Nano-drug preparation system and preparation process

Abstract

The invention discloses a nano-drug preparation system and a nano-drug preparation process. The nano-drug preparation system comprises a micro-fluidic chip, at least two feeding devices and a controller, the two feeding devices are communicated with the micro-fluidic chip and are respectively used for conveying different raw material liquids; each feeding device comprises a liquid path reversing coordination integrated block and two sucking and pushing mechanisms; the liquid path reversing coordination integrated block is provided with an input end and an output end; the two sucking and pushing mechanisms are both communicated with a fluid channel of the liquid path reversing coordination integrated block, each sucking and pushing mechanism achieves input or output of raw material liquid in a sucking or pushing mode, the driving ends of the two sucking and pushing mechanisms are both in signal connection with the controller, and the controller is used for controlling the two sucking and pushing mechanisms to alternately operate in the reverse direction; a one-way valve assembly is arranged in the liquid path reversing coordination integrated block. By means of the arrangement, the function of stably and continuously conveying raw material liquid without liquid mixing is achieved, the controllability of the preparation process of nano-drugs in the micro-fluidic chip is guaranteed, and the purpose of improving the preparation effect is achieved.

Description

Technical Field

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

[0002] Nano - drug preparation technology realizes the controllable synthesis of nanoparticle size by precisely controlling the mixing and reaction process of raw material liquids, and has important application value in fields such as targeted drug delivery and sustained - release preparations. As the core reaction unit, the microfluidic chip relies on the continuous input of stable multi - component raw material liquids to ensure the uniformity and yield of nano - drugs. However, the feeding device of the existing preparation system has the following defects during the transportation of raw material liquids: First, most existing feeding devices use a single suction or pushing mechanism (such as a single syringe or a single pump). After completing one suction or pushing action, it is necessary to stop the machine and reverse the direction, resulting in discontinuous transportation of raw material liquids. This intermittent liquid supply will cause pressure fluctuations in the flow channels inside the microfluidic chip, affecting the mixing ratio accuracy of multi - component raw material liquids, and further leading to uneven particle size distribution of nanoparticles, or even causing flow channel blockage or reaction out - of - control. Especially for industrial preparation scenarios that require long - term stable operation, the fluid interruption problem during the direction reversal of a single mechanism significantly reduces production efficiency and product quality consistency.

[0003] Second, most existing liquid - path direction - reversal devices rely on external valves or complex pipeline switching structures, and directly control the opening and closing of valves through a controller to achieve fluid direction conversion. However, such solutions have problems such as response lag and poor sealing performance, which easily lead to fluid backflow or cross - liquid of different raw material liquids during suction and pushing, destroying the raw material ratio and introducing impurities. For example, when a one - way valve fails or 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.

[0004] Therefore, a nano - drug preparation system and a preparation process are needed to solve the above problems. Summary of the Invention

[0005] The purpose of the present invention is to provide a nano - drug preparation system and a preparation process to achieve the functions of stable, continuous, and non - cross - liquid transportation of raw material liquids, ensure the controllability of the nano - drug preparation process inside the microfluidic chip, and achieve the purpose of improving the preparation effect.

[0006] To solve the above - mentioned technical problems, the present invention provides a nano - drug preparation system, which includes a microfluidic chip, at least two feeding devices, and a controller; At least two of the feeding devices are in communication with the microfluidic chip, and are respectively used for transporting different raw material liquids; Each feeding device includes a liquid - path direction - reversal coordination integration block and two suction - push mechanisms; The liquid path commutation and coordination integrated block has an input end and an output end, which are respectively used for the input and output of the raw liquid; Both of the suction and push mechanisms are communicated with the fluid channels of the liquid path commutation and coordination integrated block. Each suction and push mechanism realizes the input or output of the raw liquid by suction or pushing. The driving ends of both suction and push mechanisms are signal-connected to the controller, and the controller is used to control the reverse alternating operation of both suction and push mechanisms; The liquid path commutation and coordination integrated block is internally provided with a one-way valve assembly; The one-way valve assembly is configured as: When any one of the suction and push mechanisms performs a suction action, the raw liquid input path from the input end to this suction and push mechanism is conducted, and the raw liquid output path from the output end to this suction and push mechanism is cut off; When any one of the suction and push mechanisms performs a push action, the raw liquid output path from the output end to this suction and push mechanism is conducted, and the raw liquid input path from the input end to this suction and push mechanism is cut off.

[0007] Further, the liquid path commutation and coordination integrated block is internally provided with fluid channels, and the fluid channels are used to communicate the input end, the output end, and both suction and push mechanisms; The one-way valve assembly includes a plurality of first one-way valves, and all of the first one-way valves are arranged in the fluid channels.

[0008] Further, the fluid channels include two first flow channels, two second flow channels, and two groups of connecting flow channels; The two first flow channels are respectively communicated with the input end and the output end; The two second flow channels are respectively communicated with both suction and push mechanisms; Wherein, one of the two second flow channels is communicated with the two first flow channels through the connecting flow channel on its same side; the other one of the two second flow channels is also communicated with the two first flow channels through the connecting flow channel on its same side; two reversely arranged first one-way valves are arranged on each group of connecting flow channels.

[0009] Further, the suction and push mechanism includes a syringe, a holding structure, and a driving member; The injection end of the syringe is connected to the liquid path commutation and coordination integrated block; The syringe is inserted into the holding structure, the holding structure is used to fix the barrel of the syringe, and the driving member is connected to the push handle of the syringe and is used to drive the piston of the syringe to reciprocate in the barrel of the syringe.

[0010] Further, the driving member includes a servo motor and a reciprocating lead screw connected to the servo motor; The reciprocating lead screw is connected to the push handle of the syringe through a connecting plate, and the connecting plate reciprocates in a predetermined direction under the rotational power of the reciprocating lead screw.

[0011] Further, a pressure sensor is provided inside the connecting plate. The pressure sensor contacts the push handle of the syringe and is used to detect the pressure inside the barrel of the syringe; The controller is signal-connected to the pressure sensor and the servo motor, and is used to adjust the operating frequency of the servo motor according to the pressure signal output by the pressure sensor.

[0012] Further, the input end of each liquid path commutation and coordination integration block is connected to a containing device loaded with raw material liquid through a corresponding first pipeline; A plurality of first bubble sensors are provided on each of the first pipelines; The first bubble sensors on each of the first pipelines are signal-connected to the controller, and the controller controls the actions of the corresponding suction and push mechanisms according to the detection results of the first bubble sensors.

[0013] Further, the output end of each liquid path commutation and coordination integration block is connected to the microfluidic chip through a corresponding second pipeline. A second one-way valve is provided on the second pipeline, and the second one-way valve is used to prevent liquid cross-flow.

