Intelligent forming device for nano-liposome preparation

Abstract

The invention discloses an intelligent forming device for nano-liposome preparation, and relates to the technical field of nano-material preparation. The device comprises an injection module, a micro-fluidic chip module, a pressure sensing module and a central control module. The injection module adopts a vertical injection pump and a three-way electromagnetic valve, and independently controls the flow ratio and cycle index of a fat phase and a water phase through a double-pump parallel structure; the micro-fluidic chip module adopts a chip clamp with a magnetic attraction and hinge structure to carry a tooth groove type micro-fluidic chip; the pressure sensing module monitors the pressure of the chip inlet and outlet in real time and feeds back the pressure to the central control module; pressure threshold judgment logic is built in the central control module, dynamic adjustment of injection parameters is supported, emergency shutdown is carried out when the injection parameters exceed the limit, encryption fault logs are generated, and the upper computer achieves parameter setting, real-time data display and algorithm updating through a touch interface. By accurately controlling fluid conveying and monitoring pressure in real time, the efficiency and controllability of nano-liposome synthesis are remarkably improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of nano-drug carrier preparation, and particularly relates to an intelligent forming device for nano-liposomes based on microfluidic technology, which is applicable to drug delivery systems, vaccine development, and encapsulation of cosmetic active ingredients. Background Art

[0002] As a new type of drug carrier system, nano-liposomes have shown great potential in the field of drug delivery due to their good biocompatibility, biodegradability, targeting property, and high drug encapsulation efficiency. The core of its preparation technology lies in the self-assembly of phospholipid molecules into stable nano-structures through physical or chemical means. It can effectively improve the solubility, bioavailability, and efficacy of drugs, while reducing the toxic and side effects of drugs. Nano-liposomes are widely used in the delivery of various drugs such as anti-cancer drugs, gene drugs, and vaccines, and some products have been successfully launched on the market. However, the demand for highly efficient, stable, and controllable nano-liposome preparation technology is increasing day by day to meet its diverse needs in clinical applications.

[0003] The current mainstream preparation technologies and equipment have the following significant defects: Traditional laboratory-level microfluidic devices are complex to operate, and some still require manual addition of liquids, and cannot ensure accurate flow rates and two-phase ratios; In addition, during the preparation process, the lipid phase 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 state of the chip cannot be accurately detected in a timely manner, the microfluidic chip may rupture due to excessive local pressure or other reasons, resulting in chip damage. Summary of the Invention

[0004] The purpose of the present invention is to provide an intelligent forming device for nano-liposome preparation, and to achieve the function of real-time monitoring of the pressure state of the microfluidic chip.

[0005] The technical solution adopted by the present invention to solve the above problems is: An intelligent forming device for nano-liposome preparation, characterized in that it includes:

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

[0007] Microfluidic chip module, the microfluidic chip module includes a fixture base 5.1, a grooved microfluidic chip 5.2, a chip fixture 5.3 and a T-shaped three-way joint 10. The chip fixture 5.3 fixes the microfluidic chip 5.2 through a hinge mechanism 5.3.4 and integrates fluid interfaces. The T-shaped three-way joint 10 connects the injection module and the pressure sensing module;

[0008] Pressure sensing module, the pressure sensing module includes three groups of pressure sensors 9 respectively integrated at the inlet end and the outlet end of the microfluidic chip 5.2 for real-time detection of the pressure in the microfluidic channels inside the microfluidic chip;

[0009] Central control module, the central control module includes a PCB main control board 6 and a host computer 7. The PCB main control board 6 is integrated with a microcontroller unit (MCU) and a signal conditioning circuit for controlling the operation logic of the vertical injection pump 4 and the three-way solenoid valve 3, collecting pressure sensor data, and performing data interaction with the host computer 7. The host computer 7 is used for configuring nano-liposome synthesis parameters, displaying real-time data, and analyzing synthesis results.

