Device for preparing nanoparticles by utilizing high-speed hedging mixing based on microfluidic technology

Abstract

The invention discloses a device for preparing nanoparticles by utilizing high-speed hedging mixing based on a micro-fluidic technology, which belongs to the technical field of micro-fluidic chips and mainly comprises a micro-fluidic chip, a flow control system, a sample cell and a conduit. According to the invention, rapid and efficient fluid mixing can be realized by means of active mixing of high-speed hedging and passive mixing brought by the mixing chamber with a unique structure, and such efficient mixing can greatly improve the utilization rate of raw materials for preparing nano-particles and the product rate of the nano-particles. And meanwhile, based on a microfluidic means, the uniformity and the size control capability of the prepared product can be obviously improved. The nano-particle preparation device provided by the invention is high in integration level, ingenious in design and simple to operate. Efficient mixing of two-phase fluid in limited space and limited time is achieved through turbulent flow generated by high-speed impact, the single-chip microcomputer is used for controlling the flow pump to drive the fluid, and integration of the device can be achieved.

Description

Technical Field

[0001] The invention belongs to the technical field of biomedical microfluidics, and relates to a device for preparing nanoparticles by utilizing high-speed counter-mixing based on microfluidics technology. Background Art

[0002] The study of nanoparticles is an important part of biology, medicine, and pharmacy, among which the preparation of nanoparticles is a key link in the research. The commonly used method for preparing nanoparticles is the mixing precipitation method. The birth of microfluidics has brought new development prospects for the preparation of nanoparticles. In recent years, methods for preparing nanoparticles using continuous mixing precipitation methods based on microfluidics have emerged. These methods have solved the problem of uniformity of nanoparticle size to a certain extent. However, these generation methods have the problem of extremely low raw material utilization due to the constraints of molecular diffusion at the interface. This restricts the research of microfluidics in the field of nanoparticles and related fields. Therefore, it is urgent to develop a new microfluidics technology in the field of nanoparticle preparation.

[0003] After years of research, there are three mixing methods for preparing nanoparticles by mixed precipitation: bulk mixing, continuous mixing, and rapid mixing. So far, there are two types of methods, one is the nanoparticle preparation technology using bulk mixing, and the other is the nanoparticle preparation technology using continuous mixing, such as the following patent: an efficient microfluidic nanoparticle synthesis device (patent number: 2023217144758). These technical means are already very mature and can be used for the preparation of nanoparticles in some cases where the size requirements do not require high uniformity, the output requirements are not large, and the raw material prices are low. However, for scenarios that need to meet the above three requirements at the same time, it seems stretched.

[0004] Therefore, it is urgent to propose a technology that can simultaneously meet the three requirements of uniform size of generated nanoparticles, high output, and high utilization rate of raw materials. The use of rapid mixing nanoprecipitation to prepare nanoparticles is a new method proposed in recent years. Unlike the continuous mixing precipitation method that relies on molecular diffusion at the interface of two-phase flow, rapid mixing relies on high-speed impact of two-phase fluids to mix evenly in a very short time so that the solution quickly reaches a local supersaturated state, breaking through the energy barrier of particle nucleation to precipitate crystals and then nucleate and grow. This method can convert raw materials into a large number of nanoparticles in a very short time. Combining this method with microfluidics technology to improve the uniformity and size controllability of nanoparticles, it also realizes the miniaturization of the mixing chamber, making integration and portability of the device possible, and its application is no longer limited to industrial scenarios. Laboratory researchers can also prepare nanoparticles that meet their needs based on such small equipment. Summary of the invention

[0005] The present invention aims to provide a device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology. Through rapid mixing, two counter-mixing fluids can be mixed evenly in a confined chamber in a very short time to reach a supersaturated state, so that the raw materials can be precipitated and crystallized to the greatest extent and then nucleated and grown into nanoparticles that meet the requirements. The problem that the existing nanoparticle preparation technology cannot meet the three requirements of good product uniformity, high material utilization rate and large output is solved.