[0014] Further, a sample recovery pipe is further included. The liquid inlet end of the sample recovery pipe is connected to the outlet end of the microfluidic chip. A dilution phase inlet pipe and a waste recovery pipe are sequentially arranged on the sample recovery pipe along the liquid output direction; The dilution phase inlet pipe is used to dilute the raw material liquid mixture output by the microfluidic chip to form a nano-drug stock solution; A plurality of second bubble sensors and a peristaltic pump are sequentially arranged on the dilution phase inlet pipe along the output direction; Control valves are provided on both the waste recovery pipe and the sample recovery pipe. The control valve on the waste recovery pipe and the control valve on the sample recovery pipe are in a mutually exclusive working state; A plurality of the second bubble sensors, the peristaltic pump, and the two control valves are all signal-connected to the controller, and 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.

[0015] On the other hand, a nano-drug preparation process is also proposed, including the following steps: S1. Provide the nano-drug preparation system as described in the above embodiment; S2. The controller of the nano-drug preparation system controls the two suction and pushing mechanisms to operate in reverse alternately. During this process, through the fluid path commutation coordination integrated block with built-in fluid channels and one-way valve components, the raw material liquid is continuously input into the fluid path commutation coordination integrated block from the accommodating device loaded with the raw material liquid under the suction and pushing actions of the two suction and pushing mechanisms, and is output from the output end of the fluid path commutation coordination integrated block to the microfluidic chip; 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 the nano-drug stock solution; S4. The prepared nano-drug stock solution is transported to the sample collection container.

[0016] Further, the process of the controller controlling the two suction and pushing mechanisms to operate in reverse alternately includes: S21. Start syringe A: Start one of the suction and pushing mechanisms so that the syringe A of this suction and pushing mechanism performs a pushing action; S22. Collect the thrust data of syringe A: Collect the thrust data of the uniform speed section of syringe A through the pressure sensor corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering; S23. Pre-press syringe B: According to 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 pushing mechanism, and set the approaching speed according to the deviation algorithm to make the pressure in the cylinder of syringe B quickly approach 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 uniform speed section speed; S24. Commutation: Start commutation when the pushing position of syringe A reaches the preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, so that the speed of syringe A decreases while the speed of syringe B increases, and the sum of their speeds is maintained equal to the uniform speed section speed; when the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section speed, the commutation is completed; S25. Collect the thrust data of syringe B: Collect the thrust data of the uniform speed section of syringe B through the pressure sensor corresponding to syringe B, and obtain the working thrust P2 of syringe B after filtering; S26. Pre-press syringe A: According to the working thrust P1 of syringe A, set the pressure target value W1 of the pressure sensor corresponding to syringe A, and set the approaching speed according to the deviation algorithm to make the pressure in the cylinder of 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 uniform speed section speed; S27. Commutation: Commutation starts when the pushing position of syringe B reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, causing the speed of syringe A to increase while the speed of syringe B decreases, and maintaining the sum of their speeds equal to the speed in the uniform speed segment. When the speed of syringe B is 0 and the speed of syringe A is equal to the speed in the uniform speed segment, the commutation is completed. S28. Collect the thrust data of syringe A: Collect the thrust data of syringe A in the uniform speed segment through the pressure sensor corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering. S29. Pre-press syringe B: According to 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 approaching speed according to the deviation algorithm to quickly approach the pressure target value W2 in the barrel of syringe B. After reaching the pressure target value W2, set the initial speed parameter of syringe B according to the preset ratio of the uniform speed segment speed. S30. Repeat steps S24 - S29 until the preparation of the nano-drug is completed.

[0017] Furthermore, the process of the controller controlling the two suction and pushing mechanisms to operate in reverse alternately includes: S21. Start syringe A: Start one of the suction and pushing mechanisms to make the syringe A of this suction and pushing mechanism perform the pushing action. S22. Collect the thrust data of syringe A: Collect the thrust data of syringe A in the uniform speed segment through the pressure sensor corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering. S23. Pre-press syringe B: According to 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 pushing mechanism, and set the approaching speed according to the deviation algorithm to quickly approach the pressure target value W2' in the barrel of syringe B. After reaching the pressure target value W2', set the initial speed parameter of syringe B according to the preset ratio of the uniform speed segment speed. S24. Commutation: Commutation starts when the pushing position of syringe A reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, causing the speed of syringe A to decrease while the speed of syringe B increases, and maintaining the sum of their speeds equal to the speed in the uniform speed segment. When the speed of syringe A is 0 and the speed of syringe B is equal to the speed in the uniform speed segment, the commutation is completed. S25. Collect the thrust data of syringe B: Collect the thrust data of syringe B in the uniform speed segment through the pressure sensor corresponding to syringe B, and obtain the working thrust P2 of syringe B after filtering. 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 approaching speed according to the deviation algorithm to rapidly approach the pressure target value W1 of the pressure inside the barrel of syringe A; after reaching the pressure target value W1, set the initial speed parameter of syringe A according to the preset ratio of the constant-speed section speed; S27. Commutation: Start commutation when the pushing position of syringe B reaches the preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, causing the speed of syringe A to increase while the speed of syringe B decreases, and keeping the sum of their speeds equal to the constant-speed section speed; when the speed of syringe B is 0 and the speed of syringe A is equal to the constant-speed section speed, the commutation is completed; S28. Pre-pressurize 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 approaching speed according to the deviation algorithm to rapidly approach the pressure target value W2 of the pressure inside the barrel of syringe B; after reaching the pressure target value W2, set the initial speed parameter of syringe B according to the preset ratio of the constant-speed section speed; S29. Commutation: Start commutation when the pushing position of syringe A reaches the preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, causing the speed of syringe A to decrease while the speed of syringe B increases, and keeping the sum of their speeds equal to the constant-speed section speed; when the speed of syringe A is 0 and the speed of syringe B is equal to the constant-speed section speed, the commutation is completed; S30. Repeat steps S26 - S29 until the preparation of the nano-drug is completed.

[0018] Furthermore, in step S2, it also includes: Detect the bubbles in the corresponding pipelines through the first bubble sensor and the second bubble sensor respectively; When the first bubble sensor detects bubbles, the controller controls the corresponding suction and pushing mechanism to stop the suction action and gives an alarm prompt; When the second bubble sensor detects bubbles, the controller controls the peristaltic pump to stop running, closes the control valve on the sample recovery pipe, and correspondingly opens the control valve on the waste recovery pipe, and gives an alarm prompt.

[0019] Furthermore, in step S2, it also includes: Detect the bubbles in the corresponding pipelines through the first bubble sensor and the second bubble sensor respectively; When the first bubble sensor detects bubbles, enter the first response state; After 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 time period is discharged into the waste recovery pipe, and the nano-drug stock solution during the non-bubble-affected time period is discharged into the sample recovery pipe; If the first bubble sensor continuously receives 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; When the second bubble sensor receives a bubble signal, it enters the fourth response state; After 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 time period is discharged into the waste recovery pipe, and the nano-drug stock solution during the non-bubble-affected time period is discharged into the sample recovery pipe; If the second bubble sensor continuously receives 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 at the same time the peristaltic pump stops running and gives an alarm prompt.

