A nanomedicine preparation device
Patent Information
- Application Number
- CN202521091086.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2025-05-30
- Publication Date
- 2026-10-20
- Estimated Expiration
- 2035-05-30
AI Technical Summary
但此类方案存在响应滞后、密封性能差等问题,易导致抽吸与推送过程中出现流体回流或不同原料液串液,破坏原料配比并引入杂质
[0083]通过设置包括液路换向协调集成块和两个吸推机构的送料装置,且令液路换向协调集成块的输入端和输出端分别与原料液以及微流控芯片连通,并令两个吸推机构的反向交替运行以及在液路换向协调集成块内配置单向阀组件,使得两个吸推机构在反向交替运行时,能够配合单向阀组件,使得始终仅存在与其中一个吸推机构连通的原料液输入路径以及与另一吸推机构连通的原料液输出路径处于导通状态,以此令两个吸推机构在抽吸或推送时能够将原料液不间断地输入至液路换向协调集成块中或由液路换向协调集成块输出至微流控芯片内,且液路换向协调集成块内原料液不会出现串流的情况,从而实现了原料液稳定、连续以及无串液输送的功能,保障微流控芯片内纳米药物制备过程的可控性,达到提升制备效果的目的。
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Figure CN224865308U_ABST
Abstract
Description
Technical Field
[0001] This utility model relates to the field of nanomedicine preparation, and in particular to a nanomedicine preparation device. Background Technology
[0002] Nanoparticle preparation technology achieves controllable synthesis of nanoparticles by precisely controlling the mixing and reaction processes of raw material solutions, and has significant application value in targeted drug delivery and sustained-release formulations. Microfluidic chips, as the core reaction unit, rely on a stable, continuous input of multi-component raw material solutions to ensure the uniformity and yield of nanomedicines. However, existing feeding devices in preparation systems have the following drawbacks in the raw material delivery process:
[0003] I. Existing feeding devices mostly employ a single suction or pushing mechanism (such as a single syringe or pump). After completing one suction or pushing action, the machine must be stopped and reversed, resulting in discontinuous delivery of the raw material liquid. This intermittent liquid supply causes pressure fluctuations in the flow channels within the microfluidic chip, affecting the mixing accuracy of multi-component raw material liquids, which in turn leads to uneven nanoparticle size distribution and may even cause flow channel blockage or reaction runaway. Especially for industrial preparation scenarios requiring long-term stable operation, the fluid interruption problem during single-mechanism reversal significantly reduces production efficiency and product quality consistency.
[0004] II. Existing fluid reversing devices mostly rely on external valves or complex pipeline switching structures, using a controller to directly control the valve opening and closing to achieve fluid direction conversion. However, such solutions suffer from problems such as response lag and poor sealing performance, which can easily lead to fluid backflow or cross-contamination of different raw material liquids during suction and push, disrupting the raw material ratio and introducing impurities. For example, if the check valve fails or the valve switching is asynchronous, the high-pressure raw material liquid at the output end may flow back into the input end, causing raw material contamination or malfunction of the preparation system.
[0005] Therefore, a nanomedicine preparation device is needed to solve the above problems. Utility Model Content
[0006] The purpose of this invention is to provide a nanomedicine preparation device that enables stable, continuous, and cross-contamination-free transport of raw material liquids, ensuring the controllability of the nanomedicine preparation process within a microfluidic chip and thereby improving the preparation effect.
[0007] To solve the above-mentioned technical problems, this utility model provides a nanomedicine preparation device, including a microfluidic chip, at least two feeding devices and a controller;
[0008] At least two of the feeding devices are connected to the microfluidic chip and are used for conveying different raw material liquids respectively;
[0009] Each of the aforementioned feeding devices includes a liquid path reversing coordination integrated block and two suction and push mechanisms;
[0010] The fluid circuit reversing coordination integrated block has an input terminal and an output terminal, which are used for the input and output of raw material liquid, respectively.
[0011] Both suction and push mechanisms are connected to the fluid channel of the liquid circuit reversing coordination integrated block. Each suction and push mechanism realizes the input or output of raw material liquid by suction or push. The drive end of both suction and push mechanisms is connected to the controller signal. The controller is used to control the two suction and push mechanisms to run alternately in opposite directions.
[0012] The fluid circuit reversing coordination integrated block has a built-in check valve assembly.
[0013] The one-way valve assembly is configured as follows:
[0014] When any of the suction and push mechanisms performs a suction action, the input end is connected to the raw material liquid input path of the suction and push mechanism, and the output end is disconnected from the raw material liquid output path of the suction and push mechanism.
[0015] When any of the suction and push mechanisms performs a pushing action, the output end is connected to the raw material liquid output path of the suction and push mechanism, and the input end is disconnected from the raw material liquid input path of the suction and push mechanism.
[0016] Furthermore, the fluid circuit reversing coordination integrated block has a built-in fluid channel, which is used to connect the input end, the output end, and the two suction and push mechanisms;
[0017] The one-way valve assembly includes a plurality of first one-way valves, all of which are disposed in the fluid channel.
[0018] Furthermore, the fluid channel includes two first flow channels, two second flow channels, and two sets of connecting flow channels;
[0019] The two first flow channels are respectively connected to the input terminal and the output terminal;
[0020] The two second flow channels are respectively connected to the two suction and push mechanisms;
[0021] One of the two second flow channels is connected to the two first flow channels through a connecting flow channel on the same side; the other of the two second flow channels is also connected to the two first flow channels through a connecting flow channel on the same side; two first one-way valves arranged in opposite directions are arranged on each set of connecting flow channels.
[0022] Furthermore, the suction and push mechanism includes a syringe, a holding structure, and a drive component;
[0023] The injection end of the syringe is connected to the fluid circuit reversing coordination integrated block;
[0024] The syringe is inserted into the holding structure, which is used to fix the syringe barrel. The driving member is connected to the syringe plunger and is used to drive the syringe piston to reciprocate within the syringe barrel.
[0025] Furthermore, the driving component includes a servo motor and a reciprocating lead screw connected to the servo motor;
[0026] The reciprocating lead screw is connected to the plunger of the syringe via a connecting plate, and the connecting plate moves reciprocally in a predetermined direction under the rotational power of the reciprocating lead screw.
[0027] Furthermore, a pressure sensor is provided inside the connecting plate, and the pressure sensor contacts the plunger of the syringe to detect the pressure inside the syringe barrel;
[0028] The controller is connected to the pressure sensor and the servo motor signal, and is used to adjust the operating frequency of the servo motor according to the pressure signal output by the pressure sensor.
[0029] Furthermore, the input end of each of the liquid circuit reversing coordination integrated blocks is connected to a container containing raw material liquid through its corresponding first pipeline;
[0030] Each of the first pipelines is equipped with several first bubble sensors;
[0031] The first bubble sensor on each of the first pipelines is connected to the controller via a signal. The controller controls the action of the corresponding suction and push mechanism based on the detection result of the first bubble sensor.
