CN110452695B

CN110452695B - AIE carbon quantum dot and preparation method and application thereof

Info

Publication number: CN110452695B
Application number: CN201910849630.9A
Authority: CN
Inventors: 蒋兴宇; 李轩宇; 李凯
Original assignee: Southern University of Science and Technology
Current assignee: Southern University of Science and Technology
Priority date: 2019-09-09
Filing date: 2019-09-09
Publication date: 2022-07-12
Anticipated expiration: 2039-09-09
Also published as: CN110452695A

Abstract

The invention relates to an AIE carbon quantum dot and a preparation method and application thereof, wherein a micro-fluidic chip is used in the preparation method, the micro-fluidic chip comprises a first liquid inlet, a second liquid inlet, a third liquid inlet, a mixing channel and a liquid outlet, and the preparation method comprises the following steps: and enabling a mixed solution of AIE molecules and phospholipid to enter the microfluidic chip through the third liquid inlet, enabling water to enter the microfluidic chip through the first liquid inlet and the second liquid inlet, enabling the mixed solution and water to flow through the mixing channel, and obtaining the AIE carbon quantum dots at the liquid outlet. According to the invention, the AIE carbon quantum dots with the average diameter of less than or equal to 10nm can be prepared by a method of pre-mixing AIE molecules and phospholipids and then introducing the mixture into the microfluidic chip, so that the off-target problem that a large amount of AIE dots are accumulated in the liver in vivo is solved.

Description

AIE carbon quantum dot and preparation method and application thereof

Technical Field

The invention relates to the technical field of microfluidics, in particular to an AIE carbon quantum dot and a preparation method and application thereof.

Background

Aggregation Induced Emission (AIE) refers to the phenomenon of a large increase in fluorescence of a fluorophore in an aggregated state. Such fluorophores contain groups that can be rotated, such as peripheral phenyl groups connected by carbon-carbon single bonds. AIE monomer molecules tend to be highly hydrophobic. By ultrasonic or microfluidic mixing, hydrophobic AIE monomer molecules and amphiphilic phospholipid molecules can form thermodynamically stable nanoparticles of AIE core/phospholipid shell, also known as AIE dots. However, the minimum size achievable with AIE spots, whether ultrasonic or microfluidic mixing, is still above 30 nm. AIE spots of 30nm or more are taken up by the reticuloendothelial system in vivo and accumulated in the liver in large quantities. The massive accumulation of AIE sites in the liver reduces the imaging or therapeutic efficacy at the desired target site, increasing the liver burden.

CN109152849A discloses a composition of amphiphilic polymeric nanoparticles (e.g. DSPE PEG) encapsulating light stabilizers with Aggregation Induced Emission (AIE) characteristics. Light stable AIE reagents are small organic molecules with tetraphenylethylene moieties. Nanoparticles were synthesized by a modified nanoprecipitation method, and the size of the nanoparticles was controlled by varying the loading ratio, solvent ratio, and the ratio of hydrophilic length to hydrophobic length of the polymer. The invention realizes the size control of AIE nano particles, but the particle size of the obtained nano particles is about 10nm to 20nm at the minimum, and the particle size of the nano particles needs to be further reduced in order to avoid the accumulation of a large amount in the liver and improve the curative effect.

