Microsphere preparation system

By combining a microfluidic chip with a flow focusing structure and a microscopic detection module, the problem of uneven particle size in traditional microsphere preparation is solved, efficient and uniform microsphere preparation is achieved, and production efficiency and microsphere performance are improved.

CN223366907UActive Publication Date: 2025-09-23HANGZHOU TINKER BIOTECHNOLOGY CO LTD
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Patent Information

Application Number
CN202422805757.X
Authority / Receiving Office
CN · China
Patent Type
Utility models(China)
Current Assignee / Owner
Filing Date
2024-11-18
Publication Date
2025-09-23
Estimated Expiration
2034-11-18

AI Technical Summary

Technical Problem

The particle size of traditional microsphere preparation methods is uneven, the process is complicated, and the raw material utilization rate is low.

Method used

A microfluidic chip with a flow focusing structure is used for emulsification, and a microscopic detection module is configured to monitor the droplet preparation process inside the microfluidic chip in real time through a microscopic detection mirror. The first, second, and third temperature control units are combined to perform temperature control on the liquid storage component, pipeline, and microfluidic chip.

Benefits of technology

The microspheres have achieved a high degree of uniformity in particle size, with a particle size CV of <10%, which improves production efficiency and microsphere performance.

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Abstract

The microsphere preparation system comprises a driving assembly, a liquid storage part, a micro-fluidic chip and a collecting part, a first liquid pipeline is arranged between the liquid storage part and the micro-fluidic chip, the micro-fluidic chip is provided with a microscopic monitoring module used for monitoring the state of fluid in a micro-channel on the micro-fluidic chip in real time, the liquid storage part is provided with a first temperature control part, and the collecting part is provided with a second temperature control part. The first liquid pipeline is provided with a second temperature control piece, and the micro-fluidic chip is provided with a third temperature control piece. A micro-fluidic chip with a flow focusing structure is adopted for emulsification, a microscopic detection module is configured, the microscopic detection module is a zoom microscopic detection mirror, the preparation process of liquid drops in the micro-fluidic chip is monitored in real time, the stability of the whole preparation process and process control over the particle size of a product are ensured, and the production efficiency is improved. The liquid storage part, the first pipeline and the micro-fluidic chip are subjected to temperature control through the first temperature control part, the second temperature control part and the third temperature control part respectively, and the microsphere performance is improved while the production efficiency is improved. And the obtained product is highly uniform in particle size.
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Description

Technical Field

[0001] The utility model relates to the technical field of microsphere preparation, in particular to a microsphere preparation system. Background Art

[0002] Traditional microsphere preparation methods primarily include stirring and emulsification, high-pressure homogenization, and microfluidization. Stirring and emulsification is the most common method, which uses a high-speed rotating paddle to create shear force, breaking the raw materials into droplets. Microspheres are then obtained through cooling, solidification, and solvent evaporation. However, this method produces uneven particle size (CV ~50%), requiring sieving to obtain microspheres of the target size. This results in a complex process and low raw material utilization. Utility Model Content

[0003] In response to the technical problem of uneven microsphere particle size in the background technology, the utility model proposes a microsphere preparation system, which uses a microfluidic chip with a flow focusing structure for emulsification and is equipped with a microscopic detection module. The microscopic detection module is a zoom microscope that monitors the droplet preparation process inside the microfluidic chip in real time, ensuring the stability of the entire preparation process.

[0004] The technical solution adopted by the present invention is as follows: a microsphere preparation system includes a driving component, a liquid storage component, a microfluidic chip and a collecting component connected in sequence, a first liquid pipeline is provided between the liquid storage component and the microfluidic chip, the microfluidic chip is provided with a microscopic monitoring module for real-time monitoring of the fluid state inside the microchannel on the microfluidic chip, the liquid storage component is provided with a first temperature control component, the first liquid pipeline is provided with a second temperature control component, and the microfluidic chip is provided with a third temperature control component.

[0005] Optionally, the drive assembly includes an air compressor, a pressure reducing valve, a pressure regulating valve, and a gas pipeline connected in sequence, and the liquid storage component is provided with an air circuit interface and a liquid circuit interface, the gas pipeline is connected to the air circuit interface, and the liquid circuit interface is connected to the first liquid pipeline.