[0032] Furthermore, the output of each of the liquid circuit reversing coordination integrated blocks is connected to the microfluidic chip through a corresponding second pipeline. A second one-way valve is provided on the second pipeline to prevent cross-contamination.
[0033] Furthermore, it also includes a sample recovery tube, the inlet end of which is connected to the outlet end of the microfluidic chip, and the sample recovery tube is provided with a dilution phase inlet tube and a waste recovery tube in sequence along the liquid output direction;
[0034] The dilution phase inlet tube is used to dilute the raw material liquid mixture output by the microfluidic chip to form a nano-drug stock solution;
[0035] The dilution phase inlet pipe is sequentially equipped with several second bubble sensors and peristaltic pumps along the output direction;
[0036] Both the waste recycling tube and the sample recycling tube are equipped with control valves, and the control valves on the waste recycling tube and the sample recycling tube operate in a mutually exclusive manner.
[0037] Several second bubble sensors, the peristaltic pump, and the two control valves are all signal-connected to the controller, which controls the working state of the peristaltic pump and the two control valves based on the detection results of the second bubble sensors.
[0038] On the other hand, a nanomedicine preparation process is also proposed, including the following steps:
[0039] S1. Provide a nanomedicine preparation apparatus as described in the above embodiments;
[0040] S2. The controller of the nanomedicine preparation device controls the two suction and push mechanisms to operate alternately in opposite directions. During this process, through the fluid channel and one-way valve assembly built into the liquid circuit reversing coordination integrated block, the raw material liquid is continuously input from the container containing the raw material liquid into the liquid circuit reversing coordination integrated block under the suction and push action of the two suction and push mechanisms, and is output from the output end of the liquid circuit reversing coordination integrated block to the microfluidic chip.
[0041] S3. Different raw material liquids are mixed in the microchannels of the microfluidic chip to form a raw material liquid mixture, and the raw material liquid mixture is diluted to obtain a nano-drug stock solution;
[0042] S4. Transfer the prepared nanomedicine stock solution to the sample collection container.
[0043] Furthermore, the process by which the controller controls the two suction and push mechanisms to operate alternately in opposite directions includes:
[0044] S21. Start syringe A: Start one of the suction and push mechanisms, so that syringe A of the suction and push mechanism performs a pushing action;
[0045] S22. Collect thrust data of syringe A: Collect thrust data of syringe A in the constant speed range through the pressure sensor corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering.
[0046] S23. Pre-pressurize syringe B: Based on the working thrust P1 obtained in step S22, set the pressure target value W2' of the pressure sensor corresponding to syringe B of the other suction and push mechanism, and set the approximation speed according to the deviation algorithm so that the pressure inside the syringe B cylinder quickly approaches the pressure target value W2'; after reaching the pressure target value W2', set the initial speed parameter of syringe B according to the preset ratio of the constant speed segment speed.
[0047] S24. Reversal: When the push position of syringe A reaches the preset ratio of the target position, reversal begins. During this process, the speed parameters of syringe A and syringe B are updated in real time by the controller, so that the speed of syringe A decreases and the speed of syringe B increases, and the sum of their speeds is equal to the constant speed segment speed. When the speed of syringe A is 0 and the speed of syringe B is equal to the constant speed segment speed, the reversal is completed.
[0048] S25. Collect the thrust data of syringe B: Collect the thrust data of syringe B in the constant speed section through the pressure sensor corresponding to syringe B, and obtain the working thrust P2 of syringe B after filtering.
[0049] S26. Pre-compression of syringe A: Based on the working thrust P1 of syringe A, set the pressure target value W1 of the pressure sensor corresponding to syringe A, and set the approximation speed according to the deviation algorithm to make the pressure inside the syringe A quickly approach the pressure target value W1; after reaching the pressure target value W1, set the initial speed parameter of syringe A according to the preset ratio of the constant speed segment speed.
[0050] S27. Reversal: When the push position of syringe B reaches the preset ratio of the target position, reversal begins. During this process, the speed parameters of syringe A and syringe B are updated in real time by the controller, so that the speed of syringe A increases and the speed of syringe B decreases, and the sum of their speeds is equal to the constant speed segment speed. When the speed of syringe B is 0 and the speed of syringe A is equal to the constant speed segment speed, the reversal is completed.
[0051] S28. Collect the thrust data of syringe A: Collect the thrust data of syringe A in the constant speed section through the pressure sensor corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering.
[0052] S29. Pre-compression of syringe B: Based on the working thrust P2 obtained in step S25, set the pressure target value W2 of the pressure sensor corresponding to syringe B, and set the approximation speed according to the deviation algorithm so that the pressure inside the syringe B cylinder quickly approaches the pressure target value W2; after reaching the pressure target value W2, set the initial speed parameter of syringe B according to the preset ratio of the constant speed segment speed.
[0053] S30, repeat steps S24 to S29 until the nanomedicine preparation is complete.
[0054] Furthermore, the process by which the controller controls the two suction and push mechanisms to operate alternately in opposite directions includes:
[0055] S21. Start syringe A: Start one of the suction and push mechanisms, so that syringe A of the suction and push mechanism performs a pushing action;
[0056] S22. Collect thrust data of syringe A: Collect thrust data of syringe A in the constant speed range through the pressure sensor corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering.
[0057] S23. Pre-pressurize syringe B: Based on the working thrust P1 obtained in step S22, set the pressure target value W2' of the pressure sensor corresponding to syringe B of the other suction and push mechanism, and set the approximation speed according to the deviation algorithm so that the pressure inside the syringe B cylinder quickly approaches the pressure target value W2'; after reaching the pressure target value W2', set the initial speed parameter of syringe B according to the preset ratio of the constant speed segment speed.
[0058] S24. Reversal: When the push position of syringe A reaches the preset ratio of the target position, reversal begins. During this process, the speed parameters of syringe A and syringe B are updated in real time by the controller, so that the speed of syringe A decreases and the speed of syringe B increases, and the sum of their speeds is equal to the constant speed segment speed. When the speed of syringe A is 0 and the speed of syringe B is equal to the constant speed segment speed, the reversal is completed.
[0059] S25. Collect the thrust data of syringe B: Collect the thrust data of syringe B in the constant speed section through the pressure sensor corresponding to syringe B, and obtain the working thrust P2 of syringe B after filtering.
[0060] S26. Pre-pressurize syringe A: Based on the working thrust P1 obtained in step S22, set the pressure target value W1 of the pressure sensor corresponding to syringe A, and set the approximation speed according to the deviation algorithm to make the pressure inside the syringe A quickly approach the pressure target value W1; after reaching the pressure target value W1, set the initial speed parameter of syringe A according to the preset ratio of the constant speed segment speed.
