Nanoparticle synthesis system based on microfluidics technology and its device and method

Abstract

The present invention provides a nanoparticle synthesis system, device and method based on microfluidic technology, wherein the system comprises a microfluidic chip, a reagent bottle and a cleaning liquid bottle connected to the microfluidic chip through a control valve, and a flow control component is arranged between the valve and the reagent bottle and the cleaning liquid bottle. The system realizes high-precision flow control, and cooperates with the microfluidic chip that can realize high-efficiency and rapid mixing, and finally realizes high-throughput and highly uniform nanoparticle synthesis. Users of the same instrument can adjust to achieve different fluxes according to their needs without redesigning the instrument.

Description

Technical Field

[0001] The present invention belongs to the field of microfluidics and nano-synthesis technology, and in particular relates to a nano-particle synthesis system and device and a synthesis method based on microfluidics technology. Background Art

[0002] Nanoparticle synthesis technology is at the forefront of the rapidly developing field of nanotechnology. Its unique size-dependent characteristics make these materials have great advantages in many fields and are in an irreplaceable position. This technology has been widely used in many industries, such as drug delivery, energy and electronics. Nanoparticle synthesis technology is one of the key steps to realize the application of nanoparticles.

[0003] Since the size characteristics of nanoparticles are required in most applications, the size distribution, yield and size repeatability between batches of nanoparticle synthesis are very important parameters in the evaluation of nanoparticle synthesis. One of the traditional methods for nanoparticle synthesis is based on the principle of batch mixing. Specifically, the raw materials for preparing nanoparticles are dissolved in an organic or aqueous phase, added to another aqueous or organic phase with poor compatibility, and quickly mixed in a beaker or other equipment by stirring. However, when the traditional batch synthesis method (mixing in bulk solution) is used for large-scale production of nanoparticles, the quality of particle synthesis is poor, and there are also some uncontrollable factors, such as aggregation and heterogeneous mixing, which lead to poor size uniformity and repeatability of nanoparticles.

[0004] Microreactors based on microfluidic technology can achieve rapid mixing of reagents, temperature control, and precise spatiotemporal manipulation of reactions. Using microfluidic technology for nanoparticle synthesis, the mixing is controlled and uniform, and nanoparticles of uniform size can be produced. At the same time, the repeatability of the physical and chemical properties of the nanoparticles can also be precisely controlled. In addition, by regulating the microenvironment for nanoparticle synthesis, the size uniformity and repeatability of the nanoparticles can be further improved, thereby improving the yield of the nanoparticle preparation process.

[0005] The existing instruments on the market for nanoparticle synthesis based on microfluidic technology mainly come from Precision Nanosystems in Canada. This instrument mainly uses a syringe pump to push the organic phase and aqueous phase two-phase solution into the microfluidic chip for mixing, and collects the synthesized nanoparticles at the outlet of the microfluidic chip. The instrument achieves very high size controllability, uniformity and high repeatability of nanoparticles. Because it uses a syringe pump as the power to push the fluid, it has some inherent insurmountable shortcomings. When the syringe pump adjusts the flow rate, there are problems such as large volume, slow response speed, low adjustment accuracy, pulsation of flow, low sample use efficiency, and easy contamination. The pulsation of the flow rate and the low adjustment accuracy will affect the uniformity of mixing during the synthesis of nanoparticles, thereby reducing the uniformity of the nanoparticles. And the syringe pump needs to load the reagent into the syringe, which is complicated to operate and easy to cause contamination. In addition, the capacity of the syringe is limited, so it requires a lot of engineering design and improvement in the process of expanding production, which is not convenient for direct use in high-throughput production. Summary of the invention

[0006] In order to solve the deficiencies of the prior art, the present invention provides a nanoparticle synthesis system and device and a synthesis method based on microfluidics technology.

[0007] The purpose of the present invention is achieved through the following technical solutions:

[0008] A nanoparticle synthesis system based on microfluidic technology comprises a microfluidic chip, a reagent bottle and a cleaning liquid bottle connected to the microfluidic chip via a control valve, and a flow control component is arranged between the control valve and the reagent bottle and the cleaning liquid bottle.

[0009] Preferably, the reagent bottles include an organic phase reagent bottle and an aqueous phase reagent bottle, and the cleaning liquid bottles include an organic phase cleaning liquid bottle and an aqueous phase cleaning liquid bottle.

[0010] Preferably, two flow control components are provided, and the flow control components include a flow sensor and a pressure controller electrically connected to the flow sensor.

