Nano-drug production equipment based on microfluidic technology

Abstract

The utility model relates to nano-drug production equipment based on a microfluidic technology. The nano-drug production equipment comprises a first tank system, a second tank system and a mixing system, the first tank system comprises a first tank; the second tank system comprises a second tank; the mixing system comprises a mixing structure, and the first tank and the second tank are jointly communicated with the mixing structure. The utility model aims to provide the nano-drug production equipment based on the microfluidic technology to overcome the existing defects, so that drugs can be fully mixed, and nano-drug products which are accurate in size distribution and high in encapsulation efficiency can be obtained.

Description

Technical Field

[0001] The utility model relates to nanometer medicine production equipment based on microfluidic technology. Background Art

[0002] Microfluidics refers to the science and technology involved in systems that use microchannels (tens to hundreds of micrometers in size) to process or manipulate tiny fluids (nanoliter to attoliter in volume). It is an emerging interdisciplinary discipline involving chemistry, fluid physics, microelectronics, new materials, biology, and biomedical engineering. Due to their miniaturization and integration, microfluidic devices are often referred to as microfluidic chips, also known as labs on a chip and micro-total analytical systems.

[0003] One of the key characteristics of microfluidics is the unique fluid properties found in microscale environments, such as laminar flow and droplets. Leveraging these unique fluid phenomena, microfluidics enables a range of microfabrication and micromanipulation techniques that are difficult to accomplish with conventional methods. Currently, microfluidics is recognized for its enormous potential and broad application prospects in biomedical research.

[0004] Existing nanomedicine production requires precise control of the mixing ratio of the two phases so that they flow through the mixing structure at a certain ratio and are fully mixed in the mixing structure, thereby obtaining nanomedicine products with precise size distribution and high encapsulation rate. However, existing production equipment cannot meet the above production requirements. Therefore, to address the above problems, a nanomedicine production equipment and usage method based on microfluidic technology are proposed. Utility Model Content

[0005] The purpose of the utility model is to overcome the existing defects and provide a nano drug production equipment based on microfluidic technology, which can fully mix the drugs to obtain nano drug products with precise size distribution and high encapsulation rate.

[0006] The technical solution to achieve the above-mentioned purpose is: a nano-drug production equipment based on microfluidic technology, including a first tank system, a second tank system and a mixing system; the first tank system includes a first tank; the second tank system includes a second tank; the mixing system includes a mixing structure, and the first tank and the second tank are connected to the mixing structure.

[0007] A first stirring device is provided in the first tank; a first liquid level monitoring device is provided on the inner wall of the first tank; and the first tank is connected to a first circulation inlet.

[0008] Preferably, a second stirring device is provided in the second tank; a second liquid level monitoring device is provided on the inner wall of the second tank; and the second tank is connected to a second circulation inlet.

[0009] Preferably, the mixing system also includes a first pump, a second pump, a first flow detection device, a second flow detection device, a ninth valve and a fourteenth valve, wherein the first pump, the first flow detection device and the ninth valve are sequentially connected in series on the first delivery pipe, and one end of the first delivery pipe is connected to the mixing structure, and the other end is connected to the first circulation inlet.

[0010] Preferably, the mixing system also includes a second pump, and the second pump, the second flow detection device and the fourteenth valve are sequentially connected in series on the second delivery pipe, one end of the second delivery pipe is connected to the mixing structure, and the other end is connected to the second circulation inlet.

[0011] Preferably, the fourth valve, the eleventh valve and the seventeenth valve are connected in series on the first cleaning pipe in sequence, the left end of the first cleaning pipe is the first cleaning port, and the right end is the first air port; the first tank is connected to the third valve, and the other end of the third valve is connected to the first cleaning pipe; the first cleaning pipe is connected to the first delivery pipe through the tenth valve; the first circulation outlet is between the fourth valve and the eleventh valve.

[0012] Preferably, the eighth valve, the sixteenth valve and the eighteenth valve are connected in series on the second cleaning pipe in sequence, the left end of the second cleaning pipe is the second cleaning port, and the right end is the second air port; the second tank is connected to the seventh valve, and the other end of the seventh valve is connected to the second cleaning pipe; the second cleaning pipe is connected to the second delivery pipe through the fifteenth valve; the second circulation outlet is between the second cleaning port and the sixteenth valve.

[0013] Preferably, the first tank is provided with a first valve, a second valve and a nineteenth valve respectively; the upper end of the first valve is connected to the first fluid infusion port; the upper end of the second valve is connected to the first breathing port; the upper end of the nineteenth valve is connected to the third air port.