[0006] Optionally, the microscopic monitoring module includes a microscope, an image acquisition element and a controller, the microscope is arranged corresponding to the microfluidic chip, the image acquisition element is used to acquire the imaging results of the microscope, and the controller is used to process the acquisition results of the image acquisition element.

[0007] Optionally, the microscopic monitoring module further includes a movable frame on which the microscope is mounted.

[0008] Optionally, the first temperature control unit includes a first shell and a first heating element arranged inside the shell, and the first shell is provided with a first groove for accommodating the liquid storage component.

[0009] Optionally, the second temperature control unit includes a second shell and a second heating element installed inside the second shell, and the second shell is wrapped around the outer peripheral wall of the first liquid pipeline.

[0010] Optionally, the third temperature control unit includes a third shell and a third heating element installed inside the third shell, and the third shell is provided with a second groove for accommodating the microfluidic chip fixture.

[0011] Optionally, the third shell includes a left shell and a right shell, the left shell is provided with a latch, and the right shell is provided with a buckle that movably cooperates with the latch, and when the latch cooperates with the buckle, the left shell and the right shell are combined to form the second groove.

[0012] Optionally, a second liquid pipeline is provided between the microfluidic chip and the collecting element.

[0013] Optionally, the second liquid pipeline is provided with a low-temperature cooling component, or the collecting element is provided with a low-temperature cooling component.

[0014] The beneficial effects of the present invention are as follows: a microfluidic chip with a flow-focusing structure is used for emulsification, and a microscopic detection module is configured. The microscopic detection module is a zoom microscope that monitors the droplet preparation process inside the microfluidic chip in real time, ensuring the stability of the entire preparation process and the process control of the product particle size. The first temperature control unit, the second temperature control unit, and the third temperature control unit respectively control the temperature of the liquid storage unit, the first pipeline, and the microfluidic chip, thereby improving production efficiency and microsphere performance. The resulting product particle size is highly uniform. The particle size CV of the product prepared by the traditional method is 30%-50%, while the particle size CV of the product prepared by the system is less than 10%. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 A schematic structural diagram of a microsphere preparation system proposed in an embodiment of the present utility model;

[0016] Figure 2 A schematic diagram of a first temperature control unit of a microsphere preparation system according to an embodiment of the present invention;

[0017] Figure 3 A schematic diagram of a second temperature control unit of a microsphere preparation system according to an embodiment of the present invention;

[0018] Figure 4 A schematic diagram of the third temperature control unit of the microsphere preparation system proposed in an embodiment of the present invention;

[0019] Figure 5 A microscope image of microspheres prepared using the microsphere preparation system proposed in an embodiment of the present invention;

[0020] Figure 6This is a particle size analysis diagram of microspheres prepared using the microsphere preparation system proposed in an embodiment of the present utility model.

[0021] The marks in each drawing are: 1. pressure reducing valve; 2. pressure regulating valve; 3. liquid storage part; 4. first liquid pipeline; 5. first temperature control part; 6. second temperature control part; 7. third temperature control part; 8. first shell; 9. first groove; 10. second shell; 11. second heating element; 12. third shell; 13. third heating element; 14. second groove; 15. left shell; 16. right shell; 17. protrusion; 18. buckle; 19. low-temperature cooling assembly; 20. microscope; 21. image acquisition element; 22. movable frame; 23. collecting part. DETAILED DESCRIPTION

[0022] The present application will be further described in detail below with reference to the accompanying drawings and examples.

[0023] like Figures 1 to 6 As shown, this embodiment discloses a microsphere preparation system, comprising a sequentially connected drive assembly, a liquid reservoir 3, a microfluidic chip, and a collecting element 23. A first liquid conduit 4 is provided between the liquid reservoir 3 and the microfluidic chip. The microfluidic chip is provided with a microscopic monitoring module for real-time monitoring of the fluid state within the microchannels of the microfluidic chip. The liquid reservoir 3 is provided with a first temperature control unit 5, the first liquid conduit 4 is provided with a second temperature control unit 6, and the microfluidic chip is provided with a third temperature control unit 7. A microfluidic chip with a flow-focusing structure is used for emulsification, and a microscopic detection module is configured. The microscopic detection module is a zoom microscope that monitors the droplet preparation process within the microfluidic chip in real time, ensuring the stability of the entire preparation process and process control of the product particle size. The liquid reservoir 3, the first conduit, and the microfluidic chip are respectively temperature-controlled by the first temperature control unit 5, the second temperature control unit 6, and the third temperature control unit 7, thereby improving production efficiency and microsphere performance. The particle size of the obtained product is highly uniform. The particle size CV of the product prepared by the traditional method is 30%-50%, while the particle size CV of the product prepared by this system is less than 10%.

