An intelligent molding device for the preparation of nanoliposomes

Abstract

This invention discloses an intelligent molding device for the preparation of nanoliposomes, relating to the field of nanomaterial preparation technology. The device includes an injection module, a microfluidic chip module, a pressure sensing module, and a central control module. The injection module employs a vertical injection pump and a three-way solenoid valve, using a dual-pump parallel structure to independently control the flow ratio and circulation number of the lipid and aqueous phases. The microfluidic chip module uses a chip holder with a magnetic and hinged structure to mount a toothed microfluidic chip. The pressure sensing module monitors the pressure at the chip inlet and outlet in real time and feeds it back to the central control module. The central control module has built-in pressure threshold determination logic, supports dynamic adjustment of injection parameters, and provides emergency shutdown and encrypted fault log generation when limits are exceeded. The host computer uses a touch interface to set parameters, display real-time data, and update algorithms. This invention significantly improves the efficiency and controllability of nanoliposome synthesis through precise control of fluid delivery and real-time pressure monitoring.

Description

Technical Field

[0001] This invention belongs to the field of nanomedicine carrier preparation technology, specifically relating to an intelligent nanoliposome molding device based on microfluidic technology, which is suitable for drug delivery systems, vaccine development, and cosmetic active ingredient encapsulation. Background Technology

[0002] Nanoliposomes, as a novel drug delivery system, have shown great potential in drug delivery due to their excellent biocompatibility, biodegradability, targeting ability, and high drug encapsulation efficiency. The core of their preparation technology lies in enabling phospholipid molecules to self-assemble into stable nanostructures through physical or chemical means. This can effectively improve drug solubility, bioavailability, and efficacy, while reducing drug toxicity and side effects. Nanoliposomes have been widely used in the delivery of various drugs, including anticancer drugs, gene therapies, and vaccines, and some products have already been successfully launched on the market. However, the demand for efficient, stable, and controllable nanoliposome preparation technologies is growing to meet the diverse needs of their clinical applications.

[0003] Currently, mainstream preparation technologies and equipment have the following significant drawbacks: Traditional laboratory-grade microfluidic devices are complex to operate, and some still require manual liquid addition, and cannot guarantee precise flow rates and two-phase ratios; In addition, the lipid phase in the preparation process is usually lecithin and cholesterol dissolved in ethanol. Due to raw material defects and the influence of the preparation process, lipids or other components may become blocked in the microchannels. If the internal pressure of the chip cannot be detected in a timely and accurate manner, the microfluidic chip may rupture due to excessive local pressure, resulting in chip damage. Summary of the Invention

[0004] The purpose of this invention is to provide an intelligent molding device for the preparation of nanoliposomes, and to enable real-time monitoring of the pressure status of microfluidic chips.

[0005] The technical solution adopted by this invention to solve the above problems is: an intelligent molding device for the preparation of nanoliposomes, characterized in that it includes:

[0006] The injection module includes a three-way solenoid valve 3, a vertical injection pump 4, and a fluid delivery pipeline 12. The vertical injection pump 4 is connected to the lipid phase and aqueous phase storage units respectively through the three-way solenoid valve 3, and controls the flow ratio and circulation number of the lipid phase and aqueous phase according to a preset program.

[0007] The microfluidic chip module includes a clamp base 5.1, a toothed microfluidic chip 5.2, a chip clamp 5.3, and a T-shaped tee connector 10. The chip clamp 5.3 fixes the microfluidic chip 5.2 through a hinge mechanism 5.3.4 and integrates a fluid interface. The T-shaped tee connector 10 connects an injection module and a pressure sensing module.

