Preparation method of hydrogel hollow microspheres based on microfluidic controllable photocuring technology, product and application thereof
The preparation of hydrogel hollow microspheres by microfluidic controllable photopolymerization technology solves the problems of complex preparation and high cost in traditional methods, and realizes low-cost mass production of monodisperse micron-sized hollow microspheres for application in the field of ultrasonic metamaterials.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- ZHEJIANG UNIV
- Filing Date
- 2023-12-11
- Publication Date
- 2026-06-12
AI Technical Summary
Existing technologies for preparing micron-scale hollow microspheres suffer from problems such as complex processes, high costs, uncontrollable particle size, and uneven particle size distribution. Furthermore, traditional microfluidic methods require multi-stage microchannels and external pumps, which limits the large-scale production and application of hollow microspheres.
Microfluidic controllable photocuring technology is used to mix micro- and nano-sized inorganic oxide particles with hydrogel materials. The outer layer is cured by rolling the mixture through a curved flexible tube channel using ultraviolet light absorption, without curing the inside, thus forming hollow hydrogel microspheres. By combining droplet microfluidic technology and ultraviolet light curing technology, the size and polymerization process of the microdroplets can be controlled.
We have achieved low-cost, batch preparation of monodisperse micron-sized hollow hydrogel microspheres, which are suitable for preparing double negative acoustic metamaterials with negative equivalent mass density and negative equivalent elastic modulus, and can be applied to medical ultrasound imaging, medical ultrasound therapy, and acoustic devices.
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Figure CN117504749B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of ultrasonic metamaterials, specifically relating to a method for preparing hydrogel hollow microspheres based on microfluidic controllable photocuring technology, as well as its products and applications. Background Technology
[0002] Ultrasonic metamaterials are periodic or aperiodic materials composed of subwavelength structural units in the ultrasonic frequency band. They allow for precise manipulation of ultrasonic waves, enabling unique phenomena not found in conventional materials, such as negative refraction and negative reflection. They hold significant promise for applications in medical ultrasound imaging, medical ultrasound therapy, and acoustic devices. The two fundamental physical parameters of ultrasonic metamaterials—negative equivalent mass density and negative equivalent elastic modulus—are primarily determined by the performance, morphology, and distribution of their subwavelength structural units in the ultrasonic frequency band. Hollow microspheres at the micrometer scale are a common choice for constructing these structural units, requiring controllable particle size distribution, density, modulus, and sound velocity.
[0003] Currently, the main methods for preparing hollow microspheres at the micrometer scale include traditional methods such as emulsion polymerization, dispersion polymerization, foaming, and suspension polymerization. These methods suffer from problems such as complex preparation processes, long preparation times, uncontrollable particle size, and uneven particle size distribution. Furthermore, the preparation requirements are very stringent, requiring long periods of time and specific conditions to produce hollow microspheres with uniform size and morphology. Droplet microfluidics, on the other hand, is a technique that manipulates monodisperse droplets formed by multiphase fluid shearing within microscale (tens to hundreds of micrometers) channels. It produces microspheres with uniform size, high throughput, monodispersity, and the ability to be scalably integrated, making it an emerging technology for preparing hollow microspheres.
[0004] However, the current application of droplet microfluidics technology to prepare hollow microspheres mainly uses microfluidic chips with multi-level microchannels. For example, Chinese patent application number 202310792796.8 discloses a method for preparing hollow microspheres using microfluidics technology. It prepares oil-in-water-in-gas microdroplets based on gas phase, water phase and oil phase. It requires a large number of external pumps, a lot of consumables and complex processes, which drastically increases the production cost and limits the large-scale production and application of hollow microspheres. Summary of the Invention
[0005] The purpose of this invention is to provide a method for preparing hollow hydrogel microspheres using microfluidic controllable photocuring technology, which can prepare monodisperse micron-sized hollow hydrogel microspheres in batches at low cost.