[0010] Optionally, in the injection module, the vertical injection pump 4 adopts a dual-pump parallel structure to independently control the liquid pumping and draining operations of the lipid phase and the aqueous phase respectively;

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

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

[0013] Accurate measurement of the liquid pumping and draining volume;

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

[0015] Optionally, the central control module has a built-in pressure threshold determination logic. When it detects that the inlet or outlet pressure exceeds the preset safe range, the following operations are performed: sending an emergency stop instruction to the vertical injection pump 4, recording the abnormal timestamp, the pressure peak value, and the operation status, and generating an encrypted fault log.

[0016] The chip fixture 5.3 includes:

[0017] A chip cover plate 5.3.1 and a chip base 5.3.2, which can be opened and closed in a vertical plane through a hinge mechanism 5.3.4 to facilitate the replacement of the microfluidic chip 5.2;

[0018] A magnetic positioning component 5.3.3 is arranged on 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 to form a leak - free connection between the chip and the sealing plug 11.

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

[0021] Optionally, the main channel interface of the T - shaped three - way joint 10 connects the injection module and the microfluidic chip, and the branch pressure detection interface connects the pressure sensor. Its cross - section is a gradually tapering and expanding structure to reduce fluid resistance.

[0022] Optionally, the pressure sensing module is connected to both ends of the inlet and outlet of the microfluidic chip 5.2 through the T - shaped three - way joint 10 and real - time feedbacks pressure information to the central control module;

[0023] The central control module calculates the pressure difference between the two ends of the inlet and outlet of the chip based on the pressure information fed back by the pressure sensing module, so as to monitor the internal pressure state of the chip.

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

[0025] The micro - controller unit (MCU) supports program burning and algorithm updating of the open - source hardware platform.

[0026] Due to the adoption of the above technical solutions, the present invention has the following beneficial effects:

[0027] The present invention provides an intelligent forming device for preparing nano-liposomes, comprising: an injection module, a microfluidic chip module, a pressure sensing module, and a central control module. The device integrates multiple modules into one, with simple operation, reducing manual operation steps, lowering the operation difficulty and the requirements for the technical level of operators. At the same time, by adopting microfluidic chip technology and automated control, the preparation efficiency of nano-liposomes is greatly improved, the production cycle is shortened, and the production cost is reduced. Compared with traditional batch preparation methods, the present invention can achieve continuous and high-throughput preparation of nano-liposomes. By precisely controlling the flow rate ratio of the injection module, the channel structure of the grooved microfluidic chip, and the reaction conditions, key characteristics such as the particle size distribution, encapsulation efficiency, multi-layer structure, and uniformity of nano-liposomes can be precisely controlled, thereby obtaining nano-liposome products with more excellent performance. Through the high-precision micro-sensors in the sensing module, the pressure in the microchannels inside the microfluidic chip can be detected in real time and the pressure data can be fed back to the central control module, so that timely responses can be made when the chip is blocked or leaks, reducing waste of raw materials and avoiding secondary damage to the chip. Description of the Drawings

[0028] Figure 1 It is an axonometric view of the liposome device;

[0029] Figure 2 It is an exploded structural schematic diagram of the liposome device;

[0030] Figure 3 It is an internal structural schematic diagram of the liposome device;

[0031] Figure 4 It is a structural schematic diagram of the injection module;

[0032] Figure 5 It is a schematic diagram of the T-shaped three-way joint connection module;

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

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

[0035] Figure 8 It is a schematic diagram of the grooved microfluidic chip;

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

[0037] Figure 10 It is a working principle diagram;

[0038] Among them, 1 - liposome device housing, 2 - partition board, 3 - three-way solenoid valve, 4 - vertical injection pump, 5 - microfluidic chip module, 5.1 - fixture base, 5.2 - grooved microfluidic chip, 5.2.1 - PDMS layer, 5.2.2 - glass layer, 5.3 - chip fixture, 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 - upper computer, 8 - power supply, 9 - pressure sensor, 10 - T-shaped three-way joint, 11 - sealing plug, 12 - fluid delivery pipeline, 13 - pressure sensor interface line. Detailed implementation manners

[0039] The following combines the accompanying drawings and embodiments to further describe in detail the specific implementation manners of the present invention. The following embodiments are used to illustrate the present invention, but are not used to limit the scope of the present invention.

