A method for preparing hollow microspheres of nanoparticles using microfluidic technology
By generating hollow microspheres of nanoparticles using microfluidic technology, the problem of non-uniform assembly size in existing technologies has been solved, achieving monodispersity and size control of nanoparticle assemblies, and expanding their applications in trace substance detection and biomedicine.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SOUTHEAST UNIV
- Filing Date
- 2026-03-06
- Publication Date
- 2026-06-30
AI Technical Summary
In existing technologies, nanoparticle assemblies prepared using emulsion assembly methods have inconsistent and difficult-to-control sizes, which limits their application in various fields.
Using microfluidic technology, oil and aqueous solutions are injected into a microfluidic chip, and the flow rate is adjusted to generate monodisperse oil droplets. Subsequently, uniformly sized hollow microspheres are assembled by solvent evaporation.
The nanoparticle assemblies exhibit good monodispersity and controllable size, making them suitable for trace substance detection and biomedical applications.
Smart Images
Figure CN122298313A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a method for preparing hollow microspheres of nanoparticles using microfluidic technology, belonging to the field of nanomaterial preparation technology. Background Technology
[0002] In recent years, the design and fabrication of novel functional materials using inorganic nanoparticles as assembly building blocks has attracted widespread attention from researchers. These functional materials possess unique electronic, magnetic, and optical properties, showing great potential in various fields such as plasma sensors and surface-enhanced spectroscopy (SES). Among numerous assembly methods, emulsion-based assembly demonstrates significant development prospects due to its advantages such as micro-area confinement, interface templates, and method simplicity. By controlling the conditions, nanostructures with different shapes, such as spheres, cubes, and rings, can be obtained. Currently, most assembly methods using this approach involve directly mixing oil and aqueous phases followed by ultrasonic or high-speed stirring to generate an emulsion. Due to the limitation of droplet size, the size of the assemblies is generally at the submicron level, and the size uniformity cannot be well controlled, thus greatly limiting the application of the generated assemblies in different fields.
[0003] Microfluidics, a technique for manipulating microfluidics at the microscale, is an emerging interdisciplinary field involving numerous disciplines such as physics and chemistry. It generates microdroplets by manipulating immiscible continuous and dispersed phases, offering advantages such as good monodispersity, uniform spatial distribution, and high throughput. Using microdroplets as confined assembly spaces allows for the creation of isolated and uniform assembly environments. This invention utilizes microfluidics combined with solvent evaporation self-assembly methods to find a reliable, rapid, and universal method for generating micron-sized nanoparticle assemblies with good monodispersity. Summary of the Invention
[0004] Technical Problem: The purpose of this invention is to provide a method for preparing hollow microspheres of nanoparticles using microfluidic technology. This method is simple and easy to operate; it can efficiently prepare micron-sized assemblies with good monodispersity, thereby solving the problems existing in the prior art.
[0005] Technical solution: The first objective of this invention is to provide a method for preparing hollow microspheres of nanoparticles using microfluidic technology, the steps of which are as follows:
[0006] Step 1: Disperse the oil-soluble nanoparticles in a non-polar solvent to form an oil phase solution;
[0007] Step 2: Disperse the surfactant in ultrapure water to prepare an aqueous solution;
[0008] Step 3: Using a microfluidic device, the oil phase solution and the aqueous phase solution are injected into the microfluidic chip. The flow rates of the oil phase and the aqueous phase are adjusted so that the oil phase fluid is sheared by the aqueous phase fluid in the microchannel to generate a water-in-oil emulsion with a uniformly distributed monodisperse oil droplet size.
[0009] Step 4: Allow the oil-in-water emulsion obtained in Step 3 to stand, and assemble it into a spherical assembly, i.e., hollow microspheres of nanoparticles, by solvent evaporation.
[0010] The spherical assembly is obtained by assembling inorganic nanoparticles in an oil-in-water emulsion through solvent evaporation. The spherical assembly has a multi-layered hollow spherical shell structure with a diameter of 1-20 µm and good size monodispersity.
[0011] Preferably, in step one, the concentration of the oil-soluble nanoparticles is 0.5-20 mg / mL, the diameter of the oil-soluble nanoparticles is 2-50 nm, and the material is Au, Pt, Pd, CdSe or Fe3O4.
[0012] Preferably, the oil-soluble nanoparticles are made of Au, with a concentration greater than 2 mg / mL and a diameter of 2-6 nm.
[0013] Preferably, the nonpolar solvent in step one is n-hexane, toluene, or cyclohexane.