CN110092863A discloses a preparation method of AIE polymer nanoparticles modified by amino and polypeptide, comprising: (1) dissolving an emulsifier and an amino functional monomer in water to obtain an aqueous phase solution; (2) dissolving AIE molecules and an austenite curing effect inhibitor in hydrophobic monomers to obtain an oil phase solution; (3) adding the water phase solution into the oil phase solution, stirring and pre-emulsifying to obtain a coarse emulsion, and performing ultrasonic treatment to obtain a monomer fine emulsion; introducing nitrogen to remove oxygen, and adding a water-soluble initiator to react to prepare the AIE polymer nanoparticle emulsion modified by amino; (4) dissolving omega-maleimide alkyl acid and carbodiimide condensing agent in an acidic pH buffer solution for activation to prepare an activated intermediate solution; (5) adding the activated intermediate solution into the emulsion prepared in the step (3) to react to prepare a maleimide modified AIE polymer nanoparticle emulsion; (6) and (3) adding an aqueous solution of the polypeptide with the terminal cysteine sequence unit into the emulsion prepared in the step (5) to react to prepare the AIE polymer nano particle modified by the amino and the polypeptide. The AIE polymer nanoparticles prepared by the method have the minimum particle size of 65nm, are very easy to accumulate in the liver, influence the imaging effect or curative effect and cause liver burden.

CN104628924A58 discloses a method for preparing aggregation-induced emission type polymer fluorescent nanoparticles by miniemulsion polymerization initiated by a water-soluble initiator, wherein aggregation-induced emission fluorescent monomers and an auxiliary stabilizer are dissolved in a monomer compound to obtain an oil phase solution; dissolving a water-soluble emulsifier in water to obtain an aqueous solution of the emulsifier; adding the oil phase solution into an aqueous solution of an emulsifier, stirring for pre-emulsification to obtain a coarse emulsion, ultrasonically dispersing the coarse emulsion in an ice water bath at 0 ℃ to obtain a monomer fine emulsion, adding a water-soluble initiator, introducing nitrogen to remove oxygen, and reacting at 40-90 ℃ for 0.5 h to 2 days under the protection of nitrogen to obtain the emulsion of the aggregation-induced emission type polymer fluorescent nanoparticles. The invention has the advantages of convenient regulation and control of the size, size distribution and fluorescence brightness of the nano particles, good system stability, simple preparation process, short process flow, no need of organic solvent in the preparation and post-treatment processes, and the like. However, the AIE nanoparticles prepared by the method of the present invention have a minimum particle size of 58nm and a large size, and are likely to accumulate in the liver in a large amount, thereby affecting the imaging effect or therapeutic effect and causing a burden on the liver.

Therefore, there is a need in the art to develop a method for preparing AIE spots having a small particle size, which solves the off-target problem of large AIE spots accumulating in the liver in large amounts in vivo.

Disclosure of Invention

In view of the defects of the prior art, one of the purposes of the present invention is to provide a preparation method of an AIE carbon quantum dot. The preparation method can prepare the AIE carbon quantum dots with the average particle size of less than 10nm, and is favorable for solving the off-target problem that a large amount of large AIE dots are accumulated in the liver in vivo.

In order to achieve the purpose, the invention adopts the following technical scheme:

the invention provides a preparation method of AIE carbon quantum dots, wherein a micro-fluidic chip is used in the preparation method, the micro-fluidic chip comprises a first liquid inlet, a second liquid inlet, a third liquid inlet, a mixing channel and a liquid outlet, and the preparation method comprises the following steps:

and enabling a mixed solution of AIE molecules and phospholipid to enter the microfluidic chip through the third liquid inlet, enabling water to enter the microfluidic chip through the first liquid inlet and the second liquid inlet, enabling the mixed solution and water to flow through the mixing channel, and obtaining the AIE carbon quantum dots at the liquid outlet.

In the present invention, the AIE molecule refers to a compound having aggregation-induced emission properties.

The structure of the microfluidic chip used in the present invention is shown in fig. 1, which includes a first liquid inlet 1, a second liquid inlet 2, a third liquid inlet 3, a mixing channel 4 and a liquid outlet 5. The liquid entering from the first inlet port 1, the second inlet port 2 and the third inlet port 3 converges at the intersection point.