[0011] Preferably, the system further comprises a waste liquid bottle and a collection tube connected to the microfluidic chip via a control valve.

[0012] Preferably, the control valves are all three-way valves.

[0013] Preferably, the water phase reagent bottle and the water phase cleaning liquid bottle are connected to the normally closed valve port and the normally open valve port of the first three-way valve respectively, the common valve port of the first three-way valve is connected to the common valve port of the third three-way valve through the first flowmeter, the normally closed valve port of the third three-way valve is connected to the water phase port of the microfluidic chip; the normally open valve port of the third three-way valve is connected to the waste liquid bottle;

[0014] The organic phase reagent bottle and the organic phase cleaning bottle are respectively connected to the normally closed valve port and the normally open valve port of the second three-way valve, the common valve port of the second three-way valve is connected to the second flow meter, and the second flow meter is connected to the common port of the fourth three-way valve;

[0015] The waste liquid bottle is also connected to the normally open valve port of the fifth three-way valve, the normally closed valve port of the fifth three-way valve is connected to the collection tube, and the common port of the fifth three-way valve is connected to the outlet of the microfluidic chip;

[0016] The pressure controller is respectively connected to the air pressure control ends of the aqueous phase reagent bottle, the aqueous phase cleaning liquid bottle, the organic phase reagent bottle and the organic phase cleaning liquid bottle, and is also respectively connected to the pressure control ends of the first flowmeter and the second flowmeter.

[0017] Preferably, a device using a nanoparticle synthesis system based on microfluidic technology as described in any one of the above comprises a machine platform, a microfluidic chip component and a flow control component are respectively arranged above the machine platform, the organic phase reagent bottle, the aqueous phase reagent bottle, the organic phase cleaning liquid bottle and the aqueous phase cleaning liquid bottle are respectively placed side by side under the machine platform, and the waste liquid bottle is arranged on the inner side of the reagent bottle.

[0018] Preferably, the organic phase reagent bottle and the aqueous phase reagent bottle are provided with a height-adjustable injection needle assembly.

[0019] Preferably, the microfluidic chip assembly comprises a base and a transfer tooling embedded in the base, a chip is arranged in the transfer tooling, a flip cover is arranged on one side of the base, a locking mechanism for locking the flip cover is arranged on the other side of the base, a guide rod cooperating with a protruding injection channel on the chip is arranged on the inner wall of the flip cover, and a through hole is opened in the center of the guide rod;

[0020] The flip cover is placed on one side of the base through an elastic component, the flip cover pivot is placed on the elastic component, and sample loading channel marks are arranged on the adapter and the base.

[0021] Preferably, any one of the above methods for synthesizing nanoparticles based on microfluidic technology comprises the following steps:

[0022] S1, the flow control component presses the aqueous phase and the organic phase out of the aqueous phase reagent bottle and the organic phase reagent bottle respectively according to the setting, and enters the aqueous phase port and the organic phase port of the microfluidic chip through the corresponding three-way valve to synthesize nanoparticles;

[0023] S2. When the size of the synthesized nanoparticles does not meet the requirements, the synthesized nanoparticles that do not meet the requirements are sent to the waste liquid bottle for collection through the fifth three-way valve; when the size of the synthesized nanoparticles meets the requirements, the synthesized nanoparticles that meet the requirements are sent to the collection tube for collection through the fifth three-way valve.

[0024] Preferably, the method further includes a pretreatment step before the synthesis step, wherein the flow control component presses the aqueous phase and the organic phase out of the aqueous phase reagent bottle and the organic phase reagent bottle respectively according to the setting, and enters the waste liquid bottle through the corresponding three-way valve to remove bubbles in the pipeline.

[0025] The beneficial effects of the present invention are as follows: the system realizes high-precision flow control, and with the use of a microfluidic chip that can achieve high-efficiency and rapid mixing, high-throughput and highly uniform nanoparticle synthesis is finally achieved. Users of the same instrument can adjust the instrument to achieve different fluxes according to their needs without having to redesign the instrument. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 : Schematic diagram of the system structure of the present invention.

[0027] Figure 2 : Schematic diagram of the three-dimensional structure of the device according to the embodiment of the present invention.

[0028] Figure 3 : Figure 2 Schematic diagram of the back structure.

[0029] Figure 4 : A schematic structural diagram of the chip assembly of the present invention, wherein the flip cover is in an open state.