[0014] Furthermore, the nonpolar solvent is n-hexane.
[0015] Preferably, the surfactant in step two is an HLB value of 10-18 and the concentration of the surfactant is 2-10 wt%.
[0016] Preferably, the surfactant in step two is Tween 20, Tween 80, or CTAB.
[0017] Furthermore, the surfactant is Tween 20.
[0018] Preferably, the size of the oil droplets in step three is 40 µm.
[0019] Preferably, in step four, the oil-in-water emulsion obtained in step three is allowed to stand at room temperature.
[0020] Preferably, the spherical assembly in step four is a multi-layered hollow spherical shell structure with a diameter of 1-20 µm and good size monodispersity.
[0021] The second objective of this invention is to provide hollow microspheres of nanoparticles prepared by the above method.
[0022] Beneficial effects: Compared with the prior art, the beneficial effects of the present invention are:
[0023] (1) The method is simple, easy to implement, and the reaction conditions are mild;
[0024] (2) The size of the nanoparticle spherical assembly obtained by the present invention is controllable and is at the micrometer level, and the diameter polydispersity can be less than 5%, which provides excellent conditions for realizing complex multi-level assemblies;
[0025] (3) The nanoparticle spherical assembly obtained by the present invention can measure the SERS and scattering effect of the assembly, and therefore has a wider range of applications, such as trace substance detection and biomedicine. Attached Figure Description
[0026] The specific embodiments of the present invention will be described in further detail with the aid of the accompanying drawings, but the content of the drawings does not constitute any limitation on the present invention.
[0027] Figure 1 The image shows the characterization of the Au nanoparticles prepared in Example 1, where A is a transmission electron microscope image of the Au nanoparticles and a physical image of them dispersed in n-hexane; B is a size distribution diagram of the Au nanoparticles.
[0028] Figure 2 The image shows the UV-Vis absorption spectrum of the Au nanoparticles prepared in Example 1.
[0029] Figure 3 This is a polarized light microscope image of the microdroplets of the oil-in-water emulsion generated by microfluidics in Example 1.
[0030] Figure 4 This is a polarized light microscope image of the Au nanoparticle assembly prepared in Example 1.
[0031] Figure 5 The figures show the characterization of the Au nanoparticle assembly prepared in Example 1. In the figures, A is a scanning electron microscope image of the Au nanoparticle assembly; B is a size distribution map of the Au nanoparticle assembly; and C is a scanning electron microscope image of the multilayer structure of the Au nanoparticle assembly.
[0032] Figure 6 The images show polarized light microscope images of assemblies formed from Au nanoparticles of different concentrations in Example 2, and the relationship between polydispersity and concentration.
[0033] Figure 7 The images show polarized light microscope images of assemblies formed from Au nanoparticles of different sizes in Example 3, and the relationship between polydispersity and particle size.
[0034] Figure 8 The images show polarized light microscope images and size distribution diagrams of the Pt nanoparticle assemblies prepared in Example 4.
[0035] Figure 9 The images show polarized light microscope images and size distribution diagrams of the Pd nanoparticle assemblies prepared in Example 5.
[0036] Figure 10 The image shows a polarized microscope photograph and size distribution diagram of the CdSe quantum dot assembly prepared in Example 6.
[0037] Figure 11 The images show polarized light microscope images and size distribution diagrams of the Fe3O4 nanoparticle assembly prepared in Example 7. Detailed Implementation
[0038] The technical solution of the present invention will be clearly and completely described below with reference to preferred embodiments. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. The described content is illustrative and not restrictive, and should not be used to limit the scope of protection of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0039] Unless otherwise specified, the raw materials used in the examples in this specification are all commercially available products. Experimental methods with specific conditions not specified in the examples are generally performed under conventional conditions or under conditions recommended by the manufacturer.
[0040] Example 1
[0041] A method for preparing hollow microspheres of nanoparticles using microfluidic technology includes the following steps:
[0042] At room temperature, oil-soluble Au nanoparticles were dispersed in n-hexane to obtain an oil phase solution, wherein the Au nanoparticles had a diameter of 5 nm, a mass of 20 mg, and the n-hexane volume was 1 mL.
[0043] Oil-soluble Au nanoparticles can be prepared by various methods. This embodiment describes a typical direct reduction method, the steps of which include:
[0044] (1) Place 50 mg HAuCl4·3H2O in a 20 mL glass vial containing a 6 mL toluene and 6 mL oleylamine mixture and dissolve it completely. The vial is capped. Place 21.75 mg of borane-tert-butylamine complex in a 10 mL glass vial containing a 1 mL toluene and 1 mL oleylamine mixture and dissolve it completely. Stir at 0~10 ℃ for 20 min.