According to the invention, AIE molecules and phospholipids are mixed in advance and prepared into a mixed solution, hydrophobic AIE molecules are converged into a hydrophobic core by a water phase, the hydrophobic core is wrapped and stabilized by amphiphilic phospholipids once being formed by premixing, the hydrophobic core is prevented from growing into a core with a larger size, the hydrophobic AIE molecules are introduced into a microfluidic chip through a third liquid inlet, the mixed solution and water are mixed at a cross point and are fully mixed in a spiral mixing channel, the hydrophobic AIE molecules and the amphiphilic phospholipids form thermodynamically stable nanoparticles of an AIE core/phospholipid shell, the average diameter of the nanoparticles is less than or equal to 10nm (HRTEM particle diameter), and the carbon quantum dots are up to the level of the carbon quantum dots, so that the carbon quantum dots are called as AIE carbon quantum dots.

Preferably, the AIE molecule comprises 4, 7-bis [4- (1,2, 2-triphenylethenyl) phenyl ] benzo-2, 1, 3-thiadiazole and/or TPA-BCI, preferably 4, 7-bis [4- (1,2, 2-triphenylethenyl) phenyl ] benzo-2, 1, 3-thiadiazole (BTPEBT).

Wherein, the structure of BTPEBT is as follows:

the structure of TPA-BCI is as follows:

the two AIE molecules are preferably selected, the two compounds with special structures are mixed with phospholipid in advance and then are introduced into the microfluidic chip, AIE carbon quantum dots with smaller average diameter can be obtained, and the average diameter reaches 3-5 nm, because the molecular weight of the AIE carbon quantum dots is small, the polyphenyl ring structure is more favorable for forming a pi electron conjugated structure and is free from forming carbon quantum dots which are regularly arranged and form crystal forms.

Preferably, the phospholipid comprises any one or a combination of at least two of distearoylphosphatidylethanolamine-polyethylene glycol 2000(DSPE-PEG2k), (2, 3-dioleoyl-propyl) -trimethylamine (DOTAP), dipalmitoyl lecithin (DPPC), Dioleoylphosphatidylethanolamine (DOPE), and distearoylphosphatidylethanolamine-polyethylene glycol 5000(DSPE-PEG5k), preferably distearoylphosphatidylethanolamine-polyethylene glycol 2000.

Preferably, the mass concentration ratio of AIE molecules to phospholipids in the mixed solution is 1:0.5 to 10, for example, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, etc., preferably 1:4 to 6, and more preferably 1: 4.

In a preferred embodiment of the invention, when the mass concentration ratio of the AIE molecules to the phospholipids in the mixed solution is 1: 0.5-10 (particularly 1: 4-6, particularly 1: 4), the average diameter of the AIE carbon quantum dots can be further reduced, the average diameter is as low as 3-5 nm (HRTEM particle size), too many AIE molecules can cause the phospholipids to be insufficiently and completely coated on the AIE hydrophobic core, so that the AIE hydrophobic core grows further to reduce the specific surface area to be completely coated by the phospholipids, too few AIE molecules can cause the excessive phospholipids to self-assemble into larger liposomes or micelles, the particle size of the material is increased, and the purity of the AIE carbon quantum dots is reduced.

Preferably, the mass concentration of the AIE molecules in the mixed solution is 0.8-1.4 mg/mL, such as 0.9mg/mL, 1mg/mL, 1.1mg/mL, 1.2mg/mL, 1.3mg/mL, 1.4mg/mL, and the like, preferably 1 mg/mL.

Preferably, the concentration of the phospholipid in the mixed solution is 0.7 to 8mg/mL, for example, 0.8mg/mL, 0.9mg/mL, 1mg/mL, 2mg/mL, 3mg/mL, 4mg/mL, 5mg/mL, 6mg/mL, 7mg/mL, etc., preferably 3 to 5mg/mL, and more preferably 4 mg/mL.

According to the invention, the specific concentrations of the AIE molecules and the phospholipid are respectively optimized, and researchers find that when the AIE molecules and the phospholipid are respectively controlled within the two concentration ranges, the particle size of the obtained AIE carbon quantum dots is smaller and can reach 3-5 nm (HRTEM particle size).