[0061] S27. Reversal: When the push position of syringe B reaches the preset ratio of the target position, reversal begins. During this process, the speed parameters of syringe A and syringe B are updated in real time by the controller, so that the speed of syringe A increases and the speed of syringe B decreases, and the sum of their speeds is equal to the constant speed segment speed. When the speed of syringe B is 0 and the speed of syringe A is equal to the constant speed segment speed, the reversal is completed.
[0062] S28. Pre-compression of syringe B: Based on the working thrust P2 obtained in step S25, set the pressure target value W2 of the pressure sensor corresponding to syringe B, and set the approximation speed according to the deviation algorithm so that the pressure inside the syringe B cylinder quickly approaches the pressure target value W2; after reaching the pressure target value W2, set the initial speed parameter of syringe B according to the preset ratio of the constant speed segment speed.
[0063] S29. Reversal: When the push position of syringe A reaches the preset ratio of the target position, reversal begins. During this process, the speed parameters of syringe A and syringe B are updated in real time by the controller, so that the speed of syringe A decreases and the speed of syringe B increases, and the sum of their speeds is equal to the constant speed segment speed. When the speed of syringe A is 0 and the speed of syringe B is equal to the constant speed segment speed, the reversal is completed.
[0064] S30. Repeat steps S26 to S29 until the nanomedicine preparation is complete.
[0065] Furthermore, step S2 also includes: detecting bubbles in the corresponding pipelines using the first bubble sensor and the second bubble sensor respectively;
[0066] When the first bubble sensor detects a bubble, the controller controls the corresponding suction mechanism to stop the suction action and provides an alarm prompt.
[0067] When the second bubble sensor detects a bubble, the controller stops the peristaltic pump, closes the control valve on the sample recovery tube, and correspondingly opens the control valve on the waste recovery tube, providing an alarm notification.
[0068] Furthermore, step S2 also includes: detecting bubbles in the corresponding pipelines using the first bubble sensor and the second bubble sensor respectively;
[0069] When the first bubble sensor detects a bubble, it enters the first response state;
[0070] When the bubble information received by the first bubble sensor disappears, it enters the second response state. At this time, by switching the control valve at the back end, the nano-drug stock solution during the bubble-affected period is discharged into the waste recycling tube, and the nano-drug stock solution during the non-bubble-affected period is discharged into the sample recycling tube.
[0071] If the first bubble sensor continues to receive bubble information, it enters the third response state. At this time, the controller controls the corresponding suction and push mechanism to stop the suction action and gives an alarm prompt.
[0072] When the second bubble sensor receives a bubble signal, it enters the fourth response state;
[0073] When the bubble information received by the second bubble sensor disappears, it enters the fifth response state. At this time, by switching the control valve at the back end, the nano-drug stock solution during the bubble-affected period is discharged into the waste recycling tube, and the nano-drug stock solution during the non-bubble-affected period is discharged into the sample recycling tube.
[0074] If the second bubble sensor continues to receive bubble information, it enters the sixth response state. At this time, the controller controls the corresponding suction and push mechanism to stop the suction action, the peristaltic pump stops running, and an alarm is issued.
[0075] Furthermore, step S2 also includes: detecting bubbles in the same first pipeline using at least two first bubble sensors, and detecting bubbles in the same dilution phase inlet pipe using at least two second bubble sensors;
[0076] Once the first bubble sensor receives a bubble signal, it enters the first response state;
[0077] Once only one of the current first bubble sensor and the next first bubble sensor receives a bubble signal, the system enters the second response state.
[0078] After both the first bubble sensor and the next first bubble sensor receive bubble signals, the system enters the third response state.
[0079] Once the second bubble sensor receives a bubble signal, it enters the fourth response state;
[0080] Once only one of the current second bubble sensor and the next second bubble sensor receives a bubble signal, the system enters the fifth response state.
[0081] Once both the first and second bubble sensors receive bubble signals, the system enters the sixth response state.
[0082] Compared with the prior art, the present invention has at least the following beneficial effects:
[0083] By setting up a feeding device including a liquid path reversing coordination integrated block and two suction and push mechanisms, and connecting the input and output ends of the liquid path reversing coordination integrated block to the raw material liquid and the microfluidic chip respectively, and by having the two suction and push mechanisms operate alternately in opposite directions and configuring a one-way valve assembly within the liquid path reversing coordination integrated block, the two suction and push mechanisms, when operating alternately in opposite directions, can cooperate with the one-way valve assembly to ensure that only the raw material liquid input path connected to one suction and push mechanism and the raw material liquid output path connected to the other suction and push mechanism are always in a conductive state. This allows the two suction and push mechanisms to continuously input the raw material liquid into the liquid path reversing coordination integrated block or output it from the liquid path reversing coordination integrated block to the microfluidic chip during suction or push, without cross-flow of the raw material liquid within the liquid path reversing coordination integrated block. This achieves stable, continuous, and cross-flow-free delivery of the raw material liquid, ensuring the controllability of the nanomedicine preparation process within the microfluidic chip and improving the preparation effect. Attached Figure Description
[0084] Figure 1 This is a schematic diagram of the nanomedicine preparation device in Embodiment 1 of this utility model;
[0085] Figure 2 This is a schematic diagram of the nanomedicine preparation device from another perspective in Embodiment 1 of this utility model;
[0086] Figure 3 This is a schematic diagram of the process flow structure of the nanomedicine preparation device in Embodiment 1 of this utility model;
[0087] Figure 4 This is a schematic diagram of the liquid circuit reversing coordination integrated block of the nanomedicine preparation device in Embodiment 1 of this utility model;
[0088] Figure 5 This is a cross-sectional view of the liquid circuit reversing coordination integrated block of the nanomedicine preparation device in Embodiment 1 of this utility model;
[0089] Figure 6 This is a diagram showing the liquid flow direction within the liquid path reversal coordination integrated block when the syringe performs the aspiration action in the nanomedicine preparation device of this utility model (Embodiment 1).
[0090] Figure 7 This is a diagram showing the liquid flow direction within the liquid path reversal coordination integrated block when the syringe performs the pushing action in the nanomedicine preparation device of Embodiment 1 of this utility model.
[0091] Icon labels:
[0092] 1. Microfluidic chip;
[0093] 2. Hydraulic circuit reversing coordination integrated block; 21. Input end; 22. Output end; 23. First check valve;
[0094] 3. Suction and push mechanism; 31. Injector; 32. Drive component;
[0095] 4. Fluid channel; 41. First flow channel; 42. Second flow channel; 43. Connecting flow channel;
[0096] 5. Connecting plate;
[0097] 6. Pressure sensor;
[0098] 7. First pipeline;
[0099] 8. First bubble sensor;
[0100] 9. Second pipeline; 91. Second check valve;
[0101] 10. Dilution phase inlet pipe;
[0102] 11. Sample recovery tube;
[0103] 12. Waste recycling pipe;
[0104] 13. Second bubble sensor;
[0105] 14. Peristaltic pump;
[0106] 15. Control valve. Detailed Implementation
[0107] The nanomedicine preparation apparatus and process of this invention will be described in more detail below with reference to the schematic diagrams, which illustrate preferred embodiments of this invention. It should be understood that those skilled in the art can modify the invention described herein while still achieving its advantageous effects. Therefore, the following description should be understood as being of general knowledge to those skilled in the art and is not intended to limit this invention.
