A nano drug preparation system and preparation process

Abstract

The present invention discloses a nano drug preparation system and preparation process, including a microfluidic chip, at least two feeding devices and a controller; the two feeding devices are both connected to the microfluidic chip and are respectively used to transport different raw material liquids; each feeding device includes a liquid path reversing coordination integrated block and two suction and push mechanisms; the liquid path reversing coordination integrated block has an input end and an output end; the two suction and push mechanisms are both connected to the fluid channel of the liquid path reversing coordination integrated block, each suction and push mechanism realizes the input or output of the raw material liquid by suction or pushing, the driving ends of the two suction and push mechanisms are both connected to the controller signal, and the controller is used to control the two suction and push mechanisms to operate in reverse and alternating directions; the liquid path reversing coordination integrated block is built with a one-way valve assembly. Through the above-mentioned arrangement, the present invention realizes the function of stable, continuous and non-cross-liquid delivery of the raw material liquid, ensures the controllability of the nano drug preparation process in the microfluidic chip, and achieves the purpose of improving the preparation effect.

Description

Technical Field

[0001] The present invention relates to the field of nano drug preparation, and in particular to a nano drug preparation system and preparation process. Background Art

[0002] Nanomedicine preparation technology achieves size-controlled synthesis of nanoparticles by precisely controlling the mixing and reaction processes of raw material solutions, and has important applications in targeted drug delivery and sustained-release formulations. As the core reaction unit, microfluidic chips rely on the continuous input of stable multi-component raw material solutions to ensure the uniformity and yield of nanomedicines. However, the feeding devices of existing preparation systems have the following drawbacks during the raw material solution delivery process:

[0003] First, existing feeding devices often use a single suction or push mechanism (such as a single syringe or pump). This requires stopping and reversing after completing a single suction or push action, resulting in discontinuous feedstock delivery. This intermittent liquid supply can cause pressure fluctuations in the flow channels within the microfluidic chip, affecting the mixing ratio accuracy of the multi-component feedstocks. This can lead to uneven nanoparticle size distribution and even cause flow channel blockage or uncontrolled reactions. Especially for industrial preparation scenarios that require long-term stable operation, fluid interruption during single-mechanism reversal significantly reduces production efficiency and product quality consistency.

[0004] Second, existing fluid reversing devices often rely on external valves or complex piping switching structures, with controllers directly controlling the opening and closing of valves to achieve fluid direction conversion. However, these solutions suffer from issues such as delayed response and poor sealing performance. This can easily lead to fluid backflow or cross-contamination of different raw material liquids during the pumping and pushing process, disrupting the raw material ratio and introducing impurities. For example, if a one-way valve fails or the valve switching is out of sync, the high-pressure raw material liquid at the output end may flow back into the input end, causing raw material contamination or preparation system failure.

[0005] Therefore, a nanomedicine preparation system and preparation process are needed to solve the above problems. Summary of the Invention

[0006] The purpose of the present invention is to provide a nanomedicine preparation system and preparation process to achieve the functions of stable, continuous and cross-liquid transport of raw material liquid, ensure the controllability of the nanomedicine preparation process in the microfluidic chip, and achieve the purpose of improving the preparation effect.

[0007] To solve the above technical problems, the present invention provides a nanomedicine preparation system, comprising 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 respectively used for conveying different raw material liquids;

[0009] Each of the feeding devices includes a liquid path reversing coordination integrated block and two suction and pushing mechanisms;

[0010] The liquid path reversing coordination integrated block has an input end and an output end, which are used for input and output of raw material liquid respectively;

[0011] The two suction and push mechanisms are both connected to the fluid channel of the liquid path reversing coordination integrated block, and each of the suction and push mechanisms realizes the input or output of the raw material liquid by suction or pushing. The driving ends of the two suction and push mechanisms are both connected to the controller signal, and the controller is used to control the two suction and push mechanisms to operate alternately in opposite directions;

[0012] The fluid path reversing coordination integrated block has a built-in one-way valve assembly;

[0013] The one-way valve assembly is configured as follows:

[0014] When any of the suction-push mechanisms performs a suction action, the raw material liquid input path from the input end to the suction-push mechanism is connected, and the raw material liquid output path from the output end to the suction-push mechanism is cut off;

[0015] When any of the suction-push mechanisms performs a pushing action, the raw material liquid output path from the output end to the suction-push mechanism is connected, and the raw material liquid input path from the input end to the suction-push mechanism is cut off.

[0016] Furthermore, the fluid path reversing coordination integrated block has a built-in fluid channel, and the fluid channel 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, and the plurality of first one-way valves are all arranged in the fluid channel.

[0018] Furthermore, the fluid channel includes two first flow channels, two second flow channels and two groups of connecting flow channels;

[0019] The two first flow channels are respectively connected to the input end and the output end;

[0020] The two second flow channels are respectively connected to the two suction-push mechanisms;

[0021] Among them, one of the two second flow channels is interconnected with the two first flow channels through the connecting flow channel on the same side thereof; the other of the two second flow channels is also interconnected with the two first flow channels through the connecting flow channel on the same side thereof; and each group of the connecting flow channels is arranged with two first one-way valves set in opposite directions.

[0022] Furthermore, the suction-push mechanism includes a syringe, a holding structure and a driving member;

[0023] The injection end of the syringe is connected to the fluid path reversing coordination integrated block;

[0024] The syringe is inserted into the holding structure, which is used to fix the barrel of the syringe. The driving member is connected to the push handle of the syringe and is used to drive the piston of the syringe to move back and forth in the barrel of the syringe.

[0025] Furthermore, the driving member includes a servo motor and a reciprocating screw connected to the servo motor;

[0026] The reciprocating screw is connected to the push handle of the syringe through a connecting plate, and the connecting plate moves back and forth along a predetermined direction under the rotational power of the reciprocating screw.

[0027] Furthermore, a pressure sensor is provided in the connecting plate, and the pressure sensor contacts the push handle of the syringe and is used to detect the pressure in the barrel of the syringe;

[0028] The controller is signal-connected to the pressure sensor and the servo motor, and is configured 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 path reversing coordination integrated blocks is connected to a container loaded with the raw material liquid through a corresponding first pipeline;

[0030] Each of the first pipelines is provided with a plurality of first bubble sensors;

[0031] The first bubble sensor on each of the first pipelines is connected to the controller signal, and the controller controls the action of the corresponding suction and push mechanism according to the detection result of the first bubble sensor.

[0032] Furthermore, the output end of each of the liquid path reversing coordination integrated blocks is connected to the microfluidic chip via a corresponding second pipeline, and a second one-way valve is provided on the second pipeline to prevent liquid cross-contamination.