[0020] Further, in step S2, it also includes: detecting bubbles in the same first pipeline through at least two first bubble sensors, and detecting bubbles in the same dilution-phase inlet pipe through at least two second bubble sensors; After the previous first bubble sensor receives a bubble signal, it enters the first response state; After only one of the previous first bubble sensor and the next first bubble sensor receives a bubble signal, it enters the second response state; After both the previous first bubble sensor and the next first bubble sensor receive bubble signals, it enters the third response state; After the previous second bubble sensor receives a bubble signal, it enters the fourth response state; After only one of the previous second bubble sensor and the next second bubble sensor receives a bubble signal, it enters the fifth response state; After both the previous second bubble sensor and the next second bubble sensor receive bubble signals, it enters the sixth response state.

[0021] Compared with the prior art, the present invention has at least the following beneficial effects: By setting a feeding device including a liquid path commutation and coordination integrated block and two suction and push mechanisms, and making the input end and output end of the liquid path commutation and coordination integrated block communicate with the raw material liquid and the microfluidic chip respectively, and making the two suction and push mechanisms operate in reverse alternately and configuring a one-way valve assembly in the liquid path commutation and coordination integrated block, when the two suction and push mechanisms operate in reverse alternately, they can cooperate with the one-way valve assembly so that there is always only a raw material liquid input path communicating with one of the suction and push mechanisms and a raw material liquid output path communicating with the other suction and push mechanism in a conducting state. In this way, when the two suction and push mechanisms suck or push, they can continuously input the raw material liquid into the liquid path commutation and coordination integrated block or output the raw material liquid from the liquid path commutation and coordination integrated block to the microfluidic chip, and there will be no cross-flow of the raw material liquid in the liquid path commutation and coordination integrated block, thus realizing the functions of stable, continuous and non-cross-flow transportation of the raw material liquid, ensuring the controllability of the nano-drug preparation process in the microfluidic chip, and achieving the purpose of improving the preparation effect. Description of the Drawings

[0022] Figure 1 Schematic structural diagram of the nano-drug preparation system in Embodiment 1 of the present invention; Figure 2 Another perspective structural diagram of the nano-drug preparation system in Embodiment 1 of the present invention; Figure 3 Schematic process flow structural diagram of the nano-drug preparation system in Embodiment 1 of the present invention; Figure 4 Schematic structural diagram of the liquid path commutation and coordination integrated block of the nano-drug preparation system in Embodiment 1 of the present invention; Figure 5 Schematic cross-sectional structural diagram of the liquid path commutation and coordination integrated block of the nano-drug preparation system in Embodiment 1 of the present invention; Figure 6 Schematic diagram of the liquid flow direction in the liquid path commutation and coordination integrated block when the syringe in the nano-drug preparation system in Embodiment 1 of the present invention performs a suction action; Figure 7 Schematic diagram of the liquid flow direction in the liquid path commutation and coordination integrated block when the syringe in the nano-drug preparation system in Embodiment 1 of the present invention performs a push action.

[0023] Reference Numerals in the Drawings: 1. Microfluidic chip; 2. Liquid path commutation and coordination integrated block; 21. Input end; 22. Output end; 23. First one-way valve; 3. Suction and push mechanism; 31. Syringe; 32. Driving member; 4. Fluid channel; 41. First flow channel; 42. Second flow channel; 43. Connecting flow channel; 5. Connecting plate; 6. Pressure sensor; 7. First pipeline; 8. First bubble sensor; 9. Second pipeline; 91. Second one-way valve; 10. Dilute-phase liquid inlet pipe; 11. Sample recovery pipe; 12. Waste recovery pipe; 13. Second bubble sensor; 14. Peristaltic pump; 15. Control valve. Detailed implementation mode

[0024] The nano-drug preparation system and preparation process of the present invention will be described in more detail below with reference to the schematic diagrams, in which the preferred embodiments of the present invention are shown. It should be understood that those skilled in the art can modify the present invention described herein while still achieving the advantageous effects of the present invention. Therefore, the following description should be understood as a broad knowledge for those skilled in the art and not as a limitation to the present invention.

[0025] In the following paragraphs, the present invention will be described more specifically by way of example with reference to the accompanying drawings. According to the following description, the advantages and features of the present invention will be clearer. It should be noted that the drawings are all in a very simplified form and use non-precise scales, only for the purpose of facilitating and clearly assisting in explaining the purpose of the embodiments of the present invention.

[0026] Embodiment 1 As Figures 1 to 3 shown, an embodiment of the present invention provides a nano-drug preparation system, including a microfluidic chip 1, at least two feeding devices and a controller.

[0027] At least two of the feeding devices are all connected to the microfluidic chip 1 and are respectively used for the transportation of different raw material liquids.

[0028] Each of the feeding devices includes a liquid path commutation and coordination integrated block 2 and two suction and push mechanisms 3.

[0029] Among them, the liquid path commutation and coordination integrated block 2 has an input end 21 and an output end 22, which are respectively used for the input and output of the raw material liquid. That is, the liquid path commutation and 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 mechanisms 3.

[0030] Specifically, the two suction and push mechanisms 3 are all connected to the liquid path commutation and coordination integrated block 2. 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 all signal-connected to the controller, and the controller is used to control the reverse alternating operation of the two suction and push mechanisms 3. That is, the operation of the two suction and push mechanisms 3 is coordinated by the controller to realize the continuous input and output of the raw material liquid.

[0031] To better understand the above operating principle, an example is listed here, as shown below: For example, when one of the suction and push mechanisms 3 absorbs the raw material liquid through the input end 21 of the liquid path reversing coordination integrated block 2, the other suction and push mechanism 3 pushes the raw material liquid to the output end 22 of the liquid path reversing coordination integrated block 2. Conversely, when one of the suction and push mechanisms 3 pushes the absorbed raw material liquid to the output end 22 of the liquid path reversing coordination integrated block 2, the other suction and push mechanism 3 absorbs the raw material liquid through the input end 21 of the liquid path reversing coordination integrated block 2. In this way, the raw material liquid continuously enters the liquid path reversing coordination integrated block 2 and the raw material liquid continuously flows from the output end 22 of the liquid path reversing coordination integrated block 2 to the microfluidic chip 1, realizing the uninterrupted input and output of the raw material liquid.

[0032] In order to prevent cross-talk or interference in the input and output processes of the raw liquid when the two suction and push mechanisms 3 are running in reverse alternating directions, the liquid path reversing coordination integrated block 2 is further limited to ensure stable, continuous and cross-talk-free transportation of the raw liquid.

