 90° or less.

[0006] The microdroplet generating device includes a fluid drive mechanism, a motion control mechanism, and a liquid dispensing pipette tip as described above, wherein the liquid dispensing pipette tip has an outlet end and an inlet end and stores a first liquid inside therein; the fluid drive mechanism is connected to the inlet end of the liquid dispensing pipette tip and is used to discharge the first liquid stored inside the liquid dispensing pipette tip from the outlet end of the liquid dispensing pipette tip; and the motion control mechanism is used to control the outlet end of the liquid dispensing pipette tip to move below the liquid surface of the second liquid according to a predetermined trajectory, a predetermined velocity, or a predetermined acceleration, such that the first liquid discharged from the outlet end of the liquid dispensing pipette tip overcomes surface tension and adhesion and forms microdroplets in the second liquid.

[0007] The method for generating microdroplets is a method for generating microdroplets using a liquid dispensing pipette tip storing a first liquid as described in any one of the above embodiments, wherein a microdroplet container storing a second liquid is provided, and the first liquid is controlled to be discharged from the outlet end of the liquid dispensing pipette tip at a uniform rate, and the outlet end of the liquid dispensing pipette tip is controlled to move periodically below the liquid surface of the second liquid along the direction of extension of the needle axis at a changing square wave velocity, and in the first and second halves of the period in which the outlet end of the liquid dispensing pipette tip is moving periodically, the velocities of the outlet end of the liquid dispensing pipette tip are the same in magnitude and opposite in direction, and the first liquid and the second liquid are any two liquids that are incompatible with each other or have an interfacial reaction.

[0008] The method for generating microdroplets is a method for generating microdroplets using a liquid dispensing pipette tip storing a first liquid as described in any one of the above embodiments, wherein a microdroplet container storing a second liquid is provided, and the first liquid is controlled to be discharged at a uniform rate from the outlet end of the liquid dispensing pipette tip, so that the outlet end of the liquid dispensing pipette tip moves periodically in the interior of the second liquid with sinusoidal displacement along the direction of extension of the needle axis, and the first liquid and the second liquid are any two liquids that are incompatible with each other or have an interfacial reaction.

[0009] With the above-described liquid dispensing pipette tip, when the liquid dispensing pipette tip vibrates along the extending direction of the pipe body, the minute droplets, after falling from the outlet end of the liquid dispensing pipette tip, are separated from their trajectory due to the action of the viscous force of the second liquid and the pressure on the end face of the outlet end of the liquid dispensing pipette tip. This prevents them from being destroyed at the outlet end, thus maintaining the integrity of the generated minute droplets, and also enables the liquid dispensing pipette tip to vibrate rapidly along the extending direction of the pipe body, thereby rapidly generating minute droplets.

[0010] In view of this, this application provides a motion control mechanism including a support frame, connecting means and a drive element. The connecting means is used to connect to a liquid dispensing pipette tip. The drive element is fixed to the support frame and connected to the connecting means so as to transmit power. The outlet end of the liquid dispensing pipette tip moves at a speed that displaces sinusoidally or changes in a speed that changes in a square wave pattern, driven by the drive element. The motion control mechanism works in conjunction to generate microdroplets by moving the outlet end of the liquid dispensing pipette tip at a speed that displaces sinusoidally or changes in a speed that changes in a square wave pattern, and has the advantage of being highly efficient and uniform in generating microdroplets.

[0011] In view of this, the present application provides a fluid drive mechanism used in a microdroplet generation system, comprising a volumetric assembly and a power assembly. The volumetric assembly includes a syringe capable of storing a drive fluid and a bush rod slidably cooperating with the inner wall of the syringe, the syringe having a fluid inlet and outlet for communicating with the inlet end of a liquid dispensing pipette tip storing a first fluid. The power assembly is power-transmittable to the bush rod and is used to drive the bush rod to slide along the extending direction of the syringe. In the process of generating microdroplets, the power assembly drives the bush rod to press the drive fluid stored in the syringe, the drive fluid presses the first fluid stored in the liquid dispensing pipette tip, thereby discharging the first fluid from the outlet end of the liquid dispensing pipette tip.

[0012] The fluid drive method is a fluid drive method using a fluid drive mechanism described in any one of the above embodiments, wherein the power assembly drives the bush rod to press the drive fluid stored in the syringe, and the drive fluid presses the first liquid stored in the liquid dispensing pipette tip, thereby discharging the first liquid from the outlet end of the liquid dispensing pipette tip.

[0013] A fluid drive method using the fluid drive mechanism described above involves: connecting the liquid inlet / outlet of the variable volume assembly to the liquid storage tank via the three-way switching valve; causing the bush rod to slide inside the syringe by the interlocking of the power assembly, thereby changing the volume of the syringe and drawing the drive liquid from the liquid storage tank into the syringe; connecting the liquid inlet / outlet of the variable volume assembly to the inlet end of the liquid dispensing pipette tip via the three-way switching valve; causing the bush rod to slide inside the syringe by the interlocking of the power assembly, thereby changing the volume of the syringe and discharging gas from inside the syringe and the liquid dispensing pipette tip; and bringing the outlet end of the liquid dispensing pipette tip into the first liquid. The process includes: entering the syringe and maintaining communication between the liquid inlet / outlet of the variable volume assembly and the inlet end of the liquid dispensing pipette tip via the three-way switching valve; using the interlocking power assembly to slide the bush rod inside the syringe, thereby changing the volume of the syringe and drawing the first liquid into the liquid dispensing pipette tip; and, using the three-way switching valve to maintain communication between the liquid inlet / outlet of the variable volume assembly and the inlet end of the liquid dispensing pipette tip, using the interlocking power assembly to slide the bush rod inside the syringe, thereby changing the volume of the syringe and discharging the first liquid stored in the liquid dispensing pipette tip from the outlet end of the liquid dispensing pipette tip at a uniform flow rate.

[0014] According to the above-described fluid drive mechanism and fluid drive method, by utilizing the incompressibility of the drive fluid, it is possible to ensure that the first liquid is still discharged from the outlet end of the liquid dispensing pipette tip at a predetermined flow rate, even when the outlet end of the liquid dispensing pipette tip is vibrating at a high frequency. The fluid drive mechanism provided in this application can precisely control the volume of the generated microdroplets.

[0015] In view of this, the microdroplet generation method provided in this application comprises the steps of: providing a liquid dispensing pipette tip having an outlet end and storing a first liquid; providing a microdroplet container having an opening and storing a second liquid, wherein the first liquid and the second liquid are any two liquids that are incompatible with each other or have an interfacial reaction; and inserting the outlet end of the liquid dispensing pipette tip below the liquid surface of the second liquid through the opening of the microdroplet container; and the outlet end of the liquid dispensing pipette tip The process includes step S203, in which the first liquid is discharged from the outlet end of the liquid dispensing pipette tip while the second liquid is subjected to motion including instantaneous acceleration motion below the liquid surface of the second liquid, the first liquid discharged from the outlet end of the liquid dispensing pipette tip forms a droplet that adheres to the outlet end of the liquid dispensing pipette tip, and the droplet is detached from the outlet end of the liquid dispensing pipette tip during the process in which the outlet end of the liquid dispensing pipette tip is subjected to instantaneous acceleration motion, forming a minute droplet below the liquid surface of the second liquid.

[0016] In the above-described method for generating microdroplets, the acceleration value is relatively large when the outlet end of the liquid dispensing pipette tip undergoes instantaneous acceleration motion. The adhesive force between the droplet attached to the outlet end of the liquid dispensing pipette tip and the outlet end of the liquid dispensing pipette tip is insufficient to cause the droplet and the outlet end of the liquid dispensing pipette tip to accelerate synchronously. As a result, the droplet attached to the outlet end of the liquid dispensing pipette tip detaches from the outlet end of the liquid dispensing pipette tip and forms microdroplets below the liquid surface of the second liquid.

[0017] The microdroplet generation method provided in this application involves the outlet end of the liquid dispensing pipette tip performing motion including instantaneous acceleration below the liquid surface of the second liquid to form microdroplets. This reduces the interference exerted on the second liquid while the outlet end of the liquid dispensing pipette tip is in motion, thereby ensuring stability in the microdroplet generation process.

[0018] In view of this, the microdroplet generation method provided in this application comprises the steps of: providing a liquid dispensing pipette tip having an outlet end and storing a first liquid; providing a microdroplet container having an opening and storing a second liquid, wherein the first liquid and the second liquid are any two liquids that are incompatible with each other or have an interfacial reaction; inserting the outlet end of the liquid dispensing pipette tip through the opening of the microdroplet container below the liquid surface of the second liquid; and providing the outlet end of the liquid dispensing pipette tip to the liquid surface of the second liquid which periodically changes below the liquid surface. Step S213 includes the following steps: the pipette tip is made to move in degrees, and in the first and second halves of the period in which the velocity is changing, the velocity of the outlet end of the liquid dispensing pipette tip changes monotonically, the first liquid is discharged from the outlet end of the liquid dispensing pipette tip, the first liquid discharged from the outlet end of the liquid dispensing pipette tip forms a droplet that adheres to the outlet end of the liquid dispensing pipette tip, and in the process in which the outlet end of the liquid dispensing pipette tip is moving, the droplet detaches from the outlet end of the liquid dispensing pipette tip and forms a microdroplet below the liquid surface of the second liquid.

[0019] According to the above-described method for generating microdroplets, the outlet end of the liquid dispensing pipette tip moves at a periodically changing speed below the liquid surface of the second liquid, and the speed of the outlet end of the liquid dispensing pipette tip changes monotonically in the first and second halves of the period in which the speed is changing. During the motion process, the viscous force of the second liquid on the droplet also changes periodically in accordance with the periodic change in the speed of the outlet end of the liquid dispensing pipette tip. When the maximum adhesion force between the outlet end of the liquid dispensing pipette tip and the droplet is less than the viscous force of the second liquid on the droplet, the droplet can no longer move synchronously with the outlet end of the liquid dispensing pipette tip, and the droplet attached to the outlet end of the liquid dispensing pipette tip detaches from the outlet end of the liquid dispensing pipette tip, forming a microdroplet below the liquid surface of the second liquid.

[0020] According to the microdroplet generation method provided in this application, the outlet end of the liquid dispensing pipette tip moves below the liquid surface of the second liquid at a periodically changing speed, forming microdroplets. This reduces the interference the outlet end of the liquid dispensing pipette tip exerts on the second liquid while it is moving, thereby ensuring stability in the microdroplet generation process.

[0021] In view of this, the surface treatment method for a liquid dispensing pipette tip provided in this application comprises the steps of: S260, which is a silane treatment of the liquid dispensing pipette tip; S270, which is a treatment of the liquid dispensing pipette tip with an aqueous solution of diethyl pyrocarbonate; and S280, which is a drying of the liquid dispensing pipette tip.

[0022] According to the above surface treatment method for liquid dispensing pipette tips, the silanization treatment reduces the surface free energy of the liquid dispensing pipette tip, and the surface free energy of the liquid dispensing pipette tip is suppressed to a certain range, thereby reducing the influence of the surface characteristics of the liquid dispensing pipette tip on the microdroplet generation process.

[0023] In view of this, the fluid drive mechanism provided in this application is used in a microdroplet generation system and includes a housing, a first volumetric assembly, and a linear motor assembly. The first volumetric assembly is housed in the housing and includes a first syringe and a first bush rod, the first bush rod slidingly cooperating with the inner wall of the first syringe, the first syringe being capable of storing a first drive fluid and having a liquid inlet / outlet for communicating with the inlet end of a first liquid dispensing pipette tip for storing a third fluid. The linear motor assembly is housed in the housing and its output end is power-transmittingly connected to the first bush rod and is used to drive the first bush rod to slide along the extending direction of the first syringe.

[0024] The fluid drive method using the fluid drive mechanism described above connects the liquid inlet and outlet of the first syringe to the liquid storage tank via the switching valve, and, through the interlocking of the linear motor assembly, causes the first bush rod to slide inside the first syringe to change the volume of the first syringe, thereby drawing the first drive liquid from the liquid storage tank into the first syringe. The liquid inlet and outlet of the first syringe are connected to the inlet end of the first liquid dispensing pipette tip via the switching valve, and, through the interlocking of the linear motor assembly, causes the first bush rod to slide inside the first syringe to change the volume of the first syringe and discharge gas from inside the first syringe and the first liquid dispensing pipette tip. The outlet end of the first liquid dispensing pipette tip is introduced into the third liquid, and the liquid inlet / outlet of the first syringe is maintained in communication with the inlet end of the first liquid dispensing pipette tip via the switching valve. The power assembly is activated to cause the first bush rod to slide inside the first syringe, changing the volume of the first syringe and drawing the third liquid into the first liquid dispensing pipette tip. The liquid inlet / outlet of the first syringe is maintained in communication with the inlet end of the first liquid dispensing pipette tip via the switching valve, and the linear motor assembly is activated to cause the first bush rod to slide inside the first syringe, changing the volume of the first syringe and discharging the third liquid stored in the first liquid dispensing pipette tip from the outlet end of the first liquid dispensing pipette tip at a predetermined flow rate.

[0025] According to the above fluid driving mechanism and fluid driving method, due to the incompressibility of the first driving liquid, even when the outlet end of the first liquid ejection pipette tip is vibrating at a high frequency, it is still possible to ensure that the third liquid is discharged from the outlet end of the first liquid ejection pipette tip at a predetermined flow rate. The linear motor assembly not only has relatively high movement accuracy, but when the current is adjusted according to the actual situation such as the liquid discharge speed and the liquid discharge pressure, it can ensure that the first push rod slides smoothly at a predetermined speed or slides by a predetermined distance, and the third liquid can be accurately discharged from the outlet end of the first liquid ejection pipette tip at a predetermined flow rate and flow rate. The fluid driving mechanism provided by the present application can accurately control the volume of the generated micro-droplets.

[0026] To more clearly explain the embodiments in the present application or the aspects in the prior art, the following briefly describes the drawings necessary for explaining the embodiments or the prior art. The drawings related to the following description are only examples of the present application. On the premise of not performing creative work, it is obvious to those skilled in the art to obtain other drawings based on the provided drawings.

Brief Description of Drawings

[0027] [Figure 1] It is a schematic diagram of the overall structure of a digital PCR detector provided by an embodiment of the present application. [Figure 2] It is a micro-droplet generating device of a digital PCR detector provided by an embodiment of the present application. [Figure 3] It is a schematic diagram of a droplet receiving force when the outlet end of a liquid ejection pipette tip provided by an embodiment of the present application is moving. [Figure 4] It is a schematic diagram of the speed change of the outlet end of a liquid ejection pipette tip provided by an embodiment of the present application. [Figure 5] It is a schematic diagram of the process of generating micro-droplets when the outlet end of a liquid ejection pipette tip provided by an embodiment of the present application is moving. [Figure 6]This is a schematic diagram of a droplet that is subjected to force when the outlet end of a liquid dispensing pipette tip, as provided in another embodiment of this application, is in motion. [Figure 7] This is a schematic diagram illustrating the change in viscous resistance in an ideal state when the outlet end of a droplet-dispensing pipette tip, provided in one embodiment of this application, is in motion. [Figure 8] This is a schematic diagram illustrating a process in which the outlet end of a liquid dispensing pipette tip provided in one embodiment of this application generates one microdroplet in two motion cycles. [Figure 9] This is a schematic diagram illustrating the process by which the outlet end of a liquid dispensing pipette tip provided in one embodiment of this application generates one microdroplet per motion cycle. [Figure 10] This is a schematic diagram illustrating a process in which the outlet end of a liquid dispensing pipette tip provided in one embodiment of this application generates two microdroplets in one motion cycle. [Figure 11] This is a schematic diagram of a process for generating minute droplets when a liquid dispensing pipette tip, provided in one embodiment of this application, is oscillating. [Figure 12] This is a schematic diagram of a process for generating microdroplets when the viscosity of a second liquid changes, as provided in one embodiment of this application. [Figure 13] This is a schematic diagram of a process for generating microdroplets when a liquid dispensing pipette tip is replaced, as provided in one embodiment of this application. [Figure 14] This is a schematic diagram illustrating a process in which the outlet end of a liquid dispensing pipette tip, provided in one embodiment of this application, generates minute droplets with different motion trajectories. [Figure 15] A schematic diagram of the velocity change at the outlet end of a liquid dispensing pipette tip provided in another embodiment of this application. [Figure 16] This is a schematic diagram of the structure of the outlet end of a liquid dispensing pipette tip provided in one embodiment of this application. [Figure 17] This is a schematic diagram of the structure of the outlet end of a liquid dispensing pipette tip provided in another embodiment of this application. [Figure 18] This is a schematic diagram of the structure of a liquid dispensing pipette tip provided in one embodiment of this application. [Figure 19]This is a schematic diagram of the structure of a liquid dispensing pipette tip provided in another embodiment of this application. [Figure 20] This is a schematic diagram illustrating the process by which a diagonally cut liquid dispensing pipette tip, provided in one embodiment of this application, generates minute droplets. [Figure 21] This is a schematic diagram illustrating the process by which a diagonally cut liquid dispensing pipette tip, provided in another embodiment of this application, generates minute droplets. [Figure 22] This is a schematic diagram illustrating the process by which a bent liquid dispensing pipette tip, provided in one embodiment of this application, generates minute droplets. [Figure 23] This is a schematic diagram illustrating the process by which a bent liquid dispensing pipette tip, provided in another embodiment of this application, generates microdroplets. [Figure 24] This is a flowchart of a surface treatment method for liquid dispensing pipette tips provided in one embodiment of this application. [Figure 25] This is a flowchart of a surface treatment method for liquid dispensing pipette tips provided in other embodiments of this application. [Figure 26] This is a schematic diagram showing a fluid control mechanism provided in one embodiment of this application connected to a liquid dispensing pipette tip. [Figure 27] This is a schematic diagram of the structure of a fluid control mechanism provided in one embodiment of this application. [Figure 28] This is a schematic diagram illustrating the process by which a liquid dispensing pipette tip provided in one embodiment of this application generates minute droplets by driving a driving liquid. [Figure 29] This is a schematic diagram of the structure of a fluid control mechanism provided in another embodiment of this application. [Figure 30] This is a schematic diagram of the structure of a motion control mechanism provided in one embodiment of this application. [Figure 31] This is a diagram illustrating the principle of control for a closed-loop controlled motor provided in one embodiment of this application. [Figure 32] This is a schematic diagram of the structure of a piezoelectric motion control mechanism provided in one embodiment of this application. [Figure 33] This is a schematic diagram of the structure of an electromagnetic-elastic motion control mechanism provided in one embodiment of this application. [Figure 34] This is a schematic diagram of the structure of an electromagnetic-elastic motion control mechanism provided by another embodiment of this application. [Figure 35] This is a schematic diagram of the structure of an electromagnetic-bearing type motion control mechanism provided in one embodiment of this application. [Figure 36] This is a schematic diagram of the structure of an electromagnetic-bearing type motion control mechanism provided by another embodiment of this application. [Figure 37] This is a schematic diagram of the structure of an electromagnetic-bearing type motion control mechanism provided in yet another embodiment of this application. [Figure 38] This is a schematic side view of the overall structure of a fluid drive mechanism provided in one embodiment of this application. [Figure 39] This is a schematic diagram of a first side view of the local structure of a fluid drive mechanism provided in one embodiment of the present application. [Figure 40] This is a schematic front view of the local structure of a fluid drive mechanism provided in one embodiment of this application. [Figure 41] This is a schematic rear view of the local structure of a fluid drive mechanism provided in one embodiment of this application. [Figure 42] This is a schematic diagram of a second side view of the local structure of a fluid drive mechanism provided in one embodiment of the present application. [Figure 43] This is an exploded schematic diagram of the assembly of a fluid drive mechanism provided in one embodiment of this application. [Figure 44] This is an exploded schematic diagram of the structural assembly of a voice coil motor, connecting plate, and first variable volume assembly provided in one embodiment of the present application. [Figure 45] This is an exploded schematic diagram of the assembly of the structure of a voice coil motor and a connecting plate provided in one embodiment of this application. [Figure 46] This is a schematic diagram of a first side view of an integrally formed bobbin and connecting plate provided in one embodiment of the present application. [Figure 47] This is a schematic diagram of a second side view of an integrally formed bobbin and connecting plate provided in one embodiment of the present application. [Figure 48] This is a schematic side view of the structure of a switching valve provided in one embodiment of this application. [Figure 49] This is a schematic diagram of the front cross-sectional structure of a switching valve provided in one embodiment of this application. [Figure 50] This is a schematic diagram of the process of a fluid drive method provided in one embodiment of this application. [Modes for carrying out the invention]

[0028] The technical solutions of the embodiments of this application will be described clearly and completely below, with reference to the accompanying drawings of the embodiments. Naturally, the embodiments described herein represent only a portion, not all, of the embodiments of this application. All other embodiments that can be obtained based on the embodiments of this application without creative work by those skilled in the art should also be included within the scope of protection of this application.

[0029] To further clarify the purpose, aspects, and advantages of this application, the application will be described in more detail below with reference to examples and drawings. It should be understood that the specific examples described herein are not intended to limit this application, but are used to illustrate it.

[0030] Referring to Figure 1, in one embodiment, the digital PCR detector 1 provided in this application includes a microdroplet generator 10, a temperature control device 20, a fluorescence signal detection device 30, a quantitative analysis device 40, and a controller 50. The microdroplet generator 10 is used to atomize a nucleic acid amplification reaction solution and form a plurality of microdroplets. The temperature control device 20 is connected to the microdroplet generator 10 via rails and is used to transfer the plurality of microdroplets to the temperature control device 20 and amplify the nucleic acids by temperature circulation. The fluorescence signal detection device 30 is positioned opposite the temperature control device 20 and is used to photograph and detect the plurality of nucleic acid-amplified microdroplets. The quantitative analysis device 40 is connected to the fluorescence signal detection device 30 via data lines and is used to transmit fluorescence information of the plurality of microdroplets and perform quantitative analysis. The controller 50 is connected to the microdroplet generation device 10, the temperature control device 20, the fluorescence signal detection device 30, and the quantitative analysis device 40, respectively, and is used to control the microdroplet generation device 10, the temperature control device 20, the fluorescence signal detection device 30, and the quantitative analysis device 40.

[0031] The digital PCR detector 1 integrates the microdroplet generation device 10, the temperature control device 20, the fluorescence signal detection device 30, and the quantitative analysis device 40, enabling automated operation by the operator. The digital PCR detector 1 has relatively high operational efficiency.