Preferably, in the mixed solution, the mass concentration of AIE molecules is 0.8-1.4 mg/mL, and the concentration of phospholipids is 0.7-8 mg/mL.

Preferably, the mass concentration of AIE molecules in the mixed solution is 1mg/mL, and the concentration of phospholipid is 4 mg/mL.

Preferably, the flow rate of the mixed solution at the third liquid inlet is 2.5-4 mL/h, such as 2.6mL/h, 2.7mL/h, 2.8mL/h, 2.9mL/h, 3mL/h, 3.1mL/h, 3.2mL/h, 3.3mL/h, 3.4mL/h, 3.5mL/h, 3.6mL/h, 3.7mL/h, 3.8mL/h, 3.9mL/h, etc., preferably 3 mL/h.

Preferably, the flow rate of the water at the first inlet and the second inlet is 200-300 mL/h, such as 210mL/h, 220mL/h, 230mL/h, 240mL/h, 250mL/h, 260mL/h, 270mL/h, 280mL/h, 290mL/h, etc., preferably 240 mL/h. In the invention, water is introduced into the first liquid inlet and the second liquid inlet, the flow rate of the water in the two liquid inlets is preferably 200-300 mL/h, and the specific flow rates can be the same or different.

Preferably, the flow rate of the mixed solution at the third liquid inlet is 2.5-4 mL/h; and the flow rate of the water is 200-300 mL/h at the first liquid inlet and the second liquid inlet.

According to the invention, the flow rate of the mixed solution entering the micro-fluidic chip is preferably 2.5-4 mL/h, and the flow rate of water is 200-300 mL/h, and the two are matched, so that the AIE molecules and the phospholipid can be mixed more vigorously in a water phase, and the AIE molecules can be coated and stabilized by the amphiphilic phospholipid before being aggregated into a smaller hydrophobic core, so that the AIE carbon quantum dots with smaller average diameter can be synthesized, and the particle size can reach 3-5 nm (HRTEM).

Preferably, the flow rate of the mixed solution at the third liquid inlet is 3 mL/h; and the flow rate of the water at the first liquid inlet and the second liquid inlet is 240 mL/h.

Preferably, the solvent of the mixed solution includes any one or a combination of at least two of tetrahydrofuran, ethanol, dimethyl sulfoxide, trifluoroethanol and N, N-dimethylformamide, preferably tetrahydrofuran.

Preferably, the water is ultrapure water.

Preferably, the preparation method specifically comprises the following steps:

enabling a mixed solution of AIE molecules and distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 to enter the microfluidic chip through the third liquid inlet at a flow rate of 2.5-4 mL/h, enabling ultrapure water to enter the microfluidic chip through the first liquid inlet and the second liquid inlet at a flow rate of 200-300 mL/h, enabling the mixed solution and the ultrapure water to flow through the mixing channel, and obtaining the AIE carbon quantum dots at the liquid outlet;

in the mixed solution, the mass concentrations of the AIE molecules and the distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 are 0.8-1.4 mg/mL and 0.7-8 mg/mL respectively, and the ratio of the mass concentrations of the AIE molecules and the distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 is 1: 0.5-10.

Preferably, the mixing channel is double-helical, as shown by mixing channel 4 in fig. 1.

The second purpose of the invention is to provide an AIE carbon quantum dot, and the AIE carbon quantum dot is prepared by the preparation method of the first purpose.

Preferably, the AIE carbon quantum dots have an average diameter of 3 to 5nm (HRTEM particle size), such as 3.2nm, 3.3nm, 3.4nm, 3.5nm, 3.6nm, 3.7nm, 3.8nm, 3.9nm, 4nm, 4.1nm, 4.2nm, 4.3nm, 4.4nm, 4.5nm, 4.6nm, 4.7nm, 4.8nm, 4.9nm, and the like.

Preferably, the AIE carbon quantum dots exhibit a crystal structure.