[0006] To achieve the above objectives, the present invention adopts the following technical solutions: A device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology, comprising a microfluidic chip, a flow control system and a sample pool; The microfluidic chip comprises a first steady flow input tube, a first liquid input tube, a second steady flow input tube, a second liquid input tube, a mixing chamber, a steady flow output tube and a buffer input tube; The mixing chamber comprises a semicircular upper chamber, a conical lower chamber and a staggered herringbone-shaped channel, the semicircular upper chamber and the conical lower chamber together form a pear-shaped chamber, and the staggered herringbone-shaped channels are distributed on the chamber wall of the conical lower chamber; the first liquid input pipe and the second liquid input pipe are relatively connected to two sides of the semicircular upper chamber, the first steady flow input pipe is connected to the first liquid input pipe, the second steady flow input pipe is connected to the second liquid input pipe, one end of the steady flow output pipe is connected to the end of the conical lower chamber, and the other end is connected to the midpoint of the buffer input pipe; The flow control system includes a raw material input system and a single-chip control module; wherein the raw material input system includes a first raw material injector, a second raw material injector, a third raw material injector and a flow pump assembly respectively used for filling and extracting liquids from the three raw material injectors, the single-chip control module is connected to the flow pump assembly and controls the flow rate outputted by the flow pump assembly, the first raw material injector is connected to the inlet end of the first steady flow input tube through a conduit, the second raw material injector is connected to the inlet end of the second steady flow input tube through a conduit, and the third raw material injector is connected to the inlet end of the buffer input tube through a conduit; The sample pool is connected to the outlet end of the buffer solution input tube through a conduit.

[0007] In the above technical solution, the microfluidic chip is bonded to a glass plate, and the thickness of the glass plate is 2 mm.

[0008] In the above technical solution, the maximum inner diameter of the mixing chamber is less than or equal to 1 micron.

[0009] In the above technical solution, the aspect ratio of the staggered herringbone channel is 1:1.

[0010] In the above technical solution, the first steady-current input tube, the second steady-current input tube and the steady-current output tube are arranged in a repeated hairpin shape.

[0011] In the above technical solution, the length-to-width ratio of the steady-flow output tube is greater than 10:1.

[0012] In the above technical solution, the flow rate provided by the flow pump assembly is greater than 9 ml / min.

[0013] In the above technical solution, the staggered herringbone channel is arranged in the form of lower channel-partition platform-lower channel-partition platform repeatedly along the central axis S of the conical lower chamber, and the staggered herringbone channel is composed of two left downward and right downward channels converging at one point.

[0014] Beneficial effects of the present invention: (1) The present invention is a device for preparing nanoparticles by using a high-speed hedging and mixing nanoprecipitation method based on microfluidic technology. Different from the traditional method for preparing nanoparticles, the present invention relies on the advantages of high-speed hedging to improve the utilization rate of raw materials and the output while ensuring the uniformity of the size of the generated nanoparticles.

[0015] (2) The micro-mixing device provided by the present invention has high integration, ingenious design, and simple operation. It can achieve uniform mixing of two-phase solutions in a short time to generate nanoparticles by using high-speed counter-mixing nanoprecipitation method. The designed pear-shaped mixing chamber, staggered herringbone channels, and output tubes with a larger aspect ratio can ensure that the liquid fills the entire chamber while being more conducive to mixing. The buffer input tube designed in the chip can ensure that the product flowing out of the output tube is well preserved in the first place, so that the product quality is better.

[0016] (3) The present invention is based on microfluidic technology, which makes the micro-mixing device smaller in size and the size of the generated nanoparticles more uniform. Moreover, since the overall device volume is smaller than that of the traditional mixing device, it is easier to promote and apply to laboratory research. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a diagram showing the external structure of a device that uses high-speed counter-mixing to prepare nanoparticles based on microfluidic technology.

[0018] Figure 2 This is a diagram of the microfluidic chip platform system for preparing nanoparticles.

[0019] Figure 3 is a top view of a micro-mixing chamber comprising staggered herringbone channels.

[0020] Figure 4 is a side view of a micro-mixing chamber comprising staggered herringbone channels.

[0021] Figure 5 This is the effectiveness verification chart of the invented device for preparing nanoparticles (I).

[0022] Figure 6 This is the effectiveness verification chart of the invented device for preparing nanoparticles (II).

[0023] Figure 7 It is a top view of the microfluidic chip channel design of the inventive device.

[0024] Figure 8 This is a side view of the microfluidic chip channel.