[0033] Furthermore, it also includes a sample recovery tube, the liquid inlet end of the sample recovery tube is connected to the outlet end of the microfluidic chip, and the sample recovery tube is sequentially provided with a dilution phase liquid inlet tube and a waste recovery tube along the liquid output direction;

[0034] The dilution phase liquid inlet tube is used to dilute the raw liquid mixture output by the microfluidic chip to form a nano drug stock solution;

[0035] The dilution phase liquid inlet pipe is sequentially provided with a plurality of second bubble sensors and peristaltic pumps along the output direction;

[0036] The waste recovery tube and the sample recovery tube are both provided with a control valve, and the control valve on the waste recovery tube and the control valve on the sample recovery tube are in a mutually exclusive working state;

[0037] A plurality of the second bubble sensors, the peristaltic pump and the two control valves are all connected to the controller by signal. The controller controls the working states of the peristaltic pump and the two control valves according to the detection results of the second bubble sensors.

[0038] On the other hand, a nanomedicine preparation process is also proposed, comprising the following steps:

[0039] S1. Providing the nanomedicine preparation system as described in the above embodiment;

[0040] S2. The controller of the nanomedicine preparation system controls the two suction and push mechanisms to operate alternately in opposite directions. During this process, the raw material liquid is continuously input from the container loaded with the raw material liquid into the liquid path reversing coordination integrated block under the action of suction and push by the two suction and push mechanisms, and is output from the output end of the liquid path reversing coordination integrated block to the microfluidic chip;

[0041] S3, mixing different raw material solutions in the microchannel of the microfluidic chip to form a raw material solution mixture, and diluting the raw material solution mixture to obtain a nano drug stock solution;

[0042] S4. The prepared nanomedicine stock solution is transported to a sample collection container.

[0043] Furthermore, the process of the controller controlling the two suction and push mechanisms to operate alternately in opposite directions includes:

[0044] S21, start syringe A: start one of the suction-push mechanisms, so that syringe A of the suction-push mechanism performs a pushing action;

[0045] S22, collecting the thrust data of syringe A: collecting the thrust data of syringe A in the uniform speed section through the pressure sensor corresponding to syringe A, and obtaining 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 target pressure value W2' of the pressure sensor corresponding to syringe B of the other suction-push mechanism, and set the approach speed according to the deviation algorithm so that the pressure in the barrel of syringe B quickly approaches the target pressure value W2'. After reaching the target pressure value W2', set the initial speed parameter of syringe B according to the preset ratio of the uniform speed segment.

[0047] S24, reversing: When the push position of syringe A reaches a preset ratio of the target position, reversing 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 the speeds of the two is kept equal to the uniform speed section. When the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section, reversing is completed.

[0048] S25, collecting the thrust data of syringe B: collecting the thrust data of syringe B in the uniform speed section through the pressure sensor corresponding to syringe B, and obtaining the working thrust P2 of syringe B after filtering;

[0049] S26. Pre-pressurize syringe A: Set a target pressure value W1 for the pressure sensor corresponding to syringe A based on the working thrust P1 of syringe A, and set an approach speed based on a deviation algorithm so that the pressure inside the barrel of syringe A quickly approaches the target pressure value W1. After reaching the target pressure value W1, set the initial speed parameter of syringe A based on a preset ratio of the uniform speed segment.

[0050] S27, reversing: When the push position of syringe B reaches a preset ratio of the target position, reversing begins. During this process, the speed parameters of syringes A and 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 the speeds of the two is maintained equal to the uniform speed section. When the speed of syringe B is 0 and the speed of syringe A is equal to the uniform speed section, reversing is completed.

[0051] S28. Collecting thrust data of syringe A: The thrust data of syringe A in the uniform speed section is collected by the pressure sensor corresponding to syringe A, and the working thrust P1 of syringe A is obtained after filtering.

[0052] S29. Pre-pressurize syringe B: Based on the working thrust P2 obtained in step S25, set the target pressure value W2 of the pressure sensor corresponding to syringe B, and set the approach speed according to the deviation algorithm so that the pressure in the barrel of syringe B quickly approaches the target pressure value W2. After reaching the target pressure value W2, set the initial speed parameter of syringe B according to the preset ratio of the uniform speed section.

[0053] S30, repeat steps S24 to S29 until the nanomedicine preparation is completed.

[0054] Furthermore, the process of the controller controlling the two suction and push mechanisms to operate alternately in opposite directions includes:

[0055] S21, start syringe A: start one of the suction-push mechanisms, so that syringe A of the suction-push mechanism performs a pushing action;

[0056] S22, collecting the thrust data of syringe A: collecting the thrust data of syringe A in the uniform speed section through the pressure sensor corresponding to syringe A, and obtaining 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 target pressure value W2' of the pressure sensor corresponding to syringe B of the other suction-push mechanism, and set the approach speed according to the deviation algorithm so that the pressure in the barrel of syringe B quickly approaches the target pressure value W2'. After reaching the target pressure value W2', set the initial speed parameter of syringe B according to the preset ratio of the uniform speed segment.

[0058] S24, reversing: When the push position of syringe A reaches a preset ratio of the target position, reversing 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 the speeds of the two is kept equal to the uniform speed section. When the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section, reversing is completed.

[0059] S25, collecting the thrust data of syringe B: collecting the thrust data of syringe B in the uniform speed section through the pressure sensor corresponding to syringe B, and obtaining 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 target pressure value W1 of the pressure sensor corresponding to syringe A, and set the approach speed according to the deviation algorithm so that the pressure in the barrel of syringe A quickly approaches the target pressure value W1. After reaching the target pressure value W1, set the initial speed parameter of syringe A according to the preset ratio of the uniform speed section.

[0061] S27, reversing: When the push position of syringe B reaches a preset ratio of the target position, reversing begins. During this process, the speed parameters of syringes A and 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 the speeds of the two is maintained equal to the uniform speed section. When the speed of syringe B is 0 and the speed of syringe A is equal to the uniform speed section, reversing is completed.

[0062] S28. Pre-pressurize syringe B: Based on the working thrust P2 obtained in step S25, set the target pressure value W2 of the pressure sensor corresponding to syringe B, and set the approach speed according to the deviation algorithm so that the pressure in the barrel of syringe B quickly approaches the target pressure value W2; after reaching the target pressure value W2, set the initial speed parameter of syringe B according to the preset ratio of the uniform speed section;

[0063] S29, reversing: When the push position of syringe A reaches a preset ratio of the target position, reversing 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 the speeds of the two is kept equal to the uniform speed section. When the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section, reversing is completed.

[0064] S30, repeat steps S26 to S29 until the nanomedicine preparation is completed.

[0065] Furthermore, in step S2, the method further includes: detecting bubbles in corresponding pipelines respectively by using a first bubble sensor and a second bubble sensor;

[0066] When the first bubble sensor detects bubbles, the controller controls the corresponding suction and push mechanism to stop the suction action and gives an alarm prompt;

[0067] When the second bubble sensor detects bubbles, the controller controls the peristaltic pump to stop running, closes the control valve on the sample recovery tube, and correspondingly opens the control valve on the waste recovery tube, giving an alarm prompt.