[0032] When the digital PCR detector 1 is operating, the microdroplet generation device 10 can atomize the nucleic acid amplification reaction solution to be detected, forming a plurality of microdroplets. The temperature control device 20 amplifies the nucleic acid in the plurality of microdroplets. The fluorescence signal detection device 30 captures images of the fluorescence changes in the plurality of microdroplets in real time. Based on the changing fluorescence images of the plurality of microdroplets, a fluorescence curve changing in the plurality of microdroplets can be obtained. From the changing fluorescence curve, the Ct value of the plurality of microdroplets can be obtained, and the initial DNA concentration can be quantitatively analyzed based on the relationship between the Ct value and the initial copy number. However, the Ct value is the number of cycles that have elapsed until the fluorescence signal of each microdroplet reaches a predetermined threshold.

[0033] The temperature control device 20 causes the plurality of microdroplets to undergo a nucleic acid amplification reaction, and the fluorescence signal detection device 30 collects signals (e.g., fluorescence, ultraviolet absorption, turbidity, etc.) from the products of the plurality of microdroplets that have undergone the nucleic acid amplification reaction. By analyzing the difference in composition between the plurality of amplified microdroplets and the microdroplets that were not amplified, the number of droplets in which target sequence amplification was obtained can be analyzed, and quantitative analysis of nucleic acid molecules can ultimately be achieved. By monitoring the changing fluorescence image related to the plurality of microdroplets in real time, the detection results are direct, and the problems of false positives and false negatives in the plurality of microdroplets can be solved.

[0034] The digital PCR detector 1 integrates the microdroplet generation device 10, the temperature control device 20, the fluorescence signal detection device 30, and the quantitative analysis device 40, thus not only enabling automated operation by the operator but also offering advantages such as increased work efficiency, rapid reaction, good reusability, high sensitivity, strong specificity, and clear results.

[0035] Currently, precise manipulation of trace liquids is widely required in applied fields such as medical clinical testing, nanomaterial manufacturing, food and environmental testing, and biochemical analysis. One of the core technologies for manipulating trace liquids is to further divide microliter-level liquids into nanoliter and even picoliter-level microreaction systems. One major technological field related to the generation of microreaction systems is the creation of emulsified microdroplets.

[0036] In recent years, various microdroplet generation techniques have been described in the literature, such as membrane emulsification, spray emulsification, microfluidic controlled tip methods, and liquid dispensing pipette tip injection / jet methods. However, methods for generating emulsified microdroplets using liquid dispensing pipette tips have some drawbacks in practical application. One method involves using the interfacial energy of the trace amount of liquid and the shear force of the fluid to overcome the surface tension and adhesive force of the liquid at the outlet of the liquid dispensing pipette tip when converting to a gas-liquid phase interface. This allows the droplets discharged from the pipette tip to detach smoothly, forming droplets of controllable size in an immiscible liquid. However, this method requires the liquid dispensing pipette tip to perform shearing motion above and below the liquid surface, and also requires highly accurate positioning of the initial and endpoints of the liquid dispensing pipette tip relative to the liquid surface. From a project implementation perspective, this is quite difficult. In the above method, unstable standing waves easily form on the surface of the liquid phase during the process in which the liquid dispensing pipette tip rapidly injects and injects the liquid phase, limiting the rate of microdroplet formation. There is also a method in which the liquid dispensing pipette tip generates shear force at a uniform speed through circular or helical motion in the liquid, shearing the injected incompatible liquid to form droplets. However, with this method, the size of the droplets generated by the liquid dispensing pipette tip is relatively susceptible to errors due to changes in various system elements (e.g., liquid viscosity, ambient temperature, motion speed, motion trajectory, etc.), which can lead to errors. Furthermore, since this error accumulates as the number of generated droplets increases, it is quite difficult to control the uniformity of the volume of droplets generated in large quantities.

[0037] In light of this, there is a need to provide a method and apparatus for generating microdroplets that can rapidly generate microdroplets with high volume uniformity, addressing the challenges in conventional microdroplet generation methods and apparatuses, such as the slow rate of microdroplet generation and the considerable difficulty in controlling the uniformity of the generated microdroplets' volume.

[0038] Referring to Figure 2, in one embodiment, the microdroplet generation device 10 includes a liquid dispensing pipette tip 110, a fluid drive mechanism 120, a motion control mechanism 130, and a first controller 170. The liquid dispensing pipette tip 110 has an outlet end and an inlet end and is used to store a first liquid. The microdroplet generation device 10 is used in cooperation with a microdroplet container. A second liquid is stored in the microdroplet container, and the outlet end of the liquid dispensing pipette tip 110 is inserted below the liquid surface of the second liquid.

[0039] The first liquid and the second liquid are either immiscible with each other or have an interfacial reaction. The first liquid and the second liquid may be any two liquids that are immiscible with each other. In one embodiment of this application, the first liquid is an aqueous solution, and the second liquid is an oily liquid that is immiscible with water, such as mineral oil (including tetradecane, etc.), vegetable oil, silicone oil, or perfluoroalkane oil, and the resulting droplets are droplets of the aqueous solution. Alternatively, the first liquid may be an organic phase mineral oil such as tetradecane and n-hexane, and the second liquid may be a perfluoroalkane oil that is immiscible with mineral oil. The first liquid and the second liquid may be two aqueous phases that are immiscible with each other. In another embodiment of this application, the first liquid may be an aqueous solution, and the second liquid may be an aqueous liquid that is immiscible with water. For example, the first liquid is a dextran solution, the second liquid is an aqueous solution of polyethylene glycol (PEG), and the resulting droplets are droplets of the dextran solution.

[0040] The first and second liquids may be two liquids having an interfacial reaction. In one embodiment of this application, the first liquid is an aqueous solution of sodium alginate, and the second liquid is, for example, an aqueous solution of calcium oxide with a mass concentration of 1%, and an interfacial reaction exists between the two, and the resulting droplets are gel-like calcium alginate microspheres. This application makes it possible to sequentially form droplets of multiple different components and volumes in an open container by changing the liquid dispensing pipette tip or the components of the first liquid flowing out of the liquid dispensing pipette tip, enabling high-throughput screening of minute volumes even in batch production, and moreover, enabling ultra-trace biochemical reactions and monitoring in multiple stages, thus offering prospects for a wide range of applications.

[0041] The fluid drive mechanism 120 is connected to the inlet end of the liquid dispensing pipette tip 110 and is used to discharge the first liquid stored inside the liquid dispensing pipette tip 110 from the outlet end of the liquid dispensing pipette tip 110. The motion control mechanism 130 is used to control the first liquid discharged from the outlet end of the liquid dispensing pipette tip 110 to overcome the surface tension and the adhesion force of the liquid dispensing pipette tip 110 to the first liquid, thereby forming a microdroplet, by performing opposing motion at a predetermined trajectory, predetermined speed, or predetermined acceleration between the outlet end of the liquid dispensing pipette tip 110 and the second liquid. The first controller 170 is connected to the fluid drive mechanism 120 and the motion control mechanism 130, respectively, and is used to control the fluid drive mechanism 120 and the motion control mechanism 130 to operate in cooperation with each other.

[0042] For example, various microdroplet generation techniques such as membrane emulsification, spray emulsification, microfluidic controlled tip method, and liquid dispensing pipette tip injection / jet method have been described in the literature. Among these, the liquid dispensing pipette tip injection / jet method, as the latest microdroplet generation technique, has excellent application prospects in terms of reducing the cost of microdroplets and consumables. In the conventional liquid dispensing pipette tip injection / jet method, it is necessary to move the liquid dispensing pipette tip by shearing it above and below the liquid surface in order to generate microdroplets. However, this method may lead to the formation of unstable standing waves, potentially making the microdroplet generation process unstable.

[0043] In light of this, there is a need to provide a method for generating microdroplets that stabilizes the microdroplet generation process, addressing the problem of instability in the microdroplet generation process that exists in conventional liquid dispensing pipette tip injection / injection methods.

[0044] As shown in Figure 3, in one embodiment of this application, the operation of the motion control mechanism 130 allows the outlet end 112 of the liquid dispensing pipette tip 110 to perform motion including instantaneous acceleration motion below the liquid surface of the second liquid, where the acceleration is denoted as a1. When the first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110, it forms a droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110. At the moment the outlet end 112 of the liquid dispensing pipette tip 110 performs instantaneous acceleration motion, the droplet 195 detaches from the outlet end 112 of the liquid dispensing pipette tip 110, forming a minute droplet. The forces acting on the minute droplet until it detaches from the outlet end 112 of the liquid dispensing pipette tip 110 are gravity G, the buoyancy f1 of the second liquid, the viscous resistance f2 of the second liquid, and the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195, respectively. For a minute droplet, if its mass is m and its acceleration is a² until it detaches from the outlet end 112 of the liquid dispensing pipette tip 110, then according to Newton's second law of motion,

number

[0045] The maximum value f3 of the adhesive force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 is related to the surface free energy of the liquid dispensing pipette tip 110, the surface tension of the droplet 195, and the geometric dimensions of the liquid dispensing pipette tip 110. When the outlet end 112 of the liquid dispensing pipette tip 110 is undergoing instantaneous acceleration, the direction of the adhesive force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 is the same as the direction of acceleration. The droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 is simplified as a sphere. As can be seen from Stokes' equation, the viscous resistance of the droplet 195 when moving in the second liquid is f2 = 6πηrv, where η is the viscosity coefficient of the second liquid, r is the radius of the droplet 195, and v is the velocity of the droplet 195. Since the velocity of the droplet 195 was zero until the outlet end 112 of the liquid dispensing pipette tip 110 underwent instantaneous acceleration, the viscous resistance f2 of the droplet 195 received by the second liquid at the moment the outlet end 112 of the liquid dispensing pipette tip 110 underwent instantaneous acceleration is zero or extremely small. In the process of generating microdroplets, the diameter of the droplet 195 is generally on the order of picoliters to microliters, and the gravitational force G of the droplet 195 and the buoyancy f1 of the second liquid are in opposite directions. Therefore, the sum of the vectors of the gravitational force G of the droplet 195 and the buoyancy f1 of the second liquid is approximately zero. Since the viscous resistance f2 is zero or extremely small, and the sum of the vectors of the gravitational force G and the buoyancy f1 is approximately zero,

number

[0046] The motion control mechanism 130 can precisely control the instantaneous acceleration of the outlet end 112 of the liquid dispensing pipette tip 110. By controlling each instantaneous acceleration of the outlet end 112 of the liquid dispensing pipette tip 110 to be relatively large, droplets 195 can be effectively generated when the outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous acceleration motion.

[0047] In view of this, the present application provides a liquid dispensing pipette tip 110 having an outlet end 112 and storing a first liquid, and a microdroplet container having an opening and storing a second liquid, wherein the first liquid and the second liquid are any two liquids that are incompatible with each other or have an interfacial reaction, step S201, insert the outlet end 112 of the liquid dispensing pipette tip 110 below the liquid surface of the second liquid through the opening of the microdroplet container, and move the outlet end 112 of the liquid dispensing pipette tip 110 below the liquid surface of the second liquid, including instantaneous acceleration motion The present invention further provides a method for generating microdroplets, which includes step S203, in which a first liquid is discharged from the outlet end 112 of a liquid dispensing pipette tip 110 while it is moving, the first liquid discharged from the outlet end 112 of the liquid dispensing pipette tip 110 forms a droplet 195 that adheres to the outlet end 112 of the liquid dispensing pipette tip 110, and the droplet 195 is detached from the outlet end 112 of the liquid dispensing pipette tip 110 during the process in which the outlet end 112 of the liquid dispensing pipette tip 110 is undergoing instantaneous acceleration motion, forming a microdroplet below the liquid surface of the second liquid.

[0048] According to the above-described method for generating microdroplets, when the outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous acceleration, the acceleration is relatively large. Furthermore, the adhesive force between the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 and the outlet end 112 of the liquid dispensing pipette tip 110 is insufficient to cause the droplet 195 and the outlet end 112 of the liquid dispensing pipette tip 110 to accelerate and move in synchronously. As a result, the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 detaches from the outlet end 112 of the liquid dispensing pipette tip 110 and forms microdroplets below the liquid surface of the second liquid.

[0049] According to the microdroplet generation method provided in this application, since microdroplets are generated when the outlet end 112 of the liquid dispensing pipette tip 110 is undergoing instantaneous acceleration motion below the liquid surface of the second liquid, the interference caused to the second liquid while the outlet end 112 of the liquid dispensing pipette tip 110 is in motion can be reduced, and stability can be ensured in the microdroplet generation process.

[0050] Selectively, in step S203, the method of discharging the first liquid from the outlet end 112 of the liquid discharging pipette tip 110 may be continuous or intermittent. The specific discharging method may be designed appropriately according to the actual situation. In this embodiment, in step S203, the first liquid is continuously discharged from the outlet end 112 of the liquid discharging pipette tip 110 so as to make full use of the instantaneous acceleration motion of the outlet end 112 of the liquid discharging pipette tip 110 to form microdroplets. In one embodiment, discharging the first liquid from the outlet end 112 of the liquid discharging pipette tip 110 at a constant flow rate in step S203 means that the volume of the first liquid discharged from the outlet end 112 of the liquid discharging pipette tip 110 is always the same at the same time interval. Discharging the first liquid from the outlet end 112 of the liquid discharging pipette tip 110 at a constant flow rate can help control the generation of microdroplets by controlling the motion of the outlet end 112 of the liquid discharging pipette tip 110.

[0051] In one embodiment of this application, in step S203, the outlet end 112 of the liquid dispensing pipette tip 110 performs a periodic motion including instantaneous acceleration motion below the liquid surface of the second liquid. The periodic motion of the outlet end 112 of the liquid dispensing pipette tip 110 below the liquid surface of the second liquid means that the displacement, velocity, and acceleration of the outlet end 112 of the liquid dispensing pipette tip 110 all change periodically. While the outlet end 112 of the liquid dispensing pipette tip 110 performs a periodic motion including instantaneous acceleration motion, it is possible to generate minute droplets at equal time intervals by cooperating so that the first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a constant flow rate. Alternatively, although the flow rate of the outlet end 112 of the liquid dispensing pipette tip 110 changes, the volume of the outlet end 112 of the liquid dispensing pipette tip 110 is maintained the same within one period of motion of the outlet end 112 of the liquid dispensing pipette tip 110. Therefore, by keeping the volume of the droplet 195 the same until the outlet end 112 of the liquid dispensing pipette tip 110 undergoes accelerated motion at each instant, it is possible to ensure the formation of minute droplets with matching volumes.

[0052] If the liquid dispensing pipette tip 110 and the first liquid are not replaced, the surface free energy of the liquid dispensing pipette tip 110, the geometric dimensions of the liquid dispensing pipette tip 110, and the surface tension of the droplet 195 remain unchanged as two factors that affect the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195. Therefore, if the liquid dispensing pipette tip 110 and the first liquid are not replaced, the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 remains unchanged. The first liquid is continuously discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate through the interlocking of the fluid drive mechanism 120. The motion control mechanism 130 can accurately control the timing and instantaneous acceleration a1 of the outlet end 112 of the liquid dispensing pipette tip 110 as it performs accelerated motion according to the instantaneous acceleration a1. When the fluid drive mechanism 120 and the motion control mechanism 130 work together, it is easy to achieve the formation of minute droplets of the same volume by driving the outlet end 112 of the liquid dispensing pipette tip 110 to accelerate instantaneously according to the acceleration a1 at the moment when the volume of the droplet 195 becomes a fixed value. If the fluid drive mechanism 120 can control the first liquid to be discharged uniformly and continuously from the outlet end 112 of the liquid dispensing pipette tip 110, then the motion control mechanism 130 can drive the outlet end 112 of the liquid dispensing pipette tip 110 to perform instantaneous acceleration motion at equal time intervals, thereby forming minute droplets of the same volume.

[0053] When generating microdroplets simultaneously or sequentially using multiple liquid dispensing pipette tips 110, the surface free energy and geometric dimensions of the liquid dispensing pipette tip 110 change as two factors that affect the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195. However, when processing in large quantities, the surface free energy and geometric dimensions of the liquid dispensing pipette tip 110 can be controlled to change within a certain range. The surface tension of the droplet 195, the other factor affecting the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195, changes within an extremely small range. Therefore, the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 fluctuates only within an extremely small range. The fluid drive mechanism 120 can drive the first liquid to be continuously discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate. The motion control mechanism 130 can precisely control the timing and instantaneous acceleration a1 motion of the outlet end 112 of the liquid dispensing pipette tip 110. When the fluid drive mechanism 120 and the motion control mechanism 130 work together, it is easy to generate minute droplets of matching volume by driving the outlet end 112 of the liquid dispensing pipette tip 110 to perform instantaneous acceleration motion according to acceleration a1 at the moment when the volume of the droplet 195 becomes a fixed value. If the fluid drive mechanism 120 can be controlled to discharge the first liquid uniformly and continuously from the outlet end 112 of the liquid dispensing pipette tip 110, then by using the motion control mechanism 130 to drive the outlet end 112 of the liquid dispensing pipette tip 110 to perform instantaneous acceleration motion at equal time intervals, minute droplets of matching volume can be generated.

[0054] The fluid drive mechanism 120, while discharging the first liquid at a uniform speed from the outlet end 112 of the liquid dispensing pipette tip 110, works in cooperation with the motion control mechanism 130 to cause the droplet 195 to perform instantaneous accelerated motion with a relatively large acceleration at the moment the volume reaches a predetermined value.

[0055] The microdroplet generation method provided in this application not only ensures that droplets 195 with uniform volume are generated using the same liquid dispensing pipette tip 110, but also ensures that the volumes of microdroplets generated simultaneously or sequentially using multiple liquid dispensing pipette tips 110 are uniform. The microdroplet generation method provided in this embodiment ensures that the volume of the microdroplets is uniform and can also increase the efficiency of microdroplet generation by simultaneously generating microdroplets using multiple liquid dispensing pipette tips 110.

[0056] Furthermore, under the control of the motion control mechanism 130, one motion cycle of the outlet end 112 of the liquid dispensing pipette tip 110 includes multiple instantaneous acceleration motions, the accelerations of these multiple instantaneous acceleration motions are the same, and their timings divide one motion cycle of the outlet end 112 of the liquid dispensing pipette tip 110 on average. Including multiple instantaneous acceleration motions in one motion cycle of the outlet end 112 of the liquid dispensing pipette tip 110 helps the outlet end 112 of the liquid dispensing pipette tip 110 to generate multiple microdroplets within one motion cycle. Preferably, in step S203, the trajectory of the outlet end 112 of the liquid dispensing pipette tip 110 as it moves below the liquid surface of the second liquid includes one or more combinations of multiple types of trajectories, such as linear segments, arc segments, and polygonal shapes. One possible configuration is that when one motion cycle of the outlet end 112 of the liquid dispensing pipette tip 110 includes two instantaneous acceleration motions, the motion trajectory of the liquid dispensing pipette tip 110 is a straight line or a circular arc. When one motion cycle of the outlet end 112 of the liquid dispensing pipette tip 110 includes two or more instantaneous acceleration motions, the outlet end 112 of the liquid dispensing pipette tip 110 follows a trajectory in the second liquid in the shape of a regular polygon, such as an equilateral triangle, square, regular pentagon, or regular hexagon.

[0057] In one possible configuration, in step S203, the velocity of the outlet end 112 of the liquid dispensing pipette tip 110 changes in a rectangular wave pattern during the process in which the outlet end 112 of the liquid dispensing pipette tip 110 periodically moves below the liquid surface of the second liquid. The rectangular wave pattern change in the velocity of the outlet end 112 of the liquid dispensing pipette tip 110, followed immediately by a transition to a uniform velocity phase after the acceleration phase, helps the motion control mechanism 130 to accurately control the motion state of the outlet end 112 of the liquid dispensing pipette tip 110. Preferably, the high-level timing and low-level timing that show the rectangular wave pattern of the change in motion velocity of the outlet end 112 of the liquid dispensing pipette tip 110 may be the same or different. Furthermore, in step S203, the velocity of the outlet end 112 of the liquid dispensing pipette tip 110 changes in a square wave pattern during the process in which the outlet end 112 of the liquid dispensing pipette tip 110 periodically moves below the liquid surface of the second liquid. The high-level timing and low-level timing, which represent the rectangular wave of change in motion velocity of the outlet end 112 of the liquid dispensing pipette tip 110, are equal. When the rectangular wave representing the change in motion velocity of the outlet end 112 of the liquid dispensing pipette tip 110 is at the low level, the outlet end 112 of the liquid dispensing pipette tip 110 has a velocity of zero or a velocity in the opposite direction to that at the high level. As shown in Figure 4, furthermore, in the first and second halves of the period in which the outlet end 112 of the liquid dispensing pipette tip 110 is periodically moving, the velocities of the outlet end 112 of the liquid dispensing pipette tip 110 are of the same magnitude and in opposite directions. One motion period of the outlet end 112 of the liquid dispensing pipette tip 110 includes two instantaneous acceleration motions in opposite directions.

[0058] In this embodiment, the trajectory of the outlet end 112 of the liquid dispensing pipette tip 110 as it moves below the liquid surface of the second liquid is a linear segment. The outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous acceleration motion from one endpoint of the linear segment and instantaneous acceleration motion in the opposite direction from the other endpoint of the linear segment. The acceleration of both instantaneous acceleration motions is a1. In other embodiments, the trajectory of the outlet end 112 of the liquid dispensing pipette tip 110 as it moves below the liquid surface of the second liquid is an arc segment or a polygonal shape. Furthermore, in step S203, the frequency of the periodic movement of the outlet end 112 of the liquid dispensing pipette tip 110 below the liquid surface of the second liquid is in the range of 0.1Hz to 200Hz, making it easily achievable in the project.

[0059] As shown in Figures 4 and 5, in one specific embodiment of the present application, the fluid drive mechanism 120 controls the discharge of the first liquid from the outlet end 112 of the liquid dispensing pipette tip 110 at a constant flow rate. The motion control mechanism 130 controls the output end of the liquid dispensing pipette tip 110 to move periodically at a linear trajectory or a speed that changes in a square wave pattern. When the velocity direction of the outlet end 112 of the liquid dispensing pipette tip 110 is changed, the instantaneous acceleration of the outlet end 112 of the liquid dispensing pipette tip 110 reaches its maximum value. The droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 is also detached from the outlet end 112 of the liquid dispensing pipette tip 110 when the instantaneous acceleration of the outlet end 112 reaches its maximum value, forming a minute droplet 199. As the first liquid is discharged at a constant flow rate from the outlet end 112 of the liquid dispensing pipette tip 110, when a droplet 195 detaches from the outlet end 112 of the liquid dispensing pipette tip 110, a new droplet 195 is formed. When the outlet end 112 of the liquid dispensing pipette tip 110 is accelerated again in the opposite direction, the newly formed droplet 195 also detaches from the outlet end 112 of the liquid dispensing pipette tip 110, forming a new minute droplet 199.