[0033] Specifically, the fluid path reversing coordination integrated block 2 has a built-in one-way valve assembly.

[0034] Wherein, 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. That is, when one of the suction-push mechanisms 3 performs a suction action, the raw material liquid can only enter the suction-push mechanism 3 from the input end 21.

[0035] 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. 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 from the suction-push mechanism 3.

[0036] Therefore, through the coordinated cooperation of the one-way valve assembly and the two suction and push mechanisms 3 that operate in opposite directions, the input and output of the raw material liquid can always be in a state of dynamic equilibrium, thereby realizing the function of stable, continuous and non-cross-liquid delivery of the raw material liquid, ensuring the controllability of the nano-drug preparation process in the microfluidic chip 1, and achieving the purpose of improving the preparation effect.

[0037] In this embodiment, by providing a feeding device including a liquid path commutation and coordination integrated block 2 and two suction and push mechanisms 3, and enabling the input end 21 and the output end 22 of the liquid path commutation and coordination integrated block 2 to be respectively connected to the raw material liquid and the microfluidic chip 1, and enabling the two suction and push mechanisms 3 to operate alternately in reverse and configuring a one-way valve assembly in the liquid path commutation and coordination integrated block 2, when the two suction and push mechanisms 3 operate alternately in reverse, they can cooperate with the one-way valve assembly so that there is always only a raw material liquid input path connected to one of the suction and push mechanisms 3 and a raw material liquid output path connected to the other suction and push mechanism 3 in a conducting state. In this way, when the two suction and push mechanisms 3 suck or push, the raw material liquid can be continuously input into the liquid path commutation and coordination integrated block 2 or output from the liquid path commutation and coordination integrated block 2 to the microfluidic chip 1, and the raw material liquid in the liquid path commutation and coordination integrated block 2 will not flow crosswise, thereby realizing the function of stable, continuous and non-cross-flow transportation of the raw material liquid, ensuring the controllability of the nano-drug preparation process in the microfluidic chip 1, and achieving the purpose of improving the preparation effect.

[0038] As Figures 4 to 7 shown, in this embodiment, the liquid path commutation and 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.

[0039] Specifically, the liquid path commutation and coordination integrated block 2 is internally provided with a 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. That is, by providing 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 liquid path commutation and coordination integrated block 2 from the input end 21 orderly under the action of the suction and push mechanism 3 and then flow out from the output end 22.

[0040] Among them, the one-way valve assembly includes 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 and are used to conduct or cut off the raw material liquid input path and output path, effectively preventing the phenomenon of backflow or cross-flow of the raw material liquid during the reverse alternating operation of the suction and push mechanism 3.

[0041] 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.

[0042] 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.

[0043] Among them, one of the two second flow channels 42 is interconnected with the two first flow channels 41 through the communication flow channel 43 on its same side; and the other one of the two second flow channels 42 is also interconnected with the two first flow channels 41 through the communication flow channel 43 on its same side. That is, by providing the communication flow channel 43, the second flow channel 42 is connected to the first flow channel 41 to form an input path and an output path for the raw material liquid, so that the two suction and push mechanisms 3 can conveniently transfer the raw material liquid with the first flow channel 41 under different working states, further improving the continuity and stability of the raw material liquid transportation, and at the same time helping to balance the pressure in the flow channel and prevent the adverse effects of pressure fluctuations on the nano-drug preparation process.

[0044] It should be noted that two first one-way valves 23 arranged in opposite directions are arranged on each group of the communication flow channels 43, so that the two first one-way valves 23 can respectively control the flow direction of the raw material liquid under different working states of the suction and push mechanism 3.

[0045] For example, when a suction and push mechanism 3 performs a suction action (as Figure 6 shown), one of the first one-way valves 23 is opened, so that the raw material liquid flows from the first flow channel 41 into the second flow channel 42 corresponding to this suction and push mechanism 3 to complete the input of the raw material liquid, while the first one-way valve 23 arranged in the opposite direction corresponding to this first one-way valve 23 blocks the output path.

[0046] When this suction and push mechanism 3 performs a pushing action (as Figure 7 shown), the other first one-way valve 23 is opened, so that the raw material liquid flows from the second flow channel 42 into the first flow channel 41 and flows out from the output end 22 to complete the output of the raw material liquid, while the first one-way valve 23 arranged in the opposite direction corresponding to this first one-way valve 23 blocks the input path to prevent the raw material liquid from flowing back.

[0047] In other embodiments, a specific suction and push mechanism 3 is also proposed to further improve the stability during the input and output of the raw material liquid, thereby improving the mixing effect of the subsequent raw material liquid in the microfluidic chip 1 and improving the preparation quality of the nano-drug.

[0048] Specifically, the suction and push mechanism 3 includes a syringe 31, a holding structure, and a driving member 32.

[0049] Among them, the injection end of the syringe 31 is connected to the liquid path commutation and coordination integrated block 2, and is used to complete the input and output of the raw material liquid by suction and pushing.

[0050] 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 inputting and outputting the raw material liquid.

[0051] In this embodiment, the driving member 32 includes a servo motor and a reciprocating lead screw connected to the servo motor.

[0052] Wherein, the reciprocating lead 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 lead screw.

[0053] In addition, a pressure sensor 6 is provided inside the connecting plate 5. The pressure sensor 6 contacts the push handle of the syringe 31 and is used to detect the pressure inside the barrel of the syringe 31.

[0054] The controller is signal-connected to the pressure sensor 6 and the servo motor, and is used to adjust the operating frequency of the servo motor according to the pressure signal output by the pressure sensor 6.

[0055] That is, by setting the controller, the pressure sensor 6 and the servo motor, an intelligent feedback adjustment system is formed. For example, by installing the pressure sensor 6 inside the connecting plate 5 and contacting the push handle of the syringe 31, it can real-time monitor the pressure change inside the barrel of the syringe 31 and convert these pressure data into electrical signals for output. When the controller receives the pressure signal from the pressure sensor 6, it will analyze and process the signal to drive the push handle of the syringe 31 through the reciprocating lead screw to control the moving speed and force of the piston.

[0056] This device ensures that the pressure inside the barrel of the syringe 31 is always within a suitable range during the process of sucking and pushing the raw material liquid by real-time monitoring and adjusting the pressure. This avoids the instability of the raw material liquid transportation caused by excessive pressure fluctuations, such as preventing the raw material liquid from spraying too fast due to too high pressure and the transportation interruption due to too low pressure, continuously and stably supplies the raw material liquid to the microfluidic chip 1, and ensures the coherence of the nano-drug preparation process.

[0057] 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 moving speed of the piston, and reduce the pushing or sucking 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 moving speed of the piston, and increase the pushing or sucking force.