[0045] (2) Adjust the rotation speed of the HAuCl4·3H2O solution to 1000 rpm, and inject the borane-tert-butylamine complex solution into the HAuCl4·3H2O solution quickly using a 10 mL disposable medical syringe, and continue stirring for 1 h to obtain a wine-red solution.
[0046] (3) Place the wine-red solution obtained in step (2) into a 50 mL centrifuge tube, add 30 mL of anhydrous ethanol and mix well to precipitate. Centrifuge at 5000 rpm for 5 min and remove the supernatant. Add 1 mL of petroleum ether to redisperse, add 40 mL of anhydrous ethanol and mix well to precipitate. Repeat the centrifugation operation once and remove the supernatant to obtain Au nanoparticles with the surface modified by oleylamine molecules.
[0047] Figure 1 A shows a transmission electron microscope image of the Au nanoparticles and a physical image of the solution in this embodiment. Figure 1 B is a size distribution diagram of the Au nanoparticles in this embodiment. As can be seen from the figure, the prepared Au nanoparticles are spherical and have a uniform particle size distribution with a diameter of 4.89 nm ± 0.31 nm. They are dispersed in n-hexane as a wine-red solution.
[0048] Figure 2 The image shows the UV-Vis absorption spectrum of the Au nanoparticles in this embodiment. As can be seen from the image, the maximum absorption peak is located at approximately 525 nm, indicating that the Au nanoparticles are well dispersed.
[0049] 100 mg of Tween 20 was added to 1.9 mL of ultrapure water and dissolved completely to obtain a 5% (w / w) Tween 20 aqueous solution as the aqueous phase solution. The microfluidic device (DG-01 microdroplet preparation instrument from Shanghai Pengzan Biotechnology Co., Ltd.) was activated, and the aqueous and oil phase solutions were connected to the aqueous and oil phase ports of the microfluidic chip, respectively. The pressure of the gas valve was adjusted to maintain an aqueous phase pressure of 300 mbar and an oil phase pressure of 500 mbar. The fluid velocity in the aqueous and oil phase channels was controlled to ensure that the extruded oil droplets had a particle size of approximately 40 µm. The water-in-oil microdroplets collected on a silicon wafer substrate were allowed to stand at room temperature (25°C) for 4 h to allow the oil phase solvent to evaporate, yielding spherical assemblies of Au nanoparticles.
[0050] Figure 3 The image shows a polarized light microscope image of the microdroplets generated in the oil-in-water emulsion in this embodiment. As can be seen from the image, the generated microdroplets remain stable and have a uniform size distribution, with a particle size of about 40 µm.
[0051] Figure 4 This is a polarized light microscope image of the Au nanoparticle assembly in this embodiment. Figure 5 A is a scanning electron microscope image of the Au nanoparticle assembly in this embodiment. Figure 5B is a size distribution diagram of the Au nanoparticle assembly in this embodiment. Figure 5 C is a scanning electron microscope (SEM) image of the multilayer structure of the Au nanoparticle assembly in this embodiment. As shown in the image, the generated spherical assembly is a well-monodispersed, micron-sized assembly with a shell structure, measuring 7.5 µm ± 0.31 µm, with a polydispersity as low as 4.12%. This provides excellent conditions for subsequent realization of complex multilevel assemblies and measurement of the scattering spectra and SERS patterns of the assemblies. The image also shows small pores of varying sizes on the surface of the assembly, which is due to the slow evaporation of n-hexane from the microdroplets and partial solvent exchange with the aqueous phase.
[0052] Example 2
[0053] Same as Example 1, except that the mass concentration of Au nanoparticles is different. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, are kept exactly the same as in Example 1. Only the concentration m (mg / mL) of Au nanoparticles in the oil phase is changed. The concentrations are set to m1=0.5 mg / mL, m2=1 mg / mL, m3=2 mg / mL, m4=5 mg / mL, and m5=10 mg / mL for the experiment.
[0054] Figure 6 The figures show polarized light microscope images of assemblies formed by Au nanoparticles at different concentrations in this embodiment, as well as the relationship between polydispersity and concentration. As can be seen from the figures, when the concentration of Au nanoparticles in the oil phase is low (less than or equal to 2 mg / mL), the assemblies are small in size and have uneven morphology, with a polydispersity of over 5%. With increasing concentration, the assemblies become larger, tend to be spherical, and the polydispersity decreases, reaching a minimum of 3.35%. Therefore, the preferred Au nanoparticle concentration should be greater than 2 mg / mL.