[0108] The present invention will be described in more detail below by way of example with reference to the accompanying drawings. The advantages and features of the present invention will become clearer from the following description. It should be noted that the drawings are in a very simplified form and use non-precise proportions, and are only used to facilitate and clarify the illustration of the embodiments of the present invention.
[0109] Example 1
[0110] like Figures 1 to 3 As shown in the figure, this utility model embodiment proposes a nanomedicine preparation device, including a microfluidic chip 1, at least two feeding devices and a controller.
[0111] At least two of the feeding devices are connected to the microfluidic chip 1 and are used for conveying different raw material liquids.
[0112] Each of the feeding devices includes a liquid path reversing coordination integrated block 2 and two suction and push mechanisms 3.
[0113] The liquid circuit reversing coordination integrated block 2 has an input end 21 and an output end 22, which are used for the input and output of the raw material liquid, respectively. That is, the liquid circuit reversing coordination integrated block 2 serves as an intermediate component, and the input and output of the raw material liquid are accomplished through the suction and push mechanism 3.
[0114] Specifically, both suction and push mechanisms 3 are connected to the liquid circuit reversing coordination integrated block 2. Each suction and push mechanism 3 realizes the input or output of raw material liquid by suction or push. The drive ends of both suction and push mechanisms 3 are connected to the controller, which controls the two suction and push mechanisms 3 to operate alternately in opposite directions. That is, the controller coordinates the operation of the two suction and push mechanisms 3 to achieve uninterrupted input and output of raw material liquid.
[0115] To better understand the above operating principle, an example is provided below:
[0116] For example, when one of the suction and pushing mechanisms 3 draws in the raw material liquid through the input terminal 21 of the liquid path reversing coordination integrated block 2, the other suction and pushing mechanism 3 pushes the raw material liquid towards the output terminal 22 of the liquid path reversing coordination integrated block 2. Conversely, when one suction and pushing mechanism 3 pushes the drawn-in raw material liquid towards the output terminal 22 of the liquid path reversing coordination integrated block 2, the other suction and pushing mechanism 3 draws in the raw material liquid through the input terminal 21 of the liquid path reversing coordination integrated block 2. In this way, raw material liquid continuously enters the liquid path reversing coordination integrated block 2 and continuously flows from the output terminal 22 of the liquid path reversing coordination integrated block 2 to the microfluidic chip 1, achieving uninterrupted input and output of the raw material liquid.
[0117] To prevent cross-contamination or interference in the input and output of raw material liquid during the reverse alternating operation of the two suction and push mechanisms 3, the liquid circuit reversing coordination integrated block 2 is further restricted to ensure stable, continuous, and cross-contamination-free transport of raw material liquid.
[0118] Specifically, the hydraulic circuit reversing coordination integrated block 2 has a built-in one-way valve assembly.
[0119] The one-way valve assembly is configured as follows:
[0120] When any of the suction and push mechanisms 3 performs a suction action, the input path from the input end 21 to the suction and push mechanism 3 is opened, and the output path from the output end 22 to the suction and push mechanism 3 is closed. This ensures that when one of the suction and push mechanisms 3 performs a suction action, the raw material can only enter the suction and push mechanism 3 through the input end 21.
[0121] When any of the suction and push mechanisms 3 performs a pushing action, the output terminal 22 is connected to the raw material liquid output path of the suction and push mechanism 3, and the input terminal 21 is closed to the raw material liquid input path of the suction and push mechanism 3. Therefore, when one of the suction and push mechanisms 3 performs a pushing action, the raw material liquid can only enter the output terminal 22 through that suction and push mechanism 3.
[0122] Therefore, through the coordinated operation of the one-way valve assembly and the two suction and push mechanisms 3 operating in opposite directions, this device can keep the input and output of the raw material liquid in a dynamic balance, thereby achieving stable, continuous and cross-contamination-free transport of the raw material liquid, ensuring the controllability of the nano-drug preparation process within the microfluidic chip 1, and achieving the goal of improving the preparation effect.
[0123] In this embodiment, a feeding device including a liquid path reversing coordination integrated block 2 and two suction and push mechanisms 3 is provided. The input end 21 and output end 22 of the liquid path reversing coordination integrated block 2 are connected to the raw material liquid and the microfluidic chip 1, respectively. The two suction and push mechanisms 3 are operated alternately in opposite directions, and a one-way valve assembly is configured in the liquid path reversing coordination integrated block 2. When the two suction and push mechanisms 3 are operated alternately in opposite directions, they can cooperate with the one-way valve assembly to ensure that only the raw material liquid input path connected to one suction and push mechanism 3 and the raw material liquid output path connected to the other suction and push mechanism 3 are always in a conductive state. This allows the two suction and push mechanisms 3 to continuously input the raw material liquid into the liquid path reversing coordination integrated block 2 or output it from the liquid path reversing coordination integrated block 2 to the microfluidic chip 1 when suctioning or pushing. The raw material liquid in the liquid path reversing coordination integrated block 2 will not crossflow, thereby achieving the function of stable, continuous and crossflow-free delivery of the raw material liquid. This ensures the controllability of the nanomedicine preparation process in the microfluidic chip 1 and achieves the purpose of improving the preparation effect.
[0124] like Figures 4 to 7 As shown, in this embodiment, the liquid circuit reversing coordination integrated block 2 is further defined to cooperate with the one-way valve assembly and the two suction and push mechanisms 3 to better improve the anti-cross-flow performance.
[0125] Specifically, the fluid circuit reversing coordination integrated block 2 has a built-in fluid channel 4, which connects the input end 21, the output end 22, and the two suction and push mechanisms 3. That is, by setting the fluid channel 4, a path is provided for the flow of the raw material liquid in the system, so that the raw material liquid can enter the fluid circuit reversing coordination integrated block 2 in an orderly manner from the input end 21 under the action of the suction and push mechanisms 3, and then flow out from the output end 22.
[0126] The one-way valve assembly includes multiple first one-way valves 23, which are all disposed in the fluid channel 4 to open or close the input and output paths of the raw material liquid, effectively preventing backflow or cross-contamination of the raw material liquid during the reverse alternating operation of the suction and push mechanism 3.
[0127] In this embodiment, the fluid channel 4 includes two first flow channels 41, two second flow channels 42, and two sets of connecting flow channels 43.
[0128] The two first flow channels 41 are respectively connected to the input end 21 and the output end 22, and the two second flow channels 42 are respectively connected to the two suction and push mechanisms 3.