Preferably, the crystal structure has a pitch of 0.2 to 0.3nm, such as 0.21nm, 0.22nm, 0.23nm, 0.24nm, 0.25nm, 0.26nm, 0.27nm, 0.28nm, 0.29nm, etc., preferably 0.22 nm.

The third purpose of the present invention is to provide a drug comprising the AIE carbon quantum dots of the second purpose.

The medicine of the invention contains AIE carbon quantum dots with the average diameter less than 10nm, so that the AIE dots can not be absorbed by a reticuloendothelial system in vivo, the imaging effect or the curative effect at a required target point is increased, and the liver burden is reduced.

Compared with the prior art, the invention has the following beneficial effects:

the invention mixes AIE molecule and phospholipid in advance to prepare mixed solution, then leads the mixed solution into a micro-fluidic chip through a third liquid inlet, the mixed solution and water are mixed at a cross point and are fully mixed in a spiral mixed channel, hydrophobic AIE molecule and amphipathic phospholipid form thermodynamically stable nano-particle of AIE core/phospholipid shell, the average diameter of the nano-particle is less than 10nm (HRTEM particle diameter), and the grade of carbon quantum dot is achieved.

Drawings

FIG. 1 is a schematic structural diagram of a microfluidic chip used in an embodiment of the present invention;

wherein, 1-a first liquid inlet, 2-a second liquid inlet, 3-a third liquid inlet, 4-a mixing channel and 5-a liquid outlet.

Fig. 2 is a schematic view of the particle structure of the AIE carbon quantum dots obtained in example 1 of the present invention.

FIG. 3 is an HRTEM image of the AIE carbon quantum dots obtained in example 1 of the present invention, with a scale of 10 nm.

FIG. 4 is an HRTEM image of the AIE carbon quantum dots obtained in example 1 of the present invention, with a scale of 2 nm.

FIG. 5 is a DLS particle size histogram of AIE carbon quantum dots obtained in example 1 of the present invention.

FIG. 6 is an HRTEM image of the AIE carbon quantum dots obtained in example 2 of the present invention, with a scale of 10 nm.

FIG. 7 is an HRTEM image of the AIE carbon quantum dots obtained in example 2 of the present invention, with a scale of 2 nm.

FIG. 8 is a schematic structural view of a microfluidic chip in comparative example 1;

wherein, 6-the first channel, 7-the second channel, 8-the third channel, 9-the fourth channel, 10-the fifth channel, 11-the sixth channel, 12-the seventh channel, and 13-the eighth channel.

Detailed Description

For the purpose of facilitating an understanding of the present invention, the present invention will now be described by way of examples. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.

The structure of the microfluidic chip used in the following examples is shown in fig. 1, and includes a first liquid inlet 1, a second liquid inlet 2, a third liquid inlet 3, a mixing channel 4, and a liquid outlet 5.

Example 1

The embodiment provides a preparation method of an AIE carbon quantum dot, which specifically comprises the following steps:

enabling a mixed solution of BTPEBT and DSPE-PEG2k to enter the microfluidic chip through the third liquid inlet 3 at a flow rate of 3mL/h, enabling ultrapure water to enter the microfluidic chip through the first liquid inlet 1 and the second liquid inlet 2 at a flow rate of 240mL/h, enabling the mixed solution and the ultrapure water to flow through the mixing channel, and obtaining the AIE carbon quantum dots at the liquid outlet 5, wherein the microstructure of the AIE carbon quantum dots is shown in FIG. 2;

in the mixed solution, the mass concentrations of BTPEBT and DSPE-PEG2k are 1mg/mL and 4mg/mL respectively, namely the mass concentration ratio of BTPEBT to DSPE-PEG2k is 1:4, and the solvent of the mixed solution is tetrahydrofuran.

Example 2

The difference from example 1 is that the BTPEBT is replaced by TPA-BCI, and the mass concentration of the TPA-BCI in the mixed solution is 1 mg/mL.