[0014] Preferably, the second tank is provided with a fifth valve, a sixth valve and a twentieth valve respectively; the upper end of the fifth valve is connected to the second fluid inlet; the upper end of the sixth valve is connected to the second breathing port; the upper end of the twentieth valve is connected to the fourth air port.

[0015] Preferably, the mixing outlet of the mixing structure is connected in parallel to an eleventh valve and a twelfth valve; the eleventh valve is connected to a harvesting port; and the twelfth valve is connected to a waste outlet.

[0016] The beneficial effects of the present invention are as follows: All components of this microfluidic-based nanomedicine production equipment and method are high-pressure-resistant, ensuring that the system can withstand the pressure required for operation. The pump also has a built-in pressure monitoring function. If the pressure exceeds the set pressure, an alarm will be triggered to stop operation, preventing system damage. A flow meter is added after the pump to monitor the flow rate, ensuring the accuracy and stability of the flow rate and preventing product production from being affected by unstable flow rate or incorrect mixing ratio. A circulation pipeline is added between the pump and the tank. Before the flow rate stabilizes, the pump circulates with the tank and then mixes after the flow rate stabilizes, preventing waste of materials in the tank. The aqueous phase and the oil phase are stably mixed in a specially designed mixer structure to form a nanomedicine product in a certain ratio. If the yield of the nanomedicine product is low at the beginning of mixing, it can be discharged through the system. After passing the test, the discharge is turned off and the system is switched to collection, resulting in a more uniform nanomedicine product with a higher encapsulation rate. A clean compressed air port is provided to purge residual liquid medicine from the circulation process into the liquid storage tank, preventing liquid medicine waste. After the system is cleaned, the pipeline can be purged through the port to ensure cleanliness. A refill port is provided on the tank to replenish cleaning fluid, making it convenient to clean the entire system. During the actual production process, single or multiple groups can be selected to operate to achieve parallel amplification of nanomedicine production of different scales. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a schematic diagram of a single-group mixing system of a nanomedicine production device based on microfluidic technology of the present invention;

[0018] Figure 2 This is a schematic diagram of a multi-group mixing system of a nano drug production device based on microfluidic technology in the present invention.

[0019] In the figure: 100, first tank system; 200, second tank system; 103, first tank; 203, second tank; 300, single-group mixing system; 316, mixing structure; 316', mixing outlet; 312, first flow detection device; 320, second flow detection device; 311, first pump; 319, second pump; 106, first liquid level monitoring device; 206, second liquid level monitoring device; 108, first stirring; 208, second stirring; 101, first valve; 102, second valve; 104, third valve; 105, fourth valve; 201, fifth valve; 202, sixth valve; 204, seventh valve; 205, eighth valve; 313, ninth valve; 314, tenth valve; 315, eleventh valve; 317, twelfth valve; 318, thirteenth valve; 321, fourteenth valve Valve; 322, the fifteenth valve; 323, the sixteenth valve; 401, the seventeenth valve; 402, the eighteenth valve; 107, the nineteenth valve; 207, the twentieth valve; 101', the first fluid inlet; 201', the second fluid inlet; 102', the first breathing port; 202', the second breathing port; 401', the first air port; 402', the second air port; 107', the third air port; 207', the fourth air port; 317', the harvest port; 318', the waste outlet; 105', the first cleaning port; 205', the second cleaning port; 109', the first circulation inlet; 209', the second circulation inlet; 110', the first circulation outlet; 210', the second circulation outlet; 411, the first conveying pipeline; 412, the second conveying pipeline; 413, the first cleaning pipeline; 414, the second cleaning pipeline. DETAILED DESCRIPTION

[0020] The technical solution of the present invention will be described clearly and completely below in conjunction with the accompanying drawings. In the description of the present invention, it should be noted that the terms "center," "up," "down," "left," "right," "vertical," "horizontal," "inside," "outside," and the like, indicating directions or positional relationships, are based on the directions or positional relationships shown in the accompanying drawings and are intended only to facilitate the description of the present invention and simplify the description. They do not indicate or imply that the devices or components referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be construed as limiting the present invention. In addition, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0021] The present invention will be further described below with reference to the accompanying drawings.