[0008] The pressure sensing module includes three sets of pressure sensors 9, which are integrated into the inlet and outlet of the microfluidic chip 5.2 respectively, for real-time detection of the pressure in the microchannels inside the microfluidic chip;

[0009] The central control module includes a PCB main control board 6 and a host computer 7. The PCB main control board 6 integrates a microcontroller unit (MCU) and signal conditioning circuit, which is used to control the operating logic of the vertical injection pump 4 and the three-way solenoid valve 3, collect pressure sensor data, and interact with the host computer 7. The host computer 7 is used to configure nanoliposome synthesis parameters, display real-time data, and analyze synthesis results.

[0010] Optionally, in the injection module, the vertical injection pump 4 adopts a dual-pump parallel structure, which independently controls the pumping and discharging operations of the lipid phase and the aqueous phase.

[0011] The central control module supports multi-parameter coordinated control, including:

[0012] Synchronous or asynchronous adjustment of the pumping speed;

[0013] Precise measurement of the volume of pumped liquid;

[0014] Setting the number of cycles in multi-pump linkage mode.

[0015] Optionally, the central control module has built-in pressure threshold determination logic. When the inlet or outlet pressure is detected to exceed the preset safety range, the following operations are performed: send an emergency stop command to the vertical injection pump 4, record the abnormal timestamp, pressure peak and operating status, and generate an encrypted fault log.

[0016] The chip fixture 5.3 includes:

[0017] The chip cover 5.3.1 and the chip base 5.3.2 are connected by a hinge mechanism 5.3.4 to open and close vertically, facilitating the replacement of the microfluidic chip 5.2.

[0018] The magnetic positioning component 5.3.3 is located at the contact surface between the chip base 5.3.2 and the chip cover plate 5.3.1 to ensure accurate alignment and reliable adsorption in the closed state;

[0019] The secondary locking buckle 5.3.5 applies a uniform clamping force through the hinge linkage mechanism, so that the chip and the sealing plug 11 form a leak-free connection.

[0020] Optionally, the grooved microfluidic chip 5.2 is mainly made of PDMS material, and the flow channel is processed by photolithography. The PDMS layer 5.2.1 is bonded to the glass layer 5.2.2. The main channel width is 180μm, the depth is 80μm, the arc radius of the microchannel is 500μm, the groove width is 180μm, the protrusion height is 10μm, and the groove angle is 120°.

[0021] Optionally, the main channel interface of the T-type tee connector 10 connects the injection module and the microfluidic chip, and the branch pressure detection interface connects the pressure sensor. Its cross-section has a gradually narrowing and expanding structure to reduce fluid resistance.

[0022] Optionally, the pressure sensing module is connected to both ends of the microfluidic chip 5.2 via a T-shaped tee connector 10, and provides real-time pressure information to the central control module;

[0023] The central control module calculates the pressure difference between the inlet and outlet of the chip based on the pressure information fed back by the pressure sensing module, thereby enabling the monitoring of the internal pressure state of the chip.

[0024] Optionally, the host computer 7 includes a touch screen for receiving user input commands through a graphical interface;

[0025] The microcontroller unit (MCU) supports program burning and algorithm updates on open-source hardware platforms.

[0026] The present invention, by adopting the above technical solution, has the following beneficial effects:

[0027] This invention provides an intelligent molding device for the preparation of nanoliposomes, comprising: an injection module, a microfluidic chip module, a pressure sensing module, and a central control module. The device integrates multiple modules into one unit, simplifying operation, reducing manual steps, lowering operational difficulty, and reducing the technical requirements for operators. Simultaneously, the use of microfluidic chip technology and automated control significantly improves the preparation efficiency of nanoliposomes, shortens the production cycle, and reduces production costs. Compared with traditional batch preparation methods, this invention enables continuous, high-throughput preparation of nanoliposomes. By precisely controlling the flow rate ratio of the injection module, the channel structure of the grooved microfluidic chip, and reaction conditions, key characteristics such as particle size distribution, encapsulation efficiency, multilayer structure, and uniformity of nanoliposomes can be precisely controlled, thereby obtaining nanoliposome products with superior performance. The high-precision microsensors in the sensing module enable real-time pressure detection of the microchannels inside the microfluidic chip and feedback of pressure data to the central control module, allowing for timely response to chip blockage or leakage, reducing material waste and preventing secondary damage to the chip. Attached Figure Description

[0028] Figure 1 Axonometric view of a liposome device;

[0029] Figure 2 This is a schematic diagram of the exploded structure of a liposome device;

[0030] Figure 3 This is a schematic diagram of the internal structure of a liposome device.