[0040] The present invention relates to the technical field of nanomaterial preparation, and specifically relates to an intelligent forming device for preparing nano-liposomes, which is particularly suitable for the controllable synthesis of nano-liposomes assisted by a microfluidic chip.

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

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

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

[0044] Pressure sensing module: Three piezoresistive pressure sensors 9 are respectively installed at both ends of the chip inlet and outlet; the detection interface of the sensor 9 is connected to the T-shaped three-way joint 10 through a quick-insert sealing joint, and the other end pin passes through the partition board 2 through the pressure sensor interface line 13 and is connected to the PCB main control board 6.

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

[0046] Specifically, referring to Figure 3 and Figure 4 As shown, various parameters of the vertical injection pump 4 are set through the host computer 7, including: the flow ratio of the lipid phase to the aqueous phase (usually 1:3), the total number of circulation times (set according to the production demand), 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 draining 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 through the CAN bus.

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

[0049] Specifically, referring to Figure 5 As shown, the microfluidic chip module, the pressure sensing module, and the injection module are connected through a T-shaped three-way joint 10. The main channel interface of the T-shaped three-way joint 10 connects the injection module and the microfluidic chip 5.2, and the branch pressure detection interface connects the pressure sensor 9. It has a streamlined inner cavity, and its cross-section is a gradually shrinking and expanding structure to reduce fluid resistance.

[0050] Furthermore, the pressure sensor 9 is connected to both ends of the inlet and outlet of the microfluidic chip 5.2 through the T-shaped three-way joint 10, and the inlet pressure Pin and the outlet pressure Pout are collected in real time and the pressure information is fed back 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 two ends of the chip inlet and outlet through the pressure information fed back by the pressure sensor 9, so as to realize 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, and the chip fixture 5.3 is fixed on the fixture base 5.1. The chip fixture 5.3 includes a chip base 5.3.2 and a chip cover 5.3.1, and realizes vertical opening and closing through the hinge structure 5.3.4, which is convenient for replacing the microfluidic chip 5.2.

[0052] Specifically, referring to Figure 7 and Figure 8As shown in the figure, 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 fixture, and achieve preliminary alignment (deviation < 30μm) through the magnetic attraction component 5.3.3; apply a uniform clamping force through the secondary locking buckle 5.3.5 to complete the sealing and fixing, so that the chip forms a leak-free connection with the sealing plug 11. During operation, the fluid flows through the chip glass layer 5.2.2 through the sealing plug 11 and then enters the PDMS layer 5.2.1, thereby realizing the synthesis of liposomes.

[0053] Furthermore, referring to Figure 9 As shown in the figure, the host computer 7 includes a touch display screen, which is used to receive user input instructions through a graphical interface and dynamically display the Pin, Pout, ΔP curves and the synthesis progress bar. Among them, the microcontroller unit (MCU) supports the program burning and algorithm update of the open source hardware platform.

[0054] Specifically, referring to Figure 10 As shown in the working principle diagram, in the working state, after the pressure sensor 9 feeds back the pressure data to the PCB main control board 6, the PCB main control board 6 uploads the real-time data to the host computer 7 after data conversion. The user dynamically adjusts the parameters according to the pressure information. For example, when the pressure exceeds the limit, the operation of the injection module is paused, so as to make a timely response when the chip is blocked or leaked, so as to ensure the maximum reduction of raw material waste and avoid secondary damage to the chip.