[0022] like Figure 1-2As shown, a nanomedicine production device based on microfluidic technology includes a first tank system 100, a second tank system 200 and a mixing system 300; the first tank system 100 includes a first tank 103; the second tank system 200 includes a second tank 203; the mixing system 300 includes a mixing structure 316, and the first tank 103 and the second tank 203 are connected to the mixing structure 316.

[0023] A first stirring device 108 is installed in the first tank 103; a first liquid level monitoring device 106 is installed on the inner wall of the first tank 103; and the first tank 103 is connected to a first circulation inlet 109'. A second stirring device 208 is installed in the second tank 203; a second liquid level monitoring device 206 is installed on the inner wall of the second tank 203; and the second tank 203 is connected to a second circulation inlet 209'.

[0024] The first cleaning pipe 413 is connected in series with the fourth valve 105, the eleventh valve 315, and the seventeenth valve 401. The left end of the first cleaning pipe 413 is the first cleaning port 105', and the right end is the first air port 401'. The first tank 103 is connected to the third valve 104, and the other end of the third valve 104 is connected to the first cleaning pipe 413. The first cleaning pipe 413 is connected to the first delivery pipe 411 through the tenth valve 314. The first circulation outlet 110' is between the fourth valve 105 and the eleventh valve 315. The second cleaning pipeline 414 is connected in series with the eighth valve 205, the sixteenth valve 323, and the eighteenth valve 402. The left end of the second cleaning pipeline 414 is the second cleaning port 205', and the right end is the second air port 402'. The second tank 203 is connected to the seventh valve 204, and the other end of the seventh valve 204 is connected to the second cleaning pipeline 414. The second cleaning pipeline 414 is connected to the second delivery pipeline 412 through the fifteenth valve 322. The second circulation outlet 210' is located between the second cleaning port 205' and the sixteenth valve 323.

[0025] The mixing system 300 further includes a first pump 311, a second pump 319, a first flow rate detection device 312, a second flow rate detection device 320, a ninth valve 313, and a fourteenth valve 321. The first pump 311, the first flow rate detection device 312, and the ninth valve 313 are sequentially connected in series to the first delivery pipe 411. One end of the first delivery pipe 411 is connected to the mixing structure 316, and the other end is connected to the first circulation inlet 109'. The mixing system 300 further includes a second pump 319. The second pump 319, the second flow rate detection device 320, and the fourteenth valve 321 are sequentially connected in series to the second delivery pipe 412. One end of the second delivery pipe 412 is connected to the mixing structure 316, and the other end is connected to the second circulation inlet 209'.

[0026] The first circulation inlet 109' and the first circulation outlet 110' of the circulation pipeline are used to form a loop for the first tank system 100. The first circulation inlet 109' and the first circulation outlet 110' are provided with a first pump 311 and a first flow detection device 312. The flow detection signal is fed back by the first flow detection device 312 to adjust the rotation speed of the first pump 311 so that the material in the first tank 103 flows along the first circulation inlet 109' and the first circulation outlet 110' at a certain flow rate.

[0027] The second circulation inlet 209' and the second circulation outlet 210' are used to form a loop for the second tank system 200. A second pump 319 and a second flow detection device 320 are provided on the second circulation inlet 209' and the second circulation outlet 210' of the circulation pipeline. The flow detection signal is fed back by the second flow detection device 320 to adjust the rotation speed of the second pump 319 so that the material in the second tank 203 flows along the second circulation inlet 209' and the second circulation outlet 210' at a certain flow rate.

[0028] The first flow detection device 312 and the second flow detection device 320 can be flow meters, or the value of the liquid level signal of a liquid level monitoring device changing over time, etc. The preferred method is to use a flow meter. The first pump 311 and the second pump 319 can be selected as pumps with built-in pressure detection, or a pressure detector can be installed after the pump to obtain the pressure detection value signal after the pump. The software that can be controlled by a computer can be used to determine whether the pressure detection value signal exceeds the preset pressure alarm value signal. If so, an alarm is triggered, a signal is sent to the pump and / or valve, the pump is stopped, and the valve is triggered to prevent equipment damage, material waste, etc. The preferred method is to install a pressure detector after the pump.

[0029] The material in the first tank 103 and the material in the second tank 203 are mixed in a specially made mixing structure 316 and are connected to a harvesting port 317 ′ for collection or a waste port 318 ′ for discharge through a mixing outlet 316 ′.

[0030] The mixing structure 316 is a structure customized according to the process flow rate and formula, and a replaceable installation position is reserved. The harvesting port 317' is used to collect the product; the waste outlet 318' is used to collect the waste liquid.