[0030] Figure 5 : A schematic structural diagram of the chip assembly of the present invention, wherein the flip cover is in a closed state.

[0031] Figure 6 : Figure 5 Side view of.

[0032] Among them, 1 aqueous phase reagent bottle, 2 organic phase reagent bottle, 3 aqueous phase cleaning liquid bottle, 4 organic phase cleaning liquid bottle, 5 collecting tube, 6 first flow meter, 7 second flow meter, 25 waste liquid bottle, 11 first three-way valve, 12 second three-way valve, 13 third three-way valve, 14 fourth three-way valve, 15 fifth three-way valve, 18 fan, 23 aqueous phase injection needle assembly, 24 organic phase injection needle assembly, 26 machine, 31 base, 32 flip cover, 33 guide rod, 34 pressure block, 35 spring, 36 buckle, 332 sealing ring, 8 microfluidic chip assembly, 81 microfluidic chip, 82 groove, 83 injection channel, 84 adapter tooling, 9 operation screen, 10 pressure controller. DETAILED DESCRIPTION

[0033] The present invention discloses a nanoparticle synthesis system based on microfluidics technology, combined with Figure 1-Figure 6 As shown, it includes a microfluidic chip 81, a reagent bottle and a cleaning liquid bottle connected to the microfluidic chip 81 through a control valve, and a flow control component is arranged between the control valve and the reagent bottle and the cleaning liquid bottle. In this embodiment, the control valves are all three-way valves, including a first three-way valve 11, a second three-way valve 12, a third three-way valve 13, a fourth three-way valve 14 and a fifth three-way valve 15.

[0034] The reagent bottles include an aqueous phase reagent bottle 1 and an organic phase reagent bottle 2, and the cleaning liquid bottles include an aqueous cleaning liquid bottle 3 and an organic phase cleaning liquid bottle 4. The system also includes a waste liquid bottle 25 and a collection tube 5 connected to the microfluidic chip 81 through a control valve. Two flow control components are provided, and the flow control components include a flow meter and a pressure controller 10 electrically connected to the flow meter.

[0035] Specifically, the aqueous phase reagent bottle 1 and the aqueous phase cleaning liquid bottle 3 are connected to the normally closed valve port and the normally open valve port of the first three-way valve 11 respectively, the common valve port of the first three-way valve 11 is connected to the common valve port of the third three-way valve 13 through the first flowmeter 6, the normally closed valve port of the third three-way valve 13 is connected to the aqueous phase port of the microfluidic chip 81; the normally open valve port of the third three-way valve 13 is connected to the waste liquid bottle 25. The air pressure control ends of the aqueous phase reagent bottle 1 and the aqueous phase cleaning liquid bottle 3 are both connected to the pressure controller 10, and the pressure controller 10 is connected to the pressure control end of the first flowmeter 6 through a data line.

[0036] The organic phase reagent bottle 2 and the organic phase cleaning bottle 4 are respectively connected to the normally closed valve port and the normally open valve port of the second three-way valve 12, the common valve port of the second three-way valve 12 is connected to the second flowmeter 7, and the second flowmeter 7 is connected to the common port of the fourth three-way valve 14; the normally open valve port of the fourth three-way valve 14 is connected to the waste liquid bottle 25. The air pressure control ends of the organic phase reagent bottle 2 and the organic phase cleaning liquid bottle 4 are both connected to the pressure controller 10, and the pressure controller 10 is also connected to the pressure control end of the second flowmeter 7 through a data line.

[0037] The waste liquid bottle 25 is also connected to the normally open valve port of the fifth three-way valve 15, the normally closed valve port of the fifth three-way valve 15 is connected to the collection tube 5, and the common port of the fifth three-way valve 15 is connected to the outlet of the microfluidic chip 81. The first power module, the second power module and the flow control component are all electrically connected to the main control unit.

[0038] The present invention also discloses a device for applying any of the above nanoparticle synthesis systems based on microfluidic technology, including a left and right shell formed by mutual matching, an operation screen 9 is arranged on the shell, a pipeline control area is arranged on one side of the shell, and an industrial control area for controlling the pipeline is arranged on the other side. Among them, the pipeline control area includes a machine table 26, and a microfluidic chip component 8 and a flow control component are arranged side by side above the machine table 26. The flow control component includes a first flow meter 6 and a second flow meter 7. The microfluidic chip component 8 is exposed on the shell.