Example 3

The difference from example 1 is that the mass concentration of DSPE-PEG2k is 6mg/mL, and the ratio of the mass concentrations of BTPEBT and DSPE-PEG2k is 1: 6.

Example 4

The difference from example 1 is that the mass concentration of BTPEBT is 1.4mg/mL, the mass concentration of DSPE-PEG2k is 0.7mg/mL, and the ratio of the mass concentrations of BTPEBT and DSPE-PEG2k is 1: 0.5.

Example 5

The difference from example 1 is that the mass concentration of BTPEBT is 0.8mg/mL, the mass concentration of DSPE-PEG2k is 8mg/mL, and the ratio of the mass concentrations of BTPEBT and DSPE-PEG2k is 1: 10.

Example 6

The difference from example 1 is that the mass concentration of DSPE-PEG2k is 0.2mg/mL, and the ratio of the mass concentrations of BTPEBT and DSPE-PEG2k is 1: 0.2.

Example 7

The difference from example 1 is that the mass concentration of DSPE-PEG2k is 11mg/mL, and the ratio of the mass concentrations of BTPEBT and DSPE-PEG2k is 1: 11.

Example 8

The difference from example 1 was that the flow rate of the mixed solution was 3mL/h and the flow rate of ultrapure water was 240 mL/h.

Example 9

Example 10

The difference from example 1 is that the flow rate of the mixed solution was 3 mL/h.

Example 11

The difference from example 1 is that the flow rate of ultrapure water was 240 mL/h.

Comparative example 1

The structure of the microfluidic chip used in this comparative example is shown in fig. 8, and includes a first channel 6, a second channel 7, a third channel 8, a fourth channel 9, a fifth channel 10, a sixth channel 11, a seventh channel 12, and an eighth channel 13.

The preparation method comprises the following steps:

enabling a BTPEBT tetrahydrofuran solution with the mass concentration of 1mg/mL to enter the microfluidic chip through the third channel 8 at the flow rate of 3mL/h, enabling a DSPE-PEG2k tetrahydrofuran solution with the mass concentration of 4mg/mL to enter the microfluidic chip through the sixth channel 11 at the flow rate of 3mL/h, enabling ultrapure water to enter the microfluidic chip through the first channel 6 and the second channel 7 at the flow rate of 240mL/h, and obtaining AIE nano particles at an outlet.

Performance testing

The following performance tests were performed on the AIE carbon quantum dots and AIE nanoparticles obtained in the examples and comparative examples:

(1) high Resolution Transmission Electron Microscopy (HRTEM) testing was performed using Tecnai G2F20U-TWIN, FEI USA, with test parameters: accelerating voltage of 200kV, pulling voltage of 3950V, current of 69 muA, amplification factors of 340k and 890 k; obtaining a particle morphology image, measuring the diameter thereof and calculating the average value (HRTEM particle diameter);

(2) dynamic Light Scattering (DLS) testing was performed using Zetasizer Nano ZS, manufactured by malvern instruments ltd, uk, with test parameters: the refractive index of the material is 1.590, the absorption intensity is 0.010, the solvent is water, and the measurement angle is 173 degrees; obtaining the distribution situation of the particle diameter and the average diameter (DLS particle diameter);

the results of the above performance tests are shown in table 1.

TABLE 1

	HRTEM particle size/nm	DLS particle size/nm
			Example 1	4.0	5.6
Example 2	4.2	5.7
			Example 3	4.5	5.8
Example 4	6.1	7.1
			Example 5	6.0	7.6
Example 6	8.8	10.0
			Example 7	8.7	9.9
Example 8	4.2	5.8
			Example 9	4.3	5.9
Example 10	8.5	9.9
			Example 11	8.2	9.7
Comparative example 1	25	27.1

As can be seen from Table 1, AIE carbon quantum dots (average diameter is less than or equal to 10nm) can be obtained by the method of the embodiment, while the BTPEBT solution and the DSPE-PEG2k solution are separately added into the microfluidic chip in the comparative example 1, the effect is greatly reduced, and the obtained HRTEM particle diameter is 25nm, thereby proving that the particle diameter of the obtained nanoparticles can be effectively reduced by the method of pre-mixing BTPEBT and DSPE-PEG2k and then adding the mixture into the microfluidic chip, and the AIE carbon quantum dots with the average diameter of less than or equal to 10nm can be obtained.