[0031] The first tank system 100 is equipped with a first liquid level monitoring device 106, a first stirring device 108, a third air port 107', a first breathing port 102', a first liquid replenishment port 101', and a first cleaning port 105'. The third air port 107' is used to connect to compressed air, the first breathing port 102' is used to connect to the atmosphere, the first liquid replenishment port 101' is used to replenish liquid to the first tank 103, and the first cleaning port 105' is used to collect cleaning liquid.

[0032] The second tank system 200 is equipped with a second liquid level monitoring device 206, a second stirring device 208, a fourth air port 207', a second breathing port 202', a second liquid replenishment port 201', and a second cleaning port 205'. The fourth air port 207' is used to connect to compressed air, the second breathing port 202' is used to connect to the atmosphere, the second liquid replenishment port 201' is used to replenish liquid to the second tank 203, and the second cleaning port 205' is used to collect cleaning fluid.

[0033] The first refill port 101' and the second breathing port 202' can use refill methods including refill pump delivery, compressed air delivery or gravity delivery. The preferred method is to use a refill pump. The volume of the material in the first tank 103 is monitored by the first liquid level detection device 106. After the first tank 103 is replenished to the target volume, the refill is stopped. The first liquid level monitoring device 106 and the second liquid level monitoring device 206 can be a scale, a liquid level meter, etc. The preferred method is to use a weighing method. The first stirring device 108 and the second stirring device 208 can be used to mix the material.

[0034] The first tank 103 is equipped with a first valve 101, a second valve 102, and a nineteenth valve 107. The upper end of the first valve 101 is connected to the first fluid inlet 101'; the upper end of the second valve 102 is connected to the first breathing port 102'; and the upper end of the nineteenth valve 107 is connected to the third air port 107'. The second tank 203 is equipped with a fifth valve 201, a sixth valve 202, and a twenty-first valve 207. The upper end of the fifth valve 201 is connected to the second fluid inlet 201'; the upper end of the sixth valve 202 is connected to the second breathing port 202'; and the upper end of the twentieth valve 207 is connected to the fourth air port 207'.

[0035] The mixing outlet 316 ′ of the mixing structure 316 is connected in parallel to the eleventh valve 317 and the twelfth valve 318 ; the eleventh valve 317 is connected to a harvesting port 317 ′; and the twelfth valve 318 is connected to a waste outlet 318 ′.

[0036] A method for using a nanomedicine production device based on microfluidic technology comprises the following steps:

[0037] Production Mix:

[0038] Step 1: Open the nineteenth valve 107 of the first tank 103 and the third air port 107' to connect the first tank 103 to the atmosphere, and the pressure of the first tank 103 is reduced to atmospheric pressure; open the twentieth valve 207 of the second tank 203 and the fourth air port 207' to connect the second tank 203 to the atmosphere, and the pressure of the second tank 203 is reduced to atmospheric pressure;

[0039] Step 2: Open the first valve 101 of the first tank 103 and the first liquid infusion port 101' to connect the first tank 103 to the first liquid infusion port 101', so that the material is transported to the first tank 103 through the liquid infusion pump; monitor the volume of the material in the first tank 103 by the first liquid level monitoring device 106. After the first tank 103 is replenished to the target volume, close the first valve 101 of the first tank 103 and the first liquid infusion port 101' to stop the liquid infusion;

[0040] The fifth valve 201 of the second tank 203 is opened, and the second liquid replenishing port 201' is opened, so that the second tank 203 is connected to the second liquid replenishing port 201', and the material is replenished into the second tank 203 through the liquid replenishing pump; the volume of the material in the second tank 203 is monitored by the second liquid level monitoring device 206. After the second tank 203 is replenished to the target volume, the fifth valve 201 of the second tank 203 is closed, and the second liquid replenishing port 201' is closed to stop the liquid replenishment;

[0041] Step 3: Open the tenth valve 314 and the third valve 104, close the ninth valve 313, the eleventh valve 315, and the fourth valve 105, and start the first pump 311; feedback the flow detection signal from the first flow detection device 312, and adjust the speed of the first pump 311 so that the material in the first tank 103 circulates at a certain flow rate through the first tank 103, the first pump 311, the first flow detection device 312, the tenth valve 314, and the third valve 104;

[0042] The fifteenth valve 322 and the seventh valve 204 are opened, the fourteenth valve 321, the sixteenth valve 323, and the eighth valve 205 are closed, and the second pump 319 is started. The flow detection signal is fed back through the second flow detection device 320, and the speed of the second pump 319 is adjusted so that the material in the second tank 203 circulates at a certain flow rate through the second tank 203, the second pump 319, the second flow detection device 320, the fifteenth valve 322, and the seventh valve 204.