[0068] Furthermore, in step S2, the method further includes: detecting bubbles in corresponding pipelines respectively by using a first bubble sensor and a second bubble sensor;

[0069] When the first bubble sensor detects bubbles, it enters a first response state;

[0070] When the bubble information received by the first bubble sensor disappears, the second response state is entered. At this time, the nanomedicine stock solution in the bubble-affected time period is discharged into the waste recovery tube by switching the control valve at the rear end, and the nanomedicine stock solution in the non-bubble-affected time period is discharged into the sample recovery tube;

[0071] If the first bubble sensor continues to receive bubble information, it enters a third response state, at which 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 the bubble signal, it enters a fourth response state;

[0073] When the bubble information received by the second bubble sensor disappears, the system enters a fifth response state. At this time, the control valve at the rear end is switched to discharge the nanomedicine stock solution in the bubble-affected time period into the waste recovery tube, and the nanomedicine stock solution in the non-bubble-affected time period into the sample recovery 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, and the peristaltic pump stops running, and gives an alarm prompt.

[0075] Furthermore, in step S2, the method further includes: detecting bubbles in the same first pipeline by at least two first bubble sensors, and detecting bubbles in the same dilution phase liquid inlet pipe by at least two second bubble sensors;

[0076] When the first bubble sensor receives the bubble signal, it enters the first response state;

[0077] When only one of the first bubble sensor and the second bubble sensor receives the bubble signal, the sensor enters the second response state;

[0078] After the first bubble sensor and the second bubble sensor both receive the bubble signal, the third response state is entered;

[0079] When the second bubble sensor receives the bubble signal, it enters the fourth response state;

[0080] When only one of the first second bubble sensor and the second second bubble sensor receives the bubble signal, the fifth response state is entered;

[0081] After both the previous second bubble sensor and the next second bubble sensor receive the bubble signal, the sixth response state is entered.

[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 circuit reversing coordination integrated block and two suction and push mechanisms, and making the input end and output end of the liquid circuit reversing coordination integrated block connected to the raw material liquid and the microfluidic chip respectively, and making the two suction and push mechanisms operate in reverse alternation and configuring a one-way valve assembly in the liquid circuit reversing coordination integrated block, the two suction and push mechanisms can cooperate with the one-way valve assembly when operating in reverse alternation, so that there is always only the raw material liquid input path connected to one of the suction and push mechanisms and the raw material liquid output path connected to the other suction and push mechanism in a conductive state, so that the two suction and push mechanisms can continuously input the raw material liquid into the liquid circuit reversing coordination integrated block or output it from the liquid circuit reversing coordination integrated block to the microfluidic chip when sucking or pushing, and the raw material liquid in the liquid circuit reversing coordination integrated block will not have cross-flow, thereby realizing the function of stable, continuous and cross-flow-free delivery of the raw material liquid, ensuring the controllability of the nanomedicine preparation process in the microfluidic chip, and achieving the purpose of improving the preparation effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0084] Figure 1 Schematic diagram of the structure of the nano drug preparation system in Example 1 of the present invention;

[0085] Figure 2 This is a schematic structural diagram from another perspective of the nanomedicine preparation system in Example 1 of the present invention;

[0086] Figure 3 This is a schematic diagram of the process structure of the nanomedicine preparation system in Example 1 of the present invention;

[0087] Figure 4 This is a schematic structural diagram of a fluid path reversing coordination integrated block of a nanomedicine preparation system in Example 1 of the present invention;

[0088] Figure 5 Schematic diagram of the cross-sectional structure of the liquid path reversing coordination integrated block of the nano-drug preparation system in Example 1 of the present invention;

[0089] Figure 6 This is a diagram of the liquid flow direction in the liquid path reversing coordination integrated block when the syringe in the nanomedicine preparation system in Example 1 of the present invention performs a suction action;

[0090] Figure 7 This is a diagram of the liquid flow direction in the liquid path reversing coordination integrated block when the syringe performs a pushing action in the nanomedicine preparation system in Example 1 of the present invention.

[0091] Figure Number:

[0092] 1. Microfluidic chip;

[0093] 2. Liquid path reversing coordination integrated block; 21. Input end; 22. Output end; 23. First one-way valve;

[0094] 3. Suction and push mechanism; 31. Syringe; 32. Driving element;

[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 one-way valve;

[0101] 10. Diluted phase liquid 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 DESCRIPTION

[0107] The nanomedicine preparation system and preparation process of the present invention will be described in more detail below in conjunction with schematic diagrams, which show preferred embodiments of the present invention. It should be understood that those skilled in the art can modify the present invention described herein while still achieving the beneficial effects of the present invention. Therefore, the following description should be understood as being generally known to those skilled in the art and not as limiting the present invention.

[0108] The following paragraphs describe the present invention in more detail by way of example with reference to the accompanying drawings. The advantages and features of the present invention will become more apparent from the following description. It should be noted that the drawings are greatly simplified and not to exact scale, and are provided solely for the purpose of assisting in the description of the embodiments of the present invention.

[0109] Example 1

[0110] like Figures 1 to 3 As shown, an embodiment of the present invention provides a nanomedicine preparation system, 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 respectively 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 pushing mechanisms 3.

[0113] The fluid path reversing coordination integrated block 2 has an input end 21 and an output end 22 for inputting and outputting the raw material liquid, respectively. That is, the fluid path reversing coordination integrated block 2 serves as an intermediate component, and the input and output of the raw material liquid are completed through the suction and push mechanism 3.

[0114] Specifically, both suction and push mechanisms 3 are connected to the liquid path reversing coordination integrated block 2. Each suction and push mechanism 3 inputs or outputs the raw material liquid by suction or pushing. The driving ends of both suction and push mechanisms 3 are signal-connected to the controller, which is used to control the two suction and push mechanisms 3 to operate alternately in opposite directions. In other words, the controller coordinates the operation of the two suction and push mechanisms 3 to achieve uninterrupted input and output of the raw material liquid.

[0115] To better understand the above operating principle, an example is given below:

[0116] For example, when one of the suction and push mechanisms 3 draws the raw material liquid through the input end 21 of the fluid path reversing and coordinating integrated block 2, the other suction and push mechanism 3 pushes the raw material liquid toward the output end 22 of the fluid path reversing and coordinating integrated block 2. Conversely, when one of the suction and push mechanisms 3 pushes the drawn raw material liquid toward the output end 22 of the fluid path reversing and coordinating integrated block 2, the other suction and push mechanism 3 draws the raw material liquid through the input end 21 of the fluid path reversing and coordinating integrated block 2. In this way, raw material liquid continuously enters the fluid path reversing and coordinating integrated block 2 and continuously flows from the output end 22 of the fluid path reversing and coordinating integrated block 2 to the microfluidic chip 1, achieving uninterrupted input and output of the raw material liquid.