[0025] In the figure: 1 is the power switch; 2 is the control panel; 3 is the device housing; 4 is the transfer knob; 5 is the catheter; 6 is the sample pool; 7 is the microfluidic chip; 7-1 is the inlet and outlet of the microfluidic chip; 7-2 is the flow stabilizing tube; 7-3 is the mixing chamber; 7-3-1 is the semicircular upper chamber; 7-3-2 is the conical lower chamber; 7-3-3 is the staggered herringbone channel; 7-4 is the buffer inlet tube; 7-5 is the liquid inlet tube; 8 is the syringe; 9 is the lower ditch; 10 is the partition table. DETAILED DESCRIPTION

[0026] The specific implementation of the present invention is further described below in conjunction with the accompanying drawings and technical solutions.

[0027] Example Figure 1 The figure shows the external structure of a device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology of the present invention, which includes a microfluidic chip 7, a flow control system, a sample pool 6 and a catheter 5.

[0028] like Figure 2 As shown, the micro-mixing part based on the microfluidic chip includes three inlets and one outlet (microfluidic chip inlet and outlet 7-1), and three syringes 8, and the three syringes 8 are respectively connected to the three inlets of the connected microfluidic chip. The main structure of the microfluidic chip 7 is Figure 2 The flow stabilizing tube 7-2 is designed as a serpentine channel and is combined with the liquid input tubes 7-5 symmetrically distributed on both sides of the mixing chamber 7-3, serving as the inlet of the microfluidic chip, and is connected to the first syringe and the second syringe through the conduit 5 respectively; the mixing chamber 7-3 includes Figure 3The middle semicircular upper chamber 7-3-1, the conical lower chamber 7-3-2 in the shape of a contracting cone, and the staggered herringbone channel 7-3-3; the steady flow output tube is connected to the lower end of the conical lower chamber and connected to the buffer input tube 7-4 at its midpoint; the main body of the buffer input tube 7-4 is a direct current channel, with two fluid inlets and outlets, one inlet as a buffer input port connected to the syringe 8 (the third syringe), and one outlet as a sample outlet connected to the conduit 5 to flow to the sample pool 6. In addition, the microfluidic chip is bonded to a glass plate, the glass thickness is 2 mm, and the channel height of the microfluidic chip is Figure 6 H1 is shown, while the channel depth of the staggered herringbone hybrid channel is H2 = 40 microns.

[0029] like Figure 3 and Figure 4 The structure shown is Figure 2 The mixing chamber 7-3 shown in the microfluidic chip platform is a pear-shaped micro-mixing chamber 7-3 comprising staggered herringbone channels 7-3-3. Figure 3 and Figure 4 The top view and side view of the micro-mixer chamber 7-3 are shown respectively. The top view shows the details of the mixing chamber 7-3 including the semicircular upper chamber 7-3-1, the conical lower chamber 7-3-2 and the staggered herringbone channels 7-3-3. Specifically, from the top view and the middle view, we can see that the staggered herringbone channels are evenly distributed in the conical lower chamber, and from the side view, we can see that the staggered herringbone channels are located below the conical mixing chamber. Therefore, the heights of the staggered herringbone channels and the pear-shaped chamber are separated, namely H2 and H1. The height of the pear-shaped mixing chamber is the same as the height of the microfluidic channel, both of which are H1 = 200 microns. Figure 3 Top view and Figure 7 From the top view, we can see that the staggered herringbone channels are not symmetrically distributed on both sides of the central axis S of the lower conical mixing chamber. The figure shows that the line connecting the vertices of the staggered herringbone channels in the upper part of the conical contraction chamber is parallel to the central axis S of the pear-shaped mixing chamber, and the line connecting the vertices of the staggered herringbone channels in the lower part of the conical contraction mixing chamber is parallel to the central axis S of the mixing chamber. After introducing the distribution of the staggered herringbone channels, the design and size of the staggered herringbone channels are described in detail. Specifically, it can be seen Figure 8 and Figure 4 From the side view, it can be seen that the staggered herringbone channel is in the shape of a herringbone. The two channels downward left and downward right converge at one point to form a herringbone channel. The herringbone channel is divided into the lower channel 9 of the herringbone channel and the partition 10 between the lower channels of the herringbone channel. In this way, the lower channel-partition platform-lower channel is arranged along the central axis S. From the side view, it can be seen that the width of the channel 9 and the partition platform 10 are both D2 and the same value as the height of the staggered herringbone channel H2, D2=H2=40 microns.

[0030] like Figure 5 and Figure 6 The figure shows the effectiveness verification chart of the invented device for preparing nanoparticles, which proves that the invented device can meet the design requirements.