[0043] Step 4: Run the first pump 311 at the flow rate, close the tenth valve 314, open the eleventh valve 315, the third valve 104, and the seventeenth valve 401, and open the first air port 401' to allow compressed air to pass through the seventeenth valve 401, the eleventh valve 315, and the third valve 104 to blow the material in the pipeline back to the first tank 103;

[0044] Run the second pump 319 at the flow rate, close the fifteenth valve 322, open the sixteenth valve 323, the seventh valve 204, and the eighteenth valve 402, and open the second air port 402' to allow compressed air to pass through the eighteenth valve 402, the sixteenth valve 323, and the seventh valve 204, and blow the material in the pipeline back to the second tank 203;

[0045] Step 5: Run the first pump 311 according to the flow rate, close the seventeenth valve 401, the eleventh valve 315, the third valve 104, close the first air port 401', and stop blowing the material in the pipeline back to the first tank 103;

[0046] Operate the second pump 319 at the flow rate, close the eighteenth valve 402, the sixteenth valve 323, and the seventh valve 204, close the second air port 402', and stop blowing the material in the pipeline back to the second tank 203. Since the material in the first tank 103 and the second tank 203 may be valuable, this material can be recovered by purge. Alternatively, the material in some tanks can be recovered while the material in others cannot be recovered. The purge time is based on the time required to blow the liquid back into the tanks. A timing device, such as a computer with control software, can be used to preset the purge time. Once the purge time is reached, proceed to the next step.

[0047] Step 6: Run the first pump 311 according to the flow rate, close the tenth valve 314, open the ninth valve 313 and the thirteenth valve 318, and open the waste outlet 318'; the material in the first tank 103 is discharged through the first pump 311, the first flow detection device 312, the ninth valve 313, the mixing structure 316, and the waste outlet 318';

[0048] The second pump 319 is operated at the flow rate, the fifteenth valve 322 is closed, the fourteenth valve 321 and the thirteenth valve 318 are opened, and the waste outlet 318' is opened; the material in the second tank 203 is discharged through the second pump 319, the second flow detection device 320, the fourteenth valve 321, the mixing structure 316, and the thirteenth valve 318 through the waste outlet 318'. Since the quality of the nanomedicine product in the initial mixing stage may not meet the requirements, this part of the material can be discharged through the waste outlet. A timing device, such as a computer with control software, can be used to preset a recovery time, and when the recovery time is reached, the next step is entered. The preset recovery time can be determined by sample measurement data. The waste discharge time can be determined by sample test data. A timing device, such as a computer with control software, can be used to preset a waste discharge time. When the waste discharge time is reached, the next step is entered.

[0049] At this time, the material in the first tank 103 passes through the ninth valve 313, and the material in the second tank 203 passes through the fourteenth valve 321, and is mixed in the mixing structure 316 at a stable flow rate and discharged through the waste outlet 318';

[0050] Step 7: Run the first pump 311 according to the flow rate, close the tenth valve 314, open the ninth valve 313 and the twelfth valve 317, and open the harvesting port 317';

[0051] The material in the first tank 103 is collected through the first pump 311, the first flow detection device 312, the ninth valve 313, the mixing structure 316, the twelfth valve 317, and the harvesting port 317'; the second pump 319 is operated according to the flow rate, the fifteenth valve 322 is closed, the fourteenth valve 321 and the twelfth valve 317 are opened, and the harvesting port 317' is opened;

[0052] The material in the second tank 203 is collected through the harvesting port 317' through the second pump 319, the second flow detection device 320, the fourteenth valve 321, the mixing structure 316, the thirteenth valve 318; at this time, the material in the first tank 103 is mixed in the mixing structure 316 at a stable flow rate through the ninth valve 313, and the material in the second tank 203 is mixed through the fourteenth valve 321 at a stable flow rate, and is collected through the harvesting port 317'; mixing is performed after the flow rate stabilizes, which can save the waste of raw materials when the flow rate, flow rate and ratio do not meet the standards after the pump is started, thereby improving the yield of nano drug products.