[0024] The preparation steps are:

[0025] (1) Assemble the microfluidic chip into the instrument through the chip fixture, connect the liquid storage part 3 with the corresponding inlet of the chip fixture through the first liquid pipeline 4, and connect the outlet of the chip fixture to the collecting part 23 through the outlet tube.

[0026] (2) Set the temperature of the first temperature control unit 5 and the second temperature control unit 6 to 55°C, the temperature of the third temperature control unit 7 to 55°C, and the low-temperature cooling component 19 to 4°C. After the first temperature control unit 5, the second temperature control unit 6, the third temperature control unit 7 and the low-temperature cooling component 19 reach the target temperature, wait for 30 minutes to stabilize.

[0027] (3) Add 100 mL of liquid paraffin solution containing Span 80 to the continuous phase reservoir 3, and add 10 mL of 15 wt% gelatin solution to the dispersed phase reservoir 3.

[0028] (4) Turn on the image acquisition component 21 and control the three-dimensional translation stage to adjust the position of the microscope 20 to ensure that the flow channel of the microfluidic chip can be clearly imaged.

[0029] (5) Connect the gas pipeline to the gas interface of the two-phase liquid storage component 3, set the output pressure of the two phases to allow the two-phase fluid to enter the microfluidic chip, and observe through the image acquisition element 21 that at the cross flow focusing position of the microfluidic chip, the dispersed phase (15 wt% gelatin solution) solution can be seen to be continuously sheared into droplets by the continuous phase (containing Span80 liquid paraffin) solution.

[0030] (6) The prepared droplets pass through the outlet of the microfluidic chip fixture and enter the collection pool to cool and solidify.

[0031] (7) The collected gelatin microspheres were photographed under a microscope and their particle size distribution was analyzed. The average particle size was 103.45 μm, and the product particle size CV was 3.0%.

[0032] like Figure 1 As shown, the drive assembly includes an air compressor, a pressure reducing valve 1, a pressure regulating valve 2, and a gas pipeline, all connected in sequence. The liquid reservoir 3 is equipped with a gas and liquid interface, the gas pipeline being connected to the gas interface, and the liquid interface being connected to the first liquid pipeline 4. The pressure output by the air compressor passes through the pressure reducing valve 1, maintaining a constant pressure, and enters the precision pressure regulating valve 2. This precision pressure regulating valve 2 precisely controls the pressure output to the liquid reservoir. When pressure is applied to the interior of the liquid reservoir 3, the liquid (raw material) within the reservoir 3 is forced into the microfluidic chip. By adjusting the pressure output by the precision pressure regulating valve 2 into the reservoir, the flow rate of the liquid (raw material) entering the microfluidic chip can be controlled. A second liquid pipeline is provided between the microfluidic chip and the collecting element 23. A low-temperature cooling assembly 19 is provided in this second liquid pipeline, or in the collecting element 23. The low-temperature cooling assembly 19 can be an air heat exchanger or a water-cooled heat exchanger, as is conventional technology.

[0033] like Figure 1 As shown, the microscopic monitoring module includes a microscope 20, an image acquisition element 21, and a controller. The microscope 20 is positioned corresponding to the microfluidic chip. The image acquisition element 21 is used to acquire imaging results from the microscope 20, and the controller is used to process the acquisition results of the image acquisition element 21. The image acquisition element is a high-speed camera. The microscopic monitoring module also includes a mobile frame 22, on which the microscope 20 is mounted. The mobile frame 22 is a three-dimensional translation stage.

[0034] like Figure 2 As shown, the first temperature control unit 5 includes a first housing 8 and a first heating element disposed inside the housing. The first housing 8 is provided with a first recess 9 for accommodating the liquid storage unit 3. The first housing 8, which contains the first heating element, is wrapped around the outer wall of the liquid storage unit 3, achieving a good heating effect.