[0117] In order to prevent cross-contamination or interference in the input and output processes of the raw liquid when the two suction and push mechanisms 3 operate in reverse alternating operation, the liquid path reversing coordination integrated block 2 is further limited to ensure stable, continuous and cross-contamination-free transportation of the raw liquid.

[0118] Specifically, the fluid path reversing coordination integrated block 2 has a built-in one-way valve assembly.

[0119] Wherein, the one-way valve assembly is configured as follows:

[0120] When any of the suction-push mechanisms 3 performs a suction operation, the raw material liquid input path from the input end 21 to the suction-push mechanism 3 is opened, and the raw material liquid output path from the output end 22 to the suction-push mechanism 3 is blocked. That is, when one of the suction-push mechanisms 3 performs a suction operation, the raw material liquid can only enter the suction-push mechanism 3 through the input end 21.

[0121] When any of the suction-push mechanisms 3 performs a pushing action, the raw material liquid output path from the output end 22 to the suction-push mechanism 3 is opened, and the raw material liquid input path from the input end 21 to the suction-push mechanism 3 is blocked. That is, when one of the suction-push mechanisms 3 performs a pushing action, the raw material liquid can only enter the output end 22 through the suction-push mechanism 3.

[0122] Therefore, through the coordinated cooperation of the one-way valve assembly and the two suction and push mechanisms 3 operating in opposite directions, the input and output of the raw material liquid can always be in a dynamic equilibrium state, thereby realizing the function of stable, continuous and non-cross-liquid delivery of the 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.

[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, and the input end 21 and the output end 22 of the liquid path reversing coordination integrated block 2 are respectively connected to the raw material liquid and the microfluidic chip 1, and the two suction and push mechanisms 3 are operated in reverse alternation and a one-way valve assembly is configured in the liquid path reversing coordination integrated block 2, so that the two suction and push mechanisms 3 can cooperate with the one-way valve assembly when operating in reverse alternation, so that there is always only the raw material liquid input path connected to one of the suction and push mechanisms 3 and the raw material liquid output path connected to the other suction and push mechanism 3 in a conductive state, so that 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 sucking or pushing, and the raw material liquid in the liquid path reversing coordination integrated block 2 will not have cross-flow, thereby realizing the function of stable, continuous and non-cross-flow delivery of the 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.

[0124] like Figures 4 to 7 As shown, in this embodiment, the liquid path reversing coordination integrated block 2 is further limited to cooperate with the one-way valve assembly and the two suction and push mechanisms 3 to better improve the anti-fluid cross-linking performance.

[0125] Specifically, the fluid path reversing and coordinating manifold 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. Specifically, the provision of the fluid channel 4 provides a path for the flow of the raw material liquid in the system, allowing the raw material liquid to enter the fluid path reversing and coordinating manifold block 2 in an orderly manner from the input end 21 and then flow out from the output end 22 under the action of the suction and push mechanisms 3.

[0126] Among them, the one-way valve assembly includes multiple first one-way valves 23, and the multiple first one-way valves 23 are all arranged in the fluid channel 4, which are used to open or close the raw liquid input path and output path, effectively preventing the raw liquid from flowing back or mixing 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 groups 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-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 thereof; 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 thereof. In other words, by providing the connecting flow channel 43, the second flow channels 42 are connected to the first flow channels 41 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 to and from the first flow channels 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 two first one-way valves 23 are arranged in opposite directions on each group of the communicating flow channels 43, so that when the suction and push mechanism 3 is in different working states, the two first one-way valves 23 can respectively control the flow direction of the raw material liquid.

[0131] For example, when a suction-pushing mechanism 3 performs a suction action (such as Figure 6 As shown in the figure, one of the first one-way valves 23 is turned on, 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, completing the input of the raw material liquid, and the first one-way valve 23 set in the opposite direction corresponding to the first one-way valve 23 cuts off the output path.

[0132] When the suction-pushing mechanism 3 performs a pushing action (such as Figure 7 As shown in FIG, another first one-way 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 of the output end 22, completing the output of the raw material liquid, while the first one-way valve 23 corresponding to and set in the opposite direction to the first one-way 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 also proposed to further improve the stability of the raw material liquid input and output process, thereby improving the subsequent mixing effect of the raw material liquid in the microfluidic chip 1 and improving the preparation quality of the nanomedicine.

[0134] Specifically, the suction-push mechanism 3 includes a syringe 31 , a holding structure, and a driving member 32 .

[0135] The injection end of the syringe 31 is connected to the liquid path reversing coordination integrated block 2, and is used to complete the input and output of the raw material liquid by suction and pushing.

[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 move back and forth in the barrel of the syringe 31 to complete the function of inputting and outputting the raw material liquid.

[0137] In this embodiment, the driving member 32 includes a servo motor and a reciprocating screw connected to the servo motor.

[0138] The reciprocating screw is connected to the push handle of the syringe 31 through a connecting plate 5 , and the connecting plate 5 reciprocates along a predetermined direction under the rotational power of the reciprocating screw.

[0139] In addition, a pressure sensor 6 is provided in 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 in the barrel of 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] Specifically, a controller, pressure sensor 6, and servo motor are provided to form an intelligent feedback control system. For example, by installing pressure sensor 6 within connecting plate 5 and contacting the push handle of syringe 31, it can monitor pressure changes within syringe 31 in real time and convert this pressure data into an electrical signal for output. Upon receiving the pressure signal from pressure sensor 6, the controller analyzes and processes the signal, driving the push handle of syringe 31 via a reciprocating screw to control the speed and force of the piston's movement.

[0142] By monitoring and adjusting pressure in real time, this device ensures that the pressure in the syringe 31 remains within an appropriate range during the process of drawing and pushing the raw material liquid. This avoids unstable raw material liquid delivery caused by excessive pressure fluctuations, such as preventing excessive pressure from causing the raw material liquid to be ejected too quickly, or preventing delivery interruption due to excessive pressure. It continuously and stably supplies raw material liquid to the microfluidic chip 1, ensuring the consistency of the nanomedicine preparation process.

[0143] In a specific example, when it is detected that the pressure exceeds the set threshold, the controller will reduce the operating frequency of the servo motor, slow down the movement of the piston, and reduce the pushing or suction force; conversely, when it is detected that the pressure is lower than the set threshold, the controller will increase the operating frequency of the servo motor, speed up the movement of the piston, and increase the pushing or suction force.

[0144] In other embodiments, the fluid path reversing coordination integrated block 2 is further defined. Specifically, the input end 21 of each fluid path reversing coordination integrated block 2 is connected to a container loaded with raw material liquid through a corresponding first pipeline 7 .

[0145] Among them, each first pipeline 7 is provided with a plurality of first bubble sensors 8, and each first bubble sensor 8 on the first pipeline 7 is connected to the controller signal, and the controller controls the action of the corresponding suction and push mechanism 3 according to the detection results of the first bubble sensor 8.

[0146] The device is provided with a plurality of first bubble sensors 8 on the first pipeline 7 to detect in sections whether the raw material liquid in the first pipeline 7 is evacuated.