Claims

1. An intelligent forming device for preparing nano-liposomes, characterized in that Comprising: An injection module, which contains a three-way solenoid valve (3), a vertical injection pump (4) and a fluid delivery pipeline (12) therein. The vertical injection pump (4) is respectively connected to the lipid phase and aqueous phase liquid storage units through the three-way solenoid valve (3), and controls the flow rate ratio and circulation times of the lipid phase and aqueous phase according to a preset program; A microfluidic chip module, which includes a fixture base (5.1), a grooved microfluidic chip (5.2), a chip fixture (5.3) and a T-shaped three-way joint (10). The chip fixture (5.3) fixes the microfluidic chip (5.2) through a hinge mechanism (5.3.4) and integrates fluid interfaces. The T-shaped three-way joint (10) connects the injection module and the pressure sensing module; A pressure sensing module, which includes three groups of pressure sensors (9) respectively integrated at the inlet end and outlet end of the grooved microfluidic chip (5.2) for real-time detecting the pressure of the microchannel inside the chip; A central control module, which includes a PCB main control board (6) and a host computer (7). The PCB main control board (6) is integrated with a microcontroller unit (MCU) and a signal conditioning circuit for controlling the operation logic of the vertical injection pump (4) and the three-way solenoid valve (3), and collecting pressure sensor data for data interaction with the host computer (7). The host computer (7) is used for configuring nano-liposome synthesis parameters, displaying real-time data and analyzing synthesis results.

2. An intelligent forming device for nano-liposome preparation according to claim 1, characterized in that: In the injection module, the vertical injection pump (4) adopts a double-pump parallel structure to independently control the liquid pumping and discharging operations of the lipid phase and aqueous phase respectively; The central control module supports multi-parameter collaborative control, including: Synchronous or asynchronous adjustment of the liquid pumping and discharging speed; Accurate measurement of the liquid pumping and discharging volume; Setting of the circulation times in the multi-pump linkage mode.

3. An intelligent forming device for nano-liposome preparation according to claim 1, characterized in that: The central control module has a built-in pressure threshold determination logic. When it detects that the inlet or outlet pressure exceeds the preset safety range, the following operations are performed: sending an emergency stop instruction to the vertical injection pump (4), recording the abnormal timestamp, pressure peak value and operation status, and generating an encrypted fault log.

4. An intelligent forming device for nano-liposome preparation according to claim 1, characterized in that: The chip fixture (5.3) includes: A chip cover plate (5.3.1) and a chip base (5.3.2), which can be opened and closed in a vertical plane through a hinge mechanism (5.3.4) for facilitating the replacement of the microfluidic chip (5.2); A magnetic positioning component (5.3.3) is arranged on 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; A secondary locking buckle (5.3.5) applies a uniform clamping force through a hinge linkage mechanism to form a leak-free connection between the chip (5.2) and the sealing plug (11).

5. An intelligent forming device for nano-liposome preparation according to claim 1, characterized in that: The grooved microfluidic chip (5.2) is formed by bonding a PDMS layer (5.2.1) and a glass layer (5.2.2). The width of the main channel of the flow path is 180 μm, the depth is 80 μm, the arc radius of the microchannel is 500 μm, the width of the groove is 180 μm, the height of the protrusion is 10 μm, and the groove angle is 120°.

6. An intelligent forming device for nano-liposome preparation according to claim 1, characterized in that: The T-shaped tee joint (10) includes a main channel interface for connecting an injection module to the microfluidic chip, a branch pressure detection interface for connecting a pressure sensor, and the cross-section of the streamlined inner cavity is a tapered and expanding structure to reduce fluid resistance.

7. An intelligent forming device for nano-liposome preparation according to claim 1, characterized in that: The pressure sensing module is connected to both ends of the inlet and outlet of the grooved microfluidic chip (5.2) through a T-shaped tee joint (10), and real-time feedbacks pressure information to the central control module; The central control module calculates the pressure difference between the two ends of the inlet and outlet of the chip through the pressure information fed back by the pressure sensing module, so as to monitor the internal pressure state of the chip.

8. An intelligent forming device for nano-liposome preparation according to claim 1, characterized in that: The upper computer (7) includes a touch display screen for receiving user input instructions through a graphical interface; The microcontroller unit (MCU) supports program burning and algorithm updating of the open source hardware platform.

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