[0035] like Figure 3 As shown, the second temperature control unit 6 includes a second shell 10 and a second heating element 11 installed inside the second shell 10 , and the second shell 10 is wrapped around the outer peripheral wall of the first liquid pipeline 4 .

[0036] like Figure 4 As shown, the third temperature control unit 7 includes a third shell 12 and a third heating element 13 installed inside the third shell 12. The third shell 12 is provided with a second groove 14 for accommodating a microfluidic chip fixture. After the microfluidic chip is wrapped with the fixture, it is placed in the second groove 14, and the second heating element 11 heats the microfluidic chip. The first heating element, the second heating element 11, and the third heating element 13 can be heating wires, heating belts, or heating sheets. The third shell 12 includes a left shell 15 and a right shell 16. The left shell 15 is provided with a latch 17, and the right shell 16 is provided with a buckle 18 that movably cooperates with the latch 17. When the latch 17 cooperates with the buckle 18, the left shell and the right shell are combined to form the second groove 14.

[0037] It is understandable that the specific embodiments described above are only used to explain the relevant utility model, rather than to limit the utility model. It should also be noted that, for the convenience of description, only the parts related to the utility model are shown in the accompanying drawings. Multiple technical solutions in the same embodiment, as well as multiple technical solutions in different embodiments, can be arranged and combined to form new technical solutions that do not have contradictions or conflicts. Any equivalent structural transformation made using the contents of the description and drawings of this utility model, directly or indirectly used in other related technical fields, are also included in the protection scope of this utility model.

Claims

1. A microsphere preparation system, characterized in that: The invention comprises a driving component, a liquid storage component, a microfluidic chip and a collecting component connected in sequence. A first liquid pipeline is provided between the liquid storage component and the microfluidic chip. The microfluidic chip is provided with a microscopic monitoring module for real-time monitoring of the internal fluid state of the microchannel on the microfluidic chip. The liquid storage component is provided with a first temperature control component, the first liquid pipeline is provided with a second temperature control component, and the microfluidic chip is provided with a third temperature control component.

2. The microsphere preparation system according to claim 1, characterized in that: The driving assembly includes an air compressor, a pressure reducing valve, a pressure regulating valve, and a gas pipeline connected in sequence. The liquid storage component is provided with an air circuit interface and a liquid circuit interface. The gas pipeline is connected to the air circuit interface, and the liquid circuit interface is connected to the first liquid pipeline.

3. The microsphere preparation system according to claim 1, characterized in that: The microscopic monitoring module includes a microscope, an image acquisition element and a controller. The microscope is arranged corresponding to the microfluidic chip. The image acquisition element is used to acquire imaging results of the microscope, and the controller is used to process the acquisition results of the image acquisition element.

4. The microsphere preparation system according to claim 3, characterized in that: The microscopic monitoring module further includes a movable frame on which the microscope is mounted.

5. The microsphere preparation system according to claim 1, characterized in that: The first temperature control unit includes a first shell and a first heating element arranged inside the shell. The first shell is provided with a first groove for accommodating a liquid storage component.

6. The microsphere preparation system according to claim 1, characterized in that: The second temperature control unit includes a second shell and a second heating element installed inside the second shell, and the second shell is wrapped around the outer peripheral wall of the first liquid pipeline.

7. The microsphere preparation system according to claim 1, characterized in that: The third temperature control unit includes a third shell and a third heating element installed inside the third shell. The third shell is provided with a second groove for accommodating the microfluidic chip fixture.

8. The microsphere preparation system according to claim 7, characterized in that: The third shell includes a left shell part and a right shell part. The left shell part is provided with a locking protrusion, and the right shell part is provided with a buckle that movably cooperates with the locking protrusion. When the locking protrusion cooperates with the buckle, the left shell part and the right shell part are combined to form the second groove.

9. The microsphere preparation system according to claim 1, characterized in that: A second liquid pipeline is provided between the microfluidic chip and the collecting element.

10. The microsphere preparation system according to claim 9, characterized in that: The second liquid pipeline is provided with a low-temperature cooling component, or the collecting component is provided with a low-temperature cooling component.

Citation Information

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