[0031] Figure 4 This is a schematic diagram of the injection module structure;

[0032] Figure 5 This is a schematic diagram of a T-type tee connector connecting the module;

[0033] Figure 6 This is a schematic diagram of a microfluidic chip module;

[0034] Figure 7 This is a schematic diagram of a chip fixture;

[0035] Figure 8 This is a schematic diagram of a toothed microfluidic chip;

[0036] Figure 9 This is a schematic diagram of the central control module;

[0037] Figure 10 This is a schematic diagram of the working principle;

[0038] Among them, 1-liposome device shell, 2-partition, 3-three-way solenoid valve, 4-vertical injection pump, 5-microfluidic chip module, 5.1-clamp base, 5.2-toothed microfluidic chip, 5.2.1-PDMS layer, 5.2.2-glass layer, 5.3-chip clamp, 5.3.1-chip cover plate, 5.3.2-chip base, 5.3.3-magnetic positioning component, 5.3.4-hinge mechanism, 5.3.5-locking buckle, 6-PCB main control board, 7-host computer, 8-power supply, 9-pressure sensor, 10-T-type three-way connector, 11-sealing plug, 12-fluid delivery pipeline, 13-pressure sensor interface cable. Detailed Implementation

[0039] The specific embodiments of the present invention will be described in further detail below with reference to the accompanying drawings and examples. The following examples are for illustrative purposes only and are not intended to limit the scope of the invention.

[0040] This invention relates to the field of nanomaterial preparation technology, specifically to an intelligent molding device for the preparation of nanoliposomes, which is particularly suitable for the controllable synthesis of nanoliposomes assisted by microfluidic chips.

[0041] like Figure 1 and Figure 2 As shown, the device includes the following modules:

[0042] Injection module: The vertical injection pump 4 adopts a dual-pump parallel structure, which is connected to the lipid phase reservoir unit and the aqueous phase reservoir unit respectively; the three-way solenoid valve 3 is connected to the outlet of the injection pump 4 through the PTFE fluid delivery pipeline 12; the two pumps are independently controlled, and the flow ratio and circulation number of the lipid phase and aqueous phase are controlled according to the preset program.

[0043] Microfluidic chip module: includes a clamp base 5.1, a toothed microfluidic chip 5.2, a chip clamp 5.3, and a T-shaped tee connector 10; the toothed microfluidic chip 5.2 is fixed by a magnetic chip clamp 5.3; the chip clamp 5.3 integrates a magnetic positioning component 5.3.3 (neodymium iron boron magnet), and after closing, a uniform clamping force is applied by a secondary locking buckle 5.3.4; the T-shaped tee connector 10 connects the injection module to the chip inlet and outlet.

[0044] Pressure sensing module: Three sets of piezoresistive pressure sensors 9 are respectively installed at the inlet and outlet of the chip; the detection interface of the sensor 9 is connected to the T-type tee connector 10 through a quick-connect sealing connector, and the other end pin is connected to the PCB main control board 6 through the pressure sensor interface line 13 through the partition 2.

[0045] Central control module: The PCB main control board 6 integrates a microcontroller unit (MCU) and signal conditioning circuit, which is used to control the operation logic of the injection pump and solenoid valve, collect pressure sensor data, and interact with the host computer 7. The host computer 7 communicates with the main control board through the CAN bus to configure nanoliposome synthesis parameters, display real-time data, and analyze synthesis results.