[0147] In a specific example, when several first bubble sensors 8 detect the presence of bubbles, the suction-pushing mechanism 3 is controlled to stop operating.

[0148] In a further embodiment, the output end 22 of each fluid-path switching and coordination integrated block 2 is connected to the microfluidic chip 1 via a corresponding second pipeline 9, and a second one-way valve 91 is provided on each second pipeline 9. The second one-way valve 91 is used to prevent cross-flow of the raw materials in the plurality of second pipelines 9 due to flow rate fluctuations (e.g., when the flow rate of the raw materials in one second pipeline 9 is faster than that of another second pipeline 9).

[0149] In other embodiments, the nanomedicine preparation system further includes a sample recovery tube 11, the liquid inlet end of the sample recovery tube 11 is connected to the outlet end of the microfluidic chip 1, and the sample recovery tube 11 is sequentially provided with a dilution phase liquid inlet tube 10 and a waste recovery tube 12 along the liquid output direction.

[0150] The dilution phase liquid inlet tube 10 is used to dilute the raw liquid mixture output by the microfluidic chip 1 to form a nano drug stock solution.

[0151] The dilution phase inlet pipe 10 is sequentially provided with a plurality of second bubble sensors 13 and a peristaltic pump 14 along the output direction. The second bubble sensors 13 are provided to monitor the dilution liquid, that is, to monitor whether the dilution liquid is evacuated, and the peristaltic pump 14 is provided to provide power for the input of the dilution liquid.

[0152] The waste recovery tube 12 and the sample recovery tube 11 are both provided with control valves 15. The control valves 15 on the waste recovery tube 12 and the control valves 15 on the sample recovery tube 11 are in mutually exclusive working states. That is, when one control valve 15 is open, the other control valve 15 is closed, achieving unidirectional outflow of the nanomedicine stock solution, thereby completing sample recovery of the nanomedicine stock solution or waste recovery of the raw material liquid mixture, respectively.

[0153] The plurality of second bubble sensors 13 , the peristaltic pump 14 and the two control valves 15 are all connected to the controller signal, and the controller controls the working states of the peristaltic pump 14 and the two control valves 15 according to the detection results of the second bubble sensors 13 .

[0154] For example, when the second bubble sensor 13 detects bubbles, it indicates that the diluent has been evacuated. Therefore, 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 correspondingly closes the control valve 15 on the sample recovery tube 11 to prevent the raw liquid mixture from entering the sample recovery tube 11 and contaminating the obtained nano drug stock solution, thereby achieving the purpose of ensuring product quality and classification recovery efficiency.

[0155] Example 2

[0156] Based on the first embodiment, this embodiment further proposes a nanomedicine preparation process, which includes the following steps:

[0157] S1. Providing the nanomedicine preparation system as described in the above embodiment;

[0158] S2, the controller of the nanomedicine preparation system controls the two suction and push mechanisms 3 to operate alternately in opposite directions. During this process, the raw material liquid is continuously input from the container loaded with the raw material liquid into the liquid path reversing coordination integrated block 2 under the action of suction and push of the two suction and push mechanisms 3, and is output from the output end 22 of the liquid path reversing coordination integrated block 2 to the microfluidic chip 1;

[0159] S3, mixing different raw material liquids in the microchannel of the microfluidic chip 1 to form a raw material liquid mixture, and diluting the raw material liquid mixture to obtain a nano drug stock solution;

[0160] S4. The prepared nanomedicine stock solution is transported to a 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 sucking or pushing, and there will be no cross-flow of the raw material liquid in the liquid path reversing coordination integrated block 2, thereby realizing the function of stable, continuous and non-cross-flow delivery of the 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 the raw material liquid, the control method of the controller is further limited.

[0163] Specifically, the process of the controller controlling the two suction and push mechanisms 3 to alternately operate in opposite directions includes:

[0164] S21, start syringe A: start one of the suction-push mechanisms 3, so that the syringe A of the suction-push mechanism 3 performs a pushing action;

[0165] S22, collecting the thrust data of syringe A: collecting the thrust data of syringe A in the uniform speed section through the pressure sensor 6 corresponding to syringe A, and obtaining the working thrust P1 of syringe A after filtering;

[0166] S23. Pre-pressing syringe B: Based on the working thrust P1 obtained in step S22, a target pressure value W2' is set for the pressure sensor 6 corresponding to syringe B of the other suction-push mechanism 3. An approach speed is set according to a deviation algorithm so that the pressure inside the barrel of syringe B quickly approaches the target pressure value W2'. After reaching the target pressure value W2', the initial speed parameter of syringe B is set according to a preset ratio of the uniform speed segment.

[0167] S24, reversing: When the push position of syringe A reaches a preset ratio of the target position, reversing 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 the speeds of the two is kept equal to the uniform speed section. When the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section, reversing is completed.

[0168] S25, collecting the thrust data of syringe B: collecting the thrust data of syringe B in the uniform speed section through the pressure sensor 6 corresponding to syringe B, and obtaining the working thrust P2 of syringe B after filtering;

[0169] S26. Pre-pressurize syringe A: Set a target pressure value W1 for syringe A's corresponding pressure sensor 6 based on the working thrust P1 of syringe A, and set an approach speed based on a deviation algorithm so that the pressure inside syringe A quickly approaches the target pressure value W1. After reaching the target pressure value W1, set the initial speed parameter of syringe A based on a preset ratio of the uniform speed segment.

[0170] In a specific example, when the pressure in the barrel of syringe A reaches the target value W1, the speed of syringe A is set to 7‰ of the speed in the uniform speed section.

[0171] S27, reversing: When the push position of syringe B reaches a preset ratio of the target position, reversing begins. During this process, the speed parameters of syringes A and 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 the speeds of the two is maintained equal to the uniform speed section. When the speed of syringe B is 0 and the speed of syringe A is equal to the uniform speed section, reversing is completed.

[0172] S28, collecting the thrust data of syringe A: collecting the thrust data of syringe A in the uniform speed section through the pressure sensor 6 corresponding to syringe A, and obtaining the working thrust P1 of syringe A after filtering;

[0173] S29. Pre-pressurize syringe B: Based on the working thrust P2 obtained in step S25, set the target pressure value W2 of syringe B's corresponding pressure sensor 6, and set the approach speed according to the deviation algorithm so that the pressure in the barrel of syringe B quickly approaches the target pressure value W2. After reaching the target pressure value W2, set the initial speed parameter of syringe B according to the preset ratio of the uniform speed section.

[0174] S30, repeat steps S24 to S29 until the nanomedicine preparation is completed.

[0175] This method realizes the efficient coordinated work of the two suction and push mechanisms 3 through the triple mechanism of pressure preloading-speed compensation-data feedback, ensures the pressure and flow stability of the raw material liquid during the transportation process, and provides a reliable liquid circuit control basis for the preparation of nanomedicines. By re-collecting the working thrust before each preloading, it can effectively eliminate the influence of other factors (such as deformation of the syringe stopper) and complex situations on the pressure in the syringe, further ensuring the stability of the pressure and flow of the raw material liquid during the transportation process.