[0060] In this embodiment, the outlet end 112 of the liquid dispensing pipette tip 110 can generate two microdroplets 199 in one motion cycle, and a square wave pattern is easily realized in the project. In other embodiments, the outlet end 112 of the liquid dispensing pipette tip 110 generates one microdroplet 199 in one motion cycle. In the embodiment, it is preferable that the outlet end 112 of the liquid dispensing pipette tip 110 moves in a square wave pattern along a linear trajectory in an arbitrary direction in the second liquid 699. This motion includes motion in a square wave pattern along a linear trajectory in a plane perpendicular to the extending direction of the liquid dispensing pipette tip 110, motion in a square wave pattern along a linear trajectory in a plane at an arbitrary angle to the extending direction of the liquid dispensing pipette tip 110, and motion in a square wave pattern along a linear trajectory along the extending direction of the liquid dispensing pipette tip 110. In other embodiments relating to this application, when the motion trajectory of the outlet end 112 of the liquid dispensing pipette tip 110 is an arc segment or polygonal shape, the outlet end 112 of the liquid dispensing pipette tip 110 moves in a linear trajectory along an arbitrary direction in the second liquid 699 in a square wave pattern. This motion includes motion in a linear trajectory in a square wave pattern in a plane perpendicular to the extending direction of the liquid dispensing pipette tip 110, motion in a linear trajectory in a square wave pattern in a plane making an arbitrary angle with the extending direction of the liquid dispensing pipette tip 110, and motion in a linear trajectory in a square wave pattern along the extending direction of the liquid dispensing pipette tip 110.

[0061] In other embodiments relating to this application, the outlet end 112 of the liquid dispensing pipette tip 110 moves at a periodically changing speed below the liquid surface of the second liquid due to the interlocking motion control mechanism 130, and the speed of the outlet end 112 of the liquid dispensing pipette tip 110 changes monotonically in both the first and second halves of the period in which the speed is changing. Monotonically changing means that in both the first and second halves of the period in which the speed is changing, the speed of the outlet end 112 of the liquid dispensing pipette tip 110 at the next time point is always greater than or less than the speed at the previous time point. For example, in the first half of the period in which the speed is changing, the speed of the outlet end 112 of the liquid dispensing pipette tip 110 increases continuously, or a portion of the speed increases continuously and a portion of the speed remains unchanged. On the other hand, in the second half of the period in which the speed is changing, the speed of the outlet end 112 of the liquid dispensing pipette tip 110 decreases continuously, or a portion of the speed decreases continuously and a portion of the speed remains unchanged. The first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110, forming a droplet 195 that adheres to the outlet end 112 of the liquid dispensing pipette tip 110. When the velocity of the outlet end 112 of the liquid dispensing pipette tip 110 reaches a certain level, the droplet 195 detaches from the outlet end 112 of the liquid dispensing pipette tip 110, forming a microdroplet 199. As shown in Figure 6, the forces acting on the microdroplet 199 until it detaches from the outlet end 112 of the liquid dispensing pipette tip 110 are gravity G, the buoyancy f1 of the second liquid 699, the viscous resistance f2 of the second liquid 699, and the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195, respectively. Regarding the minute droplet 199, if we let its mass be m, its velocity be v, and its acceleration be a2 until it detaches from the outlet end 112 of the liquid dispensing pipette tip 110, then the droplet 195 is subjected to the synergistic effect of viscous force f2, gravity G, buoyancy f1, and adhesion force f3 during the motion process of the second liquid 699, that is,

number

number

[0062] The maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 is related to the surface free energy of the liquid dispensing pipette tip 110, the surface tension of the droplet 195, and the geometric dimensions of the liquid dispensing pipette tip 110. The droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 is simplified as a sphere. According to Stokes' equation, the viscous resistance of the droplet 195 as it moves through the second liquid 699 is f2 = 6πηrv, where η is the viscosity coefficient of the second liquid 699, r is the radius of the droplet 195, and v is the velocity of the droplet 195. In the process of generating microdroplets 199, generally, the diameter range of the droplets 195 is on the order of picoliters to microliters, and the viscosity coefficient of the second liquid 699 is generally relatively large. Therefore, generally,

number

number

[0063] In view of this, the microdroplet generation method provided in this application includes the steps of: providing a liquid dispensing pipette tip 110 having an outlet end 112 and storing a first liquid; providing a microdroplet container 60 having an opening and storing a second liquid 699, wherein the first liquid and the second liquid 699 are any two liquids that are incompatible with each other or have an interfacial reaction; inserting the outlet end 112 of the liquid dispensing pipette tip 110 below the liquid surface of the second liquid 699 through the opening of the microdroplet container 60; and causing the outlet end 112 of the liquid dispensing pipette tip 110 to perform a motion with a periodically changing velocity below the liquid surface of the second liquid 699. The process includes step S213, in which, during the first and second halves of a period in which the velocity is changing, the velocity of the outlet end 112 of the liquid dispensing pipette tip 110 changes monotonically, dispensing the first liquid from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform velocity, the first liquid discharged from the outlet end 112 of the liquid dispensing pipette tip 110 forms a droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110, the droplet 195 detaches from the outlet end 112 of the liquid dispensing pipette tip 110 during the process in which the outlet end 112 of the liquid dispensing pipette tip 110 is in motion, and forms a microdroplet 199 below the liquid surface of the second liquid 699. According to the above-described method for generating microdroplets, the outlet end 112 of the liquid dispensing pipette tip 110 moves below the liquid surface of the second liquid 699 at a periodically changing speed, and the speed of the outlet end 112 of the liquid dispensing pipette tip 110 changes monotonically in both the first and second halves of the period in which the speed is changing. During the motion process, the viscous force f2 of the second liquid 699 on the droplet 195 also changes periodically in accordance with the periodic change in the speed of the outlet end 112 of the liquid dispensing pipette tip 110. If the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 is less than the viscous force f2 of the second liquid 699 on the droplet 195, the droplet 195 will not be able to move synchronously with the outlet end 112 of the liquid dispensing pipette tip 110, and the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 will detach from the outlet end 112 of the liquid dispensing pipette tip 110, forming a minute droplet 199 below the liquid surface of the second liquid 699.

[0064] The microdroplet generation method provided in this application generates microdroplets 199 by having the outlet end 112 of the liquid dispensing pipette tip 110 move at a periodically changing speed below the liquid surface of the second liquid 699, thereby reducing interference with the second liquid 699 while the outlet end 112 of the liquid dispensing pipette tip 110 is moving, and ensuring stability in the process of generating microdroplets 199.

[0065] In this embodiment, in step S213, the first liquid is continuously discharged from the outlet end 112 of the liquid dispensing pipette tip 110. Furthermore, in step S213, the first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a constant flow rate. This means that the volume of the first liquid discharged from the outlet end 112 of the liquid dispensing pipette tip 110 is always the same at equal time intervals. When the first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a constant flow rate, controlling the outlet end 112 of the liquid dispensing pipette tip 110 to move periodically helps to generate minute droplets 199 of the same volume.

[0066] Of the factors influencing the viscous resistance f2 of droplet 195 as it moves through the second liquid 699, the motion velocity v of droplet 195 is more easily controlled. Droplet 195 maintains synchronous motion with the outlet end 112 of the liquid dispensing pipette tip 110 until it detaches from the outlet end 112 of the liquid dispensing pipette tip 110 and forms a microdroplet 199. Therefore, by controlling the motion velocity of the outlet end 112 of the liquid dispensing pipette tip 110, the motion velocity v of droplet 195 can be precisely controlled. If the first liquid is controlled to be discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate, the radius r of droplet 195 changes periodically at regular time intervals. Factors influencing the viscous resistance f2 of droplet 195 as it moves through the second liquid 699 include the viscosity coefficient η of the second liquid 699, which changes within a certain range during the process of use, although the range of change in the viscosity coefficient η of the second liquid 699 is extremely small.

[0067] When the liquid dispensing pipette tip 110 and the first liquid are not replaced, the surface free energy of the liquid dispensing pipette tip 110, the geometric dimensions of the liquid dispensing pipette tip 110, and the surface tension of the droplet 195 do not change as two factors that affect the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195. Therefore, when the liquid dispensing pipette tip 110 and the first liquid are not replaced, the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 does not change. When multiple liquid dispensing pipette tips 110 generate minute droplets 199 simultaneously or sequentially, the surface free energy of the liquid dispensing pipette tip 110 and the geometric dimensions of the liquid dispensing pipette tip 110 change as two factors that affect the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195. However, when processing in large quantities, the surface free energy of the liquid dispensing pipette tip 110 and the geometric dimensions of the liquid dispensing pipette tip 110 can be controlled to change within a certain range. The surface tension of the droplet 195, another factor that affects the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195, changes only within an extremely small range. The maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 fluctuates only within an extremely small range.

[0068] Therefore, it is sufficient to control the viscous resistance f2 of the droplet 195 as it moves through the second liquid 699 so that it is greater than the interval value of the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195. In the process of generating microdroplets 199 in the same batch, the radius r of the droplet 195 does not necessarily change. Once the parameters for testing are determined, the radius r of the droplet 195 is also determined accordingly. The speed at which the outlet end 112 of the liquid dispensing pipette tip 110 moves below the liquid surface of the second liquid 699 changes. When the speed at which the outlet end 112 of the liquid dispensing pipette tip 110 moves below the liquid surface of the second liquid 699 satisfies v>f3 / 6πηr, the droplet 195 detaches from the outlet end 112 of the liquid dispensing pipette tip 110 and forms a microdroplet 199.

[0069] The outlet end 112 of the liquid dispensing pipette tip 110 moves at a periodically changing speed below the liquid surface of the second liquid 699. When the first liquid is controlled to be discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate, the volume of the droplets 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110 also increases uniformly. The radius of the first minute droplet 199 when it falls from the outlet end 112 of the liquid dispensing pipette tip 110 is called the critical radius, and the velocity of the minute droplet 199 is called the critical velocity. The motion period of the outlet end 112 of the liquid dispensing pipette tip 110, and the outlet end 112 of the liquid dispensing pipette tip 110 By adjusting the flow rate of the first liquid discharged from the liquid dispensing pipette tip 110, after the same time interval (a multiple of the motion period of the outlet end 112 of the liquid dispensing pipette tip 110) has elapsed, the droplets 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110 simultaneously reach their critical radius and critical velocity, forming new microdroplets 199. Since the first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate, the volume of the generated microdroplets 199 becomes the same.

[0070] In one feasible configuration, in step S213, the velocity of the outlet end 112 of the liquid dispensing pipette tip 110 is centrally symmetric with respect to the midpoint during one period in which the velocity is changing. Furthermore, in step S213, the acceleration, velocity, and trajectory of the outlet end 112 of the liquid dispensing pipette tip 110 change periodically below the liquid surface of the second liquid 699. Also, in step S213, the velocity of the outlet end 112 of the liquid dispensing pipette tip 110 changes in a cosine curve shape below the liquid surface of the second liquid 699.

[0071] Selectively, step S213 includes one or a combination of several types of trajectories, such as linear segments, arc segments, and polygonal shapes, in which the trajectory of the outlet end 112 of the liquid dispensing pipette tip 110 moves below the liquid surface of the second liquid 699. Step S213 is easily implemented in the project because the frequency of the periodic movement of the outlet end 112 of the liquid dispensing pipette tip 110 below the liquid surface of the second liquid 699 is in the range of 0.1 Hz to 200 Hz.

[0072] For example, if the outlet end 112 of the liquid dispensing pipette tip 110 moves in an arc trajectory below the liquid surface of the second liquid 699, or periodically at a cosine-like velocity, then the outlet end 112 of the liquid dispensing pipette tip 110 actually moves as if oscillating, and the displacement of the motion is shown by a sinusoidal curve. As shown by curve a in Figure 7, the first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow velocity by the drive of the fluid control mechanism. If the droplet 195 does not detach from the outlet end 112 of the liquid dispensing pipette tip 110, then the viscous resistance f of the droplet 195 that it has encountered while moving in the second liquid 699 is shown as curve b in Figure 7 over time. In the initial stages when the first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate, the radius r of the droplet 195 clearly increases as the volume of the droplet 195 increases. As the radius r of the droplet 195 increases, the volume of the droplet 195 increases at a uniform rate, which necessitates a gradual increase in the radius r of the droplet 195. Consequently, during the initial multiple periods of oscillation of the outlet end 112 of the liquid dispensing pipette tip 110, the maximum value of the viscous resistance f2 of the droplet 195, which was experienced while moving in the second liquid 699, increases rapidly, and then increases slowly thereafter. As shown in Figure 7, the viscous resistance f2 of the droplet 195 as it moves through the second liquid 699 exhibits a periodicity similar to the periodic motion of the outlet end 112 of the liquid dispensing pipette tip 110. That is, the viscous resistance f2 of the droplet 195 as it moves through the second liquid 699 changes with the change in velocity of the outlet end 112 of the liquid dispensing pipette tip 110. In actual conditions, when the viscous resistance f2 of the droplet 195 as it moves through the second liquid 699 increases, and is greater than the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195, the droplet 195 detaches from the outlet end 112 of the liquid dispensing pipette tip 110, forming a minute droplet 199.

[0073] In one embodiment of this application, as shown in Figure 8, the outlet end 112 of the liquid dispensing pipette tip 110 is controlled to oscillate in an arc trajectory or in a sinusoidal displacement. When the liquid dispensing pipette tip 110 and the first liquid are not replaced, the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 does not change. As the radius r of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 increases, the viscous resistance f2 of the droplet 195, which was received while moving in the second liquid 699, also increases continuously. When the viscous resistance f2 of droplet 195, while moving through the second liquid 699, is greater than the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195, droplet 195 detaches from the outlet end 112 of the liquid dispensing pipette tip 110, forming a microdroplet 199, which becomes droplet I as shown in Figure 8. The process then transitions to a cycle for generating the next microdroplet 199.

[0074] In this embodiment, the maximum adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 is f3 = 1.8 × 10 -4 The oscillation frequency of the outlet end 112 of the liquid dispensing pipette tip 110 is 50 Hz. At the end of the second period in which the outlet end 112 of the liquid dispensing pipette tip 110 is displaced and oscillated in a sinusoidal manner, the first microdroplet 199 is generated to become droplet I in Figure 8. In the initial stage of generating the second microdroplet 199, the motion speed of the outlet end 112 of the liquid dispensing pipette tip 110 decreases slightly, but because the radius r of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 increases rapidly, the viscous resistance f2 of the droplet 195 that was received when it was moving towards the second liquid 699 does not decrease immediately but increases within a small range. Then, the radius r of the droplet 195 increases slowly, and the viscous resistance f2 of the droplet 195, which is experienced while moving in the second liquid 699, changes mainly due to the change in the velocity of the movement of the outlet end 112 of the liquid dispensing pipette tip 110.

[0075] When the first liquid is controlled to be discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate, the outlet end 112 of the liquid dispensing pipette tip 110 generates a new droplet 195 of equal volume to the first microdroplet 199 at the time of two motion cycles after the generation of the first microdroplet 199, resulting in droplet II in Figure 8. Moreover, the motion speed of the outlet end 112 of the liquid dispensing pipette tip 110 at this time is the same as that of the two motion cycles mentioned earlier. The new droplet 195 of equal volume to the first microdroplet 199 is detached from the outlet end 112 of the liquid dispensing pipette tip 110. The uniformity of the volume of the generated microdroplets 199 can be ensured by both the uniform discharge rate of the first liquid and the sinusoidal displacement and oscillation of the outlet end 112 of the liquid dispensing pipette tip 110.

[0076] In one embodiment of this application, as shown in Figure 9, the outlet end 112 of the liquid dispensing pipette tip 110 is controlled to oscillate sinusoidally in an arc trajectory. When the liquid dispensing pipette tip 110 and the first liquid are not replaced, the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 does not change. As the radius r of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 increases, the viscous resistance f2 of the droplet 195 received while moving into the second liquid 699 also increases. At the moment when the viscous resistance f2 of the droplet 195 received while moving in the second liquid 699 is greater than the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195, the droplet 195 detaches from the outlet end 112 of the liquid dispensing pipette tip 110 and forms a minute droplet 199. Then, the cycle transitions to generating the next microdroplet 199.

[0077] In this embodiment, the maximum adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 is f3 = 1.5 × 10 -4The oscillation frequency of the outlet end 112 of the liquid dispensing pipette tip 110 is 50 Hz. At the end of the first period in which the outlet end 112 of the liquid dispensing pipette tip 110 is displaced and oscillated in a sinusoidal manner, the first microdroplet 199 is generated, becoming droplet I in Figure 9. In the initial stage of generating the second microdroplet 199, the motion speed of the outlet end 112 of the liquid dispensing pipette tip 110 decreases slightly, but because the radius r of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 increases rapidly, the viscous resistance f2 of the droplet 195, which was received while moving in the second liquid 699, does not decrease immediately but increases within a small range. Then, as the radius r of the droplet 195 gradually increases, the viscous resistance f2 of the droplet 195, which is experienced while moving through the second liquid 699, changes mainly in accordance with the change in the velocity of the movement of the outlet end 112 of the liquid dispensing pipette tip 110.

[0078] When the first liquid is controlled to be discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate, the outlet end 112 of the liquid dispensing pipette tip 110 generates a new droplet 195 of equal volume to the first droplet 199 at the time of the next motion cycle, and the motion speed of the outlet end 112 of the liquid dispensing pipette tip 110 at this time is the same as that of the previous motion cycle. The new droplet 195 of equal volume to the first droplet 199 is detached from the outlet end 112 of the liquid dispensing pipette tip 110 and becomes droplet II in Figure 9. Repeating this process will generate droplets III, IV, and so on. Both the uniform discharge rate of the first liquid and the sinusoidal displacement and oscillation of the outlet end 112 of the liquid dispensing pipette tip 110 ensure the uniformity of the volume of the generated droplets 199.

[0079] In one embodiment of this application, as shown in Figures 10 and 11, the outlet end 112 of the liquid dispensing pipette tip 110 is controlled to oscillate sinusoidally in an arc trajectory. When the liquid dispensing pipette tip 110 and the first liquid are not replaced, the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 does not change. As the radius r of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 increases, the viscous resistance f2 of the droplet 195, which was received while moving in the second liquid 699, also increases continuously. When the viscous resistance f2 of droplet 195, which is moving through the second liquid 699, is greater than the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195, droplet 195 detaches from the outlet end 112 of the liquid dispensing pipette tip 110, forming a microdroplet 199, which becomes droplet I in Figure 10. The process then moves to the next cycle for generating the next microdroplet 199.

[0080] In this embodiment, the maximum adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 is f3 = 1.0 × 10 -4 As N is reached, the oscillation frequency of the outlet end 112 of the liquid dispensing pipette tip 110 is 50 Hz. During the acceleration phase in the first half of the period in which the outlet end 112 of the liquid dispensing pipette tip 110 is displaced and oscillated sinusoidally, the first microdroplet 199 is generated, becoming droplet I in Figure 10. In the initial stage of generating the second microdroplet 199, the motion speed of the outlet end 112 of the liquid dispensing pipette tip 110 decreases slightly, but because the radius r of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 increases rapidly, the viscous resistance f2 of the droplet 195, which was received while moving in the second liquid 699, does not decrease immediately but increases over a small range. Then, as the radius r of the droplet 195 gradually increases, the viscous resistance f2 of the droplet 195, which is experienced while moving in the second liquid 699, changes mainly in accordance with the change in the velocity of the movement of the outlet end 112 of the liquid dispensing pipette tip 110.

[0081] When the first liquid is controlled to be discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate, a second microdroplet 199 is generated during the acceleration phase in the latter half of the motion cycle in which the outlet end 112 of the liquid dispensing pipette tip 110 is displaced sinusoidally and oscillates, resulting in droplet II in Figure 10. Next, the process moves to a stage in which microdroplets 199 are stably generated. At the timing in the latter half of the motion cycle in which the outlet end 112 of the liquid dispensing pipette tip 110 generates the second microdroplet 199, a new droplet 195 of equal volume to the second microdroplet 199 is generated, and the motion speed of the outlet end 112 of the liquid dispensing pipette tip 110 at this time is the same as in the first half of the motion cycle. The new droplet 195 of equal volume to the second microdroplet 199 is detached from the outlet end 112 of the liquid dispensing pipette tip 110. Repeating this process will generate droplets III, IV, V, etc., as shown in Figure 10. Both the uniform discharge rate of the first liquid and the sinusoidal displacement and oscillation of the outlet end 112 of the liquid dispensing pipette tip 110 ensure uniformity in the volume of the generated microdroplets 199.

[0082] As can be seen from the above, the conditions under which a droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 detaches from the outlet end 112 of the liquid dispensing pipette tip 110 (i.e., generates a single minute droplet 199) can be approximated as follows:

number

[0083] Factors influencing the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 include the surface free energy of the liquid dispensing pipette tip 110, its geometric dimensions, and the surface tension of the first liquid. The maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 does not change when the liquid dispensing pipette tip 110 and the first liquid are not replaced. Factors influencing the viscous resistance f2 of the droplet 195 as it moves through the second liquid 699 include the viscosity coefficient η of the second liquid 699, the radius r of the droplet 195, and the velocity v of the droplet 195. When the first liquid is discharged at a uniform rate from the outlet end 112 of the liquid dispensing pipette tip 110, the radius r of the droplet 195 is determined by the interval time at which the microdroplets 199 are generated. Since the droplet 195 moves synchronously with the outlet end 112 of the liquid dispensing pipette tip 110 until it detaches from the outlet end 112 of the liquid dispensing pipette tip 110, the motion control mechanism 130 can accurately control the motion speed of the outlet end 112 of the liquid dispensing pipette tip 110. The viscosity coefficient η of the second liquid 699 may change within a certain range during the process of generating the droplet 195. However, the range of change in the viscosity coefficient η of the second liquid 699 is extremely small. As shown in Figure 12, curve a shows the displacement of the outlet end 112 of the liquid dispensing pipette tip 110, and curves b and c both show the curves for the process of generating the microdroplets 199 when the viscosity coefficient η of the second liquid 699 changes within an extremely small range. When the viscosity coefficient η of the second liquid 699 changes within an extremely small range, the timing of generating the microdroplets 199 is changed by only an extremely small range without changing the time interval for generating the microdroplets 199. As shown in Figure 12, the time intervals for generating the microdroplets 199, indicated by curves b and c, are both half-periods t / 2, thus ensuring uniformity in the volume of the generated microdroplets 199.