It is understood from comparative examples 1 and 4 to 7 that when the mass concentration ratio of the AIE molecules to the phospholipid in the mixed solution is 1:0.5 to 10 (examples 1, 4 and 5), particularly 1:4 to 6 (examples 1 and 4), the average diameter of the obtained AIE carbon quantum dots is smaller, and that the average diameter of the obtained AIE carbon quantum dots is increased when the AIE molecules are too much (example 6) or too little (example 7).

As is clear from comparison of examples 1 and 8 to 11, when the flow rate of the mixed solution was 2.5 to 4mL/h and the flow rate of water was 200 to 300mL/h (examples 1 and 8), the average diameter of the obtained AIE carbon quantum dots was smaller, and the average diameter of the obtained AIE carbon quantum dots was increased regardless of whether the flow rate of the mixed solution or the flow rate of water was outside the specific range (examples 9 and 10).

Fig. 3 and 4 are HRTEM images of the AIE carbon quantum dots obtained in example 1, from which it can be seen that the AIE carbon quantum dots have small particle diameters, and an average particle diameter of 4.0nm after measurement, and fig. 4 shows a lattice structure, and a pitch of 0.22nm after measurement.

Fig. 5 is a DLS particle size histogram of the AIE carbon quantum dots obtained in example 1, which shows that the AIE carbon quantum dots have a normal particle size distribution and an average particle size of 5.6nm as given by the instrument.

Fig. 6 and 7 are HRTEM images of the AIE carbon quantum dots obtained in example 2, from which it can be seen that the AIE carbon quantum dots have small particle diameters, and an average particle diameter of 4.2nm after measurement, and fig. 7 shows a lattice structure, and a pitch of 0.22nm is obtained after measurement.

The applicant states that the present invention is illustrated by the above examples to show the details of the process equipment and process flow of the present invention, but the present invention is not limited to the above details of the process equipment and process flow, which means that the present invention must not be implemented by relying on the above details of the process equipment and process flow. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.

Claims

1. A preparation method of AIE carbon quantum dots is characterized in that a microfluidic chip is used in the preparation method, the microfluidic chip comprises a first liquid inlet, a second liquid inlet, a third liquid inlet, a mixing channel and a liquid outlet, and the preparation method comprises the following steps:

enabling a mixed solution of AIE molecules and phospholipid to enter the microfluidic chip through the third liquid inlet, enabling water to enter the microfluidic chip through the first liquid inlet and the second liquid inlet, enabling the mixed solution and the water to flow through the mixing channel, and obtaining the AIE carbon quantum dots at the liquid outlet;

the AIE molecule comprises 4, 7-bis [4- (1,2, 2-triphenylethenyl) phenyl ] benzo-2, 1, 3-thiadiazole and/or TPA-BCI;

the TPA-BCI has the following structure:

2. the method of claim 1, wherein the AIE molecule is 4, 7-bis [4- (1,2, 2-triphenylethenyl) phenyl ] benzo-2, 1, 3-thiadiazole.

3. The method according to claim 1, wherein the phospholipid comprises any one or a combination of at least two of distearoylphosphatidylethanolamine-polyethylene glycol 2000, dipalmitoylphosphatidylcholine, dioleoylphosphatidylethanolamine and distearoylphosphatidylethanolamine-polyethylene glycol 5000.