[0046] Specifically, refer to Figure 3 and Figure 4 As shown, the parameters of the vertical injection pump 4 are set through the host computer 7, including: the ratio of lipid phase to aqueous phase flow (usually 1:3), the total number of cycles (set according to production requirements), and the single injection volume; at the same time, the control logic of the three-way solenoid valve 3 is set: when pumping liquid, ports A and C are normally open and port B is closed; when discharging liquid, ports B and C are normally open and port A is closed.

[0047] Furthermore, the host computer 7 compiles the parameters into instructions and sends them to the PCB main control board 6 via the CAN bus.

[0048] Furthermore, referring to Figure 4 As shown, the vertical injection pump 4 transmits the extracted lipid phase and aqueous phase to the toothed microfluidic chip 5.2 through the fluid delivery pipeline 12 via the three-way solenoid valve 3.

[0049] Specifically, refer to Figure 5 As shown, the microfluidic chip module, pressure sensing module, and injection module are connected by a T-shaped tee connector 10. The main channel interface of the T-shaped tee connector 10 connects the injection module and the microfluidic chip 5.2, and the branch pressure detection interface connects the pressure sensor 9. It also has a streamlined internal cavity with a gradually narrowing and expanding cross-section to reduce fluid resistance.

[0050] Furthermore, the pressure sensor 9 is connected to both ends of the microfluidic chip 5.2 via a T-shaped tee connector 10, which collects the inlet pressure Pin and outlet pressure Pout in real time and feeds back the pressure information to the PCB main control board 6 in real time. The PCB main control board 6 calculates the pressure difference ΔP = Pin - Pout between the inlet and outlet ends of the chip based on the pressure information fed back by the pressure sensor 9, thereby realizing the monitoring of the internal pressure state of the chip.

[0051] Furthermore, referring to Figure 6 As shown, the microfluidic chip 5.2 is placed in the chip fixture 5.3, which is fixed to the fixture base 5.1. The chip fixture 5.3 includes the chip base 5.3.2 and the chip cover plate 5.3.1. The vertical plane can be opened and closed through the hinge structure 5.3.4, which facilitates the replacement of the microfluidic chip 5.2.

[0052] Specifically, refer to Figure 7 and Figure 8As shown, when replacing the microfluidic chip 5.2, open the secondary locking buckle 5.3.5 to separate the base 5.3.2 from the cover plate 5.3.1; after replacing the chip, close the clamp and achieve initial alignment (deviation <30μm) through the magnetic suction component 5.3.3; apply uniform clamping force through the secondary locking buckle 5.3.5 to complete the sealing and fixing, so that the chip and the sealing plug 11 form a leak-free connection. During operation, the fluid flows through the sealing plug 11 through the chip glass layer 5.2.2 and then enters the PDMS layer 5.2.1, thereby realizing the synthesis of liposomes.

[0053] Furthermore, referring to Figure 9 As shown, the host computer 7 includes a touch screen, which is used to receive user input commands through a graphical interface and dynamically display Pin, Pout, ΔP curves and synthesis progress bar. The microcontroller unit (MCU) supports program burning and algorithm updates on open source hardware platforms.

[0054] Specifically, refer to Figure 10 The diagram shows the working principle. In operation, after the pressure sensor 9 feeds back pressure data to the PCB main control board 6, the PCB main control board 6 converts the data and uploads it to the host computer 7 in real time. The user can dynamically adjust the parameters according to the pressure information. For example, if the pressure exceeds the limit, the operation of the injection module will be paused. This allows for timely response when the chip becomes blocked or leaks, ensuring that the waste of raw materials is minimized and secondary damage to the chip is avoided.