[0129] One of the two second flow channels 42 is interconnected with the two first flow channels 41 via a connecting flow channel 43 on the same side; and the other of the two second flow channels 42 is also interconnected with the two first flow channels 41 via a connecting flow channel 43 on the same side. That is, by setting the connecting flow channel 43, the second flow channels 42 and the first flow channels 41 are connected together to form an input and output path for the raw material liquid. This allows the two suction and push mechanisms 3 to conveniently transfer the raw material liquid with the first flow channel 41 under different operating conditions, further improving the continuity and stability of the raw material liquid delivery. It also helps to balance the pressure within the flow channels, preventing pressure fluctuations from adversely affecting the nanomedicine preparation process.
[0130] It should be noted that each of the connected flow channels 43 has two first one-way valves 23 arranged in opposite directions, so that the two first one-way valves 23 can control the flow direction of the raw material liquid respectively under different working conditions of the suction and push mechanism 3.
[0131] For example, when a suction mechanism 3 performs a suction action (such as...) Figure 6 As shown), one of the first check valves 23 is open, allowing the raw material liquid to flow from the first flow channel 41 into the second flow channel 42 corresponding to the suction and push mechanism 3, thus completing the input of the raw material liquid. Meanwhile, the first check valve 23, which is set in the opposite direction to the first check valve 23, cuts off the output path.
[0132] When the suction and pushing mechanism 3 performs a pushing action (such as...) Figure 7 As shown), another first check valve 23 is turned on, allowing the raw material liquid to flow from the second flow channel 42 into the first flow channel 41 and out through the output end 22, thus completing the output of the raw material liquid. The first check valve 23, which is opposite to and reversed from the first check valve 23, cuts off the input path to prevent the raw material liquid from flowing back.
[0133] In other embodiments, a specific suction and push mechanism 3 is proposed to further improve the stability of the raw material liquid input and output process, thereby improving the mixing effect of the subsequent raw material liquid in the microfluidic chip 1 and improving the preparation quality of nanomedicine.
[0134] Specifically, the suction and push mechanism 3 includes a syringe 31, a holding structure, and a drive component 32.
[0135] The syringe 31 is connected to the liquid circuit reversing coordination integrated block 2 at its injection end, and is used to complete the input and output of raw material liquid by suction and push.
[0136] The syringe 31 is inserted into the holding structure, which is used to fix the barrel of the syringe 31. The driving member 32 is connected to the push handle of the syringe 31 and is used to drive the piston of the syringe 31 to reciprocate within the barrel of the syringe 31 to complete the functions of raw material liquid input and output.
[0137] In this embodiment, the drive unit 32 includes a servo motor and a reciprocating lead screw connected to the servo motor.
[0138] The reciprocating lead screw is connected to the push handle of the syringe 31 via a connecting plate 5, and the connecting plate 5 moves reciprocally in a predetermined direction under the rotational power of the reciprocating lead screw.
[0139] In addition, a pressure sensor 6 is provided inside the connecting plate 5. The pressure sensor 6 is in contact with the push handle of the syringe 31 and is used to detect the pressure inside the syringe 31.
[0140] The controller is connected to the pressure sensor 6 and the servo motor signal, and is used to adjust the operating frequency of the servo motor according to the pressure signal output by the pressure sensor 6.
[0141] This involves setting up a controller, pressure sensor 6, and servo motor to form an intelligent feedback control system. For example, by installing pressure sensor 6 inside the connecting plate 5 and making it contact with the plunger of syringe 31, it can monitor the pressure changes inside the syringe 31 in real time and convert these pressure data into electrical signals for output. When the controller receives the pressure signal from pressure sensor 6, it analyzes and processes the signal to drive the plunger of syringe 31 via a reciprocating screw, thereby controlling the piston's movement speed and force.
[0142] This device monitors and adjusts the pressure in real time to ensure that the pressure inside the syringe 31 remains within a suitable range during the aspiration and delivery of the raw material liquid. This avoids unstable delivery of the raw material liquid due to excessive pressure fluctuations, such as preventing excessively high pressure from causing the raw material liquid to spray too quickly or excessively low pressure from causing delivery interruption. This ensures a continuous and stable supply of raw material liquid to the microfluidic chip 1, guaranteeing the continuity of the nanomedicine preparation process.
[0143] In a specific example, when the pressure exceeds a set threshold, the controller will reduce the operating frequency of the servo motor, slowing down the piston's movement and reducing the pushing or sucking force; conversely, when the pressure is below the set threshold, the controller will increase the operating frequency of the servo motor, speeding up the piston's movement and increasing the pushing or sucking force.
[0144] In other embodiments, the fluid reversing coordination integrated block 2 is further defined. Specifically, the input terminal 21 of each fluid reversing coordination integrated block 2 is connected to a container holding the raw material liquid via a corresponding first pipeline 7.
[0145] Each of the first pipelines 7 is equipped with a plurality of first bubble sensors 8, and each first bubble sensor 8 on the first pipeline 7 is connected to the controller. The controller controls the action of the corresponding suction and push mechanism 3 according to the detection result of the first bubble sensor 8.
[0146] This device uses several first bubble sensors 8 installed on the first pipeline 7 to detect in stages whether the raw material liquid in the first pipeline 7 has been evacuated.
[0147] In a specific example, when all of the first bubble sensors 8 detect the presence of bubbles, the suction and pushing mechanism 3 is controlled to stop operating.
[0148] In a further embodiment, the output terminal 22 of each of the liquid circuit reversing coordination integrated blocks 2 is connected to the microfluidic chip 1 through its corresponding second pipeline 9, and a second one-way valve 91 is provided on the second pipeline 9. The second one-way valve 91 is used to prevent cross-contamination of the raw material liquid in multiple second pipelines 9 due to flow rate differences (such as when the flow rate of the raw material liquid in one second pipeline 9 is faster than that in another second pipeline 9).
[0149] In other embodiments, the nanomedicine preparation device further includes a sample recovery tube 11, the inlet end of which is connected to the outlet end of the microfluidic chip 1, and the sample recovery tube 11 is provided with a dilution phase inlet tube 10 and a waste product recovery tube 12 in sequence along the liquid output direction.
[0150] The dilution phase inlet pipe 10 is used to dilute the raw material liquid mixture output by the microfluidic chip 1 to form a nano-drug stock solution.
[0151] The diluent inlet pipe 10 is sequentially equipped with a plurality of second bubble sensors 13 and peristaltic pumps 14 along the output direction. The second bubble sensors 13 are used to monitor the diluent, i.e., to monitor whether the diluent has been evacuated, and the peristaltic pumps 14 are used to provide power for the input of the diluent.
[0152] Both the waste recovery tube 12 and the sample recovery tube 11 are equipped with control valves 15. The control valves 15 on the waste recovery tube 12 and the sample recovery tube 11 operate in a mutually exclusive manner. That is, when one control valve 15 is open, the other control valve 15 is closed, realizing the unidirectional outflow of the nano-drug stock solution, so as to complete the sample recovery of the nano-drug stock solution or the waste recovery of the raw material mixture, respectively.