[0053] The flow rate V103 (hereinafter referred to as V103) is detected by the first flow detection device 312. When the fluctuation of the flow rate V103 is greater than the limit value ΔV103, the flow rate V103 is considered unstable. The flow rate V203 is detected by the second flow detection device 320. When the fluctuation of the flow rate V203 is greater than the limit value ΔV203, the flow rate V203 is considered unstable. The capacity V103 of 106 is detected by the first liquid level monitoring device. When the capacity V106 is lower than the limit value MinV103, the material in the first tank 103 is considered empty. The capacity V203 of 206 is detected by the first liquid level monitoring device. When the capacity V206 is lower than the limit value MinV203, the material in the second tank 203 is considered empty.

[0054] When a single-group mixing system is running: when the flow rate V103 is unstable, the flow rate V203 is unstable, the material in the first tank 103 is empty, the material in the second tank 203 is empty and / or other alarm shutdown conditions occur, such as the overpressure alarm shutdown after the pump, stop the operation of the first pump 311 and the second pump 319, close the twelfth valve 317 or close the harvesting port 317, and stop the production and harvesting of nanomedicines in the corresponding mixing system 300.

[0055] When multiple groups of mixing modules are in operation: when the flow rate V103 is unstable, the flow rate V203 is unstable, the material in the first tank 103 is empty, the material in the second tank 203 is empty and / or other alarm shutdown conditions occur, such as the overpressure alarm shutdown after the pump, the operation of the first pump 311 and the second pump 319 is stopped, the twelfth valve 317 is closed or the harvesting port 317 is closed, and only the production and harvesting of nanomedicines in the corresponding single group mixing system 300 are stopped, and the remaining modules operate normally to ensure that the yield of each batch is further improved.

[0056] Equipment cleaning:

[0057] Step 1: Open the first valve 101 of the first tank system 100, open the first liquid infusion port 101', connect the first tank 103 to the first liquid infusion port 101', and transfer the material to the first tank 103 via the liquid infusion pump; monitor the volume of the material in the first tank 103 via the first liquid level monitoring device 106. After the first tank 103 is filled to the target volume, close the first valve 101 of the first tank system 100, close the first liquid infusion port 101', or stop the liquid infusion pump to stop the liquid infusion;

[0058] By opening the fifth valve 201 of the second tank system 200 and the second liquid infusion port 201', the second tank 203 is connected to the second liquid infusion port 201', and the liquid is infused into the second tank 203 via the liquid infusion pump; the volume of the material in the second tank 203 is monitored by the second liquid level monitoring device 206. After the second tank 203 is infused to the target volume, the fifth valve 201 of the second tank system 200 is closed, the second liquid infusion port 201' is closed, and the liquid infusion pump is stopped to stop the infusion; step 2, the tenth valve 314 and the fourth valve 105 are opened, the ninth valve 313 and the eleventh valve 315 are closed, and the first cleaning port 105' is opened; the cleaning liquid in the first tank 103 is cleaned through the first tank 103, the first pump 311, the first flow detection device 312, the tenth valve 314, and the fourth valve 105, and discharged from the first cleaning port 105';

[0059] Open the fifteenth valve 322 and the eighth valve 205, close the fourteenth valve 321 and the sixteenth valve 323, and open the second cleaning port 205'; the cleaning liquid in the second tank 203 is cleaned through the second tank 203, the second pump 319, the second flow detection device 320, the fifteenth valve 322, and the eighth valve 205, and then discharged from the second cleaning port 205';

[0060] Step 3: Close the tenth valve 314, open the seventeenth valve 401, the eleventh valve 315, and the fourth valve 105, and open the first air port 401' and the first cleaning port 105'. Compressed air passes through the seventeenth valve 401, the eleventh valve 315, and the fourth valve 105 to purge the cleaning liquid in the pipeline into the first cleaning port 105'.

[0061] Close the fifteenth valve 322, open the eighteenth valve 402, the sixteenth valve 323, and the eighth valve 205, open the second air port 402' and the second cleaning port 205', and allow compressed air to pass through the eighteenth valve 402, the sixteenth valve 323, and the eighth valve 205 to purge the cleaning liquid in the pipeline into the second cleaning port 205';

[0062] Step 4: Open the ninth valve 313 and the thirteenth valve 318, close the tenth valve 314, and open the waste outlet 318'; the cleaning liquid in the first tank 103 is cleaned through the first tank 103, the first pump 311, the first flow detection device 312, the ninth valve 313, the mixing structure 316, and the thirteenth valve 318, and then discharged from the waste outlet 318';