Claims

1. An intelligent molding device for the preparation of nanoliposomes, characterized in that, include: The injection module includes a three-way solenoid valve (3), a vertical injection pump (4), and a fluid delivery pipeline (12). The vertical injection pump (4) is connected to the lipid phase and aqueous phase storage units respectively through the three-way solenoid valve (3), and controls the flow ratio and circulation number of the lipid phase and aqueous phase according to a preset program. The microfluidic chip module includes a clamp base (5.1), a toothed microfluidic chip (5.2), a chip clamp (5.3), and a T-shaped tee connector (10). The chip clamp (5.3) fixes the microfluidic chip (5.2) through a hinge mechanism (5.3.4) and integrates a fluid interface. The T-shaped tee connector (10) connects the injection module and the pressure sensing module. The pressure sensing module includes three sets of pressure sensors (9) integrated into the inlet and outlet of the toothed microfluidic chip (5.2) respectively, for real-time detection of the pressure of the microchannel inside the chip; The central control module includes a PCB main control board (6) and a host computer (7). The PCB main control board (6) integrates a microcontroller unit (MCU) and a signal conditioning circuit, which is used to control the operating logic of the vertical injection pump (4) and the three-way solenoid valve (3), and to collect pressure sensor data and interact with the host computer (7). The host computer (7) is used to configure nanoliposome synthesis parameters, display real-time data and analyze synthesis results.

2. The intelligent molding device for the preparation of nanoliposomes according to claim 1, characterized in that: In the injection module, the vertical injection pump (4) adopts a dual-pump parallel structure, which independently controls the pumping and discharging operations of the lipid phase and the aqueous phase. The central control module supports multi-parameter coordinated control, including: Synchronous or asynchronous adjustment of the pumping speed; Precise measurement of the volume of pumped liquid; Setting the number of cycles in multi-pump linkage mode.

3. The intelligent molding device for the preparation of nanoliposomes according to claim 1, characterized in that: The central control module has built-in pressure threshold determination logic. When the inlet or outlet pressure is detected to exceed the preset safety range, the following operations are performed: send an emergency stop command to the vertical injection pump (4), record the abnormal timestamp, pressure peak and operation status, and generate an encrypted fault log.

4. The intelligent molding device for the preparation of nanoliposomes according to claim 1, characterized in that: The chip fixture (5.3) includes: The chip cover (5.3.1) and the chip base (5.3.2) are connected by a hinge mechanism (5.3.4) to open and close vertically, facilitating the replacement of the microfluidic chip (5.2). The magnetic positioning component (5.3.3) is located at the contact surface between the chip base (5.3.2) and the chip cover plate (5.3.1) to ensure accurate alignment and reliable adsorption in the closed state; The secondary locking buckle (5.3.5) applies a uniform clamping force through the hinge linkage mechanism, so that the chip (5.2) and the sealing plug (11) form a leak-free connection.

5. The intelligent molding device for the preparation of nanoliposomes according to claim 1, characterized in that: The grooved microfluidic chip (5.2) is bonded to a PDMS layer (5.2.1) and a glass layer (5.2.2). The main channel width is 180μm, the depth is 80μm, the arc radius of the microchannel is 500μm, the groove width is 180μm, the protrusion height is 10μm, and the groove angle is 120°.

6. The intelligent molding device for the preparation of nanoliposomes according to claim 1, characterized in that: The T-shaped three-way connector (10) includes a main channel interface for connecting the injection module and the microfluidic chip, a branch pressure detection interface for connecting the pressure sensor, and a streamlined inner cavity with a gradually narrowing and expanding cross-section to reduce fluid resistance.

7. The intelligent molding device for the preparation of nanoliposomes according to claim 1, characterized in that: The pressure sensing module is connected to the inlet and outlet ends of the toothed microfluidic chip (5.2) via a T-shaped three-way connector (10) and provides real-time pressure information to the central control module. The central control module calculates the pressure difference between the inlet and outlet of the chip based on the pressure information fed back by the pressure sensing module, thereby enabling the monitoring of the internal pressure state of the chip.

8. The intelligent molding device for the preparation of nanoliposomes according to claim 1, characterized in that: The host computer (7) includes a touch screen for receiving user input commands through a graphical interface; The microcontroller unit (MCU) supports program burning and algorithm updates on open-source hardware platforms.

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