[0031] like Figure 7 The figure shows a top view of the microfluidic chip channel, which also shows some of the design dimensions. The width L3=L4 of the main part of the steady flow input pipe and output pipe are both 200 microns, the width L6 of the buffer input pipe is 400 microns, and the length is 8 mm. The maximum dimension D1 of the mixing chamber does not exceed one micron. The input channel width and height ratio L3 / H1 is 1-1, and the output pipe length-width ratio L5 / L4 is greater than 10-1. The other structures of the specific microfluidic chip are Figure 3 This has been explained in detail in the description.

[0032] like Figure 8 The figure shows a side schematic diagram of the channel design of the microfluidic chip, which shows that the channel of the microfluidic chip consists of two parts, namely the main channel with a channel height of H1 and the staggered herringbone channel with a channel height of H2.

[0033] like Figure 1 As shown, the device of the present invention includes a power switch 1 on the side of the housing, which is responsible for opening and closing the power supply system of the device. There is a control panel 2 on the front of the device, which is used to control a series of operations such as flow. A microfluidic chip 7 is installed on the device housing, and there are also four catheters 5, three of which are connected to the fluid pump adapter below. The other catheter is connected to the embedded sample pool 6 on the right.

[0034] The principle of the present invention is described in detail below: (1) Mixing principle When two high-speed impact jets collide in a confined mixing chamber, the speed of the two-phase fluid suddenly decreases, which will generate a large amount of energy dissipation. Because of the huge kinetic energy dissipation, a higher energy mixing point will appear at the collision point, and the state of the liquid on both sides will change dramatically. The most obvious change is that the jets are broken up and unevenly distributed in all corners of the chamber to achieve the purpose of uniform mixing. Usually, this method can achieve the maximum mixing intensity in the shortest time, so as to achieve the purpose of uniform local supersaturation. In contrast to high-speed jets, at low Reynolds numbers, the central flow is compressed into a narrow laminar flow between two adjacent flows. The narrow width of the focused flow makes rapid mixing through diffusion possible. After such a high-speed impact active mixing, the fluid will be further mixed when it flows through the passive mixing zone with staggered herringbone channels. After these two sets of mixing methods, the mixing state of the two-phase fluid reaches the best, laying the foundation for the preparation of nanoparticles.

[0035] (2) Nucleation and growth principle The preparation method of nanoparticles is often based on mixing. Different from traditional bulk mixing and continuous mixing, the two-phase fluid counter-mixing of the present invention will show different nanoparticle preparation mechanisms according to different fluid conditions when preparing nanoparticles. It is generally believed that when the injected fluid velocity is low, the micro-mixing chamber is consistent with the traditional continuous mixing. At this time, the central flow is compressed into a narrow laminar flow between two adjacent flows. At this time, the fluid state shows a laminar state, and the narrow laminar flow makes molecular diffusion possible. Under this influence, the solute will precipitate and crystallize to achieve the purpose of generating nanoparticles. When the injected fluid velocity is high or the Reynolds number is large, the fluid shows a turbulent or eddy state and will be evenly distributed in the mixing chamber. At this time, each mixing zone is locally supersaturated, which promotes the solute in the solution to precipitate and crystallize to generate nanoparticles. Whether it is molecular diffusion nucleation or solution supersaturation nucleation growth, it involves the issue of time scale, as shown below: 1. Molecular diffusion nucleation The time scale calculation formula for molecular diffusion in laminar flow at low Reynolds numbers is: ~ ≈ (1) Where D is the diffusion rate of the solvent, is the width of the focusing flow, The channel width is 800um, and R is the ratio of the flow rate of the polymerizing flow to the total flow rate of water, which is 1 / 2.

[0036] 2. Solution supersaturation nucleation When the Reynolds number is very large, mixing becomes turbulent. Micromixing under turbulent conditions involves engulfment, where the two liquids surround each other in increasingly thinner sheets and deform by elongation and shear. The resulting laminated structure allows molecular exchange by diffusion.