[0063] Open the fourteenth valve 321 and the thirteenth valve 318, close the fifteenth valve 322, and open the waste outlet 318'; the cleaning liquid in the second tank 203 is cleaned through the second tank 203, the second pump 319, the second flow detection device 320, the fourteenth valve 321, the mixing structure 316, and the thirteenth valve 318, and then discharged from the waste outlet 318';

[0064] Step 5: Open the nineteenth valve 107 and the third air port 107' to connect the first tank 103 and the third air port 107'. Close the first valve 101 and the second valve 102 to allow compressed air to pass through the first tank 103, the first pump 311, the first flow detection device 312, the ninth valve 313, the mixing structure 316, and the thirteenth valve 318 to purge the cleaning liquid in the pipeline into the waste outlet 318' and discharge it from the waste outlet 318'.

[0065] Open the 20th valve 207 and the fourth air port 207' to connect the second tank 203 and the fourth air port 207'. Close the fifth valve 201 and the sixth valve 202 to allow compressed air to pass through the second tank 203, the second pump 319, the second flow detection device 320, the fourteenth valve 321, the mixing structure 316, and the thirteenth valve 318 to purge the cleaning liquid in the pipeline into the waste outlet 318' and discharge it from the waste outlet 318'.

[0066] Step 6: Open the ninth valve 313 and the twelfth valve 317, close the tenth valve 314, and open the harvest port 317'; allow the cleaning liquid in the first tank 103 to be cleaned through the first tank 103, the first pump 311, the first flow detection device 312, the ninth valve 313, the mixing structure 316, and the twelfth valve 317, and then be discharged from the harvest port 317'; open the fourteenth valve 321 and the twelfth valve 317, close the fifteenth valve 322, and open the harvest port 317'; allow the cleaning liquid in the second tank 203 to be cleaned through the second tank 203, the second pump 319, the second flow detection device 320, the fourteenth valve 321, the mixing structure 316, and the twelfth valve 317, and then be discharged from the harvest port 317';

[0067] Step 7: Repeat steps 1 to 6 three times, except that the first cleaning solution is water, the second cleaning solution is alkaline solution, and the third cleaning solution is water;

[0068] Step eight, open the nineteenth valve 107, open the third air port 107', so that the first tank 103 and the third air port 107' are connected, close the first valve 101 and the second valve 102, and allow the compressed air to pass through the first tank 103, the first pump 311, the first flow detection device 312, the ninth valve 313, the mixing structure 316, and the twelfth valve 317 for blowing, and blow the cleaning liquid in the pipeline into the harvesting port 317' and discharge it from the harvesting port 317'; open the twentieth valve 207, open the fourth air port 207', so that the second tank 203 and the fourth air port 207' are connected, close the fifth valve 201 and the sixth valve 202, and allow the compressed air to pass through the second tank 203, the second pump 319, the second flow detection device 320, the fourteenth valve 321, the mixing structure 316, and the twelfth valve 317 for blowing, and blow the cleaning liquid in the pipeline into the harvesting port 317' and discharge it from the harvesting port 317'.

[0069] In this embodiment, one group is used as an example, but in practice, one or more groups can be used. Each group of mixing systems is connected in parallel to multiple mixing systems. By adjusting the flow rate ratio V1:V2 of the mixing system, the flow ratio can be changed to achieve process optimization. By activating the number of mixing systems, the total flow rate can be changed, and parallel scale-up of industrial production can be achieved.

[0070] This microfluidic-based nanomedicine production equipment and method utilizes high-pressure-resistant components to ensure the system's operating pressures are met. The pump also features built-in pressure monitoring. If the pressure exceeds the set point, an alarm will sound and the system will stop, preventing damage. A flow meter is installed after the pump to monitor flow rate, ensuring accuracy and stability, preventing production disruptions caused by unstable flow rates or incorrect mixing ratios. A circulation line between the pump and the tank is added. Before the flow rate stabilizes, the system circulates the liquid through the tank, then mixes it after the flow rate stabilizes, preventing waste of material in the tank. The aqueous and oil phases are mixed in a specially designed mixer at a stable ratio to form the nanomedicine product. Initially, if the yield of the nanomedicine product is low, it can be discharged through the system. Once the product meets the required standards, the discharge is turned off and the system is collected, resulting in a more uniform and efficient nanomedicine product. A clean compressed air port is provided to purge residual drug solution from the circulation process into the storage tank, preventing waste. After the system is cleaned, the system can be used to purge the pipelines to ensure cleanliness. The tank is provided with a refill port, which can be used to add cleaning fluid to facilitate the cleaning of the entire system. The tank is also provided with a refill port, which can be used to add materials. It is highly practical and has few limitations. In the actual production process, single group or multiple groups can be selected to operate to achieve parallel amplification of nano-drug production of different scales.