[0058] In other embodiments, the liquid path commutation coordination integrated block 2 is further defined. Specifically, the input end 21 of each said liquid path commutation coordination integrated block 2 is connected to a containing device loaded with raw liquid through a corresponding first pipeline 7.

[0059] Wherein, a plurality of first bubble sensors 8 are arranged on each said first pipeline 7, and the first bubble sensors 8 on each said first pipeline 7 are all connected to the controller in signal, and the controller controls the action of the corresponding suction and push mechanism 3 according to the detection result of the first bubble sensors 8.

[0060] This device is provided with a plurality of first bubble sensors 8 on the first pipeline 7 for segmentally detecting whether the raw liquid in the first pipeline 7 is emptied.

[0061] In a specific example, when a plurality of first bubble sensors 8 all detect the appearance of bubbles, the suction and push mechanism 3 is controlled to stop running.

[0062] In a further embodiment, the output end 22 of each said liquid path commutation coordination integrated block 2 is connected to the microfluidic chip 1 through a corresponding second pipeline 9, and a second one-way valve 91 is arranged on the second pipeline 9, and the second one-way valve 91 is used to prevent liquid cross-flow. That is, by setting the second one-way valve 91 to prevent the raw liquid in multiple second pipelines 9 from flowing crosswise due to flow velocity reasons (such as when the raw liquid flow velocity in one second pipeline 9 is fast while the raw liquid flow velocity in another second pipeline 9 is slow).

[0063] In other embodiments, the nano-drug preparation system further includes a sample recovery pipe 11, the liquid inlet end of the sample recovery pipe 11 is connected to the outlet end of the microfluidic chip 1, and a dilution phase inlet pipe 10 and a waste recovery pipe 12 are sequentially arranged on the sample recovery pipe 11 along the liquid output direction.

[0064] Wherein, the dilution phase inlet pipe 10 is used to dilute the raw liquid mixture output by the microfluidic chip 1 to form a nano-drug stock solution.

[0065] A plurality of second bubble sensors 13 and a peristaltic pump 14 are sequentially arranged on the dilution phase inlet pipe 10 along the output direction. By setting the second bubble sensors 13 to monitor the dilution liquid, that is, to monitor whether the dilution liquid is emptied, and by setting the peristaltic pump 14 to provide power for the input of the dilution liquid.

[0066] Control valves 15 are provided on both the waste recycling pipe 12 and the sample recycling pipe 11. The control valve 15 on the waste recycling pipe 12 and the control valve 15 on the sample recycling pipe 11 are in a mutually exclusive working state. That is, when one of the control valves 15 is opened, the other control valve 15 is closed, realizing the unidirectional outflow of the nano-drug stock solution to respectively complete the sample recycling of the nano-drug stock solution or the waste recycling of the raw material liquid mixture.

[0067] A plurality of the second bubble sensors 13, the peristaltic pump 14, and the two control valves 15 are all connected to the controller by signals. 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.

[0068] For example, when the second bubble sensor 13 detects bubbles, it indicates that the diluent has been emptied. Therefore, 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 recycling pipe 12 and correspondingly closes the control valve 15 on the sample recycling pipe 11 to prevent the raw material liquid mixture from entering the sample recycling pipe 11 and contaminating the obtained nano-drug stock solution, achieving the purpose of ensuring product quality and classification recycling efficiency.

[0069] Embodiment 2 On the basis of Embodiment 1, this embodiment also proposes a nano-drug preparation process, including the following steps: S1. Provide the nano-drug preparation system as described in the above embodiment; S2. The controller of the nano-drug preparation system controls the two suction and push mechanisms 3 to run in reverse alternately. During this process, through the fluid channels 4 and the one-way valve assemblies built in the liquid path commutation and coordination integrated block 2, the raw material liquid is continuously input into the liquid path commutation and coordination integrated block 2 from the accommodating device loaded with the raw material liquid under the suction and push actions of the two suction and push mechanisms 3, and is output from the output end 22 of the liquid path commutation and coordination integrated block 2 to the microfluidic chip 1; S3. Different raw material liquids are mixed in the microchannels 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. Transport the prepared nano-drug stock solution to the sample collection container.

[0070] Through the above steps, the two suction and push mechanisms 3 can continuously input the raw material liquid into the liquid path commutation and coordination integrated block 2 or output it from the liquid path commutation and coordination integrated block 2 to the microfluidic chip 1 during suction or pushing, and there is no cross-flow of the raw material liquid in the liquid path commutation and coordination integrated block 2, thus realizing the functions of stable, continuous, and non-cross-flow transportation of the raw material liquid, ensuring the controllability of the nano-drug preparation process in the microfluidic chip 1, and achieving the purpose of improving the preparation effect.

[0071] In this embodiment, to further improve the performance of stable transportation of the raw material liquid, the control mode of the controller is further defined herein.

[0072] Specifically, the process in which the controller controls the two suction-push mechanisms 3 to operate in reverse alternately includes: S21. Start syringe A: Start one of the suction-push mechanisms 3 so that the syringe A of this suction-push mechanism 3 performs a pushing action; S22. Collect the thrust data of syringe A: Collect the thrust data of the uniform speed section of syringe A through the pressure sensor 6 corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering; S23. Pre-press syringe B: According to the working thrust P1 obtained in step S22, set the pressure target value W2' of the pressure sensor 6 corresponding to the syringe B of the other suction-push mechanism 3, and set the approaching speed according to the deviation algorithm to make the pressure in the barrel of syringe B quickly approach 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 uniform speed section speed; S24. Reverse: Start to reverse when the pushing position of syringe A reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, so that the speed of syringe A decreases while the speed of syringe B increases, and the sum of their speeds is kept equal to the uniform speed section speed; when the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section speed, the reverse is completed; S25. Collect the thrust data of syringe B: Collect the thrust data of the uniform speed section of syringe B through the pressure sensor 6 corresponding to syringe B, and obtain the working thrust P2 of syringe B after filtering; S26. Pre-press syringe A: According to 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 approaching speed according to the deviation algorithm to make the pressure in the barrel of 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 uniform speed section speed; 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 uniform speed section speed.

[0073] S27. Commutation: Commutation starts when the pushing position of syringe B reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, increasing the speed of syringe A and decreasing the speed of syringe B, and keeping the sum of their speeds equal to the speed in the constant-speed section. When the speed of syringe B is 0 and the speed of syringe A is equal to the speed in the constant-speed section, the commutation is completed. 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. S29. Pre-press syringe B: According to 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 approaching speed according to the deviation algorithm to make the pressure in the barrel of syringe B quickly approach 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 speed in the constant-speed section. S30. Repeat steps S24 - S29 until the preparation of the nano-drug is completed.