[0055] Example 3
[0056] Similar to Example 1, the only difference is the particle size of the Au nanoparticles. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, remain identical to Example 1. Only the particle size d (nm) of the Au nanoparticles in the oil phase is changed, set to d1=3 nm, d2=4.19 nm, d3=6 nm, d4=7 nm, and d5=8 nm for experiments. In this example, the larger-sized Au nanoparticles can be obtained by using smaller-sized Au nanoparticles as seeds via a seed growth method, the steps of which include:
[0057] (1) Take an appropriate amount of Au nanoparticle n-hexane solution and redisperse it in toluene as a seed solution. Add different amounts of HAuCl4·3H2O toluene and oleylamine mixed solution (taking 10 mg of 5 nm gold seed as an example, 14.56 mg of chloroauric acid is needed to grow to 6 nm, 34.88 mg of chloroauric acid is needed to grow to 7 nm, and 61.92 mg of chloroauric acid is needed to grow to 8 nm).
[0058] (2) The growth solution was obtained by stirring the reaction at 60 °C for 24 h. The growth solution was placed in a 50 mL centrifuge tube, 30 mL of anhydrous ethanol was added and mixed to precipitate. After centrifugation at 5000 rpm for 5 min, the supernatant was removed. 1 mL of petroleum ether was added to redisperse the solution. 40 mL of anhydrous ethanol was added and mixed to precipitate. The centrifugation operation was repeated once, and the supernatant was removed to obtain Au nanoparticles with larger particle size.
[0059] Figure 7 The figures show polarized light microscope images of assemblies formed from Au nanoparticles of different sizes in this embodiment, as well as the relationship between polydispersity and particle size. As can be seen from the figures, when the Au nanoparticle size in the oil phase is small (less than or equal to 6 nm), the polydispersity of the assemblies is good, all below 5%. With increasing particle size, the polydispersity increases, and the overall size of the assemblies tends to decrease with increasing nanoparticle size. Therefore, it is preferable that the Au nanoparticle size is less than or equal to 6 nm.
[0060] Example 4
[0061] Same as Example 1, except that the nanoparticles in the oil phase solution are different. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, are kept exactly the same as in Example 1, except that 20 mg Au nanoparticles are replaced with 1 mg Pt nanoparticles. Figure 8 The images show polarized light microscope photographs and size distribution diagrams of the Pt nanoparticle assembly in this embodiment. As can be seen from the figures, the morphology of the obtained spherical nanoparticle assembly did not change significantly, and the monodispersity was good, with a size of 4.04 µm ± 0.24 µm.
[0062] Example 5
[0063] Same as Example 1, except that the nanoparticles in the oil phase solution are different. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, are kept exactly the same as in Example 1, except that 20 mg Au nanoparticles are replaced with 1 mg Pd nanoparticles. Figure 9 The images show polarized light microscope photographs and size distribution diagrams of the Pd nanoparticle assembly in this embodiment. As can be seen from the figures, the morphology of the obtained spherical nanoparticle assembly did not change significantly, and the monodispersity was good, with a size of 4.00 µm ± 0.18 µm.
[0064] Example 6
[0065] Same as Example 1, except that the nanoparticles in the oil phase solution are different. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, are exactly the same as in Example 1. The only difference is that the 20 mg Au nanoparticles are replaced with 5 mg CdSe quantum dots. Figure 10 The images show polarized light microscope photographs and size distribution diagrams of the CdSe quantum dot assemblies in this embodiment. As can be seen from the figures, the morphology of the obtained spherical nanoparticle assemblies did not change significantly, and the monodispersity was good. The size was 14.36 µm ± 1.15 µm. The size change was caused by the change in the number and concentration of the assembly units.
[0066] Example 7
[0067] Same as Example 1, except that the nanoparticles in the oil phase solution are different. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, are kept exactly the same as in Example 1, except that 20 mg Au nanoparticles are replaced with 5 mg Fe3O4 nanoparticles. Figure 11 The images show polarized light microscope photographs and size distribution diagrams of the Fe3O4 nanoparticle assembly in this embodiment. As can be seen from the figures, the morphology of the obtained spherical nanoparticle assembly did not change significantly, and the monodispersity was good. The size was 8.77 µm ± 0.47 µm. The size change was caused by the change in the number and concentration of assembly units.