[0037] In addition, for the stage of preparing nanoparticles based on the solution supersaturation mechanism, the researchers gave a nucleation rate calculation formula. With this formula, we can clearly understand which factors are related to the nucleation rate of nanoparticles. The specific formula of nucleation rate B is as follows: B= (2) in, is a constant, y is the surface tension, v is the molar volume, k is the Boltzmann constant, T is the absolute temperature, is the local supersaturation. This relationship reveals a strong dependence of nucleation on supersaturation and temperature. Starting from the supersaturated state, nuclei begin to form once the critical nucleation concentration is reached. The nascent nucleus grows statistically by the association / aggregation of molecular species until a critical size is reached and the nucleus is stable and does not dissolve.

[0038] (3) Buffering principle The nucleation and growth process of nanoparticles is a process of competition between nucleation and growth. In this process, the solute precipitates due to the supersaturation of the solution, the nanoparticles nucleate, and then the solute in the solution is used in large quantities for the growth of the nanoparticles. This is a process in which the growth rate accelerates and the nucleation rate slows down. In theory, when this process reaches equilibrium, it is generally believed that the size of the nanoparticles reaches a stable state. However, in practical technical applications, as the nanoparticles are transported to the sample pool, the size of the nanoparticles may not stabilize. First of all, the size of the nanoparticles will continue to increase over time. This is because although the size of the nanoparticles has stabilized, there are a large number of nanoparticles in the solution and these particles are very close, which will cause them to easily agglomerate and make the final measured size too large. Secondly, as the nanoparticles continue to nucleate and grow, when the supersaturation of the solute in the solution is too low, the nanoparticles will dissolve in the solution again, causing the size of the nanoparticles to become smaller. In order to prevent these situations from happening, it is necessary to ensure that the sample is always in a highly supersaturated and highly diluted state. This not only ensures that the generated nanoparticles will not dissolve in the solution again, but also ensures that the nanoparticles will not aggregate due to being too close. Therefore, the present invention adds a buffer input tube to the micro-mixing chamber, which is connected to the serpentine output tube. A large amount of buffer is input at one end to dilute the sample solution in time to achieve the purpose of stabilizing the nanoparticles, and a large amount of buffer is also stored in the sample pool to store the sample. These measures can not only achieve the rapid delivery of the sample to the sample pool, but also ensure that the size of the nanoparticles does not change significantly during transportation.

[0039] The working process of the present invention is as follows: when the device is turned on, an organic solvent containing a stable solute (such as dimethyl sulfoxide DMSO, acetonitrile, THF, acetone, etc.) and an antisolvent (deionized water, water containing NaCl, etc.) are respectively input from a symmetrical steady-flow input tube, and the flow rate Q1 (organic solvent phase flow rate) = Q2 (antisolvent phase flow rate) of the two-phase fluid is the same, and a buffer solution (water, PBS buffer solution, etc.) is input through an input port on one side of the buffer input tube, and the flow rate size Q3 of the buffer is twice that of Q1. These three solutions are pumped into the inlet of the microfluidic chip at a required high-speed flow rate (0.1ml / min-9ml / min) through three syringes and a flow pump, wherein the stable solute is a commonly used diblock copolymer PEG (5K)-PLGA (10K) for preparing nanoparticles. The solvent and the antisolvent collide in the center of the mixing chamber through a symmetrical inlet, and the nanoparticles generated after sufficient mixing enter the serpentine output tube along with the mixed fluid. At this stage, the nanoparticles further grow until the size reaches a stable state. The size of the nanoparticles is further stabilized under the action of the buffer solution after entering the buffer solution input tube, and then the sample is stored in a sample pool containing a large amount of buffer solution through a catheter. Generally, the volume V1 of the buffer solution in the sample pool is 10 times the volume V2 of the organic solution.

[0040] Invention validity: The size distribution and particle size distribution of the nanoparticles generated by the device have been analyzed through a series of experiments. It is believed that the device can produce particles with uniform particle size, controllable size and high raw material utilization. The experimental analysis results are as follows Figure 5 and Figure 6 As shown in the figure, when the organic solvent is acetonitrile and the solute PEG-PLGA content is 5mg / ml, 10mg / ml, and 20mg / ml, the size and uniformity (PID) of the nanoparticles change as the input flow rate increases from 0.1ml / min to 0.8ml / min. It can be seen that the size and uniformity of the nanoparticles meet the design requirements.