[0074] This method realizes the efficient collaborative work of the two suction and pushing mechanisms 3 through a triple mechanism of pressure pre-pressurization - speed compensation - data feedback, ensuring the stability of the pressure and flow rate of the raw material liquid during transportation, providing a reliable liquid path control basis for the preparation of nano-drugs. And by re-collecting the working thrust before each pre-pressurization, it can effectively eliminate the influence of other factors (such as the deformation of the syringe rubber stopper) and complex situations on the pressure in the syringe, further ensuring the stability of the pressure and flow rate of the raw material liquid during transportation.

[0075] In other embodiments, another method for the controller to control the two suction and pushing mechanisms 3 is also proposed. Compared with the above control method, this method can not only ensure the stability of the raw material liquid during transportation, but also simplify the control logic to reduce the data processing volume, and correspondingly reduce the operation cost and maintenance difficulty of the equipment, achieving the purpose of facilitating popularization and application in the scenario where the outlet pressure of the raw material liquid remains unchanged.

[0076] Specifically, the process of the controller controlling the two suction and pushing mechanisms 3 to run in reverse alternately includes: S21. Start syringe A: Start one of the suction and pushing mechanisms 3, and make the syringe A of this suction and pushing mechanism 3 perform the pushing action. 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. 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 approaching speed according to the deviation algorithm to quickly approach the pressure target value W2' of the pressure inside the barrel of syringe B. 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. S24. Commutation: Start commutation when the pushing position of syringe A reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, so that the speed of syringe A decreases while the speed of syringe B increases, and the sum of their speeds is kept 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 commutation is completed. S25. Collect the thrust data of syringe B: Collect the thrust data of the constant speed segment of syringe B through the pressure sensor 6 corresponding to syringe B, and obtain the working thrust P2 of syringe B after filtering. 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 approaching speed according to the deviation algorithm to quickly approach the pressure target value W1 of the pressure inside the barrel of syringe A. 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. S27. Commutation: Start commutation when the pushing position of syringe B reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, so that the speed of syringe A increases while the speed of syringe B decreases, and the sum of their speeds is kept 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 commutation is completed. S28. Pre-pressurize 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 approaching speed according to the deviation algorithm to quickly approach the pressure target value W2 of the pressure inside the barrel of syringe B. 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. S29. Commutation: Start commutation when the pushing position of syringe A reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, so that the speed of syringe A decreases while the speed of syringe B increases, and the sum of their speeds is kept 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 commutation is completed. S30. Repeat steps S26 - S29 until the preparation of the nano - drug is completed.

[0077] By setting a fixed pre - pressing reference (i.e., always based on the initial thrust data of syringe A) and simplifying the control process (i.e., skipping some commutation data acquisition steps), compared with the method of re - acquiring the working thrust before each pre - pressing above, this method can reduce the system switching impact, lower mechanical losses and data processing loads, achieving the purposes of improving the preparation efficiency, extending the equipment life, reducing costs and simplifying maintenance.

[0078] In a further embodiment, step S2 is further defined.

[0079] Specifically, in step S2, it further includes: detecting the bubbles in the corresponding pipelines through the first bubble sensor 8 and the second bubble sensor 13 respectively; When the first bubble sensor 8 detects bubbles, the controller controls the corresponding suction - push mechanism 3 to stop the suction action and gives an alarm prompt, so as to prevent the bubbles from entering the liquid path system along with the raw material liquid, achieving the purpose of ensuring the stability and purity of the raw material liquid transportation.

[0080] 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 pipe 11, and correspondingly opens the control valve 15 on the waste recovery pipe 12, gives an alarm prompt, and prevents the raw material liquid mixture from entering the sample recovery pipe 11, so as to avoid contaminating the obtained nano - drug stock solution, achieving the purpose of ensuring product quality and classification recovery efficiency.

[0081] In addition, in step S2, it further includes: detecting the bubbles in the corresponding pipelines through the first bubble sensor 8 and the second bubble sensor 13 respectively; When the first bubble sensor 8 detects bubbles, it enters the first response state; 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 in the time period affected by bubbles is discharged into the waste recovery pipe 12, and the nano - drug stock solution in the time period not affected by bubbles is discharged into the sample recovery pipe 11; If the first bubble sensor 8 continuously receives bubble information, it enters the third response state. At this time, the controller controls the corresponding suction - 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 the fourth response state; After 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 recovery pipe 12, and the nano-drug stock solution during the non-bubble-affected period is discharged into the sample recovery pipe 11; If the second bubble sensor 13 continuously receives 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 at the same time, the peristaltic pump 14 stops running and gives an alarm prompt.

[0082] In this method, the first bubble sensor 8 and the second bubble sensor 13 are used to respectively detect the bubbles in the corresponding pipelines in real time. 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 during the bubble-affected period into the waste recovery pipe 12 and the non-bubble-affected period into the sample recovery pipe 11 by switching the control valve 15 at the back end. 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 give an 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 also 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 give an alarm. Thus, it can accurately distinguish and process the liquid with and without bubbles, achieving the purpose of minimizing the scrap rate, ensuring the quality stability of products and the safe operation of equipment to the greatest extent.

[0083] In addition, in step S2, it further includes: detecting the bubbles in the same first pipeline 7 through at least two first bubble sensors 8, and detecting the bubbles in the same dilution phase inlet pipe 10 through at least two second bubble sensors 13; After the previous first bubble sensor 8 receives the bubble signal, it enters the first response state; After only one of the previous first bubble sensor 8 and the subsequent first bubble sensor 8 receives the bubble signal, it enters the second response state; After both the previous first bubble sensor 8 and the subsequent first bubble sensor 8 receive the bubble signal, it enters the third response state; After the previous second bubble sensor 13 receives the bubble signal, it enters the fourth response state; After only one of the previous second bubble sensor 13 and the subsequent second bubble sensor 13 receives the bubble signal, it enters the fifth response state; After both the previous second bubble sensor 13 and the subsequent second bubble sensor 13 receive the bubble signal, it enters the sixth response state.

[0084] That is, by setting at least two first bubble sensors 8 and at least two second bubble sensors 13, which are respectively used for bubble warning and bubble determination, when bubble signals are received by both the front and rear first bubble sensors 8 or the two second bubble sensors 13, the corresponding devices (i.e., the driving member 32 and the peristaltic pump 14) are controlled to stop running.

[0085] In this method, at least two first bubble sensors 8 are set on the same first pipeline 7 and at least two second bubble sensors 13 are set on the same diluent inlet pipe 10 to detect bubbles. According to the situation of different sensors receiving bubble signals, they respectively enter corresponding response states, and thus can more accurately judge the distribution, quantity and dynamic change of bubbles in the pipeline, achieving the purpose of timely and targeted treatment of bubble problems and ensuring the quality of raw material liquid transportation and the preparation effect of nano drugs.

[0086] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and its equivalent technologies, the present invention also intends to include these changes and modifications.