[0084] As shown in Figure 13, when the liquid dispensing pipette tip 110 is replaced, or when the surface tension of the first liquid changes due to temperature changes or other factors, it becomes difficult to accurately control the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195. Therefore, it is important for generating microdroplets 199 with uniform dimensions that the volume of the generated microdroplets 199 is not sensitive to changes in f3 within a certain range. As shown in Figure 13, curve a shows the displacement of the outlet end 112 of the liquid dispensing pipette tip 110, and curves b and c show the curves of the microdroplet 199 generation process when the liquid dispensing pipette tip 110 is replaced. After the liquid dispensing pipette tip 110 is replaced, the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 fluctuates within a certain range, which may cause the outlet end 112 of the liquid dispensing pipette tip 110 to move at different speeds when the droplet 195 is detached. However, when the generation of microdroplets 199 is stable, the velocity of the outlet end 112 of the liquid dispensing pipette tip 110 does not change within each oscillation period when droplets 195 are detached. As shown in Figure 13, the time intervals for the generation of microdroplets 199, shown by curves b and c, are both half a period t / 2. Therefore, it is possible to ensure that the interval time for generating microdroplets 199 does not change. If the flow velocity of the outlet end 112 of the first liquid dispensing pipette tip 110 does not change, the volume of the generated microdroplets 199 will be uniform. At the same time, the flow velocity of the outlet end 112 of the first liquid dispensing pipette tip 110 and the frequency of the outlet end 112 of the liquid dispensing pipette tip 110 oscillating in the second liquid 699 can be adjusted, that is, the volume and generation speed of microdroplets 199 with uniform volume can be controlled at the same time.

[0085] In the above embodiment, when the outlet end 112 of the liquid dispensing pipette tip 110 undergoes periodic motion in a sinusoidal manner, there is a certain degree of tolerance for changes in the maximum adhesion force f3 and viscous resistance f2. That is, even when the maximum adhesion force f3 or viscous resistance f2 changes within a certain range, it is still possible to generate microdroplets 199 with uniform volume. Assuming that the generation of microdroplets 199 with uniform volume can be ensured when the outlet end 112 of the liquid dispensing pipette tip 110 undergoes periodic motion in a sinusoidal manner, the range of change in the maximum adhesion force f3 that is acceptable is called the stable period. The existence of the stable period is of great importance for the processing of the liquid dispensing pipette tip 110 and for controlling the temperature at which microdroplets 199 are generated. The existence of the stable period allows for a certain degree of reduction in the requirements for processing accuracy of the liquid dispensing pipette tip 110. That is, even if there are differences in the surface free energy of each liquid dispensing pipette tip 110 processed in the same batch, it is still possible to generate microdroplets 199 with uniform volume. Similarly, the presence of a stable phase allows the requirement for temperature control in the process of generating the microdroplets 199 to be reduced to some extent.

[0086] The presence of a stabilization period allows for a reduction in the processing accuracy requirements for the liquid dispensing pipette tip 110 or the temperature control requirements for the microdroplet 199 generation process, thereby further reducing the cost of consumables and control in the microdroplet 199 generation process.

[0087] In the above embodiment, the outlet end 112 of the liquid dispensing pipette tip 110 generates two microdroplets 199 in each motion cycle. It can be easily understood that as long as the outlet end 112 of the liquid dispensing pipette tip 110 is displaced sinusoidally and performs periodic motion, it generates one microdroplet 199 for each motion cycle of the outlet end 112 of the liquid dispensing pipette tip 110, or one microdroplet 199 for every two motion cycles, there is still some tolerance for the change in the maximum value of the adhesive force f3 and the viscous resistance f2, and a stable period exists.

[0088] The generation of the microdroplets 199 is largely unaffected by gravity and inertial forces of the microdroplets 199. Therefore, when generating the microdroplets 199, the outlet end 112 of the liquid dispensing pipette tip 110 can be displaced sinusoidally along any direction in the second liquid 699, performing periodic motion. The trajectory of the motion of the outlet end 112 of the liquid dispensing pipette tip 110 may be an arc, a straight line, or a trajectory of other shape.

[0089] As shown in Figure 14(1), in one embodiment of this application, a liquid dispensing pipette tip 110 is inserted at an angle into a second liquid 699, and the outlet end 112 of the liquid dispensing pipette tip 110 is oscillated below the liquid surface of the second liquid 699 to generate microdroplets 199. In one implementable form, as shown in Figure 14(2), the outlet end 112 of the liquid dispensing pipette tip 110 is displaced sinusoidally in a linear trajectory horizontal to the second liquid 699, performing a periodic motion to generate microdroplets 199. In another implementable form, as shown in Figure 14(3), the outlet end 112 of the liquid dispensing pipette tip 110 is displaced sinusoidally in a linear trajectory perpendicular to the second liquid 699, performing a periodic motion to generate microdroplets 199.

[0090] As shown in Figure 15, in another embodiment of this application, in step S213, the outlet end 112 of the liquid dispensing pipette tip 110 performs constant velocity motion in both the first and second halves of one period of velocity change. Furthermore, in step S213, the acceleration of the outlet end 112 of the liquid dispensing pipette tip 110 is the same in both the first and second halves of the period. The first liquid is controlled to be discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate. As the first liquid is continuously discharged, the viscous resistance f2 of the droplet 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110, which has been subjected to the motion process, also increases continuously. When the viscous resistance f2 is greater than the maximum value f3 of the adhesion force between the droplet 195 and the liquid dispensing pipette tip 110, the droplet 195 detaches from the liquid dispensing pipette tip 110 to form a microdroplet 199. Then, the process moves to the generation of the next microdroplet 199. By controlling the motion frequency and motion speed of the outlet end 112 of the liquid dispensing pipette tip 110 to match the flow velocity of the first liquid, uniformity of the volume of the generated microdroplets 199 can be ensured.

[0091] Conventional liquid dispensing pipette tips are generally straight. With such straight-tubular liquid dispensing pipette tips, the microdroplets generated can be destroyed when one end, closer to the outlet, moves rapidly along the pipette's extension direction. To maintain the integrity of the generated microdroplets, it becomes necessary to reduce the vibration frequency of the liquid dispensing pipette tip, which in turn slows down the rate of microdroplet generation.

[0092] In light of this, there is a need to provide a liquid dispensing pipette tip that can achieve both the integrity of the generated microdroplets and the speed of microdroplet generation, addressing the challenge that conventional liquid dispensing pipette tips cannot achieve simultaneously.

[0093] A liquid dispensing pipette tip 110 for generating microdroplets 199 provided in one embodiment of the present application includes a needle shaft 113 having a hollow cavity and an outlet end 112 positioned at one end of the needle shaft 113, wherein the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the needle shaft 113 is 90° or less. As the liquid dispensing pipette tip 110 vibrates along the extending direction of the main body of the pipe, the minute droplets 199 fall from the outlet end 112 of the liquid dispensing pipette tip 110. Due to the viscous force of the second liquid 699 and the pressing action of the end face of the outlet end 112 of the liquid dispensing pipette tip 110, the droplets 199 are separated from the trajectory of the outlet end 112. This prevents the minute droplets 199 from being destroyed by the outlet end 112, maintaining the integrity of the generated minute droplets 199, and also enables the liquid dispensing pipette tip 110 to vibrate rapidly in the extending direction of the main body of the pipe, thereby rapidly generating the minute droplets 199.

[0094] As shown in Figure 16, in one feasible configuration, the liquid dispensing pipette tip 110 is tubular, and the outlet end 112 of the liquid dispensing pipette tip 110 has an oblique cut structure. Obliquely cutting the outlet end 112 of the liquid dispensing pipette tip 110 allows for both the integrity and efficiency of the generated microdroplets 199, while also simplifying the structure, making it easy to implement, resulting in lower manufacturing costs and higher precision when processed in large quantities. Furthermore, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the needle shaft 113 may be set to 15°-75° depending on the actual situation. To avoid affecting the formation of microdroplets 199 or destroying them, it is undesirable for the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the needle shaft 113 to be too large or too small. Furthermore, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the needle shaft 113 is 30°-60°. Specifically, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the needle shaft 113 is 45°. An angle of 45° not only ensures the smooth formation of microdroplets 199, but also effectively pushes the generated microdroplets 199 away from the motion trajectory of the outlet end 112, preventing them from being destroyed by the outlet end 112 of the liquid dispensing pipette tip 110.

[0095] As shown in Figure 17, another feasible configuration involves a bent structure in the portion of the needle shaft 113 near the outlet end 112 of the liquid dispensing pipette tip 110. By bending the outlet end 112 of the liquid dispensing pipette tip 110, it is possible to achieve both the integrity and efficiency of the generated microdroplets 199, while also having the advantages of a simpler structure, easier implementation, lower manufacturing costs, and high precision when processed in large quantities. Furthermore, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the needle shaft 113 is 15°-75°. Depending on the actual situation, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the needle shaft 113 may be set. To avoid affecting the formation of microdroplets 199 or destroying them, it is undesirable for the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the needle shaft 113 to be too large or too small. Furthermore, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the needle shaft 113 is 30°-60°. Specifically, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the needle shaft 113 is 45°. An angle of 45° not only ensures the smooth formation of microdroplets 199, but also effectively pushes the generated microdroplets 199 away from the motion trajectory of the outlet end 112, preventing them from being destroyed by the outlet end 112 of the liquid dispensing pipette tip 110.

[0096] Preferably, the bending structure of the needle shaft 113 near the outlet end 112 of the liquid dispensing pipette tip 110 has one or a combination of broken segments, arc segments, smooth curve segments, straight segments, etc. As shown in Figure 17, in this embodiment, the portion of the needle shaft 113 near the outlet end 112 of the liquid dispensing pipette tip 110 has transitioning arc segments, specifically a combination of arc segments and straight segments. The liquid dispensing pipette tip 110, which is straight, is easy to process as it only needs to be bent into an arc shape by a predetermined angle during manufacturing.

[0097] As shown in Figures 18 and 19, a liquid dispensing pipette tip 110 provided in one embodiment of the present application includes a needle hub 114 having a liquid reservoir 115 that penetrates the needle hub 114 along the extending direction of the needle hub 114. One end of the liquid reservoir 115 communicates with one end of the needle shaft 113 away from the outlet end 112 of the liquid dispensing pipette tip 110, and the other end of the needle hub 114 away from the needle shaft 113 is the inlet end 111 of the liquid dispensing pipette tip 110. The needle hub 114 is fixedly connected to the needle shaft 113. A first liquid for generating microdroplets 199 may be stored in the needle hub 114, and it is possible to continuously generate a large quantity of microdroplets 199. Furthermore, a locking groove 116 is provided on the inner surface of the one end of the needle hub 114 away from the needle shaft 113. This locking groove 116 allows for a detachable connection to the fluid drive mechanism 120, making it possible to conveniently replace the liquid dispensing pipette tip 110.

[0098] The microdroplet 199 generating device provided in this application is used to generate microdroplets 199 below the liquid surface of a second liquid 699. The microdroplet 199 generating device includes a fluid drive mechanism 120, a motion control mechanism 130, and a liquid dispensing pipette tip 110 as described in any one of the above embodiments. A first liquid is stored inside the liquid dispensing pipette tip 110, and the liquid dispensing pipette tip 110 has an outlet end 112 and an inlet end 111. The fluid drive mechanism 120 is connected to the inlet end 111 of the liquid dispensing pipette tip 110 and is used to discharge the first liquid stored inside the liquid dispensing pipette tip 110 from the outlet end 112 of the liquid dispensing pipette tip 110. The motion control mechanism 130 is used to control the movement of the outlet end 112 of the liquid dispensing pipette tip 110 below the liquid surface of the second liquid 699 along a predetermined trajectory, at a predetermined speed, or at a predetermined acceleration, so that the first liquid discharged from the outlet end 112 of the liquid dispensing pipette tip 110 overcomes surface tension and adhesive force, and forms minute droplets 199 in the second liquid 699.

[0099] The liquid dispensing pipette tip 110 provided in this application generates minute droplets 199 below the liquid surface of a second liquid 699 during a motion process. In one implementable form, the outlet end 112 of the liquid dispensing pipette tip 110 can move below the liquid surface of the second liquid 699 at a speed that changes in a square wave pattern, where the acceleration is a1. When the first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110, it forms droplets 195 that adhere to the outlet end 112 of the liquid dispensing pipette tip 110. At the moment when the outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous acceleration motion, the droplets 195 detach from the outlet end 112 of the liquid dispensing pipette tip 110 and form minute droplets 199. As shown in Figure 3, the forces acting on the microdroplet 199 until it detaches from the outlet end 112 of the liquid dispensing pipette tip 110 are gravity G, the buoyancy f1 of the second liquid 699, the viscous resistance f2 of the second liquid 699, and the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195. If we let the mass of the microdroplet 199 be m and its acceleration be a2 until it detaches from the outlet end 112 of the liquid dispensing pipette tip 110, then according to Newton's second law of motion,

number

[0100] The maximum value f3 of the adhesive force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 is related to the surface free energy of the liquid dispensing pipette tip 110, the surface tension of the droplet 195, and the geometric dimensions of the liquid dispensing pipette tip 110. When the outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous acceleration, the direction of the adhesive force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 is the same as the direction of acceleration. The droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 is simplified as a sphere. As can be seen from Stokes' equation, the viscous resistance of the droplet 195 when moving in the second liquid 699 is f2 = 6πηrv, where η is the viscosity coefficient of the second liquid 699, r is the radius of the droplet 195, and v is the velocity of the droplet 195. Since the velocity of the droplet 195 is zero until the outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous acceleration, the viscous resistance f2 of the droplet 195 acting on the second liquid 699 at the moment the outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous acceleration is zero or extremely small. In the process of generating microdroplets 199, the diameter range of the droplets 195 is generally on the order of picoliters to microliters, and since the gravity G of the droplet 195 and the buoyancy f1 of the second liquid 699 are in opposite directions, the sum of the vectors of the gravity G of the droplet 195 and the buoyancy f1 of the second liquid 699 is approximately zero. That is,

number

[0101] The interlocking motion control mechanism 130 allows for precise control of the instantaneous acceleration of the outlet end 112 of the liquid dispensing pipette tip 110. If the acceleration of the outlet end 112 of the liquid dispensing pipette tip 110 can be controlled to be relatively large at each instant, then when the outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous acceleration motion, droplets 195 can be effectively generated. Preferably, the outlet end 112 of the liquid dispensing pipette tip 110 forms one or more microdroplets 199 in one motion cycle.

[0102] As shown in Figure 20, in one embodiment of the present application, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the pipe body is 45°, and the outlet end 112 of the liquid dispensing pipette tip 110 has a beveled cut structure. The liquid surface of the second liquid 699 is upward, and the liquid dispensing pipette tip 110 is installed vertically. The outlet end 112 of the liquid dispensing pipette tip 110 moves below the liquid surface of the second liquid 699, along the trajectory of the vertical line segment, at a speed that changes in a square wave pattern. The outlet end 112 of the liquid dispensing pipette tip 110 generates one minute droplet 199 in one motion cycle. The first liquid is stored in the liquid dispensing pipette tip 110. The fluid drive mechanism 120 controls the liquid dispensing pipette tip 110 to discharge an equal volume of the first liquid from the outlet end 112 in each motion cycle of the liquid dispensing pipette tip 110. When the droplet 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110 reaches a predetermined volume, the outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous downward acceleration motion with an acceleration of magnitude a1 from its upper limit position, causing the droplet 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110 to detach from the outlet end 112 and form a minute droplet 199. Due to the viscous force of the second liquid 699 and the pressing action of the end face of the outlet end 112 of the liquid dispensing pipette tip 110, the minute droplet 199 moves away from the motion trajectory of the outlet end 112 and approaches the side wall of the liquid dispensing pipette tip 110. As the outlet end 112 of the liquid dispensing pipette tip 110 moves continuously downward, the first liquid is still discharged from the outlet end 112 of the liquid dispensing pipette tip 110, forming a droplet 195 that adheres to the outlet end 112 of the liquid dispensing pipette tip 110. When the outlet end 112 of the liquid dispensing pipette tip 110 moves to its lower limit position, the outlet end 112 of the liquid dispensing pipette tip 110 moves upward from the lower limit position. During the process in which the outlet end 112 of the liquid dispensing pipette tip 110 moves upward from the lower limit position, the first liquid is still discharged from the outlet end 112 of the liquid dispensing pipette tip 110, and the volume of the droplet 195 that adheres to the outlet end 112 of the liquid dispensing pipette tip 110 increases.When the outlet end 112 of the liquid dispensing pipette tip 110 moves to the upper limit position, the volume of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 is equal to the volume of the previously detached microdroplet 199. The outlet end 112 of the liquid dispensing pipette tip 110 then undergoes instantaneous downward acceleration with an acceleration of magnitude a1 from the upper limit position, forming a new microdroplet 199. This process is repeated.

[0103] As shown in Figure 21, in one embodiment of the present application, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the pipe body is 45°, and the outlet end 112 of the liquid dispensing pipette tip 110 has a beveled cut structure. The liquid surface of the second liquid 699 is upward, and the liquid dispensing pipette tip 110 is installed vertically. The outlet end 112 of the liquid dispensing pipette tip 110 moves below the liquid surface of the second liquid 699, along the trajectory of the vertical line segment, at a speed that changes in a square wave pattern. The outlet end 112 of the liquid dispensing pipette tip 110 generates two minute droplets 199 in one motion cycle. The first liquid is stored in the liquid dispensing pipette tip 110. The fluid drive mechanism 120 controls the first liquid to be discharged from the outlet end 112 at a uniform flow velocity. When the droplet 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110 reaches a predetermined volume, the outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous downward acceleration motion from its upper limit position with an acceleration of magnitude a1, causing the droplet 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110 to detach from the outlet end 112 and form a minute droplet 199. Due to the viscous force of the second liquid 699 and the pressing action of the end face of the outlet end 112 of the liquid dispensing pipette tip 110, the minute droplet 199 moves away from the trajectory of the outlet end 112 and approaches the side wall of the liquid dispensing pipette tip 110. As the outlet end 112 of the liquid dispensing pipette tip 110 continues to move downward, the first liquid is still discharged from the outlet end 112 of the liquid dispensing pipette tip 110, forming a droplet 195 that adheres to the outlet end 112 of the liquid dispensing pipette tip 110, and the volume of the droplet 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110 increases.

[0104] When the outlet end 112 of the liquid dispensing pipette tip 110 moves to the lower limit position, the volume of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 is equal to the volume of the previously detached minute droplet 199. When the outlet end 112 of the liquid dispensing pipette tip 110 undergoes instantaneous upward acceleration with an acceleration of magnitude a1 from the lower limit position, the droplet 195 attached to the outlet end 112 is detached from the outlet end 112, forming a new minute droplet 199. The minute droplet 199 generated when the outlet end 112 of the liquid dispensing pipette tip 110 is at the lower limit position moves upward for a small distance due to the adhesive force of the outlet end 112, and then gradually falls due to the second liquid 699. When the outlet end 112 of the liquid dispensing pipette tip 110 reaches the lower limit, it moves upward. During this process, the first liquid is still discharged from the outlet end 112 of the liquid dispensing pipette tip 110, and the volume of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 increases. When the outlet end 112 of the liquid dispensing pipette tip 110 moves to the upper limit, the volume of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 is equal to the volume of the previously detached microdroplet 199. The outlet end 112 of the liquid dispensing pipette tip 110 then undergoes another instantaneous downward acceleration motion from the upper limit with an acceleration of magnitude a1, forming a new microdroplet 199. This process is repeated. When the outlet end 112 of the liquid dispensing pipette tip 110 is moving downward again from the upper limit position, if a minute droplet 199 is still present in the trajectory range directly below the outlet end 112, the generated minute droplet 199 will collide with a droplet 195 attached to the outlet end 112, and will move along the normal to the end face of the outlet end 112, thus moving away from the trajectory of the outlet end 112.

[0105] The liquid dispensing pipette tip 110 provided in this application generates microdroplets 199 in the process of moving below the surface of a second liquid 699. In another possible embodiment, the outlet end 112 of the liquid dispensing pipette tip 110 moves in a sinusoidal displacement below the surface of the second liquid 699. The first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 and forms droplets 195 that adhere to the outlet end 112 of the liquid dispensing pipette tip 110. When the movement speed of the outlet end 112 of the liquid dispensing pipette tip 110 reaches a certain level, the droplets 195 detach from the outlet end 112 of the liquid dispensing pipette tip 110 and form microdroplets 199. As shown in Figure 6, the forces acting on the microdroplet 199 until it detaches from the outlet end 112 of the liquid dispensing pipette tip 110 are gravity G, the buoyancy f1 of the second liquid 699, the viscous resistance f2 of the second liquid 699, and the maximum adhesion force f3 between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195, respectively. If we consider the microdroplet 199 to have mass m, velocity v, and acceleration a2 until it detaches from the outlet end 112 of the liquid dispensing pipette tip 110, then during its motion in the second liquid 699, the droplet 195 is subjected to a synergistic effect of viscous force f2, gravity G, buoyancy f1, and adhesion force f3, that is,

number

number

[0106] The maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195 is related to the surface free energy of the liquid dispensing pipette tip 110, the surface tension of the droplet 195, and the geometric dimensions of the liquid dispensing pipette tip 110. The droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 is simplified as a sphere. According to Stokes' equation, the viscous resistance of the droplet 195 as it moves through the second liquid 699 is f2 = 6πηrv, where η is the viscosity coefficient of the second liquid 699, r is the radius of the droplet 195, and v is the velocity of the droplet 195. In the process of generating microdroplets 199, generally, the diameter range of the droplets 195 is on the order of picoliters to microliters, and the viscosity coefficient of the second liquid 699 is generally relatively large. Therefore, generally,

number

number

[0107] As shown in Figure 22, in one embodiment of the present application, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the pipe body is 45°, and the portion of the needle shaft 113 close to the outlet end 112 of the liquid dispensing pipette tip 110 has a bent structure. The liquid surface of the second liquid 699 is upward, and the liquid dispensing pipette tip 110 is installed vertically. The outlet end 112 of the liquid dispensing pipette tip 110 moves sinusoidally, displacing below the liquid surface of the second liquid 699 along the trajectory of the vertical line segment. The outlet end 112 of the liquid dispensing pipette tip 110 generates one microdroplet 199 in one motion cycle. The first liquid is stored in the liquid dispensing pipette tip 110. The fluid drive mechanism 120 controls the controlled liquid dispensing pipette tip 110 so that an equal volume of the first liquid is dispensed from the outlet end 112 during each motion cycle of the liquid dispensing pipette tip 110. The outlet end 112 of the liquid dispensing pipette tip 110 generates the first microdroplet 199 as it descends in an accelerating motion by being displaced sinusoidally and moving in a straight line. In the initial stage of generating the second microdroplet 199, although the outlet end 112 of the liquid dispensing pipette tip 110 is in a downward deceleration phase, the radius r of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 increases rapidly. As a result, the viscous resistance f2 of the droplet 195, which was experienced while moving through the second liquid 699, does not decrease immediately but increases over a small range. Then, the radius r of the droplet 195 gradually increases, and the viscous resistance f2 of the droplet 195, which is experienced while moving in the second liquid 699, changes mainly in accordance with the change in the velocity of the movement of the outlet end 112 of the liquid dispensing pipette tip 110. As the outlet end 112 of the liquid dispensing pipette tip 110 moves down to its limit position and then rises, the volume of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 continuously increases.