[0068] Example 8
[0069] Same as Example 1, except for the type of surfactant in the aqueous solution. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, remain exactly the same as in Example 1, except that Tween 20 is changed to Tween 80. The resulting Au nanoparticle spherical assemblies show no significant changes.
[0070] Example 9
[0071] Same as Example 1, except for the type of surfactant in the aqueous solution. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, remain exactly the same as in Example 1, except that Tween 20 is replaced with CTAB. The resulting Au nanoparticle spherical assemblies show no significant changes.
[0072] Example 10
[0073] Same as Example 1, except that the mass concentration of the surfactant in the aqueous solution is different. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, are kept exactly the same as in Example 1, except that 5% (w / w) is changed to 2% (w / w). The resulting Au nanoparticle spherical assemblies showed no significant changes.
[0074] Example 11
[0075] Same as Example 1, except that the mass concentration of surfactant in the aqueous solution is different. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, are kept exactly the same as in Example 1, except that 5% (w / w) is changed to 10% (w / w). The resulting Au nanoparticle spherical assemblies showed no significant changes.
[0076] Example 12
[0077] Same as Example 1, except that the nonpolar solvent in the oil phase solution is different. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, are exactly the same as in Example 1, except that hexane is replaced with toluene. The resulting Au nanoparticle spherical assemblies show no significant changes.
[0078] Example 13
[0079] Same as Example 1, except that the nonpolar solvent in the oil phase solution is different. All other parameters, such as the microfluidic chip structure and the two-phase pressure ratio, are exactly the same as in Example 1, except that n-hexane is replaced with cyclohexane. The resulting Au nanoparticle spherical assemblies show no significant changes.
[0080] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention and are not intended to limit the implementation of the present invention. For those skilled in the art, other variations or modifications can be made based on the above description. It is impossible to exhaustively list all embodiments here. Any obvious variations or modifications derived from the technical solutions of the present invention are still within the protection scope of the present invention.
Claims
1. A method for preparing hollow microspheres of nanoparticles using microfluidic technology, characterized in that, The steps are as follows: Step 1: Disperse the oil-soluble nanoparticles in a non-polar solvent to form an oil phase solution; Step 2: Disperse the surfactant in ultrapure water to prepare an aqueous solution; Step 3: Using a microfluidic device, the oil phase solution and the aqueous phase solution are injected into the microfluidic chip. The flow rates of the oil phase and the aqueous phase are adjusted so that the oil phase fluid is sheared by the aqueous phase fluid in the microchannel to generate a water-in-oil emulsion with a uniformly distributed monodisperse oil droplet size. Step 4: Allow the oil-in-water emulsion obtained in Step 3 to stand, and assemble it into a spherical assembly, i.e., hollow microspheres of nanoparticles, by solvent evaporation.
2. The method for preparing hollow microspheres of nanoparticles using microfluidic technology according to claim 1, characterized in that, In step one, the concentration of oil-soluble nanoparticles is 0.5-20 mg / mL, the diameter of the oil-soluble nanoparticles is 2-50 nm, and the material is Au, Pt, Pd, CdSe or Fe3O4.
3. The method for preparing hollow microspheres of nanoparticles using microfluidic technology according to claim 2, characterized in that, The oil-soluble nanoparticles are made of Au, with a concentration greater than 2 mg / mL and a diameter of 2-6 nm.
4. The method for preparing hollow microspheres of nanoparticles using microfluidic technology according to claim 1, characterized in that, The non-polar solvent in step one is n-hexane, toluene, or cyclohexane.
5. The method for preparing hollow microspheres of nanoparticles using microfluidic technology according to claim 1, characterized in that, In step two, the surfactant is an HLB value of 10-18 and the concentration of the surfactant is 2-10 wt%.
6. The method for preparing hollow microspheres of nanoparticles using microfluidic technology according to claim 4, characterized in that, The surfactant used in step two is Tween 20, Tween 80, or CTAB.
7. The method for preparing hollow microspheres of nanoparticles using microfluidic technology according to claim 1, characterized in that, The size of the oil droplets in step three is 40 µm.
8. The method for preparing hollow microspheres of nanoparticles using microfluidic technology according to claim 1, characterized in that, In step four, the oil-in-water emulsion obtained in step three is left to stand at room temperature.
9. A method for preparing hollow microspheres of nanoparticles using microfluidic technology according to claim 1, characterized in that, In step four, the spherical assembly is a multi-layered hollow spherical shell structure with a diameter of 1-20 µm and good size monodispersity.
10. Hollow microspheres of nanoparticles prepared by the method of any one of claims 1-9.