Claims

1. A nano-drug preparation system, characterized in that, It includes a microfluidic chip (1), at least two feeding devices and a controller; At least two of the feeding devices are both connected to the microfluidic chip (1) and are respectively used for transporting different raw material liquids; Each of the feeding devices includes a liquid path commutation and coordination integrated block (2) and two suction and push mechanisms (3); The liquid path commutation and coordination integrated block (2) has an input end (21) and an output end (22), which are respectively used for the input and output of the raw material liquid; The two suction and push mechanisms (3) are both connected to the fluid channels of the liquid path commutation and coordination integrated block (2). Each of the suction and push mechanisms (3) realizes the input or output of the raw material liquid by means of suction or pushing. The driving ends of the two suction and push mechanisms (3) are both signal-connected to the controller, and the controller is used to control the two suction and push mechanisms (3) to operate in reverse alternation; The liquid path commutation and coordination integrated block (2) is internally provided with a one-way valve assembly; The one-way valve assembly is configured as: When any one of the suction and push mechanisms (3) performs a suction action, it conducts the raw material liquid input path from the input end (21) to this suction and push mechanism (3), and cuts off the raw material liquid output path from the output end (22) to this suction and push mechanism (3); When any one of the suction and push mechanisms (3) performs a push action, it conducts the raw material liquid output path from the output end (22) to this suction and push mechanism (3), and cuts off the raw material liquid input path from the input end (21) to this suction and push mechanism (3).

2. The nano-drug preparation system according to claim 1, wherein, The liquid path commutation and coordination integrated block (2) is internally provided with a 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 includes 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).

3. The nano-drug preparation system according to claim 2, wherein, The fluid channel (4) includes 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); Among them, one of the two second flow channels (42) is interconnected with the two first flow channels (41) through the connecting flow channel (43) on its same side; the other one of the two second flow channels (42) is also interconnected with the two first flow channels (41) through the connecting flow channel (43) on its same side; two first one-way valves (23) arranged in opposite directions are arranged on each group of connecting flow channels (43).

4. The nano-drug preparation system according to claim 1, wherein, The suction and push mechanism (3) includes a syringe (31), a holding structure and a driving member (32); The injection end of the syringe (31) is connected to the liquid path commutation and coordination integrated block (2); The syringe (31) is inserted into the holding structure for fixing the barrel of the syringe (31), and the driving member (32) is connected to the push handle of the syringe (31) for driving the piston of the syringe (31) to reciprocate within the barrel of the syringe (31).

5. The nano-drug preparation system according to claim 4, characterized in that, The driving member (32) includes a servo motor and a reciprocating lead screw connected to the servo motor; The reciprocating lead screw is connected to the push handle of the syringe (31) through a connecting plate (5), and the connecting plate (5) reciprocates in a predetermined direction under the rotational power of the reciprocating lead screw.

6. The nano-drug preparation system according to claim 5, characterized in that, A pressure sensor (6) is provided within the connecting plate (5), and the pressure sensor (6) contacts the push handle of the syringe (31) for detecting the pressure within the barrel of the syringe (31); The controller is signal-connected to the pressure sensor (6) and the servo motor for adjusting the operating frequency of the servo motor according to the pressure signal output by the pressure sensor (6).

7. The nano-drug preparation system according to claim 1, characterized in that, The input end (21) of each liquid path commutation and coordination integrated block (2) is connected to a containing device loaded with raw material liquid through a corresponding first pipeline (7); A plurality of first bubble sensors (8) are provided on each of the first pipelines (7); The first bubble sensors (8) on each of the first pipelines (7) are signal-connected to the controller, and the controller controls the operation of the corresponding suction and push mechanism (3) according to the detection results of the first bubble sensors (8).

8. The nano-drug preparation system according to claim 1, wherein, The output end (22) of each liquid path commutation and coordination integrated block (2) is connected to the microfluidic chip (1) through a corresponding second pipeline (9), and a second one-way valve (91) is provided on the second pipeline (9) for preventing liquid backflow.

9. The nano-drug preparation system according to claim 1, characterized in that, It 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 a dilution phase inlet tube (10) and a waste recovery tube (12) are sequentially arranged on the sample recovery tube (11) along the liquid output direction; The dilution phase inlet tube (10) is used for diluting the raw material liquid mixture output by the microfluidic chip (1) to form a nano-drug stock solution; A plurality of second bubble sensors (13) and a peristaltic pump (14) are sequentially arranged on the dilution phase inlet tube (10) along the output direction; Control valves (15) are provided on both the waste recovery tube (12) and the sample recovery tube (11), 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 operating state; A plurality of the second bubble sensors (13), the peristaltic pump (14), and the two control valves (15) are all signal-connected to the controller, and the controller controls the operating states of the peristaltic pump (14) and the two control valves (15) according to the detection results of the second bubble sensors (13).

10. A preparation process of a nano-drug, characterized in that, It includes the following steps: S1. Provide the nano-drug preparation system according to any one of claims 1-9; S2. The controller of the nano-drug preparation system controls the two suction-push mechanisms (3) to operate in reverse and alternately. During this process, through the fluid channel (4) and the one-way valve assembly built in the liquid path commutation and coordination integrated block (2), the raw material liquid is continuously input into the liquid path commutation and coordination integrated block (2) from the accommodating device loaded with the raw material liquid under the suction and push effects of the two suction-push mechanisms (3), and is output from the output end (22) of the liquid path commutation and coordination integrated block (2) to the microfluidic chip (1); S3. Different raw material liquids are mixed in the microchannels of the microfluidic chip (1) to form a raw material liquid mixture, and the raw material liquid mixture is diluted to obtain the nano-drug stock solution; S4. The prepared nano-drug stock solution is transported to the sample collection container.