[0108] When controlling the first liquid to be discharged at a uniform flow rate from the outlet end 112 of the liquid dispensing pipette tip 110, the outlet end 112 of the liquid dispensing pipette tip 110 generates a new droplet 195 of equal volume to the first microdroplet 199 at the timing of the next motion cycle after the first microdroplet 199 was generated, and at this time, the motion speed of the outlet end 112 of the liquid dispensing pipette tip 110 is the same as that of the previous motion cycle. The new droplet 195 of equal volume to the first microdroplet 199 is detached from the outlet end 112 of the liquid dispensing pipette tip 110. This process is repeated.

[0109] Both the uniform discharge rate of the first liquid and the sinusoidal displacement and oscillation of the outlet end 112 of the liquid dispensing pipette tip 110 ensure uniformity in the volume of the generated microdroplets 199. When the outlet end 112 of the liquid dispensing pipette tip 110 is again moving downward from the upper limit position, if microdroplets 199 are still present in the trajectory range directly below the outlet end 112, the generated microdroplets 199 collide with droplets 195 attached to the outlet end 112, move along the normal to the end face of the outlet end 112, and move away from the trajectory of the outlet end 112.

[0110] As shown in Figure 23, in one embodiment of the present application, the angle between the normal to the end face of the outlet end 112 of the liquid dispensing pipette tip 110 and the extending direction of the pipe body is 45°, and the portion of the needle shaft 113 close to the outlet end 112 of the liquid dispensing pipette tip 110 has a bent structure. The liquid surface of the second liquid 699 is upward, and the liquid dispensing pipette tip 110 is positioned vertically. The outlet end 112 of the liquid dispensing pipette tip 110 moves with sinusoidal displacement along the trajectory of a vertical line segment below the liquid surface of the second liquid 699. The outlet end 112 of the liquid dispensing pipette tip 110 generates two microdroplets 199 in one motion cycle. The first liquid is stored in the liquid dispensing pipette tip 110. The fluid drive mechanism 120 controls the first liquid to be discharged from the outlet end 112 at a uniform flow velocity. As the radius r of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 increases, the viscous resistance f2 of the droplet 195 as it moves through the second liquid 699 also increases steadily. When the outlet end 112 of the liquid dispensing pipette tip 110 is in the downward acceleration phase, the viscous resistance f2 of the droplet 195 as it moves through the second liquid 699 becomes greater than the maximum value f3 of the adhesion force between the outlet end 112 of the liquid dispensing pipette tip 110 and the droplet 195, causing the droplet 195 to detach from the outlet end 112 of the liquid dispensing pipette tip 110 and form a minute droplet 199. Due to the viscous force of the second liquid 699 and the pressing action of the end face of the outlet end 112 of the liquid dispensing pipette tip 110, the minute droplet 199 moves away from the trajectory of the outlet end 112 and approaches the side wall of the liquid dispensing pipette tip 110.

[0111] The outlet end 112 of the liquid dispensing pipette tip 110 moves continuously downward, and only begins to rise after the outlet end 112 of the liquid dispensing pipette tip 110 has reached its limit. Simultaneously, the first liquid is still discharged from the outlet end 112 of the liquid dispensing pipette tip 110, forming a droplet 195 that adheres to the outlet end 112 of the liquid dispensing pipette tip 110, and the volume of the droplet 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110 increases. In the initial stage of generating the second microdroplet 199, the movement speed of the outlet end 112 of the liquid dispensing pipette tip 110 decreases slightly, but because the radius r of the droplet 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110 increases rapidly, the viscous resistance f2 of the droplet 195 that it has experienced while moving through the second liquid 699 increases within a small range without immediately decreasing. Subsequently, the radius r of the droplet 195 increases slightly, and the viscous resistance f2 of the droplet 195, which is experienced while moving through the second liquid 699, changes mainly due to the change in the velocity of the movement of the outlet end 112 of the liquid dispensing pipette tip 110.

[0112] After half a cycle of time has elapsed, the outlet end 112 of the liquid dispensing pipette tip 110 is in an upward accelerating position. The volume of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 is equal to the volume of the previously detached minute droplet 199. At the same time, the velocity of the outlet end 112 of the liquid dispensing pipette tip 110 is the same as the previous half cycle, and the droplet 195 attached to the outlet end 112 is detached from the outlet end 112, forming a new minute droplet 199. The minute droplet 199 generated when the outlet end 112 of the liquid dispensing pipette tip 110 is in an upward accelerating position moves upward for a short distance due to the adhesive force of the outlet end 112, and then gradually begins to descend in the second liquid 699. At the same time, the first liquid is still discharged from the outlet end 112 of the liquid dispensing pipette tip 110, forming a droplet 195 that adheres to the outlet end 112 of the liquid dispensing pipette tip 110, and the volume of the droplet 195 adhering to the outlet end 112 of the liquid dispensing pipette tip 110 increases.

[0113] After half a cycle has elapsed, the outlet end 112 of the liquid dispensing pipette tip 110 is in the downward acceleration phase. The volume of the droplet 195 attached to the outlet end 112 of the liquid dispensing pipette tip 110 is equal to the volume of the previously detached microdroplet 199. At the same time, the velocity of the outlet end 112 of the liquid dispensing pipette tip 110 is the same as the previous half cycle, and the droplet 195 attached to the outlet end 112 is detached from the outlet end 112, forming a new microdroplet 199. This process is repeated. The first liquid is controlled to be discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate. The outlet end 112 of the liquid dispensing pipette tip 110 moves sinusoidally along the trajectory of the vertical segment, and after generating a second microdroplet 199 in the acceleration phase of the latter half of the cycle, it transitions to a phase in which microdroplets 199 are stably generated. Both the uniform discharge rate of the first liquid and the sinusoidal displacement and oscillation of the outlet end 112 of the liquid dispensing pipette tip 110 ensure uniformity in the volume of the generated microdroplets 199. When the outlet end 112 of the liquid dispensing pipette tip 110 is again moving downward from its upper limit position, if microdroplets 199 are still present in the trajectory range directly below the outlet end 112, the generated microdroplets 199 will collide with droplets 195 attached to the outlet end 112, move along the normal to the end face of the outlet end 112, and move away from the trajectory of the outlet end 112.

[0114] The microdroplet generation apparatus and method provided in this application have a wide range of applications in fields such as medical clinical testing, nanomaterial manufacturing, food and environmental testing, and biochemical analysis. One specific example of application is the application of the microdroplet generation apparatus and method provided in this application to polymerase chain reaction (PCR).

[0115] Since the cross-sectional dimensions of liquid dispensing pipette tips 110 are generally at the micron level, conventional surface treatment methods are often used for relatively large parts and are not easily applicable to the relatively small liquid dispensing pipette tips 110.

[0116] In light of this, conventional surface treatment methods are used for relatively large parts, but are difficult to fully apply to relatively small liquid dispensing pipette tips 110. Therefore, there is a need to provide a surface treatment method that can be applied to liquid dispensing pipette tips 110 at the micron level.

[0117] As shown in Figure 24, a surface treatment method for a liquid dispensing pipette tip 110 provided in one embodiment of the present application is for treating the surface of a liquid dispensing pipette tip 110 and includes a step S260 of performing a silanation treatment on the liquid dispensing pipette tip 110, a step S270 of treating the liquid dispensing pipette tip 110 with an aqueous solution of diethyl pyrocarbonate (DEPC), and a step S280 of drying the liquid dispensing pipette tip 110.

[0118] The above surface treatment method for the liquid dispensing pipette tip 110 reduces the surface free energy of the liquid dispensing pipette tip 110 through silanization treatment, and also limits the surface free energy of the liquid dispensing pipette tip 110 to a certain range, thereby reducing the influence of the surface characteristics of the liquid dispensing pipette tip 110 on the process of generating minute droplets 199.

[0119] As shown in Figure 25, one embodiment of the present application further includes a step S240 prior to step S260 for pre-treating the liquid dispensing pipette tip 110. Step S240 includes one or more operations such as degreasing, soil removal, or washing of the liquid dispensing pipette tip 110. Degreasing, soil removal, and washing of the liquid dispensing pipette tip 110 effectively removes contaminants or obstructions adhering to the surface of the liquid dispensing pipette tip 110 in the preceding processing steps. Furthermore, step S240 includes auxiliary degreasing, auxiliary soil removal, or auxiliary washing of the surface of the liquid dispensing pipette tip 110 using ultrasonic vibration. Degreasing, soil removal, and washing of the liquid dispensing pipette tip 110 in an ultrasonic environment, in cooperation with chemical and mechanical means, ensures the effect of pre-treating the surface of the liquid dispensing pipette tip 110. Specifically, in step S240, the liquid dispensing pipette tip 110 is made of stainless steel, and the liquid dispensing pipette tip 110 is cleaned with a stainless steel cleaning agent. The stainless steel cleaning agent has a higher cleaning effect for the liquid dispensing pipette tip 110 made of stainless steel. In other embodiments, the pretreatment of the surface of the liquid dispensing pipette tip 110 may be by any method that can clean the surface of the liquid dispensing pipette tip 110. In other embodiments of this application, the liquid dispensing pipette tip 110 is one of the following: a quartz capillary, a glass tube, and a double fiber capillary.

[0120] In one embodiment of this application, step S250 is further included after step S240 and before step S260, in which the liquid dispensing pipette tip is electropolished. Electropolishing reduces the relatively small surface roughness of the liquid dispensing pipette tip 110, and moreover, the surface quality of the liquid dispensing pipette tip 110 can be made to meet the requirements for silane formation. Electropolishing is extremely important for the surface quality of the liquid dispensing pipette tip 110 and is essential for achieving the target surface quality of a liquid dispensing pipette tip 110 made of stainless steel. In one embodiment of this application, a liquid dispensing pipette tip 110 made of stainless steel is used as the anode, and copper or the like, which is insoluble in the electrolyte, is used as the cathode. When the two electrodes are simultaneously immersed in an electrolytic groove and a direct current is passed through them, the liquid dispensing pipette tip 110, which is the anode, is selectively dissolved, and the surface of the liquid dispensing pipette tip 110 is polished. This achieves the objective. In this embodiment, the parameters for the step of electropolishing the liquid dispensing pipette tip 110 are shown below. [Table 1]

[0121] In the electropolishing process, the liquid dispensing pipette tip 110 used had an inner diameter of 60 μm and an outer diameter of 150 μm. After the electropolishing was completed, observation under a metallurgical microscope at 50x magnification revealed no obvious scratches.

[0122] According to step S260, an amorphous silicon film can be formed on the surface of the liquid dispensing pipette tip 110, and it is preferable to form the amorphous silicon film on the surface of the liquid dispensing pipette tip 110 by chemical vapor deposition (CVD). The thickness of the amorphous silicon film is preferably 100 Å to 1000 Å.

[0123] As shown in Figure 25, in one embodiment of the present application, step S260 includes step S261 of washing or immersing the liquid dispensing pipette tip 110 with deionized water, step S262 of treating the liquid dispensing pipette tip 110 with a silanating reagent, and step S263 of washing or immersing the liquid dispensing pipette tip 110 with deionized water.

[0124] Before silanization, the electrolyzed liquid dispensing pipette tip 110 is washed or immersed in deionized water to remove surface contaminants and static electricity. The silanization process reduces the surface free energy of the liquid dispensing pipette tip 110, limits the surface free energy of the liquid dispensing pipette tip 110 to a certain range, and reduces the influence of the surface characteristics of the liquid dispensing pipette tip 110 on the microdroplet generation process 199. After silanization, the silanized liquid dispensing pipette tip 110 is washed or immersed in deionized water to remove surface contaminants and static electricity. In step S262, it is preferable to form an amorphous silicon film on the surface of the liquid dispensing pipette tip 110 using chemical vapor deposition with a silanization reagent. Preferably, the silanization reagent contains silicon tetrahydride gas, and more preferably, a mixed gas of silicon tetrahydride and phosphorus hydride as a dopant. By forming an amorphous silicon film on the surface of the liquid dispensing pipette tip 110, the surface free energy of the liquid dispensing pipette tip 110 can be reduced.

[0125] In this embodiment, the specific steps for silanizing the surface of stainless steel are as follows: a liquid dispensing pipette tip 110 made of electrolytically treated stainless steel is placed in a chemical vapor deposition chamber to remove water vapor from the surface of the liquid dispensing pipette tip 110; the chemical vapor deposition chamber is evacuated to a vacuum; a mixed gas of silicon tetrahydride and phosphorus hydride is introduced; the atmospheric pressure for vapor deposition is controlled to 0.1 Pa-500 Pa; and the temperature for vapor deposition is controlled to 180°C-500°C; chemical vapor deposition is carried out; deposition is performed for 0.4-8 hours; and once deposition is complete, nitrogen gas is introduced to lower the temperature to room temperature. Specifically, the volume percentage of silicon tetrahydride in the mixed gas is 95.0%-99.9%, and the volume percentage of phosphorus hydride in the mixed gas is 0.1%-5.0%.

[0126] As shown in Figure 25, step S270 includes step S271, in which the liquid dispensing pipette tip 110 is immersed in a 0.5%-1.5% volume fraction diethyl pyrocarbonate aqueous solution for 10-20 minutes, and step S272, in which the liquid dispensing pipette tip 110 is sterilized under high pressure. By immersing the liquid dispensing pipette tip 110 in a 1% volume fraction DEPC aqueous solution and ensuring that the surface of the liquid dispensing pipette tip 110 is free of ribonuclease (RNase) and deoxyribonuclease (DNase), interference with subsequent operations using the liquid dispensing pipette tip 110 is reduced. Sterilizing the liquid dispensing pipette tip 110 under high pressure effectively removes any remaining DPEC aqueous solution from the surface of the liquid dispensing pipette tip 110, as well as effectively removes RNase and DNase that could not be removed by the DPEC aqueous solution.

[0127] The immersion time of the liquid dispensing pipette tip 110 in a 1% volume fraction DEPC aqueous solution may be set according to the specific circumstances. Furthermore, in step S271, the immersion time of the liquid dispensing pipette tip 110 in a 1% volume fraction DEPC aqueous solution is 15 minutes. As can be seen from the measurement results, 15 minutes is sufficient to completely remove RNase and DNase from the surface of the liquid dispensing pipette tip 110. Furthermore, in step S280, the liquid dispensing pipette tip 110 is further purified in a nitrogen gas purification furnace, and the liquid dispensing pipette tip 110 is purified, dried and calcined. Nitrogen gas is used as a protective gas when drying the liquid dispensing pipette tip 110. Using nitrogen gas as a protective gas effectively avoids chemical reactions between the surface of the liquid dispensing pipette tip 110 and gases with relatively active chemical properties in the atmosphere, thereby achieving effective protection for the liquid dispensing pipette tip 110.

[0128] In one specific embodiment of this application, the liquid dispensing pipette tip 110 used in the electropolishing process has an inner diameter of 60 μm and an outer diameter of 150 μm. The electrolyzed liquid dispensing pipette tip 110 is immersed in deionized water for 5 minutes. Then, the liquid dispensing pipette tip 110 is placed in a chemical vapor deposition chamber, and under vacuum, a mixed gas of silicon tetrahydride and phosphorus hydride is introduced. The atmospheric pressure for vapor deposition is controlled to 300 ± 20 Pa, and the vapor deposition temperature is controlled to 350 ± 20 °C. The mixed gas contains 97.0% by volume of silicon tetrahydride and 3.0% by volume of phosphorus hydride. Deposition is carried out for 2 hours, and once deposition is complete, nitrogen gas is introduced to lower the temperature to room temperature. The silane-treated liquid dispensing pipette tip 110 is washed with deionized water. The entire liquid dispensing pipette tip 110 is immersed in a 1% DEPC aqueous solution for 15 minutes, and the liquid dispensing pipette tip 110 is sterilized under high pressure. Finally, the liquid dispensing pipette tip 110 is placed in a nitrogen purification furnace and its surface is washed.

[0129] The surface treatment method for liquid dispensing pipette tips 110 provided in the embodiment of this application is used to process 18 liquid dispensing pipette tips 110 of the same dimensions together, and a droplet suspension test is performed on each of the 18 liquid dispensing pipette tips 110. The fluid control mechanism discharges the first liquid from the outlet end 112 of the liquid dispensing pipette tip 110 at a flow rate of 1.0 nL / s. The falling time of 100 minute droplets 199 is calculated for each liquid dispensing pipette tip 110, starting from the timing when the first minute droplet 199 falls. The average falling times of the corresponding 100 droplets 195 for each of the 18 liquid dispensing pipette tips 110 are shown in the table below. [Table 2]

[0130] For 18 liquid dispensing pipette tips 110, the relative range of change in the average fall time of each corresponding microdroplet 199 directly reflects the relative range of change in surface free energy among the 18 liquid dispensing pipette tips 110. As can be seen from the above test data, the standard deviation of the surface free energy of the liquid dispensing pipette tips 110 treated in a batch by the liquid dispensing pipette tip 110 surface treatment method provided in the embodiments of this application is 1.33%, and the requirement for uniformity is fully met for each type of volume that generates microdroplets 199.

[0131] In one embodiment of the present application, the liquid dispensing pipette tip 110 has an outlet end 112 at one end, and the surface treatment method for the liquid dispensing pipette tip is used to surface treat the outlet end 112 and the outer wall of the liquid dispensing pipette tip 110. Simultaneously, in the step of surface treating the outlet end 112 and the outer wall of the liquid dispensing pipette tip 110 to generate microdroplets 199, the uniform surface of the outlet end and outer wall of the liquid dispensing pipette tip 110 pushes out the generated microdroplets 199, thereby effectively avoiding the destruction of the microdroplets 199.

[0132] In conventional processes for generating microdroplets using a fluid-driven mechanism, the outlet end of the liquid dispensing pipette tip is in motion, resulting in unstable and uncontrollable liquid flow velocity. Consequently, the generated microdroplets exhibit randomness in volume. In light of this, there is a need to provide a fluid-driven mechanism that can ensure the liquid dispensing pipette tip dispenses liquid at a predetermined flow velocity, addressing the problem of randomness in microdroplet volume resulting from the unstable and uncontrollable liquid flow velocity when the liquid dispensing pipette tip is in motion.

[0133] In the process of generating microdroplets 199, the first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a predetermined flow rate. When the outlet end 112 of the liquid dispensing pipette tip 110 performs periodic motion including instantaneous acceleration motion, it can not only effectively generate microdroplets 199 but also help control the size of the generated microdroplets 199. When the outlet end 112 of the liquid dispensing pipette tip 110 is displaced sinusoidally and performs periodic motion, it can not only effectively generate microdroplets 199 but also ensure good volume uniformity of the generated microdroplets 199. In the two processes for generating the microdroplets 199 described above, the first liquid is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a predetermined flow rate by the drive of the fluid drive mechanism 120.

[0134] As shown in Figures 26 and 27, the fluid drive mechanism 120 provided in this application is used in a microdroplet generation system and includes a volumetric assembly 121 and a power assembly 122. The volumetric assembly 121 includes a syringe 1211 and a bush rod 1212. The bush rod 1212 cooperates to slide against the inner wall of the syringe 1211 and is capable of storing a drive fluid 1214 in the syringe 1211. The syringe 1211 has a fluid inlet / outlet 1213 for communicating with the inlet end 111 of a liquid dispensing pipette tip 110 that stores a first fluid 190. The power assembly 122 is power-transmittingly connected to the bush rod 1212 and is used to drive the bush rod 1212 to slide along the extending direction of the syringe 1211. In the process of generating microdroplets 199, the power assembly 122 drives the bush rod 1212 to press the drive liquid 1214 stored in the syringe 1211, the drive liquid 1214 presses the first liquid 190 stored in the liquid dispensing pipette tip 110, and then discharges the first liquid 190 from the outlet end 112 of the liquid dispensing pipette tip 110.

[0135] The fluid drive mechanism 120 provided in this application ensures that the first liquid 190 is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at a predetermined flow rate, even when the outlet end 112 of the liquid dispensing pipette tip 110 is vibrating at a high frequency, due to the incompressibility of the liquid (driving liquid 1214). The fluid drive mechanism 120 provided in this application can accurately control the volume of the generated minute droplets 199. The fluid drive mechanism 120 provided in this application is not limited to the above embodiment, and for example, a peristaltic pump, a pressurized drive pump, a pneumatic drive pump, an electro-immersion drive pump, etc., may be applied.