[0176] In other embodiments, another controller is proposed to control the two suction and push mechanisms 3. Compared with the above control method, this method can not only ensure the stability of the raw material liquid during the transportation process under the scenario where the outlet pressure of the raw material liquid remains unchanged, but also simplify the control logic to reduce the data processing volume, and correspondingly reduce the operating cost and maintenance difficulty of the equipment, thereby achieving the purpose of facilitating promotion and application.

[0177] Specifically, the process of the controller controlling the two suction and push mechanisms 3 to alternately operate in opposite directions includes:

[0178] S21, start syringe A: start one of the suction-push mechanisms 3, so that the syringe A of the suction-push mechanism 3 performs a pushing action;

[0179] S22, collecting the thrust data of syringe A: collecting the thrust data of syringe A in the uniform speed section through the pressure sensor 6 corresponding to syringe A, and obtaining the working thrust P1 of syringe A after filtering;

[0180] S23. Pre-pressing syringe B: Based on the working thrust P1 obtained in step S22, a target pressure value W2' is set for the pressure sensor 6 corresponding to syringe B of the other suction-push mechanism 3. An approach speed is set according to a deviation algorithm so that the pressure inside the barrel of syringe B quickly approaches the target pressure value W2'. After reaching the target pressure value W2', the initial speed parameter of syringe B is set according to a preset ratio of the uniform speed segment.

[0181] S24, reversing: When the push position of syringe A reaches a preset ratio of the target position, reversing 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 the speeds of the two is kept equal to the uniform speed section. When the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section, reversing is completed.

[0182] S25, collecting the thrust data of syringe B: collecting the thrust data of syringe B in the uniform speed section through the pressure sensor 6 corresponding to syringe B, and obtaining 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 target pressure value W1 of syringe A's corresponding pressure sensor 6, and set the approach speed according to the deviation algorithm so that the pressure in the barrel of syringe A quickly approaches the target pressure value W1. After reaching the target pressure value W1, set the initial speed parameter of syringe A according to the preset ratio of the uniform speed section.

[0184] S27, reversing: When the push position of syringe B reaches a preset ratio of the target position, reversing begins. During this process, the speed parameters of syringes A and 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 the speeds of the two is maintained equal to the uniform speed section. When the speed of syringe B is 0 and the speed of syringe A is equal to the uniform speed section, reversing is completed.

[0185] S28. Pre-pressurize syringe B: Based on the working thrust P2 obtained in step S25, set the target pressure value W2 of syringe B's corresponding pressure sensor 6, and set the approach speed according to the deviation algorithm so that the pressure in the barrel of syringe B quickly approaches the target pressure value W2. After reaching the target pressure value W2, set the initial speed parameter of syringe B according to the preset ratio of the uniform speed section.

[0186] S29, reversing: When the push position of syringe A reaches a preset ratio of the target position, reversing 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 the speeds of the two is kept equal to the uniform speed section. When the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section, reversing is completed.

[0187] S30, repeat steps S26 to S29 until the nanomedicine preparation is completed.

[0188] This method sets a fixed pre-pressing reference (i.e., always based on the initial thrust data of syringe A) and simplifies the control process (i.e., skips some reversing data collection steps). Compared with the above-mentioned method of re-collecting the working thrust before each pre-pressing, it can reduce the system switching impact, reduce mechanical loss and data processing load, 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, in step S2, it further includes: detecting bubbles in corresponding pipelines respectively by the first bubble sensor 8 and the second bubble sensor 13;

[0191] When the first bubble sensor 8 detects bubbles, 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 system along with the raw material liquid, thereby 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 on the sample recovery tube 11, and correspondingly opens the control valve 15 on the waste recovery tube 12, giving an alarm prompt to prevent the raw liquid mixture from entering the sample recovery tube 11 and contaminating the obtained nano drug stock solution, thereby achieving the purpose of ensuring product quality and classification recovery efficiency.

[0193] In addition, in step S2, it also includes: detecting bubbles in the corresponding pipelines by the first bubble sensor 8 and the second bubble sensor 13 respectively;

[0194] When the first bubble sensor 8 detects bubbles, it enters a first response state;

[0195] When the bubble information received by the first bubble sensor 8 disappears, the second response state is entered. At this time, the control valve 15 at the rear end is switched to discharge the nanomedicine stock solution in the bubble-affected time period into the waste recovery tube 12, and the nanomedicine stock solution in the non-bubble-affected time period into the sample recovery tube 11;

[0196] If the first bubble sensor 8 continues to receive bubble information, it enters the third response state, at which 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 the bubble signal, it enters the fourth response state;

[0198] When the bubble information received by the second bubble sensor 13 disappears, the fifth response state is entered. At this time, the control valve 15 at the rear end is switched to discharge the nanomedicine stock solution in the bubble-affected time period into the waste recovery tube 12, and the nanomedicine stock solution in the non-bubble-affected time period into the sample recovery 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, and the peristaltic pump 14 stops running, and gives an alarm prompt.

[0200] This method uses the first bubble sensor 8 and the second bubble sensor 13 to detect bubbles in the corresponding pipeline in real time respectively. When the first bubble sensor 8 detects bubbles, it enters the first response state. After the bubble information disappears, it enters the second response state and discharges the nano-drug stock solution in the bubble-affected time period to the waste recovery tube 12 by switching the back-end control valve 15, and discharges the nano-drug stock solution in the non-bubble-affected time period to the sample recovery tube 11. If the bubble information persists, it enters the third response state and controls the corresponding suction and push mechanism 3 to stop the suction action and alarm. When the second bubble sensor 13 detects bubbles, it enters the fourth response state. After the bubble information disappears, it enters the fifth response state and similarly switches the control valve 15 for classified discharge. If the bubble information persists, it enters the 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 alarm, thereby being able to accurately distinguish and process liquids containing bubbles and liquids without bubbles, thereby achieving the purpose of minimizing the scrap rate, ensuring product quality stability and safe operation of the equipment.

[0201] In addition, in step S2, the method further 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 liquid inlet pipe 10 by at least two second bubble sensors 13;

[0202] When the first bubble sensor 8 receives the bubble signal, it enters the first response state;

[0203] When only one of the first bubble sensor 8 and the second bubble sensor 8 receives the bubble signal, the sensor enters the second response state;

[0204] When both the first bubble sensor 8 and the second first bubble sensor 8 receive the bubble signal, the third response state is entered;

[0205] When the second bubble sensor 13 receives the bubble signal, it enters the fourth response state;

[0206] When only one of the first second bubble sensor 13 and the second second bubble sensor 13 receives the bubble signal, the fifth response state is entered;

[0207] After both the first second bubble sensor 13 and the second bubble sensor 13 receive the bubble signal, the sixth response state is entered.