11. The nano-drug preparation process according to claim 10, characterized in that, The process of the controller controlling the two suction-push mechanisms (3) to operate in reverse and alternately includes: S21. Start syringe A: Start one of the suction-push mechanisms (3) to make the syringe A of this suction-push mechanism (3) perform a pushing action; S22. Collect the thrust data of syringe A: Collect the thrust data of the uniform speed section of syringe A through the pressure sensor (6) corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering; S23. Pre-press syringe B: According to the working thrust P1 obtained in step S22, set the pressure target value W2' of the pressure sensor (6) corresponding to syringe B of the other suction-push mechanism (3), and set the approaching speed according to the deviation algorithm to make the pressure in the cylinder of syringe B quickly approach 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 uniform speed section speed; S24. Commutation: Start commutation when the pushing position of syringe A reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, so that the speed of syringe A decreases while the speed of syringe B increases, and the sum of their speeds remains equal to the uniform speed section speed; when the speed of syringe A is 0 and the speed of syringe B is equal to the uniform speed section speed, the commutation is completed; S25. Collect the thrust data of syringe B: Collect the thrust data of the uniform speed section of syringe B through the pressure sensor (6) corresponding to syringe B, and obtain the working thrust P2 of syringe B after filtering; S26. Pre-press syringe A: According to 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 approaching speed according to the deviation algorithm to make the pressure in the cylinder of 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 uniform speed section speed; S27. Commutation: Commutation starts when the pushing position of syringe B reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, causing the speed of syringe A to increase while the speed of syringe B decreases, and maintaining the sum of their speeds equal to the speed in the uniform speed segment. When the speed of syringe B is 0 and the speed of syringe A is equal to the speed in the uniform speed segment, the commutation is completed. S28. Collect the thrust data of syringe A: Collect the thrust data of syringe A in the uniform speed segment through the pressure sensor (6) corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering. S29. Pre-pressurize syringe B: According to 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 approaching speed according to the deviation algorithm to quickly approach the pressure target value W2 of the pressure inside the barrel of syringe B. After reaching the pressure target value W2, set the initial speed parameter of syringe B according to the preset ratio of the uniform speed segment speed. S30. Repeat steps S24 - S29 until the preparation of the nano-drug is completed.

12. The nano-drug preparation process according to claim 10, wherein, The process of the controller controlling the two suction and pushing mechanisms (3) to run in reverse alternately includes: S21. Start syringe A: Start one of the suction and pushing mechanisms (3) to make the syringe A of this suction and pushing mechanism (3) perform the pushing action. S22. Collect the thrust data of syringe A: Collect the thrust data of syringe A in the uniform speed segment through the pressure sensor (6) corresponding to syringe A, and obtain the working thrust P1 of syringe A after filtering. S23. Pre-pressurize syringe B: According to the working thrust P1 obtained in step S22, set the pressure target value W2' of the pressure sensor (6) corresponding to syringe B of the other suction and pushing mechanism (3), and set the approaching speed according to the deviation algorithm to quickly approach the pressure target value W2' of the pressure inside the barrel of syringe B. After reaching the pressure target value W2', set the initial speed parameter of syringe B according to the preset ratio of the uniform speed segment speed. S24. Commutation: Commutation starts when the pushing position of syringe A reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, causing the speed of syringe A to decrease while the speed of syringe B increases, and maintaining the sum of their speeds equal to the speed in the uniform speed segment. When the speed of syringe A is 0 and the speed of syringe B is equal to the speed in the uniform speed segment, the commutation is completed. S25. Collect the thrust data of syringe B: Collect the thrust data of syringe B in the uniform speed segment through the pressure sensor (6) corresponding to syringe B, and obtain the working thrust P2 of syringe B after filtering. S26. Pre-pressurize syringe A: According to 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 approaching speed according to the deviation algorithm to quickly approach the pressure target value W1 of the pressure inside the barrel of syringe A. After reaching the pressure target value W1, set the initial speed parameter of syringe A according to the preset ratio of the uniform speed segment speed. S27. Commutation: Commutation starts when the pushing position of syringe B reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, causing the speed of syringe A to increase while the speed of syringe B decreases, and maintaining the sum of their speeds equal to the speed in the constant-speed section. When the speed of syringe B is 0 and the speed of syringe A is equal to the speed in the constant-speed section, the commutation is completed. S28. Pre-pressing of syringe B: Based on the working thrust P2 obtained in step S25, set the pressure target value W2 for the pressure sensor (6) corresponding to syringe B, and set the approaching speed according to the deviation algorithm to rapidly approach the pressure target value W2 of the cylinder of syringe B. After reaching the pressure target value W2, set the initial speed parameter of syringe B according to a preset ratio of the constant-speed section speed. S29. Commutation: Commutation starts when the pushing position of syringe A reaches a preset ratio of the target position. During this process, the controller updates the speed parameters of syringe A and syringe B in real time, causing the speed of syringe A to decrease while the speed of syringe B increases, and maintaining the sum of their speeds equal to the speed in the constant-speed section. When the speed of syringe A is 0 and the speed of syringe B is equal to the speed in the constant-speed section, the commutation is completed. S30. Repeat steps S26 - S29 until the preparation of the nano-drug is completed.

13. The nano-drug preparation process according to claim 10, characterized in that, In step S2, it also includes: Detecting air bubbles in the corresponding pipelines through the first air bubble sensor (8) and the second air bubble sensor (13) respectively. When the first air bubble sensor (8) detects an air bubble, the controller controls the corresponding suction and pushing mechanism (3) to stop the suction action and gives an alarm prompt. When the second air bubble sensor (13) detects an air bubble, the controller controls the peristaltic pump (14) to stop running, closes the control valve (15) on the sample recovery pipe (11), and correspondingly opens the control valve (15) on the waste recovery pipe (12), and gives an alarm prompt.

14. The nano-drug preparation process according to claim 10, characterized in that, In step S2, it also includes: Detecting air bubbles in the corresponding pipelines through the first air bubble sensor (8) and the second air bubble sensor (13) respectively. When the first air bubble sensor (8) detects an air bubble, enter the first response state. When the air bubble information received by the first air bubble sensor (8) disappears, enter the second response state. At this time, by switching the control valve (15) at the back end, the nano-drug stock solution during the air bubble-affected time period is discharged into the waste recovery pipe (12), and the nano-drug stock solution during the non-air bubble-affected time period is discharged into the sample recovery pipe (11). If the first air bubble sensor (8) continuously receives air bubble information, enter the third response state. At this time, the controller controls the corresponding suction and pushing mechanism (3) to stop the suction action and gives an alarm prompt. When the second air bubble sensor (13) receives an air bubble signal, enter the fourth response state. After 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 time period is discharged into the waste recovery pipe (12), and the nano-drug stock solution during the non-bubble-affected time period is discharged into the sample recovery pipe (11). If the second bubble sensor (13) continuously receives 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 at the same time, the peristaltic pump (14) stops running and gives an alarm prompt.

15. The nanopharmaceutical preparation process according to claim 10, characterized in that, In step S2, it also includes: detecting bubbles in the same first pipeline (7) through at least two first bubble sensors (8), and detecting bubbles in the same dilution-phase inlet pipe (10) through at least two second bubble sensors (13). After the previous first bubble sensor (8) receives a bubble signal, it enters the first response state. After only one of the previous first bubble sensor (8) and the next first bubble sensor (8) receives a bubble signal, it enters the second response state. After both the previous first bubble sensor (8) and the next first bubble sensor (8) receive bubble signals, it enters the third response state. After the previous second bubble sensor (13) receives a bubble signal, it enters the fourth response state. After only one of the previous second bubble sensor (13) and the next second bubble sensor (13) receives a bubble signal, it enters the fifth response state. After both the previous second bubble sensor (13) and the next second bubble sensor (13) receive bubble signals, it enters the sixth response state.

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