[0153] Several second bubble sensors 13, the peristaltic pump 14, and the two control valves 15 are all connected to the controller. The controller controls the working state of the peristaltic pump 14 and the two control valves 15 according to the detection results of the second bubble sensors 13.
[0154] When the second bubble sensor 13 detects a bubble, it indicates that the diluent has been evacuated. At this time, the controller controls the peristaltic pump 14 to stop running, and at the same time opens the control valve 15 on the waste recovery tube 12 and closes the control valve 15 on the sample recovery tube 11 accordingly. This prevents the raw material liquid mixture from entering the sample recovery tube 11 and contaminating the obtained nano-drug stock solution, thereby ensuring product quality and classification and recycling efficiency.
[0155] Example 2
[0156] Based on Example 1, this embodiment also proposes a nanomedicine preparation process, including the following steps:
[0157] S1. Provide a nanomedicine preparation apparatus as described in the above embodiments;
[0158] S2. The controller of the nanomedicine preparation device controls the two suction and push mechanisms 3 to operate alternately in opposite directions. During this process, through the fluid channel 4 and one-way valve assembly built into the liquid circuit reversing coordination integrated block 2, the raw material liquid is continuously input from the container containing the raw material liquid into the liquid circuit reversing coordination integrated block 2 under the suction and push action of the two suction and push mechanisms 3, and is output from the output end 22 of the liquid circuit reversing coordination integrated block 2 to the microfluidic chip 1.
[0159] S3. Different raw material liquids are mixed in the microchannel of the microfluidic chip 1 to form a raw material liquid mixture, and the raw material liquid mixture is diluted to obtain a nano-drug stock solution;
[0160] S4. Transfer the prepared nanomedicine stock solution to the sample collection container.
[0161] Through the above steps, the two suction and push mechanisms 3 can continuously input the raw material liquid into the liquid path reversing coordination integrated block 2 or output it from the liquid path reversing coordination integrated block 2 to the microfluidic chip 1 when suctioning or pushing. The raw material liquid in the liquid path reversing coordination integrated block 2 will not crossflow, thereby realizing the function of stable, continuous and crossflow-free transport of raw material liquid, ensuring the controllability of the nanomedicine preparation process in the microfluidic chip 1, and achieving the purpose of improving the preparation effect.
[0162] In this embodiment, in order to further improve the performance of stable delivery of raw material liquid, the control method of the controller is further limited.
[0163] Specifically, the process by which the controller controls the two suction and push mechanisms 3 to operate alternately in opposite directions includes:
[0164] S21. Start syringe A: Start one of the suction and push mechanisms 3, so that syringe A of the suction and push mechanism 3 performs a pushing action;
[0165] S22. Collect the thrust data of syringe A: Collect the thrust data of syringe A in the constant speed section through the pressure sensor 6 corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering.
[0166] S23. Pre-pressurize syringe B: Based on the working thrust P1 obtained in step S22, set the pressure target value W2' of the pressure sensor 6 corresponding to syringe B of another suction and push mechanism 3, and set the approximation speed according to the deviation algorithm so that the pressure inside the syringe B cylinder quickly approaches the pressure target value W2'; after reaching the pressure target value W2', set the initial speed parameters of syringe B according to the preset ratio of the constant speed segment speed.
[0167] S24. Reversal: When the push position of syringe A reaches the preset ratio of the target position, reversal begins. During this process, the speed parameters of syringe A and syringe B are updated in real time by the controller, so that the speed of syringe A decreases and the speed of syringe B increases, and the sum of their speeds is equal to the constant speed segment speed. When the speed of syringe A is 0 and the speed of syringe B is equal to the constant speed segment speed, the reversal is completed.
[0168] S25. Collect the thrust data of syringe B: Collect the thrust data of syringe B in the constant speed section through the pressure sensor 6 corresponding to syringe B, and obtain the working thrust P2 of syringe B after filtering.
[0169] S26. Pre-pressurize syringe A: Based on the working thrust P1 of syringe A, set the pressure target value W1 of the pressure sensor 6 corresponding to syringe A, and set the approximation speed according to the deviation algorithm so that the pressure inside the syringe A cylinder quickly approaches the pressure target value W1; after reaching the pressure target value W1, set the initial speed parameter of syringe A according to the preset ratio of the constant speed segment speed.
[0170] In a specific example, once the pressure inside syringe A reaches the target value W1, the speed of syringe A is set to 7‰ of the constant speed range.
[0171] S27. Reversal: When the push position of syringe B reaches the preset ratio of the target position, reversal begins. During this process, the speed parameters of syringe A and syringe B are updated in real time by the controller, so that the speed of syringe A increases and the speed of syringe B decreases, and the sum of their speeds is equal to the constant speed segment speed. When the speed of syringe B is 0 and the speed of syringe A is equal to the constant speed segment speed, the reversal is completed.
[0172] S28. Collect the thrust data of syringe A: Collect the thrust data of syringe A in the constant speed section through the pressure sensor 6 corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering.
[0173] S29. Pre-compression of syringe B: Based on the working thrust P2 obtained in step S25, set the pressure target value W2 of the pressure sensor 6 corresponding to syringe B, and set the approximation speed according to the deviation algorithm so that the pressure inside the syringe B cylinder quickly approaches the pressure target value W2; after reaching the pressure target value W2, set the initial speed parameter of syringe B according to the preset ratio of the constant speed segment speed.
[0174] S30, repeat steps S24 to S29 until the nanomedicine preparation is complete.
[0175] This method achieves efficient collaborative work between the two suction and push mechanisms 3 through a triple mechanism of pressure pre-compression, speed compensation, and data feedback. This ensures the stability of the pressure and flow rate of the raw material liquid during the delivery process, providing a reliable liquid path control basis for nanomedicine preparation. Furthermore, by re-collecting the working thrust before each pre-compression, the influence of other factors (such as syringe stopper deformation) and complex situations on the pressure inside the syringe can be effectively eliminated, further ensuring the stability of the pressure and flow rate of the raw material liquid during the delivery process.
[0176] In other embodiments, another method of controller controlling the two suction and push mechanisms 3 is proposed. Compared with the above control method, this method can not only ensure the stability of the raw material liquid during the transportation process when the outlet pressure of the raw material liquid remains unchanged, but also simplify the control logic to reduce the amount of data processing, and correspondingly reduce the operating cost and maintenance difficulty of the equipment, so as to facilitate its promotion and application.
[0177] Specifically, the process by which the controller controls the two suction and push mechanisms 3 to operate alternately in opposite directions includes:
[0178] S21. Start syringe A: Start one of the suction and push mechanisms 3, so that syringe A of the suction and push mechanism 3 performs a pushing action;
[0179] S22. Collect the thrust data of syringe A: Collect the thrust data of syringe A in the constant speed section through the pressure sensor 6 corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering.