[0136] In one feasible configuration, the liquid inlet / outlet 1213 of the syringe 1211 is connected to the inlet end 111 of the liquid dispensing pipette tip 110 via a capillary tube 123. The syringe 1211 and the capillary tube 123 contain a driving fluid 1214. A power assembly 122 is power-transmittingly connected to a bush rod 1212 of a volumetric assembly 121, and the power assembly 122 is used to push the bush rod 1212 of the volumetric assembly 121 so that it slides over the syringe 1211. In the process of generating the microdroplets 199, the power assembly 122 pushes out the bush rod 1212 of the variable volume assembly 121, the bush rod 1212 presses the drive liquid 1214 stored in the syringe 1211 and the capillary tube 123, the drive liquid 1214 presses the first liquid 190 stored in the liquid dispensing pipette tip 110, and then the first liquid 190 is discharged from the outlet end 112 of the liquid dispensing pipette tip 110. By connecting the liquid inlet / outlet 1213 of the syringe 1211 to the inlet end 111 of the liquid dispensing pipette tip 110 using the capillary tube 123, firstly, because the inner diameter of the capillary tube 123 is relatively small, the volume of the dispensing liquid can be precisely controlled by controlling the stroke of the bush rod 1212. Secondly, the capillary tube 123 allows for free positioning and distance between the syringe 1211 and the liquid dispensing pipette tip 110, and facilitates the installation of other necessary equipment between the syringe 1211 and the liquid dispensing pipette tip 110.

[0137] In one embodiment of the present application, the power assembly 122 pushes the pusher bush rod 1212 to slide the syringe 1211 at a uniform speed, in other words, the pusher bush rod 1212 pushes the liquid 1214 out of the liquid inlet / outlet 1213 of the variable volume assembly 121 at a uniform flow rate and drives it to enter the liquid dispensing pipette tip 110 at a uniform flow rate through the capillary tube 123. The first liquid 190 stored in the liquid dispensing pipette tip 110 is then pushed out of the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate by the pusher fluid 1214. By utilizing the driving liquid 1214 as a transmission medium and controlling the bush rod 1212 to discharge the driving liquid 1214 at a uniform flow rate, the fluid drive mechanism 120 provided in this embodiment can not only discharge the first liquid 190 at a uniform flow rate from the outlet end 112 of the liquid dispensing pipette tip 110 when the liquid dispensing pipette tip 110 is stationary, but can also ensure that the fluid drive mechanism 120 provided in this embodiment can still discharge the first liquid 190 at a uniform flow rate from the outlet end 112 of the liquid dispensing pipette tip 110 even when the liquid dispensing pipette tip 110 is rapidly vibrating. The fluid drive mechanism 120 provided in this embodiment can significantly improve the uniformity of the volume of the generated microdroplets 199.

[0138] The power assembly 122 is responsible for ensuring that the bush rod 1212 slides along the syringe 1211 either away from or towards the liquid inlet / outlet 1213. Preferably, the power assembly 122 is an assembly such as a cylinder or hydraulic cylinder that directly outputs linear motion, for example, a combination of a motor and a synchronous pulley or a combination of a motor and a threaded rod 1222 and a slide block 1223. The assembly may also convert circular motion, such as a combination, into linear motion. The specific structure of the power assembly 122 is not limited in this application. As shown in Figure 27, in one embodiment of this application, the power assembly 122 includes a drive motor 1221, a threaded rod 1222, and a slide block 1223. The drive motor 1221 has its output shaft connected to one end of the threaded rod 1222 in a power-transmitting manner, and the slide block 1223 has a female thread and is connected in cooperation with a male thread on the surface of the threaded rod 1222. The outer edge of the slide block 1223 is fixedly connected to one end of the bush rod 1212 away from the syringe 1211. The slide block 1223 works in cooperation with the threaded rod 1222 to convert the rotational motion output by the drive motor 1221 into linear motion of the slide block 1223 along the axial direction of the threaded rod 1222, and is linked to the bush rod 1212 of the volumetric assembly 121 to slide over the syringe 1211. Furthermore, the drive motor 1221 used in this embodiment is a servo motor. A servo motor has the characteristic of being able to precisely feedback control the displacement of the output angle.

[0139] As shown in Figure 28, in one embodiment of the present application, the fluid drive mechanism 120 further includes a three-way switching valve 124 and a liquid storage tank 125. The three-way switching valve 124 has a first port, a second port and a third port. The inlet end 111 of the liquid dispensing pipette tip 110, the liquid inlet / outlet 1213 of the variable volume assembly 121 and the liquid storage tank 125 are in communication with the first port, the second port and the third port of the three-way switching valve 124, respectively. The three-way switching valve 124 can control the fluid drive mechanism 120 to perform at least two modes. In the first mode, the liquid inlet / outlet 1213 of the variable volume assembly 121 is connected to the inlet end 111 of the liquid dispensing pipette tip 110, and the variable volume assembly 121 applies a driving force to the liquid in the liquid dispensing pipette tip 110 through the interlocking of the power assembly 122, causing the first liquid 190 in the liquid dispensing pipette tip 110 to be discharged from the outlet end 112 of the liquid dispensing pipette tip 110, or to draw the first liquid 190 into the liquid dispensing pipette tip 110 from the outlet end 112. In the second mode, the liquid inlet / outlet 1213 of the variable volume assembly 121 is connected to the liquid storage tank 125, and the variable volume assembly 121 applies a driving liquid 1214 in the liquid storage tank 125 to be drawn into the syringe 1211 of the variable volume assembly 121, or to push the driving liquid in the variable volume assembly 121 into the liquid storage tank 125.

[0140] As shown in Figure 28, an embodiment of the present application further provides a fluid drive method utilizing the above fluid drive mechanism, comprising the following four steps: Step (1) The liquid inlet / outlet 1213 of the variable volume assembly 121 is connected to the liquid storage tank 125 via the three-way switching valve 124, and the power assembly 122 interlocks the bush rod 1212 to slide inside one end of the syringe 1211 away from the liquid inlet / outlet 1213, thereby changing the volume of the syringe 1211 and drawing the drive fluid 1214 from the liquid storage tank 125 into the syringe 1211. Step (2) The liquid inlet / outlet 1213 of the variable volume assembly 121 is connected via the three-way switching valve 124 By connecting 13 to the inlet end 111 of the liquid dispensing pipette tip 110, the power assembly 122 is activated to cause the bush rod 1212 to slide inside one end of the syringe 1211 that is close to the liquid inlet / outlet 1213, thereby changing the volume of the syringe 1211 and discharging gas from inside the syringe 1211, the capillary tube 123, and the liquid dispensing pipette tip 110. In step (3), the outlet end 112 of the liquid dispensing pipette tip 110 is introduced into the first liquid 190, and the liquid inlet / outlet 1213 of the variable volume assembly 121 is kept in communication with the inlet end 111 of the liquid dispensing pipette tip 110 via the three-way switching valve 124. The power assembly 122 is then engaged to slide the bush rod 1212 inside one end of the syringe 1211 away from the liquid inlet / outlet 1213, thereby changing the volume of the syringe 1211 and drawing the first liquid 190 into the liquid dispensing pipette tip 110. In step (4), the three-way switching valve 124 maintains communication between the liquid inlet / outlet 1213 of the variable volume assembly 121 and the inlet end 111 of the liquid dispensing pipette tip 110. The power assembly 122 interlocks the bush rod 1212, which slides at a uniform speed within one end of the syringe 1211 away from the liquid inlet / outlet 1213, thereby changing the volume of the syringe 1211 and discharging the first liquid 190 stored in the liquid dispensing pipette tip 110 from the outlet end 112 of the liquid dispensing pipette tip 110 at a uniform flow rate.

[0141] In order to ensure that the gas inside the syringe 1211 is smoothly discharged in the second step described above, as shown in Figure 27, when the syringe 1211 is installed, the liquid inlet / outlet 1213 of the syringe 1211 is facing upward and the bush rod 1212 slides vertically inside the syringe 1211.

[0142] To increase the efficiency of generating microdroplets 199, one feasible configuration involves having multiple liquid dispensing pipette tips 110, which may be arranged in parallel and spaced apart, or in other configurations. Each liquid dispensing pipette tip 110 is connected to a first port of a three-way switching valve 124 via a separate capillary tube 123. There is one volumetric assembly 121, the liquid inlet / outlet 1213 of which is connected to a second port of the three-way switching valve 124. A third port of the three-way switching valve 124 is connected to a liquid storage tank 125. The power assembly 122 drives the bush rod 1212 to slide the syringe 1211 at a uniform speed along the direction approaching the liquid inlet / outlet 1213, while simultaneously pressing the drive liquid 1214 against the multiple liquid dispensing pipette tips 110. Since multiple capillaries 123 are connected in parallel, the flow rate of the driving liquid 1214 in each capillary 123 is the same, and it can be confirmed that the first liquid 190 in multiple liquid dispensing pipette tips 110 is discharged from the outlet end 112 of the liquid dispensing pipette tip 110 at an equivalent and constant flow rate, and furthermore, the uniformity of the volume of the generated microdroplets 199 can be confirmed.

[0143] To increase the efficiency of generating microdroplets 199, another possible configuration involves having multiple liquid dispensing pipette tips 110 and multiple volumetric assemblies 121. Multiple liquid dispensing pipette tips 110 may be spaced apart in parallel or arranged in other configurations. Each liquid dispensing pipette tip 110 communicates with a first port of a three-way switching valve 124 via a separate capillary tube 123. The liquid inlet / outlet 1213 of each volumetric assembly 121 also communicates with a second port of the three-way switching valve 124 via a capillary tube 123. A third port of the three-way switching valve 124 communicates with a liquid storage tank 125. Multiple volumetric assemblies 121 may be spaced apart in parallel or arranged in other configurations. Multiple volumetric assemblies 121 are fixed with one end of a bush rod 1212, which separates from the syringe 1211, facing each other, and are synchronously pushed out by a power assembly 122. The power assembly 122 drives multiple bush rods 1212 to slide each syringe 1211 at a uniform speed along the direction approaching the liquid inlet / outlet 1213, while simultaneously pushing the drive liquid 1214 to the multiple liquid dispensing pipette tips 110. Because the multiple capillaries 123 are connected in parallel, the flow rate of the drive liquid 1214 in each capillary 123 is the same, ensuring that the first liquid 190 in the multiple liquid dispensing pipette tips 110 is discharged from the outlet end 112 of the liquid dispensing pipette tips 110 at an equal and constant flow rate, and further ensuring the uniformity of the volume of the generated microdroplets 199.

[0144] To increase the efficiency of generating microdroplets 199, a third feasible configuration, as shown in Figure 29, is one in number and multiple in all of them, comprising liquid dispensing pipette tips 110, volumetric assemblies 121, and three-way switching valves 124. Each inlet end 111 of each liquid dispensing pipette tip 110 is connected to a first port of one three-way switching valve 124 via a separate capillary 123. Each liquid inlet / outlet 1213 of each volumetric assembly 121 is connected to a second port of one three-way switching valve 124 via a separate capillary 123. Each third port of each three-way switching valve 124 is connected to a liquid storage tank 125. Preferably, there is one or more liquid storage tanks 125. The first liquid 190 in each liquid dispensing pipette tip 110 may be the same or different. The multiple volumetric assemblies 121 may be spaced in parallel or arranged in other configurations. Multiple volumetric assemblies 121 are fixed with one end of a bush rod 1212 facing the syringe 1211, and are synchronously pushed out by a power assembly 122. Driven by the power assembly 122, the multiple bush rods 1212 slide at a uniform speed along each syringe 1211 in a direction approaching the liquid inlet / outlet 1213. Multiple different types of microdroplets 199 can be generated simultaneously.

[0145] To increase the efficiency of generating microdroplets 199, in a fourth feasible configuration, the liquid dispensing pipette tips 110, volumetric assemblies 121, and three-way switching valves 124 are of equal number and multiple in all cases. The inlet end 111 of each liquid dispensing pipette tip 110 is connected to the first port of one three-way switching valve 124 via individual capillaries 123. The liquid inlet / outlet 1213 of each volumetric assembly 121 is connected to the second port of one three-way switching valve 124 via individual capillaries 123. The third port of each three-way switching valve 124 is connected to a liquid storage tank 125. Preferably, there is one or more liquid storage tanks 125. The first liquid 190 in each liquid dispensing pipette tip 110 may be the same or different. The multiple volumetric assemblies 121 are spaced apart in parallel and may be arranged in other configurations. Each variable-volume assembly 121 corresponds to an individual power assembly 122. The power assembly 122 drives multiple bush rods 1212 to slide along their respective syringes 1211 at a uniform speed in a direction approaching the liquid inlet / outlet 1213. This not only allows for the simultaneous generation of multiple different types of microdroplets 199, but also ensures uniformity in the volume of the microdroplets 199 generated by each liquid dispensing pipette tip 110. Furthermore, it allows for individual control of the volume of each type of droplet 195, which helps in individually controlling the generation state of microdroplets 199 from multiple liquid dispensing pipette tips 110.

[0146] In processes using conventional motion control mechanisms, the opposing motion between the outlet end of the liquid dispensing pipette tip and the oil phase composition cannot be precisely controlled, resulting in relatively low uniformity of volume of the generated microdroplets.

[0147] In light of this, when generating microdroplets by injection / injection of a liquid dispensing pipette tip, conventional motion control mechanisms cannot accurately control the opposing motion between the outlet end of the liquid dispensing pipette tip and the oil phase composition, resulting in relatively low uniformity of volume in the generated microdroplets. Therefore, there is a need to provide a motion control mechanism that can accurately control the opposing motion between the outlet end of the liquid dispensing pipette tip and the oil phase composition.

[0148] In the process of generating microdroplets 199, the outlet end 112 of the liquid dispensing pipette tip 110 performs periodic motion including instantaneous acceleration motion, which not only effectively generates microdroplets 199 but also helps to conveniently control the size of the generated microdroplets 199. The outlet end 112 of the liquid dispensing pipette tip 110 displaces sinusoidally and performs periodic motion, which not only effectively generates microdroplets 199 but also ensures that the generated microdroplets 199 have good volume uniformity. The outlet end 112 of the liquid dispensing pipette tip 110 performs periodic motion including instantaneous acceleration motion, or periodic motion by displacing sinusoidally, driven by the motion control mechanism 130.

[0149] As shown in Figure 30, the motion control mechanism 130 provided in this application includes a support frame 131, a connecting means 132, and a drive element. The connecting means 132 is used to connect to a liquid dispensing pipette tip 110. The drive element is fixed to the support frame 131 and connected to the connecting means 132 so as to transmit power. The outlet end 112 of the liquid dispensing pipette tip 110 vibrates with a sinusoidal displacement or a square wave velocity when driven by the drive element. The motion control mechanism 130 provided in this application has the advantage of high efficiency and high uniformity in generating microdroplets 199 by generating microdroplets 199 in conjunction with the outlet end 112 of the liquid dispensing pipette tip 110 vibrating with a sinusoidal displacement or a square wave velocity. The motion control mechanism 130 according to this application may be modified to apply other rotary drive devices, such as an oscillating cylinder or a rotating electromagnet 137.

[0150] In one embodiment of the present application, the drive element includes a vibration motor 133, which is preferably a galvanometer motor whose output shaft is connected to a connecting means 132 in a power-transmitting manner. A galvanometer motor is capable of stable and high-speed reciprocating oscillation and reciprocating linear motion, and since the amplitude and frequency of the oscillation can be set as required, the range of applications for the motion control mechanism 130 according to the present application is greatly expanded. Preferably, the rotary motor is a voice coil motor or a piezoelectric motor. Furthermore, the vibration motor 133 may be a motor having a closed-loop controlled oscillation angle or position. By driving the vibration of the output end of the liquid dispensing pipette tip 110 with a motor having a closed-loop controlled oscillation angle or position, the oscillation trajectory of the liquid dispensing pipette tip 110 can be precisely controlled, and interference from the environment and systems can be further reduced.

[0151] The application of the motor with closed-loop control of vibration angle or position in this invention will be described below with reference to Figure 31. The motor with closed-loop control of vibration angle or position includes components such as an infrared position sensor, a control circuit, and a signal processing circuit. In this embodiment, an infrared position sensor is mounted on the rotation axis of the motion control mechanism 130, and the position signal detected by the infrared position sensor is fed back to the control circuit. The control circuit processes proportional, integral, and differential operations on the fed-back position signals based on the principle of PID automated control, and combines this with signal processing circuits such as position feedforward, velocity ring, and current ring to achieve precise control of the absolute position when the motor is in motion. Using a motor with closed-loop control of vibration angle or position helps to avoid changes in the vibration position of other vibration motors 133 due to changes in the complex load environment, and helps to precisely control the volume and generation rate of droplets 195 in the project.

[0152] In one embodiment of the present application, the connecting means 132 includes a coupling 1321. The coupling 1321 is connected to the output shaft of a vibration motor 133 so as to transmit power. The coupling 1321 is a hollow tube, one end of which is connected to a liquid dispensing pipette tip 110, and the other end of which is connected to a fluid control mechanism of the liquid dispensing pipette tip 110. The liquid dispensing pipette tip 110 stores a first liquid 190 for generating microdroplets 199, and the fluid control mechanism is responsible for discharging the first liquid 190 in the liquid dispensing pipette tip 110 at a predetermined flow rate for the process of generating microdroplets 199. The first liquid 190 stored in the liquid dispensing pipette tip 110 is discharged at a constant flow rate under the control of the fluid control mechanism. Alternatively, the flow rate may vary regularly, or it may be set to another type of predetermined flow rate. In this embodiment, the first liquid 190 in the liquid dispensing pipette tip 110 is discharged at a constant flow rate from the outlet end 112 of the liquid dispensing pipette tip 110 under the control of a fluid control mechanism. Specifically, the fluid control mechanism is connected to one end of a fitting 1321, the capillary tubing 123 of which is separated from the liquid dispensing pipette tip 110. The fitting 1321 simultaneously connects the liquid dispensing pipette tip 110 to the fluid control mechanism and also acts in conjunction with the movement of the liquid dispensing pipette tip 110. In one possible configuration, the fitting 1321 is coaxial with the liquid dispensing pipette tip 110 after it has been connected to it.

[0153] To facilitate the attachment and detachment of the liquid dispensing pipette tip 110, one end of the connector 1321 adjacent to the liquid dispensing pipette tip 110 has an inverted frustoconical outer edge, and the liquid dispensing pipette tip 110 is positioned around the inverted frustoconical end of the connector 1321. Because one end of the connector 1321 adjacent to the liquid dispensing pipette tip 110 has an inverted frustoconical outer edge, the resistance to attaching and detaching the liquid dispensing pipette tip 110 is reduced, and the secure attachment of the liquid dispensing pipette tip 110 is facilitated. Furthermore, the connecting means 132 includes a connecting shaft 1322, which is rotatably positioned on the support frame 131, and the connecting shaft 1322 is connected to a vibration motor 133 so as to transmit power. There are multiple connectors 1321, and the multiple connectors 1321 are fixedly positioned on the connecting shaft 1322 at intervals. Multiple connectors 1321 can be attached to a single connecting shaft 1322 at intervals, and multiple liquid dispensing pipette tips 110 can be attached simultaneously using the multiple connectors 1321, thereby significantly increasing the efficiency of generating microdroplets 199.

[0154] Preferably, the connecting shaft 1322 is rotatably positioned on the support frame 131, with both ends, including the connecting shaft 1322, rotatably connected to the support frame 131, and the other position of the connecting shaft 1322 rotatably connected to the support frame 131. In this embodiment, the connecting shaft 1322 is rotatably positioned on the support frame 131 at both ends, with one end connected to a vibration motor 133 for power transmission, and a plurality of couplings 1321 are fixedly positioned between the ends of the connecting shaft 1322. Since both ends of the connecting shaft 1322 are rotatably positioned on the support means, rotational stability can be increased for the entire rotating shaft. In one implementable form, both ends of the connecting shaft 1322 are rotatably positioned on the support frame 131 by rotating bearings. In other embodiments, the other position of the connecting shaft 1322 may be rotatably positioned on the support frame 131 if the rotation and transmission conditions are met.

[0155] When the joint 1321 is fixed to the connecting shaft 1322, the angle between the axial direction of the joint 1321 and the axial direction of the connecting shaft 1322 can change the trajectory and velocity of the outlet end 112 of the liquid dispensing pipette tip 110. In one feasible configuration, the axial direction of the joint 1321 and the axial direction of the connecting shaft 1322 are perpendicular to each other. If the axial direction of the joint 1321 and the axial direction of the connecting shaft 1322 can be maintained perpendicular to each other, it helps the liquid dispensing pipette tip 110 to fully utilize the rotation of the connecting shaft 1322 to achieve its own vibration. Furthermore, multiple joints 1321 are spaced equally apart between both ends of the connecting shaft 1322. The liquid dispensing pipette tips 110, which are arranged at equal intervals, uniformly interfere with the second liquid 699 during the process of vibrating below the liquid surface of the second liquid 699, ensuring that the environment and conditions for each liquid dispensing pipette tip 110 to generate minute droplets 199 are the same.

[0156] In one embodiment of this application, the driving element includes a piezoelectric ceramic 135 and an elastic means 136. When the piezoelectric ceramic 135 is energized and deformed in a first direction, it drives the coupling 1321 of the connecting means 132 to move in the first direction, causing the elastic means 136 connected to the connecting means 132 to be elastically deformed. On the other hand, when the piezoelectric ceramic 135 is energized and deformed in the opposite direction to the first direction, the elastic means 136 is interlocked so that the coupling 1321 of the interlocking connecting means 132 moves in the opposite direction to the first direction while its elastic deformation is restored. Repeating this process, the connecting means 132 is interlocked so that the outlet end 112 of the liquid dispensing pipette tip 110 moves with a sinusoidal displacement or a square wave-like velocity. Specifically, as shown in Figure 32, the piezoelectric method can cause the outlet end 112 of the liquid dispensing pipette tip 110 to vibrate in an arc trajectory with a sinusoidal displacement or a square wave-like velocity. The coupling 1321 is rotatably positioned on the support frame 131 via a bearing, and a liquid dispensing pipette tip 110 is circumferentially mounted on one end of the coupling 1321, allowing the liquid dispensing pipette tip 110 to perform arc-shaped trajectory motion with the bearing axis as its midpoint. A symmetrical extending plate 134 is located where the coupling 1321 is rotatably connected to the support frame 131, with the extending direction of the extending plate 134 being perpendicular to the extending direction of the coupling 1321. The driving element includes a piezoelectric ceramic 135 and an elastic means 136, which cooperate to drive the connecting means 132. The piezoelectric ceramic 135 and the elastic means 136 enable rapid vibration of the outlet end 112 of the liquid dispensing pipette tip 110 via the driving extending plate 134. The piezoelectric method has the advantages of a simple structure and stable driving performance.