[0208] That is, by setting at least two first bubble sensors 8 and at least two second bubble sensors 13, they are used for bubble warning and bubble determination respectively. When the two front and rear first bubble sensors 8 or the two second bubble sensors 13 receive bubble signals, the corresponding equipment (i.e., the driving member 32 and the 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 liquid inlet pipe 10. Different sensors enter corresponding response states according to the situation of receiving bubble signals, thereby being able to more accurately judge the distribution, quantity and dynamic changes of bubbles in the pipeline, thereby achieving the purpose of timely and targeted treatment of bubble problems and ensuring the quality of raw material liquid transportation and the effect of nanomedicine preparation.

[0210] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.

Claims

1. A nano drug preparation system, characterized in that: It comprises 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 respectively used for conveying different raw material liquids; Each of the feeding devices comprises a liquid path reversing coordination integrated block (2) and two suction and pushing mechanisms (3); The liquid path reversing coordination integrated block (2) has an input end (21) and an output end (22), which are used for inputting and outputting the raw material liquid respectively; The two suction and push mechanisms (3) are both connected to the fluid channel of the liquid path reversing coordination integrated block (2), and each of the suction and push mechanisms (3) realizes the input or output of the raw material liquid by suction or pushing. The driving ends of the two suction and push mechanisms (3) are both connected to the controller signal, and the controller is used to control the two suction and push mechanisms (3) to operate in reverse and alternating directions; The liquid path 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-push mechanisms (3) performs a suction action, the raw material liquid input path from the input end (21) to the suction-push mechanism (3) is connected, and the raw material liquid output path from the output end (22) to the suction-push mechanism (3) is cut off; When any of the suction-push mechanisms (3) performs a pushing action, the raw material liquid output path from the output end (22) to the suction-push mechanism (3) is connected, and the raw material liquid input path from the input end (21) to the suction-push mechanism (3) is cut off; The fluid path reversing coordination integrated block (2) has a built-in fluid channel (4), and the fluid channel (4) is used to connect the input end (21), the output end (22) and the two suction and push mechanisms (3); The one-way valve assembly comprises a plurality of first one-way valves (23), and the plurality of first one-way valves (23) are all arranged in the fluid channel (4); The fluid channel (4) comprises two first flow channels (41), two second flow channels (42) and two groups of connecting flow channels (43); 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 interconnected with the two first flow channels (41) through the connecting flow channel (43) on the same side thereof; the other of the two second flow channels (42) is also interconnected with the two first flow channels (41) through the connecting flow channel (43) on the same side thereof; Two first one-way valves (23) arranged in opposite directions are arranged on each group of the communicating flow channels (43).

2. The nanomedicine preparation system according to claim 1, characterized in that: The suction-push mechanism (3) comprises a syringe (31), a holding structure, and a driving member (32); The injection end of the syringe (31) is connected to the liquid path reversing coordination integrated block (2); The syringe (31) is inserted into the holding structure, and the holding structure 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 move back and forth in the barrel of the syringe (31).

3. The nano drug preparation system according to claim 2, characterized in that: The driving member (32) includes a servo motor and a reciprocating 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 back and forth in a predetermined direction under the rotational power of the reciprocating screw.

4. The nano drug preparation system according to claim 3, characterized in that: A pressure sensor (6) is provided in the connecting plate (5), and the pressure sensor (6) contacts the push handle of the syringe (31) and is used to detect the pressure in the barrel of 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).

5. The nanomedicine preparation system according to claim 1, characterized in that: The input end (21) of each of the liquid path reversing coordination integrated blocks (2) is connected to a container loaded with raw material liquid via a corresponding first pipeline (7); Each of the first pipelines (7) is provided with a plurality of first bubble sensors (8); The first bubble sensor (8) on each of the first pipelines (7) is connected to the controller signal, and the controller controls the action of the corresponding suction and push mechanism (3) according to the detection result of the first bubble sensor (8).

6. The nanomedicine preparation system according to claim 1, characterized in that: The output end (22) of each of the liquid path reversing coordination integrated blocks (2) is connected to the microfluidic chip (1) via a corresponding second pipeline (9), and a second one-way valve (91) is provided on the second pipeline (9), and the second one-way valve (91) is used to prevent cross-flow of liquids.

7. The nanomedicine preparation system according to claim 1, characterized in that: It also includes a sample recovery tube (11), the liquid inlet end of the sample recovery tube (11) is connected to the outlet end of the microfluidic chip (1), and the sample recovery tube (11) is sequentially provided with a dilution phase liquid inlet tube (10) and a waste recovery tube (12) along the liquid output direction; The dilution phase liquid inlet tube (10) is used to dilute the raw liquid mixture output by the microfluidic chip (1) to form a nano drug stock solution; The dilution phase liquid inlet pipe (10) is provided with a plurality of second bubble sensors (13) and peristaltic pumps (14) in sequence along the output direction; The waste recovery tube (12) and the sample recovery tube (11) are both provided with a control valve (15), and the control valve (15) on the waste recovery tube (12) and the control valve (15) on the sample recovery tube (11) are in a mutually exclusive working state; A plurality of the second bubble sensors (13), the peristaltic pump (14) and the two control valves (15) are all connected to the controller signal, and the controller controls the working states of the peristaltic pump (14) and the two control valves (15) according to the detection results of the second bubble sensors (13).

8. A process for preparing nanomedicine, characterized in that: The steps include: S1. Providing a nanomedicine preparation system according to any one of claims 1 to 7; S2, the controller of the nano-drug preparation system controls the two suction and push mechanisms (3) to operate in reverse and alternating directions. During this process, the raw material liquid is continuously input from the container loaded with the raw material liquid into the liquid path reversing and coordinating integrated block (2) through the built-in fluid channel (4) and the one-way valve assembly of the liquid path reversing and coordinating integrated block (2) under the action of suction and push of the two suction and push mechanisms (3), and is output from the output end (22) of the liquid path reversing and coordinating integrated block (2) to the microfluidic chip (1); 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; S4. The prepared nanomedicine stock solution is transported to a sample collection container.