[0180] S23. Pre-pressurize syringe B: Based on the working thrust P1 obtained in step S22, set the pressure target value W2' of the pressure sensor 6 corresponding to syringe B of another suction and push mechanism 3, and set the approximation speed according to the deviation algorithm so that the pressure inside the syringe B cylinder quickly approaches the pressure target value W2'; after reaching the pressure target value W2', set the initial speed parameters of syringe B according to the preset ratio of the constant speed segment speed.
[0181] S24. Reversal: When the push position of syringe A reaches the preset ratio of the target position, reversal begins. During this process, the speed parameters of syringe A and syringe B are updated in real time by the controller, so that the speed of syringe A decreases and the speed of syringe B increases, and the sum of their speeds is equal to the constant speed segment speed. When the speed of syringe A is 0 and the speed of syringe B is equal to the constant speed segment speed, the reversal is completed.
[0182] S25. Collect the thrust data of syringe B: Collect the thrust data of syringe B in the constant speed section through the pressure sensor 6 corresponding to syringe B, and obtain the working thrust P2 of syringe B after filtering.
[0183] S26. Pre-pressurize syringe A: Based on the working thrust P1 obtained in step S22, set the pressure target value W1 of the pressure sensor 6 corresponding to syringe A, and set the approximation speed according to the deviation algorithm so that the pressure inside the syringe A cylinder quickly approaches the pressure target value W1; after reaching the pressure target value W1, set the initial speed parameter of syringe A according to the preset ratio of the constant speed segment speed.
[0184] S27. Reversal: When the push position of syringe B reaches the preset ratio of the target position, reversal begins. During this process, the speed parameters of syringe A and syringe B are updated in real time by the controller, so that the speed of syringe A increases and the speed of syringe B decreases, and the sum of their speeds is equal to the constant speed segment speed. When the speed of syringe B is 0 and the speed of syringe A is equal to the constant speed segment speed, the reversal is completed.
[0185] S28. Pre-compression of syringe B: Based on the working thrust P2 obtained in step S25, set the pressure target value W2 of the pressure sensor 6 corresponding to syringe B, and set the approximation speed according to the deviation algorithm so that the pressure inside the syringe B cylinder quickly approaches the pressure target value W2; after reaching the pressure target value W2, set the initial speed parameter of syringe B according to the preset ratio of the constant speed segment speed.
[0186] S29. Reversal: When the push position of syringe A reaches the preset ratio of the target position, reversal begins. During this process, the speed parameters of syringe A and syringe B are updated in real time by the controller, so that the speed of syringe A decreases and the speed of syringe B increases, and the sum of their speeds is equal to the constant speed segment speed. When the speed of syringe A is 0 and the speed of syringe B is equal to the constant speed segment speed, the reversal is completed.
[0187] S30. Repeat steps S26 to S29 until the nanomedicine preparation is complete.
[0188] This method, by setting a fixed pre-compression benchmark (i.e., always based on the initial thrust data of syringe A) and simplifying the control process (i.e. skipping some reversal data acquisition steps), can reduce system switching impact, reduce mechanical wear and data processing load compared to the above method of re-acquiring the working thrust before each pre-compression, thereby achieving the goals of improving preparation efficiency, extending equipment life, reducing costs and simplifying maintenance.
[0189] In a further embodiment, step S2 is further defined.
[0190] Specifically, step S2 further includes: detecting bubbles in the corresponding pipelines by using the first bubble sensor 8 and the second bubble sensor 13 respectively;
[0191] When the first bubble sensor 8 detects a bubble, the controller controls the corresponding suction and push mechanism 3 to stop the suction action and gives an alarm prompt, thereby preventing bubbles from entering the liquid circuit system with the raw material liquid and achieving the purpose of ensuring the stability and purity of the raw material liquid transportation.
[0192] When the second bubble sensor 13 detects bubbles, the controller controls the peristaltic pump 14 to stop running, closes the control valve 15 located on the sample recovery tube 11, and correspondingly opens the control valve 15 located on the waste recovery tube 12, giving an alarm prompt to prevent the raw material liquid mixture from entering the sample recovery tube 11 and contaminating the obtained nano-drug raw liquid, thereby achieving the purpose of ensuring product quality and classification and recycling efficiency.
[0193] In addition, step S2 also includes: detecting bubbles in the corresponding pipelines by using the first bubble sensor 8 and the second bubble sensor 13 respectively;
[0194] When the first bubble sensor 8 detects a bubble, it enters the first response state;
[0195] When the bubble information received by the first bubble sensor 8 disappears, it enters the second response state. At this time, by switching the control valve 15 at the back end, the nano-drug stock solution during the bubble-affected period is discharged into the waste recycling tube 12, and the nano-drug stock solution during the non-bubble-affected period is discharged into the sample recycling tube 11.
[0196] If the first bubble sensor 8 continues to receive bubble information, it enters the third response state. At this time, the controller controls the corresponding suction and push mechanism 3 to stop the suction action and gives an alarm prompt.
[0197] When the second bubble sensor 13 receives a bubble signal, it enters the fourth response state;
[0198] When the bubble information received by the second bubble sensor 13 disappears, it enters the fifth response state. At this time, by switching the control valve 15 at the back end, the nano-drug stock solution during the bubble-affected period is discharged into the waste recycling tube 12, and the nano-drug stock solution during the non-bubble-affected period is discharged into the sample recycling tube 11.
[0199] If the second bubble sensor 13 continues to receive bubble information, it enters the sixth response state. At this time, the controller controls the corresponding suction and push mechanism 3 to stop the suction action, the peristaltic pump 14 stops running, and an alarm prompt is given.
[0200] This method uses a first bubble sensor 8 and a second bubble sensor 13 to detect bubbles in the corresponding pipelines in real time. When the first bubble sensor 8 detects a bubble, it enters a first response state. After the bubble information disappears, it enters a second response state and switches the back-end control valve 15 to discharge the nano-drug stock solution during the bubble-affected period to the waste recovery pipe 12 and the solution during the non-bubble-affected period to the sample recovery pipe 11. If the bubble information persists, it enters a third response state and controls the corresponding suction and push mechanism 3 to stop the suction action and triggers an alarm. When the second bubble sensor 13 detects a bubble, it enters a fourth response state. After the bubble information disappears, it enters a fifth response state and similarly switches the control valve 15 for classified discharge. If the bubble information persists, it enters a sixth response state and controls the corresponding suction and push mechanism 3 to stop the suction action, the peristaltic pump 14 to stop running, and triggers an alarm. This allows for accurate differentiation and processing of liquids containing and without bubbles, achieving the goal of minimizing the scrap rate, ensuring product quality stability, and ensuring safe equipment operation.
[0201] In addition, step S2 also includes: detecting bubbles in the same first pipeline 7 by at least two first bubble sensors 8, and detecting bubbles in the same dilution phase inlet pipeline 10 by at least two second bubble sensors 13;
[0202] When the first bubble sensor 8 receives a bubble signal, it enters the first response state;
[0203] Once only one of the current first bubble sensor 8 and the next first bubble sensor 8 receives a bubble signal, the system enters the second response state.