[0157] In one embodiment of the present application, the driving element includes an electromagnet 137, a magnetic means 138, and an elastic means 136, where one end of the elastic means 136 is fixedly positioned on a support frame 131, a connecting means 132 is fixedly positioned on the other end of the elastic means 136, and the magnetic means 138 is fixedly connected to a coupling 1321 of the connecting means 132. When the electromagnet 137 is energized and applies a force in a first direction to the magnetic means 138, the elastic means 136 elastically deforms while the magnetic means 138 and the coupling 1321 of the connecting means 132 move in the first direction. When the electromagnet 137 is disconnected, the elastic means 136 causes the coupling 1321 of the connecting means 132 and the magnetic means 138 to move in the opposite direction to the first direction. By controlling the power supply to the electromagnet 137, the magnetic means 138 is linked via the connecting means 132 to cause the outlet end 112 of the liquid dispensing pipette tip 110 to move with a sinusoidal displacement or a square wave-like velocity.

[0158] Specifically, as shown in Figure 33, the outlet end 112 of the liquid dispensing pipette tip 110 can vibrate in an arc trajectory with a sinusoidal displacement or a square wave-like velocity. In this embodiment, the motion trajectory of the outlet end 112 of the liquid dispensing pipette tip 110 is close to the horizontal segment of a planar arc. The elastic means 136 is fixed at one end to the support frame 131 and fixedly connected at the other end to the joint 1321. The liquid dispensing pipette tip 110 is mounted around one end of the joint 1321. The driving element includes an electromagnet 137 and a magnetic means 138, the magnetic means 138 being fixedly connected to the connecting means 132, and the electromagnet 137 driving the connecting means 132 by the magnetic means 138. Since the electromagnet 137 is fixedly positioned on the support frame 131, the magnetic means 138, which is attracted to the electromagnet 137, is fixedly positioned on the coupling 1321 and held at a distance where it can operate together with the electromagnet 137. A position sensor detects the movement position of the magnetic means 138, and the position of the outlet end 112 of the liquid dispensing pipette tip 110 can be calculated by computation. When the electromagnet 137 is energized, it attracts the magnetic means 138, and the elastic means 136 stores energy through elastic deformation as the liquid dispensing pipette tip 110 moves in a direction that approaches the electromagnet 137. When the outlet end 112 of the liquid dispensing pipette tip 110 has moved close to the electromagnet 137 to a first predetermined position, the electromagnet 137 is disconnected. The liquid dispensing pipette tip 110 moves away from the electromagnet 137 due to the recovery force of the elastic means 136. When the outlet end 112 of the liquid dispensing pipette tip 110 moves away from the electromagnet 137 to a second predetermined position, the electromagnet 137 is energized. The electromagnet 137 attracts the magnetic means 138, and the elastic means 136 stores energy through elastic deformation while the liquid dispensing pipette tip 110 moves toward the electromagnet 137 in conjunction with this. This process is repeated. Depending on the specific situation, the operating parameters of the electromagnet 137 and the elastic modulus of the elastic means 136 can be adjusted to realize vibration of the outlet end 112 of the liquid dispensing pipette tip 110 with a sinusoidal displacement or a square wave-like velocity. In one implementable form, the elastic means 136 may include an elastic steel billet or other material that satisfies elastic requirements.

[0159] As shown in Figure 34, in one embodiment of the present application, the outlet end 112 of the liquid dispensing pipette tip 110 can vibrate in an arc trajectory with a sinusoidal displacement or a square wave-like velocity by an electromagnetic method. In this embodiment, the motion trajectory of the outlet end 112 of the liquid dispensing pipette tip 110 is close to the vertical segment of a planar arc. The elastic means 136 is fixed at one end to the support frame 131 and fixedly connected at the other end to the joint 1321. The liquid dispensing pipette tip 110 is positioned around one end of the joint 1321. An electromagnet 137 is fixedly positioned on the support frame 131, and a magnetic means 138 attracted to the electromagnet 137 is fixedly positioned on the joint 1321 and held within a distance range that allows it to operate together with the electromagnet 137. A position sensor can detect the motion position of the magnetic means 138 and calculate the position of the outlet end 112 of the liquid dispensing pipette tip 110 by calculation. When the electromagnet 137 is energized, it attracts the magnetic means 138, and the elastic means 136 stores energy through elastic deformation while the liquid dispensing pipette tip 110 moves toward the electromagnet 137 in conjunction with it. When the outlet end 112 of the liquid dispensing pipette tip 110 is approaching the electromagnet 137 and has moved to a first predetermined position, the electromagnet 137 is disconnected. The liquid dispensing pipette tip 110 moves away from the electromagnet 137 due to the recovery force of the elastic means 136. When the outlet end 112 of the liquid dispensing pipette tip 110 has moved away from the electromagnet 137 and has moved to a second predetermined position, the electromagnet 137 is energized again. The electromagnet 137 attracts the magnetic means 138, and the elastic means 136 stores energy through elastic deformation while the liquid dispensing pipette tip 110 moves toward the electromagnet 137 in conjunction with it. This process is repeated. Depending on the specific circumstances, the operating parameters of the electromagnet 137 and the elastic modulus of the elastic means 136 can be adjusted to achieve vibration of the outlet end 112 of the liquid dispensing pipette tip 110 with a sinusoidal displacement or a square wave-like velocity. In one implementable form, the elastic means 136 may include an elastic steel billet or other material that satisfies elastic requirements.

[0160] In one embodiment of the present application, the driving element includes an electromagnet 137 and a magnetic means 138, the magnetic means 137 being fixedly connected to a coupling 1321 of a connecting means 132, the electromagnet 137 generating a changing magnetic field, and the magnetic means 138 moving through the changing magnetic field. The magnetic means 137 is linked via the connecting means 132 to cause the outlet end 112 of the liquid dispensing pipette tip 110 to move with a sinusoidal displacement or a square wave-like velocity.

[0161] Furthermore, as shown in Figure 35, the electromagnet 137 can cause the outlet end 112 of the liquid dispensing pipette tip 110 to vibrate in an arc trajectory with a sinusoidal displacement or a square wave-like velocity. The joint 1321 is rotatably mounted on the support frame 131 by bearings, and the liquid dispensing pipette tip 110 is mounted around one end of the joint 1321. Since the electromagnet 137 is fixedly mounted on the support frame 131, a magnetic means 138 attracted to the electromagnet 137 is fixedly mounted on the joint 1321 and held within a distance range that allows it to operate together with the electromagnet 137. The position sensor can detect the rotation angle of the joint 1321 and calculate the position of the outlet end 112 of the liquid dispensing pipette tip 110. When the electromagnet 137 is energized, it attracts the magnetic means 138, causing the liquid dispensing pipette tip 110 to move toward the electromagnet 137. When the outlet end 112 of the liquid dispensing pipette tip 110 moves toward the electromagnet 137 to a first predetermined position, the direction of energization of the electromagnet 137 is changed. The liquid dispensing pipette tip 110 moves away from the electromagnet 137 due to the reaction force of the electromagnet 137. When the outlet end 112 of the liquid dispensing pipette tip 110 moves toward a second predetermined position, the direction of energization of the electromagnet 137 is changed again. The electromagnet 137 attracts the magnetic means 138, causing the liquid dispensing pipette tip 110 to move toward the electromagnet 137. This process is repeated. Depending on the specific situation, the operating parameters of the electromagnet 137 can be adjusted to achieve vibration of the outlet end 112 of the liquid dispensing pipette tip 110 with a sinusoidal displacement or a square wave-like velocity.

[0162] In the above embodiment, the vibration motor 133 outputs rotation, and the outlet end 112 of the liquid dispensing pipette tip 110 vibrates in a circular arc trajectory with a sinusoidal displacement or a speed that changes in a square wave pattern. In other embodiments, the outlet end 112 of the liquid dispensing pipette tip 110 may vibrate in a straight line trajectory with a sinusoidal displacement or a speed that changes in a square wave pattern.

[0163] As shown in Figure 36, in one embodiment of the present application, the outlet end 112 of the liquid dispensing pipette tip 110 can be vibrated by the electromagnet 137 in a linear trajectory with a sinusoidal displacement or a square wave-like velocity. In this embodiment, the outlet end 112 of the liquid dispensing pipette tip 110 vibrates in a linear trajectory in the horizontal plane. The joint 1321 is slidably positioned on the support frame 131 via a linear bearing, and the liquid dispensing pipette tip 110 is positioned around one end of the joint 1321. Since the electromagnet 137 is fixedly positioned on the support frame 131, the magnetic means 138 attracted to the electromagnet 137 is fixedly positioned on the joint 1321 and held within a distance range that allows it to operate together with the electromagnet 137. The position sensor can detect the sliding position of the joint 1321 and calculate the position of the outlet end 112 of the liquid dispensing pipette tip 110. When energized, the electromagnet 137 attracts the magnetic means 138, causing the liquid dispensing pipette tip 110 to slide toward the electromagnet 137. When the outlet end 112 of the liquid dispensing pipette tip 110 is close to the electromagnet 137 and has moved to a first predetermined position, the direction of energization of the electromagnet 137 is changed. The liquid dispensing pipette tip 110 slides toward the electromagnet 137 due to the reaction force of the electromagnet 137. When the outlet end 112 of the liquid dispensing pipette tip 110 has moved toward a second predetermined position, the direction of energization of the electromagnet 137 is changed again. The electromagnet 137 attracts the magnetic means 138, causing the liquid dispensing pipette tip 110 to slide toward the electromagnet 137. This process is repeated. Depending on the specific situation, the operating parameters of the electromagnet 137 can be adjusted to achieve vibrations in which the outlet end 112 of the liquid dispensing pipette tip 110 changes in displacement in a sinusoidal pattern or in velocity in a square wave pattern.

[0164] As shown in Figure 37, in one embodiment of the present application, the outlet end 112 of the liquid dispensing pipette tip 110 vibrates in a linear trajectory with a sinusoidal displacement or a square wave-like velocity due to the electromagnet 137. In this embodiment, the outlet end 112 of the liquid dispensing pipette tip 110 vibrates in a linear trajectory in a vertical plane. The coupling 1321 is slidably positioned on the support frame 131 via a linear bearing, and the liquid dispensing pipette tip 110 is positioned around one end of the coupling 1321. The electromagnet 137 is fixedly positioned on the support frame 131, and a magnetic means 138 attracted to the electromagnet 137 is fixedly positioned on the coupling 1321 and held within a distance range that allows it to operate together with the electromagnet 137. A position sensor can detect the sliding position of the coupling 1321 and calculate the position of the outlet end 112 of the liquid dispensing pipette tip 110. When energized, the electromagnet 137 attracts the magnetic means 138, causing the liquid dispensing pipette tip 110 to slide toward the electromagnet 137. When the outlet end 112 of the liquid dispensing pipette tip 110 is close to the electromagnet 137 and has moved to a first predetermined position, the direction of energization of the electromagnet 137 is changed. The liquid dispensing pipette tip 110 slides toward the electromagnet 137 due to the reaction force of the electromagnet 137. When the outlet end 112 of the liquid dispensing pipette tip 110 moves toward a second predetermined position away from the electromagnet 137, the direction of energization of the electromagnet 137 is changed again. The electromagnet 137 attracts the magnetic means 138, causing the liquid dispensing pipette tip 110 to slide toward the electromagnet 137. This process is repeated. Depending on the specific situation, the operating parameters of the electromagnet 137 can be adjusted to achieve vibration of the outlet end 112 of the liquid dispensing pipette tip 110 with a sinusoidal displacement or a square wave-like velocity.

[0165] A galvanomirror motor can output reciprocating linear motion. In another embodiment of this application, the galvanomirror motor drives the outlet end 112 of the liquid dispensing pipette tip 110 to vibrate in a straight line with a sinusoidal displacement or a square wave-like velocity.

[0166] A galvanomirror motor can output reciprocating linear motion. In another embodiment of this application, the galvanomirror motor drives the outlet end 112 of the liquid dispensing pipette tip 110 to vibrate in a straight line with a sinusoidal displacement or a square wave-like velocity.

[0167] The microdroplet generation apparatus and method provided in this application have a wide range of applications in fields such as medical clinical testing, nanomaterial manufacturing, food and environmental testing, and biochemical analysis. One specific example of application is the application of the microdroplet generation apparatus and method provided in this application to polymerase chain reaction (PCR).

[0168] Conventional fluid drive mechanisms and methods suffer from the problem that when a liquid dispensing pipette tip is driven and moved, the flow velocity of the discharged liquid is unstable and uncontrollable, resulting in randomness in the volume of minute droplets. This invention provides a fluid drive mechanism and method that can ensure that the liquid dispensing pipette tip discharges liquid at a predetermined flow velocity.

[0169] As shown in Figures 38-43, the fluid drive mechanism 120 provided in this application is used to control the flow velocity and flow rate of a third liquid 820 discharged from the outlet end of a first liquid dispensing pipette tip 830 in the process of generating microdroplets by a microdroplet generation system. The fluid drive mechanism 120 provided in this application includes a housing 100, a first volumetric assembly 200, and a linear motor assembly 300. The housing 100 of the fluid drive mechanism 120 also serves as a support, the first volumetric assembly 200 is the execution unit of the fluid drive process, and the linear motor assembly 300 is the drive unit of the fluid drive process. Both the first volumetric assembly 200 and the linear motor assembly 300 are mounted in the housing 100. The first volumetric assembly 200 includes a first syringe 201 and a first bush rod 202, the outer wall of the first syringe 201 being fixedly mounted to the inner wall of the housing 100, and the first bush rod 202 slidingly cooperating with the inner wall of the first syringe 201, in other words, the first bush rod 202 being slidably mounted on the first syringe 201. The first syringe 201 is capable of storing a first drive fluid 810, and the first syringe 201 has a fluid inlet and outlet, the fluid inlet and outlet being able to communicate with the inlet end of a first liquid dispensing pipette tip 830, the first liquid dispensing pipette tip 830 storing a third fluid 820. The output end of the linear motor assembly 300 is power-transmittingly connected to the first bush rod 202 and is used to drive the first bush rod 202 to slide along the extending direction of the first syringe 201. In the process of generating microdroplets, the output end of the linear motor assembly 300 drives the first bush rod 202 to press the first drive liquid 810 stored in the first syringe 201, and the pressed first drive liquid 810 then presses the third liquid 820 stored in the first liquid dispensing pipette tip 830, ultimately discharging the third liquid 820 from the outlet end of the first liquid dispensing pipette tip 830. The flow velocity and flow rate of the third liquid 820 discharged from the first liquid dispensing pipette tip 830 are based on the motion state of the output end of the linear motor assembly 300.

[0170] The fluid drive mechanism 120, due to the incompressibility of the first drive liquid 810, can ensure that the third liquid 820 is still discharged from the outlet end of the first liquid dispensing pipette tip 830 at a predetermined flow velocity and flow rate, even when the outlet end of the first liquid dispensing pipette tip 830 is vibrating at a high frequency. The linear motor assembly 300 has relatively high motion precision, and by freely adjusting the current according to actual conditions such as liquid discharge speed and liquid discharge pressure, it can ensure that the first bush rod 202 slides at a predetermined speed or slides by a predetermined distance, and accurately realize that the third liquid 820 is discharged from the outlet end of the first liquid dispensing pipette tip 830 at a predetermined flow velocity and flow rate. The fluid drive mechanism 120 provided in this application allows for precise control of the volume of the generated microdroplets.

[0171] The first syringe 201 according to this application may be straight or bent. The liquid inlet / outlet of the first syringe 201 may be located at one end or in the middle of the first syringe 201. This application does not limit the specific structure of the first syringe 201 or the first bush rod 202 or their specific positional relationship. For the sake of explanation, as shown in Figures 41 and 42, this application has given as an example a first syringe 201 which is straight, has a liquid inlet / outlet at one end of the first syringe 201, and a first bush rod 202 which is slidably mounted with the first syringe 201 and passes through the other end of the first syringe 201. However, in other embodiments of this application, the first volumetric assembly 200 may have a structure that enables any volumetric function.

[0172] In one embodiment of the present application, as shown in Figure 38-43, the linear motor assembly 300 includes a voice coil motor 301, the primary side 311 of the voice coil motor 301 being fixedly mounted to the inner wall of the housing 100, and the secondary side 312 of the voice coil motor 301 being fixedly connected to a first bush rod 202 along the sliding direction of the first bush rod 202. The voice coil motor 301 has the advantages of not only fast response, high speed, and high acceleration, but also a simple structure, small volume, and easy control. The secondary side 312 of the voice coil motor 301 can maintain a predetermined sliding speed even when the sliding resistance increases or decreases by controlling the current, and can easily maintain a predetermined liquid discharge velocity even when the liquid discharge pressure of the third liquid 820 changes. The voice coil motor 301 can operate according to a predetermined sliding position, a predetermined sliding speed, or a predetermined drive pressure value, depending on the actual situation, and the first variable volume assembly 200 can accurately achieve that the third liquid 820 is discharged from the first liquid dispensing pipette tip 830 in a predetermined volume, discharged from the first liquid dispensing pipette tip 830 at a predetermined flow rate, or discharged from the first liquid dispensing pipette tip 830 at a predetermined discharge pressure.

[0173] Furthermore, as shown in Figures 39-40, the voice coil motor 301 is positioned on one side of the first syringe 201, the sliding direction of the secondary side 312 of the voice coil motor 301 is parallel to the sliding direction of the first bush rod 202 in the first syringe 201, and the secondary side 312 of the voice coil motor 301 is connected to the first bush rod 202 in a power-transmitting manner. Positioning the voice coil motor 301 on one side of the first syringe 201 allows for a reduction in the dimensions of the fluid drive mechanism 120 along the extending direction of the first syringe 201, and the fact that the sliding direction of the secondary side 312 of the voice coil motor 301 is the same as the sliding direction of the first bush rod 202 simplifies the connection method between the secondary side 312 of the voice coil motor 301 and the first bush rod 202. In one feasible embodiment, as shown in Figure 39-42, the linear motor assembly 300 further includes a connecting plate 302, one end of which is fixedly connected to the secondary side 312 of the voice coil motor 301, and the other end of which is fixedly connected to one end of a first bush rod 202 located outside the first syringe 201. It is understood that the connecting plate 302 is movably positioned in the housing 100, the connecting plate 302 slides synchronously with the secondary side 312 of the voice coil motor 301, and the secondary side 312 of the voice coil motor 301 is interlocked by the connecting plate 302 so that the first bush rod 202 slides synchronously with the first syringe 201. In other embodiments, the sliding direction of the secondary side 312 of the voice coil motor 301 may be coaxial with, perpendicular to, or otherwise feasible.

[0174] Furthermore, as shown in Figure 42-47, the secondary side 312 of the voice coil motor 301 includes a bobbin 3121 and a coil 3122, with the coil 3122 wound around the bobbin 3121, and the bobbin 3121 and the connecting plate 302 being integrally molded. The integrally molded bobbin 3121 and connecting plate 302 further eliminate operational errors between the secondary side 312 of the voice coil motor 301 and the first bush rod 202, ensuring that the first bush rod 202 and the secondary side 312 of the voice coil motor 301 move synchronously with accuracy. In other embodiments, the connection between the secondary side 312 of the voice coil motor 301 and the connecting plate 302 may be fixed by connecting means such as screws or engagements. This application does not limit the method of connection between the secondary side 312 of the voice coil motor 301 and the connecting plate 302. The secondary side 312 of the voice coil motor 301 only needs to be able to interlock with the first bush rod 202 via the connecting plate 302 so that it slides synchronously.

[0175] In one embodiment of the present application, as shown in Figures 40 and 42, the linear motor assembly 300 further includes a guide means 303, the guide means 303 including a guide rail and a slide block, the guide rail being fixedly positioned in the housing 100, the extending direction of the guide rail being parallel to the sliding direction of the first bush rod 202, the slide block being slidably positioned on the guide rail, and the slide block being fixedly connected to a connecting plate 302. The guide means 303 acts as a guide during the sliding process of the connecting plate 302, ensuring stability during the process in which the secondary side 312 of the voice coil motor 301 slides synchronously in conjunction with the connecting plate 302, and enabling precise control of the discharge of the third liquid 820 from the first liquid dispensing pipette tip 830 at a predetermined flow rate or velocity. Furthermore, the linear motor assembly 300 further includes a displacement sensor positioned in the housing 100 and electrically connected to the voice coil motor 301. The displacement sensor is used to detect the sliding position and sliding speed of the synchronously sliding voice coil secondary side 312, connecting plate 302, and first bush rod 202. The displacement sensor is electrically connected to the voice coil motor 301, enabling closed-loop control of the voice coil motor 301. Preferably, the displacement sensor includes raster type, magnetic grid type, resistance type, or differential transformer (LVDT) type displacement sensors. Specifically, the displacement sensor is a photoelectric linear displacement sensor. In other embodiments of this application, the voice coil motor 301 itself is a servo motor, and the closed-loop control system for the voice coil motor 301 is integrated inside the voice coil motor 301, thus further reducing the volume of the fluid drive mechanism 120 provided in this application.

[0176] In one embodiment of the present application, as shown in Figure 42-45, the voice coil motor 301 includes a primary side 311 and a secondary side 312. The primary side 311 includes a first magnetic body pair 3111 and a second magnetic body pair 3112, which are sequentially arranged in the housing 100 along the sliding direction of the secondary side 312, with the opposite magnetic poles of the two magnetic bodies in the first magnetic body pair 3111 facing each other, and the opposite magnetic poles of the two magnetic bodies in the second magnetic body pair 3112 facing each other, and the direction of the magnetic induction lines between the first magnetic body pair 3111 and the direction of the magnetic induction lines between the second magnetic body pair 3112 being opposite. The secondary side 312 includes a bobbin 3121 and a coil 3122, the coil 3122 being wound on the bobbin 3121, and the coil 3122 having a first stage 3125 and a second stage 3126 with opposite current directions when energized, the first stage 3125 of the coil 3122 sliding between the first pair of magnetic bodies 3111, and the second stage 3126 of the coil 3122 sliding between the second pair of magnetic bodies 3112. The two pairs of magnetic bodies and the coil 3122 can simultaneously generate the same large inductive force in the first stage 3125 and the second stage 3126 of the coil 3122, which helps the secondary side 312 of the voice coil motor 301 to operate rapidly and can increase the sensitivity of the voice coil motor 301.