9. The process for preparing nanomedicine according to claim 8, wherein: The process of the controller controlling the two suction and push mechanisms (3) to operate in reverse and alternating directions includes: S21, start syringe A: start one of the suction-push mechanisms (3), so that syringe A of the suction-push mechanism (3) performs a pushing action; S22, collecting the thrust data of syringe A: collecting the thrust data of syringe A in the uniform speed section through the pressure sensor (6) corresponding to syringe A, and obtaining the working thrust P1 of syringe A after filtering; S23, syringe B is pre-pressed: according to the working thrust P1 obtained in step S22, the target pressure value W2' of the pressure sensor (6) corresponding to syringe B of another suction-push mechanism (3) is set, and the approach speed is set according to the deviation algorithm so that the pressure in the barrel of syringe B quickly approaches the target pressure value W2'; after reaching the target pressure value W2', the initial speed parameter of syringe B is set according to the preset ratio of the uniform speed section; S24, reversing: When the push position of syringe A reaches a preset ratio of the target position, reversing 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 the speeds of the two is kept equal to the uniform speed section. When the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section, reversing is completed. S25, collecting the thrust data of syringe B: collecting the thrust data of syringe B in the uniform speed section through the pressure sensor (6) corresponding to syringe B, and obtaining the working thrust P2 of syringe B after filtering; S26, syringe A is pre-pressurized: according to the working thrust P1 of syringe A, the target pressure value W1 of the pressure sensor (6) corresponding to syringe A is set, and the approach speed is set according to the deviation algorithm, so that the pressure in the barrel of syringe A quickly approaches the target pressure value W1; after reaching the target pressure value W1, the initial speed parameter of syringe A is set according to the preset ratio of the uniform speed section; S27, reversing: When the push position of syringe B reaches a preset ratio of the target position, reversing begins. During this process, the speed parameters of syringes A and 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 the speeds of the two is maintained equal to the uniform speed section. When the speed of syringe B is 0 and the speed of syringe A is equal to the uniform speed section, reversing is completed. S28, collecting the thrust data of syringe A: collecting the thrust data of syringe A in the uniform speed section through the pressure sensor (6) corresponding to syringe A, and obtaining the working thrust P1 of syringe A after filtering; S29, syringe B is pre-pressed: according to the working thrust P2 obtained in step S25, the target pressure value W2 of the pressure sensor (6) corresponding to syringe B is set, and the approach speed is set according to the deviation algorithm, so that the pressure in the barrel of syringe B quickly approaches the target pressure value W2; after reaching the target pressure value W2, the initial speed parameter of syringe B is set according to the preset ratio of the uniform speed section; S30, repeat steps S24 to S29 until the nanomedicine preparation is completed.

10. The process for preparing nanomedicine according to claim 8, wherein: The process of the controller controlling the two suction and push mechanisms (3) to operate in reverse and alternating directions includes: S21, start syringe A: start one of the suction-push mechanisms (3), so that syringe A of the suction-push mechanism (3) performs a pushing action; S22, collecting the thrust data of syringe A: collecting the thrust data of syringe A in the uniform speed section through the pressure sensor (6) corresponding to syringe A, and obtaining the working thrust P1 of syringe A after filtering; S23, syringe B is pre-pressed: according to the working thrust P1 obtained in step S22, the target pressure value W2' of the pressure sensor (6) corresponding to syringe B of another suction-push mechanism (3) is set, and the approach speed is set according to the deviation algorithm so that the pressure in the barrel of syringe B quickly approaches the target pressure value W2'; after reaching the target pressure value W2', the initial speed parameter of syringe B is set according to the preset ratio of the uniform speed section; S24, reversing: When the push position of syringe A reaches a preset ratio of the target position, reversing 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 the speeds of the two is kept equal to the uniform speed section. When the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section, reversing is completed. S25, collecting the thrust data of syringe B: collecting the thrust data of syringe B in the uniform speed section through the pressure sensor (6) corresponding to syringe B, and obtaining the working thrust P2 of syringe B after filtering; S26, syringe A is pre-pressurized: according to the working thrust P1 obtained in step S22, the target pressure value W1 of the pressure sensor (6) corresponding to syringe A is set, and the approach speed is set according to the deviation algorithm, so that the pressure in the barrel of syringe A quickly approaches the target pressure value W1; after reaching the target pressure value W1, the initial speed parameter of syringe A is set according to the preset ratio of the uniform speed section; S27, reversing: When the push position of syringe B reaches a preset ratio of the target position, reversing begins. During this process, the speed parameters of syringes A and 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 the speeds of the two is maintained equal to the uniform speed section. When the speed of syringe B is 0 and the speed of syringe A is equal to the uniform speed section, reversing is completed. S28, syringe B is pre-pressed: according to the working thrust P2 obtained in step S25, the target pressure value W2 of the pressure sensor (6) corresponding to syringe B is set, and the approach speed is set according to the deviation algorithm, so that the pressure in the barrel of syringe B quickly approaches the target pressure value W2; after reaching the target pressure value W2, the initial speed parameter of syringe B is set according to the preset ratio of the uniform speed section; S29, reversing: When the push position of syringe A reaches a preset ratio of the target position, reversing 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 the speeds of the two is kept equal to the uniform speed section. When the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section, reversing is completed. S30, repeat steps S26 to S29 until the nanomedicine preparation is completed.

11. The process for preparing nanomedicine according to claim 8, wherein: In step S2, the method further includes: detecting bubbles in corresponding pipelines respectively by using a first bubble sensor (8) and a second bubble sensor (13); When the first bubble sensor (8) detects bubbles, the controller controls the corresponding suction and push mechanism (3) to stop the suction action and gives an alarm prompt; 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.

12. The process for preparing nanomedicine according to claim 8, wherein: In step S2, the method further includes: detecting bubbles in corresponding pipelines respectively by using a first bubble sensor (8) and a second bubble sensor (13); When the first bubble sensor (8) detects bubbles, it enters a first response state; When the bubble information received by the first bubble sensor (8) disappears, the second response state is entered, at which time the nano drug stock solution in the bubble-affected time period is discharged into the waste recovery tube (12) by switching the rear-end control valve (15), and the nano drug stock solution in the non-bubble-affected time period is discharged into the sample recovery tube (11); If the first bubble sensor (8) continues to receive bubble information, it enters a third response state, at which time the controller controls the corresponding suction and push mechanism (3) to stop the suction action and gives an alarm prompt; When the second bubble sensor (13) receives a bubble signal, it enters a fourth response state; When the bubble information received by the second bubble sensor (13) disappears, the fifth response state is entered, at which time the nanomedicine stock solution in the bubble-affected time period is discharged into the waste recovery tube (12) by switching the rear-end control valve (15), and the nanomedicine stock solution in the non-bubble-affected time period is discharged into the sample recovery tube (11); If the second bubble sensor (13) continues to receive bubble information, it enters the sixth response state, at which time the controller controls the corresponding suction and push mechanism (3) to stop the suction action, and the peristaltic pump (14) stops running, and gives an alarm prompt.

13. The process for preparing nanomedicine according to claim 8, wherein: In step S2, the method further 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 liquid inlet pipe (10) by at least two second bubble sensors (13); When a first bubble sensor (8) receives a bubble signal, it enters a first response state; When only one of the first bubble sensor (8) and the second bubble sensor (8) receives a bubble signal, the sensor enters a second response state; After the first bubble sensor (8) and the second bubble sensor (8) both receive the bubble signal, they enter a third response state; When the second bubble sensor (13) receives the bubble signal, it enters a fourth response state; When only one of the first second bubble sensor (13) and the second second bubble sensor (13) receives the bubble signal, the fifth response state is entered; After the first second bubble sensor (13) and the second second bubble sensor (13) both receive the bubble signal, they enter a sixth response state.

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