[0039] The aqueous phase reagent bottle 1, the organic reagent bottle 2, the aqueous phase cleaning liquid bottle 3 and the organic cleaning liquid bottle 4, and the collecting tube 5 are respectively arranged side by side below the machine 26, and the waste liquid bottle 25 is arranged on the inner side of the reagent bottle. Each reagent bottle can adopt different capacities as needed, and the reagent bottle is generally threaded to form an airtight connection with the device. Among them, the aqueous phase reagent bottle 1 and the organic phase reagent bottle 2 are respectively provided with a height-adjustable aqueous phase injection needle assembly 23 and an organic phase injection needle assembly 24. In order to better cooperate with the injection needle assembly to control the height of the injection needle, a height adjustment groove is correspondingly opened on the shell, and the height control part of the injection needle assembly is penetrated from the groove and placed outside the shell.

[0040] The microfluidic chip assembly 8 includes a base 31 and a transfer fixture 84 embedded in the base 31, and a microfluidic chip 81 is arranged in the transfer fixture 84. A sample injection channel 83 is provided on the microfluidic chip 81, and a sealing ring 332 is provided in the sample injection channel 83. In order to better determine the sample injection channel, the transfer fixture 84 and the base 31 are provided with corresponding sample loading marks. In this embodiment, the sample loading mark of the transfer fixture 84 is a groove 82. Since the chip generally has three channels, three grooves 82 are provided in this embodiment. Correspondingly, the sample loading mark of the base 31 is a protrusion matching the groove 82.

[0041] A flip cover 32 is disposed on one side of the base 31 , and a locking mechanism for locking the flip cover 32 is disposed on the other side of the base 31 , wherein a buckle 36 is disposed on the locking mechanism.

[0042] The inner wall of the flip cover 32 is provided with a guide rod 33 that cooperates with the protruding injection channel 83 on the microfluidic chip 81, and a through hole 331 is opened in the center of the guide rod 33;

[0043] Specifically, the flip cover 32 is placed on one side of the base 31 through an elastic component, and the flip cover 32 is pivoted on the elastic component. The elastic component includes a pressing block 34, and a spring 35 is arranged between the pressing block and the base 31. The flip cover 32 is flipped to drive the pressing block 34 to press the spring 35, and the flip cover 32 is locked to the microfluidic chip 81 through the buckle 36. When locked, the guide rod 33 presses the sealing ring 332 and seals the injection channel 83, and the through hole 331 in the guide rod 33 is connected to the injection channel 83. A button is arranged on the locking mechanism, and the button is linked with the buckle 36. Pressing the button can open the lock between the buckle 36 and the flip cover 32.

[0044] The industrial control area includes first and second power modules, and a heat dissipation module for heat dissipation. In this embodiment, the heat dissipation module is a fan.

[0045] At the same time, the present invention also discloses a method for synthesizing nanoparticles using the nanoparticle synthesis system based on microfluidic technology, comprising the following steps:

[0046] S1, the flow control component presses the aqueous phase and the organic phase out of the aqueous phase reagent bottle 1 and the organic phase reagent bottle 2 respectively according to the setting, and enters the aqueous phase port and the organic phase port of the microfluidic chip through the corresponding three-way valve to synthesize the nanoparticles;

[0047] S2. When the synthesis starts, if the size of the synthesized nanoparticles does not meet the requirements because the flow rate cannot reach the preset value immediately, the synthesized nanoparticles that do not meet the requirements can be sent to the waste liquid bottle for collection by opening the valve port in the fifth three-way valve 15 connected to the waste liquid bottle 25. When the flow rate reaches the preset value, the size of the synthesized nanoparticles meets the requirements, the synthesized nanoparticles that meet the requirements can be sent to the collection tube for collection by opening the valve port in the fifth three-way valve 15 connected to the collection tube 5.

[0048] In order to make the reagent flow in the system more stable, the method also includes a pretreatment step before the synthesis step. The flow control component presses the aqueous phase and the organic phase out of the aqueous phase reagent bottle 1 and the organic phase reagent bottle 2 respectively according to the setting, and enters the waste liquid bottle through the corresponding three-way valve to remove the bubbles in the pipeline.

[0049] When the system pipeline needs to be cleaned, the corresponding cleaning liquid valve port can be opened by control to clean the pipeline.

[0050] Finally, it should be noted that the terms "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. indicate positions or positional relationships based on the positions or positional relationships shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first", "second", and "third" are used for descriptive purposes only and cannot be understood as indicating or implying relative importance.