[0071] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A nanomedicine production device based on microfluidic technology, characterized in that: The invention comprises a first tank system (100), a second tank system (200) and a mixing system (300); the first tank system (100) comprises a first tank (103); the second tank system (200) comprises a second tank (203); the mixing system (300) comprises a mixing structure (316), and the first tank (103) and the second tank (203) are connected to the mixing structure (316).

2. The nanomedicine production equipment based on microfluidic technology according to claim 1, characterized in that: A first stirring device (108) is provided in the first tank (103); a first liquid level monitoring device (106) is provided on the inner wall of the first tank (103); and the first tank (103) is connected to a first circulation inlet (109').

3. The nanomedicine production equipment based on microfluidic technology according to claim 2, characterized in that: A second stirring device (208) is provided in the second tank (203); a second liquid level monitoring device (206) is provided on the inner wall of the second tank (203); and the second tank (203) is connected to a second circulation inlet (209').

4. The nanomedicine production equipment based on microfluidic technology according to claim 3, characterized in that: The mixing system (300) further comprises a first pump (311), a second pump (319), a first flow detection device (312), a second flow detection device (320), a ninth valve (313) and a fourteenth valve (321); the first pump (311), the first flow detection device (312) and the ninth valve (313) are sequentially connected in series on a first delivery pipe (411); one end of the first delivery pipe (411) is connected to the mixing structure (316), and the other end is connected to the first circulation inlet (109').

5. The nanomedicine production equipment based on microfluidic technology according to claim 4, characterized in that: The mixing system (300) further includes a second pump (319), wherein the second pump (319), a second flow detection device (320) and the fourteenth valve (321) are sequentially connected in series on a second delivery pipe (412), and one end of the second delivery pipe (412) is connected to the mixing structure (316), and the other end is connected to the second circulation inlet (209').

6. The nanomedicine production equipment based on microfluidic technology according to claim 5, characterized in that: The first cleaning pipe (413) is connected in series with a fourth valve (105), an eleventh valve (315) and a seventeenth valve (401). The left end of the first cleaning pipe (413) is a first cleaning port (105'), and the right end is a first air port (401'). The first tank (103) is connected to a third valve (104), and the other end of the third valve (104) is connected to the first cleaning pipe (413). The first cleaning pipe (413) is connected to the first delivery pipe (411) through the tenth valve (314). A first circulation outlet (110') is located between the fourth valve (105) and the eleventh valve (315).

7. The nanomedicine production equipment based on microfluidic technology according to claim 6, characterized in that: The second cleaning pipe (414) is connected in series with the eighth valve (205), the sixteenth valve (323) and the eighteenth valve (402). The left end of the second cleaning pipe (414) is the second cleaning port (205'), and the right end is the second air port (402'). The second tank (203) is connected to the seventh valve (204), and the other end of the seventh valve (204) is connected to the second cleaning pipe (414). The second cleaning pipe (414) is connected to the second delivery pipe (412) through the fifteenth valve (322). The second circulation outlet (210') is between the second cleaning port (205') and the sixteenth valve (323).

8. The nanomedicine production equipment based on microfluidic technology according to claim 7, characterized in that: The first tank (103) is respectively provided with a first valve (101), a second valve (102) and a nineteenth valve (107); the upper end of the first valve (101) is connected to the first fluid infusion port (101'); the upper end of the second valve (102) is connected to the first breathing port (102'); and the upper end of the nineteenth valve (107) is connected to the third air port (107').

9. The nanomedicine production equipment based on microfluidic technology according to claim 8, characterized in that: The second tank (203) is respectively provided with a fifth valve (201), a sixth valve (202) and a twentieth valve (207); the upper end of the fifth valve (201) is connected to the second fluid infusion port (201'); the upper end of the sixth valve (202) is connected to the second breathing port (202'); and the upper end of the twentieth valve (207) is connected to the fourth air port (207').

10. The nanomedicine production equipment based on microfluidic technology according to claim 5, characterized in that: The mixing outlet (316') of the mixing structure (316) is connected in parallel to the eleventh valve (317) and the twelfth valve (318); the eleventh valve (317) is connected to a harvesting port (317'); and the twelfth valve (318) is connected to a waste outlet (318').

Images