[0177] As one possible configuration, as shown in Figures 43-45, the first magnetic body pair 3111 and the second magnetic body pair 3112 are both rectangular plate-shaped magnetic bodies, and both the first magnetic body pair 3111 and the second magnetic body pair 3112 are fixedly mounted to the inner wall of the housing 100. One end of the first magnetic body pair 3111 is mounted in contact with one end of the second magnetic body pair 3112 along the sliding direction of the secondary side 312 of the voice coil motor 301. The bobbin 3121 is a hollow, rounded rectangle, and a rounded rectangular ring-shaped groove is provided on one end face of the bobbin 3121. Similarly, the coil 3122, which is also hollow and rounded rectangular, is fixedly mounted in the ring-shaped groove of the bobbin 3121. When current flows through coil 3122, the first stage 3125 and the second stage 3126 simultaneously generate the same large inductive force in the same direction. Since the first magnetic body pair 3111 and the second magnetic body pair 3112 are both fixed, the energized coil 3122 slides in the direction of the inductive force, and the bobbin 3121 fixed to coil 3122 moves synchronously with coil 3122. The secondary side 312 of the voice coil motor 301 moves synchronously in conjunction with the first bush rod 202 via the connecting plate 302. When the displacement sensor detects that the connecting plate 302, which slides synchronously with the first bush rod 202, has slid to a predetermined position, the displacement sensor transmits a signal, the power to the voice coil motor 301 is cut off, and the secondary side 312 of the voice coil motor 301 stops sliding. Alternatively, when the displacement sensor generates minute waves at the sliding speed of the connecting plate 302 which slides synchronously with the first bush rod 202, the displacement sensor transmits a signal and adjusts the current flowing to the voice coil motor 301 accordingly. This ensures that the secondary side 312 of the voice coil motor 301 is linked to the connecting plate 302 so that the first bush rod 202 slides at a predetermined speed, thereby enabling the discharge of the third liquid 820 from the first liquid dispensing pipette tip 830 at a predetermined flow rate and the generation of uniform minute droplets. In other embodiments of this application, the voice coil motor 301 may have a different type of structure.

[0178] Furthermore, as shown in Figures 43-44, the housing 100 includes opposing first mounting end faces 141 and second mounting end faces 143, with first mounting holes 142 and second mounting holes 144 provided on the first mounting end face 141 and second mounting end face 143, respectively, and the first mounting holes 142 and second mounting holes 144 facing each other. The primary side 311 of the voice coil motor 301 further includes a first mounting plate 3114 and a second mounting plate 3115, the first mounting plate 3114 and the second mounting plate 3115 being detachably fixed to the first mounting holes 142 and second mounting holes 144, respectively. The two magnetic bodies in the first magnetic body pair 3111 are mounted on one end of the first mounting plate 3114 and the second mounting plate 3115, respectively, along the sliding direction of the secondary side 312, and the two magnetic bodies in the second magnetic body pair 3112 are mounted on the other end of the first mounting plate 3114 and the second mounting plate 3115, respectively, along the sliding direction of the secondary side 312. The voice coil motor 301 can be removed entirely from the housing 100, or mounted entirely to the housing 100 after assembly is complete, thereby ensuring the assembly accuracy of the voice coil motor 301 and improving the ease of attaching and detaching the voice coil motor 301. In one possible configuration, the first mounting hole 142 and the second mounting hole 144 are both rounded rectangular holes, and the first mounting plate 3114 and the second mounting plate 3115 are correspondingly rounded rectangular plates. The first mounting plate 3114 and the second mounting plate 3115 are fixed by screws to the first mounting hole 142 and the second mounting hole 144, respectively. Both opposing sides of the first mounting plate 3114 and the second mounting plate 3115 have rectangular grooves for mounting the first magnetic body pair 3111 and the second magnetic body pair 3112, and the first magnetic body pair 3111 and the second magnetic body pair 3112 are mounted in the rectangular grooves of the first and second mounting plates, respectively.

[0179] Furthermore, the housing 100 is a hollow rectangular prism, and both the first volume variable assembly 200 and the linear motor assembly 300 of the fluid drive mechanism 120 are mounted inside the housing 100. A connection hole is provided on one end face of the housing 100, and multiple housings 100 are mounted in parallel on the base via the connection hole. When multiple fluid drive mechanisms 120 are mounted in parallel, multiple microdroplet generation processes can be controlled simultaneously, and the efficiency of microdroplet generation can be greatly increased. In one implementable form, as shown in Figures 38, 39, and 43, during the operation process of the fluid drive mechanism 120, the housing 100 has a ceiling end face 145 and a bottom end face 140 that face each other in the vertical direction of space, and the extending direction of the first syringe 201 in the housing 100 and the sliding direction of the secondary side 312 of the voice coil motor 301 are both in the vertical direction of space. The housing 100 has two side end faces 150 facing each other in the direction from the first syringe 201 to the voice coil motor 301, and also has a first mounting end face 141 and a second mounting end face 143 facing each other in the direction from the first mounting plate 3114 to the second mounting plate 3115. When multiple fluid mounting mechanisms are mounted in parallel, they are sequentially attached between the first mounting end face 141 and the second mounting end face 143 of the multiple housings 100. The connection holes of the housings 100 are provided on the same one end face 150 of the housing 100, or on two side end faces 150. Each housing 100 is fixedly mounted to the base by screws that are screwed into the connection holes. In one specific embodiment, the dimensions of the housing 100 in the direction extending in parallel are 18 mm, or in other words, the distance between the opposing first mounting end face 141 and second mounting end face 143 on the housing 100 is 18 mm. After being mounted in parallel, the multiple fluid drive mechanisms 120 can simultaneously control the discharge of a third liquid 820 from the first liquid dispensing pipette tip 830 at a predetermined flow rate and flow rate into multiple reagent grooves spaced 18 mm apart, thereby effectively generating microdroplets. In other embodiments of this application, the distance between the multiple fluid drive mechanisms 120 mounted in parallel may be of a different size, if possible, to match the spacing between the multiple reagent grooves.

[0180] Based on the fluid drive mechanism 120 according to the above embodiment, a fluid drive method further provided by this application includes the steps of: driving a linear motor assembly 300 so that a first bush rod 202 presses a first drive fluid 810 stored in a first syringe 201; the first drive fluid 810 presses a third fluid 820 stored in a first liquid dispensing pipette tip 830; and the third fluid 820 being discharged from the outlet end of the first liquid dispensing pipette tip 830. The fluid drive method utilizes the incompressibility of the first drive fluid 810 to ensure that the third fluid 820 is still discharged from the outlet end of the first liquid dispensing pipette tip 830 at a predetermined flow velocity and flow rate, even when the outlet end of the first liquid dispensing pipette tip 830 vibrates at a high frequency. It is understandable that the first drive fluid 810 and the third fluid 820 do not dissolve in each other and that there is no exchange of substances between them. Generally, the density of the first driving liquid 810 is lower than the density of the third liquid 820. Preferably, the first driving liquid 810 is mineral oil or an alkane. In one implementable form, the third liquid 820 discharged from the first liquid dispensing pipette tip 830 falls into a storage container that stores the first driving liquid 810, and the third liquid 820 that has fallen into the storage container falls onto the first driving liquid 810. The linear motor assembly 300 not only has relatively high motion accuracy, but by freely adjusting the current according to actual conditions such as liquid discharge speed and liquid discharge pressure, it is possible to ensure that the first bush rod 202 slides at a predetermined speed or slides by a predetermined distance, thereby enabling accurate discharge of the third liquid 820 from the outlet end of the first liquid dispensing pipette tip 830 at a predetermined flow velocity and flow rate. The fluid driving method provided in this application can accurately control the volume of the generated microdroplets.

[0181] In one embodiment of the present application, as shown in Figures 40-41 and 48-49, the fluid drive mechanism 120 further includes a switching valve 400, the switching valve 400 including a first switching valve port 411, a second switching valve port 412, and a third switching valve port 413, the first switching valve port 411, the second switching valve port 412, and the third switching valve port 413 communicating with the inlet end of a first liquid dispensing pipette tip 830, a liquid inlet / outlet, and a liquid storage tank for storing a first drive fluid 810, respectively. When operating, the switching valve 400 can communicate with the first switching valve port 411 and the second switching valve port 412, or with the third switching valve port 413 and the second switching valve port 412. The switching valve 400 can control the fluid drive mechanism 120 to achieve at least two modes. In the first mode, the liquid inlet and outlet of the first variable volume assembly 200 are connected to the inlet end of the first liquid dispensing pipette tip 830, and the linear motor assembly 300 interlocks the first variable volume assembly 200 to apply a liquid driving force to the first liquid dispensing pipette tip 830, causing the third liquid 820 in the first liquid dispensing pipette tip 830 to be discharged from the outlet end of the first liquid dispensing pipette tip 830, or the third liquid 820 to be drawn into the first liquid dispensing pipette tip 830 from the outlet end of the first liquid dispensing pipette tip 830. In the second mode, the liquid inlet and outlet of the first variable volume assembly 200 are connected to the liquid storage tank, and the linear motor assembly 300 interlocks the first variable volume assembly 200 to draw the first driving liquid 810 in the liquid storage tank into the first syringe 201 of the first variable volume assembly 200, or push the driving liquid in the first variable volume assembly 200 into the liquid storage tank.

[0182] Furthermore, as shown in Figures 48-49, the switching valve 400 includes a valve body 410 and a communication block 420, the valve body 410 including a first switching valve port 411, a second switching valve port 412, and a third switching valve port 413. The communication block 420 is provided with a first flow path 421, a second flow path 422, and a third flow path 423, all independent of each other, and the first flow path 421, the second flow path 422, and the third flow path 423 all pass through the communication block 420. One end of the first flow path 421, the second flow path 422, and the third flow path 423 is connected to the first switching valve port 411, the second switching valve port 412, and the third switching valve port 413, respectively, and the other end is connected to the inlet end of the first liquid dispensing pipette tip 830, the liquid inlet and outlet, and the storage tank that stores the first drive liquid 810. The connecting block 420, which has one or more channels installed, has the advantages of a simple structure and stable communication. Furthermore, the inner surfaces of the first channel 421, the second channel 422, and the third channel 423 are polished and transitioned to rounded corners. The inner surfaces of the first channel 421, the second channel 422, and the third channel 423 all have no blind spots, effectively preventing the retention and adsorption of air bubbles.

[0183] Based on the fluid drive mechanism 120 in the above embodiment, another fluid drive method further provided by this application, as shown in Figure 50, includes the following steps: Step (1) Connect the liquid inlet and outlet of the first syringe 201 to a liquid storage tank via a switching valve 400, and, by the interlocking of the linear motor assembly 300, cause the first bush rod 202 to slide inside the first syringe 201, thereby changing the volume of the first syringe 201 and drawing the first drive fluid 810 from the liquid storage tank into the first syringe 201. Step (2) The liquid inlet and outlet of the first syringe 201 are connected to the inlet end of the first liquid dispensing pipette tip 830 via the switching valve 400, and the first bush rod 202 slides inside the first syringe 201 by the interlocking of the linear motor assembly 300, changing the volume of the first syringe 201 and discharging gas from inside the first syringe 201 and the first liquid dispensing pipette tip 830. Step (3), the outlet end of the first liquid dispensing pipette tip 830 enters the third liquid 820, maintaining communication between the liquid inlet and outlet of the first syringe 201 and the inlet end of the first liquid dispensing pipette tip 830 via the switching valve 400, and the first bush rod 202 slides inside the first syringe 201 due to the interlocking of the linear motor assembly 300, changing the volume of the first syringe 201 and drawing the third liquid 820 into the first liquid dispensing pipette tip 830. Step (4), the switching valve 400 communicates the liquid inlet and outlet of the first syringe 201 with the inlet end of the first liquid dispensing pipette tip 830, and the linear motor assembly 300 interlocks the first bush rod 202, which slides inside the first syringe 201, changing the volume of the first syringe 201 and discharging the third liquid 820 stored in the first liquid dispensing pipette tip 830 at a predetermined flow rate from the outlet end of the first liquid dispensing pipette tip 830.

[0184] Furthermore, in the above fluid drive method, the linear motor assembly 300 operates at a uniform speed, which in turn causes the first bush rod 202 to slide the first syringe 201 at a uniform speed. Ultimately, this enables the first drive liquid 810 or the third liquid 820 to be drawn into or discharged from the first syringe 201 at a uniform flow rate, ensuring the stability of the entire process of generating microdroplets and that the volume of the generated microdroplets is uniform.

[0185] In one feasible configuration, as shown in Figure 38-43, the housing 100 is a hollow rectangular prism, the switching valve 400 is fixedly mounted in the housing 100 in close proximity to the bottom end face 140 and one end face 150, and the first volume variable assembly 200 is mounted above the communication block 420 of the switching valve 400. The voice coil motor 301 is mounted on the side of the first volume variable assembly 200, and the secondary side 312 of the voice coil motor 301 and the first volume variable assembly 200 are fixedly connected via a connecting plate 302, and a guide means 303 is mounted in the housing 100 between the voice coil motor 301 and the first syringe 201 of the first volume variable assembly 200. The fluid drive mechanism 120 further includes a power port 500, which is mounted on the ceiling end face 145 of the housing 100, and the power port 500, voice coil motor 301, switching valve 400, and displacement sensor are all electrically connected. The power port 500 may be electrically connected to an external power supply to provide power to the elements within the fluid drive mechanism 120.

[0186] Each of the above embodiments can be widely applied to various fields such as medical clinical testing, nanomaterial manufacturing, food and environmental testing, and biochemical analysis. One specific application example is the application of the microdroplet generation apparatus and generation method provided in this application to polymerase chain reaction (PCR).

[0187] The technical features of the above embodiments can be combined in any way, and for the sake of brevity, not all possible combinations of the technical features in the above embodiments have been described. However, as long as these combinations of technical features are not contradictory, they are considered to fall within the scope described herein.

[0188] The above embodiments illustrate in detail and specifically only some embodiments of this application, but should be understood not to limit the scope of protection of this application. Those skilled in the art will understand that several modifications and improvements can be made without departing from the creative concept of this application, and all of these should fall within the scope of protection of this application. Therefore, the scope of protection of this application is based on the claims.

[0189] Finally, in this specification, the numbers of the components themselves, such as "first," "second," etc., are used solely to distinguish the subject of description and have no order or technical meaning. Furthermore, in this application, "connection" and "linking" include both direct and indirect connections (linking) unless otherwise specified. In the description of this application, directions or positional relationships indicated by terms such as "up," "down," "front," "back," "left," "right," "vertical," "horizontal," "top," "bottom," "inside," "outside," "clockwise," and "counterclockwise" are merely for the purpose of facilitating and simplifying the description of this application, based on the directions or positional relationships shown in the drawings, and should be understood as not limiting the present invention as they do not indicate or suggest that the referred devices or components necessarily have a specific direction and are constructed and operated in a specific direction.

[0190] In this specification, unless otherwise expressly specified and limited, the description of a first feature as "above" or "below" a second feature may mean that the first feature is in direct contact with the second feature, or that the first feature is in indirect contact with the second feature through an intermediate medium. Furthermore, the description of a first feature as "above," "above," and "upperside" a second feature means that the first feature is directly above or diagonally above the second feature, or simply that the horizontal height of the first feature is greater than that of the second feature. The description of a first feature as "below," "below," and "belowside" a second feature means that the first feature is directly below or diagonally below the second feature, or simply that the horizontal height of the first feature is lower than that of the second feature.

[0191] In this specification, relational terms such as "first," "second," etc., are used solely to distinguish one entity or operation from another, and it is not necessarily required or suggested that such an actual relationship or order exists between these entities or operations. Furthermore, the terms “equip,” “include,” or other variations are intended to cover non-exclusive inclusion. A process, method, article, or apparatus comprising a set of elements includes not only those elements but also other elements not expressly enumerated, or elements specific to such a process, method, article, or apparatus. Unless further restrictions are found, an element limited by the phrase “includes” does not preclude the presence of other identical elements in a process, method, article, or apparatus that includes that element.

[0192] Each embodiment in this specification will be described step by step, and the differences from other embodiments will be noted, with references being made between embodiments for parts that are the same or similar.

[0193] Based on the above description of the disclosed embodiments, those skilled in the art can implement or use this application. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined herein can be implemented in other embodiments as long as they do not depart from the spirit or scope of this application. Therefore, this application is not limited to the embodiments disclosed herein and should conform to the broadest scope that is consistent with the principles and novel features disclosed herein.

Claims

1. It includes a fluid drive mechanism (120), a motion control mechanism (130), and a liquid dispensing pipette tip. The liquid dispensing pipette tip includes a needle shaft (113) having a hollow cavity and an outlet end (112) positioned at one end of the needle shaft (113), wherein the angle between the normal to the end face of the outlet end (112) of the liquid dispensing pipette tip and the extending direction of the needle shaft (113) is greater than 0° and less than or equal to 90°, and a first liquid is stored inside, and further has an inlet end (111), and the fluid drive mechanism (120) is connected to the inlet end (111) of the liquid dispensing pipette tip and is used to discharge the first liquid stored inside the liquid dispensing pipette tip from the outlet end (112) of the liquid dispensing pipette tip. The motion control mechanism is used to control the movement of the liquid dispensing pipette tip so that the outlet end (112) of the liquid dispensing pipette tip moves below the surface of the second liquid, which is in a static state, causing the first liquid discharged from the outlet end (112) of the liquid dispensing pipette tip to form a droplet that adheres to the outlet end of the liquid dispensing pipette tip, and then moves the outlet end of the liquid dispensing pipette tip below the surface of the second liquid, thereby causing the droplet, which has reached a predetermined volume, to detach from the outlet end of the liquid dispensing pipette tip and form a minute droplet in the second liquid. A microdroplet generating device characterized by forming a microdroplet in a second liquid by causing the outlet end (112) of the liquid dispensing pipette tip to undergo instantaneous acceleration motion to an instantaneous acceleration value that allows the droplet to instantaneously detach from the outlet end (112) of the liquid dispensing pipette tip.

2. The microdroplet generating apparatus according to claim 1, characterized in that the liquid dispensing pipette tip is straight tubular, and the outlet end (112) of the liquid dispensing pipette tip has an oblique cut structure.

3. The microdroplet generating apparatus according to claim 1, characterized in that the needle shaft (113) includes a bent structure in the portion close to the outlet end (112) of the liquid dispensing pipette tip.

4. The microdroplet generating apparatus according to claim 3, characterized in that the needle shaft (113) has a transitioning arc segment in a bent structure close to the outlet end (112) of the liquid dispensing pipette tip.

5. Further including a needle hub (114), The needle hub (114) has a liquid reservoir (115) that penetrates the needle hub (114) along the direction of extension of the needle hub (114), The liquid reservoir (115) is connected at one end to the other end of the needle shaft (113), which is separated from the outlet end (112) of the liquid dispensing pipette tip. The microdroplet generating apparatus according to any one of claims 1 to 4, characterized in that one end of the needle hub (114), which is separated from the needle shaft (113), is the inlet end (111) of the liquid dispensing pipette tip.

6. The microdroplet generating apparatus according to claim 5, characterized in that a locking groove (116) is provided on the inner surface of one end of the needle hub (114) that is separated from the needle shaft (113).

7. The microdroplet generating apparatus according to any one of claims 1 to 4, characterized in that the angle between the normal to the end face of the outlet end (112) of the liquid dispensing pipette tip and the extending direction of the needle shaft (113) is in the range of 15° to 75°.

8. The microdroplet generating apparatus according to claim 7, characterized in that the angle between the normal to the end face of the outlet end (112) of the liquid dispensing pipette tip and the extending direction of the needle shaft (113) is in the range of 30° to 60°.

9. The microdroplet generating apparatus according to claim 8, characterized in that the angle between the normal to the end face of the outlet end (112) of the liquid dispensing pipette tip and the extending direction of the needle shaft (113) is 45°.

10. The microdroplet generating apparatus according to claim 1, characterized in that, in one period during which the velocity is changing, the velocity of the outlet end of the liquid dispensing pipette tip is centrally symmetric with respect to the midpoint, or, in one period during which the velocity is changing, the outlet end of the liquid dispensing pipette tip performs constant velocity change motion in both the first and second halves of the period, or, both the acceleration and trajectory of the outlet end of the liquid dispensing pipette tip change periodically below the liquid surface of the second liquid, or, below the liquid surface of the second liquid, the velocity of the outlet end of the liquid dispensing pipette tip changes in a cosine curve.

11. The microdroplet generating apparatus according to claim 1, characterized in that, during the acceleration phase in the first half of the cycle in which the velocity of the outlet end of the liquid dispensing pipette tip is changing, and during the acceleration phase in the second half of the cycle, one droplet is detached from the outlet end of the liquid dispensing pipette tip to form a microdroplet.

12. The microdroplet generating apparatus according to claim 1, characterized in that the acceleration of the outlet end of the liquid dispensing pipette tip is the same in the first half and second half of the cycle.

13. The microdroplet generating apparatus according to claim 1, characterized in that the velocity of the outlet end of the liquid dispensing pipette tip changes monotonically during the first and second halves of the period in which the velocity is changing.

14. The microdroplet generating apparatus according to claim 1, characterized in that the outlet end of the liquid dispensing pipette tip forms the microdroplets when it moves upward below the liquid surface of the second liquid.

15. The microdroplet generating apparatus according to claim 1, characterized in that the outlet end of the liquid dispensing pipette tip performs an oscillating motion below the liquid surface of the second liquid.

16. The microdroplet generating apparatus according to claim 1, characterized in that the direction of movement of the outlet end of the liquid dispensing pipette tip is perpendicular, parallel, or at any angle with respect to the extending direction of the liquid dispensing pipette tip.

17. The microdroplet generating apparatus according to claim 1, characterized in that, below the liquid surface of the second liquid, the trajectory of the outlet end of the liquid dispensing pipette tip includes one or more combinations of several types of trajectories, such as straight segments, arc segments, and polygonal shapes.

18. The microdroplet generating apparatus according to claim 1, characterized in that the outlet end of the liquid dispensing pipette tip performs a periodic motion including instantaneous acceleration motion below the liquid surface of the second liquid.

19. The microdroplet generating apparatus according to claim 18, characterized in that, in the step in which the outlet end of the liquid dispensing pipette tip performs periodic motion below the liquid surface of the second liquid, the velocity of the outlet end of the liquid dispensing pipette tip changes in a rectangular wave shape.

20. The minute liquid according to claim 18, characterized in that when the velocity direction of the outlet end of the liquid dispensing pipette tip is changed, the instantaneous acceleration of the outlet end of the liquid dispensing pipette tip reaches its maximum value. Droplet generator.

21. The microdroplet generating apparatus according to claim 18, characterized in that the velocity of the outlet end of the liquid dispensing pipette tip is zero until the outlet end of the liquid dispensing pipette tip undergoes instantaneous acceleration motion.

Images