[0204] After both the first bubble sensor 8 and the next first bubble sensor 8 receive bubble signals, the system enters the third response state.
[0205] After the first second bubble sensor 13 receives a bubble signal, it enters the fourth response state;
[0206] Once only one of the current second bubble sensor 13 and the next second bubble sensor 13 receives a bubble signal, the system enters the fifth response state.
[0207] Once both the first and second bubble sensors 13 receive bubble signals, the system enters the sixth response state.
[0208] That is, by setting at least two first bubble sensors 8 and at least two second bubble sensors 13, respectively, bubble warning and bubble detection are used. When both first bubble sensors 8 or both second bubble sensors 13 receive bubble signals, the corresponding equipment (i.e., drive unit 32 and peristaltic pump 14) is controlled to stop running.
[0209] This method detects bubbles by setting at least two first bubble sensors 8 in the same first pipeline 7 and at least two second bubble sensors 13 in the same dilution phase inlet pipeline 10. Based on the bubble signals received by different sensors, the method enters the corresponding response state, thereby enabling more accurate judgment of the distribution, quantity and dynamic changes of bubbles in the pipeline. This achieves timely and targeted handling of bubble problems, ensuring the quality of raw material liquid delivery and the effectiveness of nanomedicine preparation.
[0210] Obviously, those skilled in the art can make various modifications and variations to this utility model without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this utility model and their equivalents, this utility model also intends to include these modifications and variations.
Claims
1. A nanomedicine preparation device, characterized in that, Includes a microfluidic chip (1), at least two feeding devices, and a controller; At least two of the feeding devices are connected to the microfluidic chip (1) and are used for conveying different raw material liquids respectively; Each of the feeding devices includes a liquid path reversing coordination integrated block (2) and two suction and push mechanisms (3); The liquid circuit reversing coordination integrated block (2) has an input terminal (21) and an output terminal (22), which are used for the input and output of raw material liquid, respectively; Both suction and push mechanisms (3) are connected to the fluid channel of the liquid circuit reversing coordination integrated block (2). Each suction and push mechanism (3) realizes the input or output of raw material liquid by suction or push. The driving end of both suction and push mechanisms (3) is connected to the controller signal. The controller is used to control the two suction and push mechanisms (3) to run alternately in opposite directions. The suction and push mechanism (3) includes a syringe (31) and a drive (32). The injection end of the syringe (31) is connected to the liquid circuit reversing coordination integrated block (2), and the driving member (32) is connected to the push handle of the syringe (31) to drive the piston of the syringe (31) to reciprocate within the syringe (31). The fluid circuit reversing coordination integrated block (2) has a built-in one-way valve assembly; The one-way valve assembly is configured as follows: When any of the suction and push mechanisms (3) performs a suction action, the input end (21) to the raw material liquid input path of the suction and push mechanism (3) is opened, and the output end (22) to the raw material liquid output path of the suction and push mechanism (3) is closed; When any of the suction and push mechanisms (3) performs a pushing action, the output end (22) is connected to the raw material liquid output path of the suction and push mechanism (3), and the input end (21) is cut off to the raw material liquid input path of the suction and push mechanism (3); The fluid circuit reversing coordination integrated block (2) has a built-in fluid channel (4), which is used to connect the input end (21), the output end (22) and the two suction and push mechanisms (3). The fluid channel (4) includes two first channels (41), two second channels (42), and two sets of connecting channels (43).
2. The nanomedicine preparation apparatus as described in claim 1, characterized in that, The one-way valve assembly includes a plurality of first one-way valves (23), all of which are disposed in the fluid channel (4).
3. The nanomedicine preparation apparatus as described in claim 2, characterized in that, The two first flow channels (41) are respectively connected to the input end (21) and the output end (22); The two second flow channels (42) are respectively connected to the two suction and push mechanisms (3); One of the two second flow channels (42) is connected to the two first flow channels (41) through the connecting flow channel (43) on the same side; the other of the two second flow channels (42) is also connected to the two first flow channels (41) through the connecting flow channel (43) on the same side; two first check valves (23) arranged in opposite directions are arranged on each set of the connecting flow channels (43).
4. The nanomedicine preparation apparatus as described in claim 1, characterized in that, The suction and push mechanism (3) also includes a holding structure; The syringe (31) is inserted into the holding structure, which is used to fix the barrel of the syringe (31).
5. The nanomedicine preparation apparatus as described in claim 4, characterized in that, The drive unit (32) includes a servo motor and a reciprocating lead screw connected to the servo motor; The reciprocating screw is connected to the push handle of the syringe (31) via a connecting plate (5), and the connecting plate (5) moves reciprocally in a predetermined direction under the rotational power of the reciprocating screw.
6. The nanomedicine preparation apparatus as described in claim 5, characterized in that, The connecting plate (5) is provided with a pressure sensor (6), which is in contact with the push handle of the syringe (31) and is used to detect the pressure inside the syringe (31). The controller is connected to the pressure sensor (6) and the servo motor signal, and is used to adjust the operating frequency of the servo motor according to the pressure signal output by the pressure sensor (6).
7. The nanomedicine preparation apparatus as described in claim 1, characterized in that, The input end (21) of each of the liquid circuit reversing coordination integrated blocks (2) is connected to the container containing the raw material liquid through its corresponding first pipeline (7); Each of the first pipelines (7) is equipped with several first bubble sensors (8); The first bubble sensor (8) on each of the first pipelines (7) is connected to the controller. The controller controls the action of the corresponding suction and push mechanism (3) according to the detection result of the first bubble sensor (8).
8. The nanomedicine preparation apparatus as described in claim 1, characterized in that, The output end (22) of each of the liquid circuit reversing coordination integrated blocks (2) is connected to the microfluidic chip (1) through its corresponding second pipeline (9). A second one-way valve (91) is provided on the second pipeline (9) to prevent cross-contamination of liquid.
9. The nanomedicine preparation apparatus as described in claim 1, characterized in that, It also includes a sample recovery tube (11), the inlet end of which is connected to the outlet end of the microfluidic chip (1), and the sample recovery tube (11) is provided with a dilution phase inlet tube (10) and a waste recovery tube (12) in sequence along the liquid output direction. The dilution phase inlet tube (10) is used to dilute the raw material liquid mixture output by the microfluidic chip (1) to form a nano-drug stock solution; The dilution phase inlet pipe (10) is provided with several second bubble sensors (13) and peristaltic pumps (14) in sequence along the output direction. Both the waste recycling tube (12) and the sample recycling tube (11) are equipped with control valves (15), and the control valves (15) on the waste recycling tube (12) and the sample recycling tube (11) are in a mutually exclusive working state. Several second bubble sensors (13), the peristaltic pump (14) and the two control valves (15) are all connected to the controller. The controller controls the working state of the peristaltic pump (14) and the two control valves (15) according to the detection results of the second bubble sensors (13).