[0041] Technical difficulties: In this example, the microfluidic chip is made of a special preparation process and a polymer material. This material is not easy to stick to foreign matter, so after each use, the device only needs to be simply cleaned to be clean without drug residue. The top view and side view of the microfluidic chip are shown in Figure 1. Figure 7 and Figure 8 As shown, it includes a steady flow input pipe 7-2, a mixing chamber 7-3 and a buffer input pipe 7-4. Figure 2, where the microchannel height H1 = 200 μm, the input pipe section is a square with a side length of L3 = H1 = 200 μm, the minimum section width of the cone tube L4 = 200 μm, the cone angle is about 30 degrees, the cone length L2 = 1.0 mm, the maximum section width of the cone tube 800 μm, and the semicircular upper cavity diameter D1 = 800 μm. The buffer input pipe 7-4 has a pipe width L6 = 400 μm, a width height = 200 μm, and a buffer input pipe length L = 8 mm.

[0042] In this embodiment, when applied specifically, the microfluidic mixing device of the present invention needs to filter out the first batch of samples generated as normal loss, which requires setting a threshold time. The nanoparticles prepared thereafter can be collected, tested and applied as products prepared on demand.

[0043] The device for preparing nanoparticles by high-speed impact mixing based on microfluidic technology provided by the present invention has high integration, ingenious design and simple operation. The rapid and uniform mixing of two-phase fluids in the mixing chamber is utilized to achieve the maximum utilization rate of raw materials in a small space and a short time. The flow control system is combined with the micro-mixing chip to make the device integrated, miniaturized and convenient, and can be used in the fields of biology, chemistry, environment, etc.

[0044] The present invention does not elaborate on some of the common technologies of those skilled in the art. The above-described embodiments are only descriptions of preferred implementations of the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific implementations described. Without departing from the design spirit of the present invention, various modifications and improvements made by ordinary technicians in this field to the technical solution of the present invention should fall within the scope of protection determined by the claims of the present invention.

Claims

1. A device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology, characterized in that: Including microfluidic chip, flow control system and sample pool; The microfluidic chip comprises a first steady flow input tube, a first liquid input tube, a second steady flow input tube, a second liquid input tube, a mixing chamber, a steady flow output tube and a buffer input tube; The mixing chamber comprises a semicircular upper chamber, a conical lower chamber and a staggered herringbone-shaped channel, the semicircular upper chamber and the conical lower chamber together form a pear-shaped chamber, and the staggered herringbone-shaped channels are distributed on the chamber wall of the conical lower chamber; The first liquid input pipe and the second liquid input pipe are connected to two sides of the semicircular upper chamber, the first steady flow input pipe is connected to the first liquid input pipe, the second steady flow input pipe is connected to the second liquid input pipe, one end of the steady flow output pipe is connected to the end of the conical lower chamber, and the other end is connected to the midpoint of the buffer input pipe; The flow control system includes a raw material input system and a single-chip control module; wherein the raw material input system includes a first raw material injector, a second raw material injector, a third raw material injector and a flow pump assembly respectively used for filling and extracting liquids from the three raw material injectors, the single-chip control module is connected to the flow pump assembly and controls the flow rate outputted by the flow pump assembly, the first raw material injector is connected to the inlet end of the first steady flow input tube through a conduit, the second raw material injector is connected to the inlet end of the second steady flow input tube through a conduit, and the third raw material injector is connected to the inlet end of the buffer input tube through a conduit; The sample pool is connected to the outlet end of the buffer solution input tube through a conduit.

2. The device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology according to claim 1, characterized in that: The microfluidic chip is bonded to a glass plate, and the thickness of the glass plate is 2 mm.

3. The device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology according to claim 1, characterized in that: The maximum inner diameter of the mixing chamber is less than or equal to 1 micron.

4. The device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology according to claim 1, characterized in that: The aspect ratio of the staggered herringbone channel is 1:

1.

5. The device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology according to claim 1, characterized in that: The first steady-current input tube, the second steady-current input tube and the steady-current output tube are arranged in a repeated hairpin shape.

6. The device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology according to claim 1, characterized in that: The length-to-width ratio of the steady-flow output tube is greater than 10:

1.

7. The device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology according to claim 1, characterized in that: The flow rate provided by the flow pump assembly is greater than 9 ml / min.

8. The device for preparing nanoparticles by high-speed counter-mixing based on microfluidic technology according to claim 1, characterized in that: The staggered herringbone channel is arranged in the form of lower channel-partition platform-lower channel-partition platform repeatedly along the central axis S of the conical lower chamber. The staggered herringbone channel is composed of two left downward channels and right downward channels converging at one point.

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