4. The method according to claim 3, wherein the phospholipid is distearoylphosphatidylethanolamine-polyethylene glycol 2000.

5. The method according to claim 1, wherein the ratio of the mass concentration of the AIE molecules to the mass concentration of the phospholipid in the mixed solution is 1: 0.5-10.

6. The method according to claim 5, wherein the mass concentration ratio of the AIE molecules to the phospholipids in the mixed solution is 1:4 to 6.

7. The method according to claim 6, wherein the ratio of the mass concentration of the AIE molecules to the phospholipid in the mixed solution is 1: 4.

8. The method according to claim 1, wherein the mass concentration of AIE molecules in the mixed solution is 0.8-1.4 mg/mL.

9. The method according to claim 8, wherein the mass concentration of the AIE molecule in the mixed solution is 1 mg/mL.

10. The method according to claim 1, wherein the concentration of the phospholipid in the mixed solution is 0.7 to 8 mg/mL.

11. The method according to claim 10, wherein the concentration of the phospholipid in the mixed solution is 3 to 5 mg/mL.

12. The method according to claim 11, wherein the concentration of the phospholipid in the mixed solution is 4 mg/mL.

13. The method according to claim 1, wherein the AIE molecule is contained in the mixed solution at a concentration of 0.8 to 1.4mg/mL and the phospholipid is contained in the mixed solution at a concentration of 0.7 to 8 mg/mL.

14. The method according to claim 13, wherein the AIE molecule is present in the mixed solution at a mass concentration of 1mg/mL and the phospholipid is present at a concentration of 4 mg/mL.

15. The preparation method according to claim 1, wherein the flow rate of the mixed solution at the third inlet is 2.5-4 mL/h.

16. The method of claim 15, wherein the flow rate of the mixed solution at the third inlet is 3 mL/h.

17. The preparation method according to claim 1, wherein the flow rate of the water at the first liquid inlet and the second liquid inlet is 200-300 mL/h.

18. The method of claim 17, wherein the flow rate of the water at the first inlet and the second inlet is 240 mL/h.

19. The preparation method of claim 1, wherein the flow rate of the mixed solution at the third inlet is 2.5-4 mL/h; and the flow rate of the water is 200-300 mL/h at the first liquid inlet and the second liquid inlet.

20. The preparation method according to claim 19, wherein the flow rate of the mixed solution at the third inlet is 3 mL/h; and the flow rate of the water at the first liquid inlet and the second liquid inlet is 240 mL/h.

21. The method according to claim 1, wherein the solvent of the mixed solution comprises any one or a combination of at least two of tetrahydrofuran, ethanol, dimethyl sulfoxide, trifluoroethanol, and N, N-dimethylformamide.

22. The method according to claim 21, wherein the solvent of the mixed solution includes tetrahydrofuran.

23. The production method according to claim 1, wherein the water is ultrapure water.

24. The preparation method according to claim 1, characterized in that the preparation method comprises the following steps:

in the mixed solution, the mass concentrations of the AIE molecules and the distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 are 0.8-1.4 mg/mL and 0.7-8 mg/mL respectively, and the mass concentration ratio of the AIE molecules to the distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 is 1: 0.5-10.

25. The method of claim 24, wherein the mixing channel is in the form of a double helix.

26. An AIE carbon quantum dot, which is prepared by the preparation method of any one of claims 1 to 25.

27. The AIE carbon quantum dot of claim 26, wherein the AIE carbon quantum dot has an average diameter of 3 to 5 nm.

28. The AIE carbon quantum dot of claim 26, wherein the AIE carbon quantum dot exhibits a crystal structure.

29. The AIE carbon quantum dot of claim 28, wherein the crystal structure has a pitch of 0.2 to 0.3 nm.

30. The AIE carbon quantum dot of claim 29, wherein a pitch of the crystal structure is 0.22 nm.

31. A medicament comprising the AIE carbon quantum dot of any one of claims 26-30.