[0051] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A nanoparticle synthesis system based on microfluidics, characterized by: It includes a microfluidic chip, a reagent bottle and a cleaning liquid bottle connected to the microfluidic chip through a control valve, and a flow control component is arranged between the control valve and the reagent bottle and the cleaning liquid bottle; The reagent bottles include an organic phase reagent bottle and an aqueous phase reagent bottle, and the cleaning liquid bottles include an organic phase cleaning liquid bottle and an aqueous phase cleaning liquid bottle; The flow control components are provided with two, and the flow control components include a flow meter and a pressure controller connected to the flow meter; The system also includes a waste liquid bottle and a collection tube connected to the microfluidic chip through a control valve; The control valves are all three-way valves; The water phase reagent bottle and the water phase cleaning liquid bottle are respectively connected to the normally closed valve port and the normally open valve port of the first three-way valve; the common valve port of the first three-way valve is connected to the common valve port of the third three-way valve through the first flowmeter; the normally closed valve port of the third three-way valve is connected to the water phase port of the microfluidic chip; the normally open valve port of the third three-way valve is connected to the waste liquid bottle; The organic phase reagent bottle and the organic phase cleaning liquid bottle are connected to the normally closed valve port and the normally open valve port of the second three-way valve respectively; the common valve port of the second three-way valve is connected to the second flow meter, and the second flow meter is connected to the common port of the fourth three-way valve; the normally open valve port of the fourth three-way valve is connected to the waste liquid bottle, and the other valve port of the fourth three-way valve is connected to the organic phase port of the microfluidic chip; The waste liquid bottle is also connected to the normally open valve port of the fifth three-way valve, the normally closed valve port of the fifth three-way valve is connected to the collection tube, and the common port of the fifth three-way valve is connected to the outlet of the microfluidic chip; The pressure controller is respectively connected to the air pressure control ends of the aqueous phase reagent bottle, the aqueous phase cleaning liquid bottle, the organic phase reagent bottle and the organic phase cleaning liquid bottle, and is also respectively connected to the pressure control ends of the first flowmeter and the second flowmeter.

2. The device for using the nanoparticle synthesis system based on microfluidic technology as claimed in claim 1 is characterized in that: It includes a machine platform, a microfluidic chip component and a flow control component are respectively arranged on the top of the machine platform, the organic phase reagent bottle, the aqueous phase reagent bottle, the organic phase cleaning liquid bottle and the aqueous phase cleaning liquid bottle are respectively placed side by side under the machine platform, the waste liquid bottle is arranged on the inner side of the reagent bottle, and the organic phase reagent bottle and the aqueous phase reagent bottle are provided with a height-adjustable injection needle component.

3. The device of the nanoparticle synthesis system based on microfluidic technology as claimed in claim 2, characterized in that: The microfluidic chip assembly includes a base and a transfer tooling embedded in the base, a chip is arranged in the transfer tooling, a flip cover is arranged on one side of the base, a locking mechanism for locking the flip cover is arranged on the other side of the base, a guide rod is arranged on the inner wall of the flip cover to cooperate with the protruding injection channel on the chip, and a through hole is opened in the center of the guide rod; The flip cover is placed on one side of the base through an elastic component, the flip cover pivot is placed on the elastic component, and sample loading channel marks are arranged on the adapter and the base.

4. The method for synthesizing nanoparticles based on microfluidic technology as claimed in claim 1, characterized in that: The steps include: S1, the flow control component presses the aqueous phase and the organic phase out of the aqueous phase reagent bottle and the organic phase reagent bottle respectively according to the setting, and enters the aqueous phase port and the organic phase port of the microfluidic chip through the corresponding three-way valve to synthesize nanoparticles; S2. When the size of the synthesized nanoparticles does not meet the requirements, the synthesized nanoparticles that do not meet the requirements are sent to the waste liquid bottle for collection through the fifth three-way valve; when the size of the synthesized nanoparticles meets the requirements, the synthesized nanoparticles that meet the requirements are sent to the collection tube for collection through the fifth three-way valve.

5. The method for synthesizing nanoparticles based on microfluidic technology as claimed in claim 4, characterized in that: The method also includes a pretreatment step before the synthesis step, wherein the flow control component presses the aqueous phase and the organic phase out of the aqueous phase reagent bottle and the organic phase reagent bottle respectively according to the setting, and enters the waste liquid bottle through the corresponding three-way valve to remove bubbles in the pipeline.

Images