[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:
[0007] A method for preparing hydrogel hollow microspheres based on microfluidic controllable photocuring technology, the method comprising:
[0008] (1) After mixing micro-nano inorganic oxide particles with water, gel material is added to prepare an aqueous solution;
[0009] (2) Prepare oil phase solution;
[0010] (3) The aqueous solution and the oil solution are injected into the aqueous microchannel and the oil microchannel of the droplet microfluidic chip respectively by an external pump to generate microdroplets;
[0011] (4) When the microdroplets flow through the curved flexible tube channel, they are irradiated with ultraviolet light and solidified to obtain hydrogel hollow microspheres.
[0012] The preparation method provided by this invention uses microfluidic controllable photocuring technology, which combines droplet microfluidic technology with hydrogel ultraviolet light curing technology. The key point is to use inorganic oxide particles with good ultraviolet light absorption capacity to make microdroplets roll continuously in the curved tube channel due to friction with the tube wall, so that only the outer layer is cured under ultraviolet light while the inside is not cured, thus producing hydrogel hollow microspheres.
[0013] The specific technical principle is as follows: Aqueous and oil solutions are driven by an external pump into the microchannels of a microfluidic chip. Based on the principle of two-phase immiscibility, water-in-oil microdroplets are formed at the junction of the aqueous and oil microchannels. Microdroplets containing inorganic oxide particles that can absorb ultraviolet light are fully mixed by rolling continuously with friction against the tube wall in the curved flexible tube channel (the tube irradiated by ultraviolet light is curved to ensure sufficient friction between the microdroplets and the tube wall so that the microdroplets can roll fully; otherwise, it would be difficult to obtain hydrogel hollow microspheres). The hydrogel microdroplets polymerize under the initiation of an initiator and ultraviolet light. Because the inorganic oxide particles inside the hydrogel microdroplets can absorb ultraviolet light, they cannot complete polymerization and solidification in a short time under ultraviolet light, resulting in the solidification of the microdroplet shell while the interior remains liquid, thus forming hydrogel hollow microspheres, and producing hydrogel hollow microspheres in batches.
[0014] In step (1), the micro-nano inorganic oxide particles are selected from titanium dioxide, zinc oxide, iron oxide, cuprous oxide or iron(II,III) oxide (which have good ultraviolet light absorption or refraction ability); the gel material includes photocurable microsphere gel material and photoinitiator, and the photocurable microsphere gel material is selected from polyethylene glycol diacrylate or methacrylated gelatin.
[0015] Furthermore, the photoinitiator is selected from 2-hydroxy-2-methyl-1-phenylpropanone or 1-hydroxycyclohexylbenzophenone.
[0016] Furthermore, the mass-volume fraction of the micro / nano inorganic oxide particles in the aqueous phase is 1–6 wt%, the volume fraction of the photocurable microsphere gel material in the aqueous phase is 8–50%, and the proportion of the photoinitiator in the aqueous phase is 1–3 wt%.
[0017] Preferably, the synthesis steps of the aqueous solution are as follows: first, micro / nano inorganic particles, surfactants, and water are mixed evenly using an ultrasonic pulverizer or a high-speed homogenizer; then, photocurable microsphere gel material and photoinitiator are added; finally, the mixture is stirred evenly with magnetic force. The surfactants include sodium poly(4-styrene sulfonate) and sodium dodecyl sulfate.
[0018] In step (2), the oil phase includes silicone oil, liquid paraffin or n-hexadecane, and contains 1 to 5 wt% of Span series surfactants.
[0019] In step (2), the external pump is selected from a micro-injection pump or a micro-pressure peristaltic pump; the microfluidic chip includes a T-shaped chip, a flow focusing chip or a coaxial flow chip, a PDMS chip or a metal droplet generator.
[0020] In step (3), the radii of the aqueous microchannel and the oil microchannel in the microfluidic chip are 50–500 μm, the flow rates of the aqueous phase and the oil phase are independently 10–200 μL / min, and the ratio of the aqueous phase flow rate to the oil phase flow rate is 1:1–10; in step (4), the ultraviolet light intensity received by each microdroplet is 30–80 mW / cm. 2 The illumination time is 20-60 seconds.
[0021] The preparation method provided by this invention can further control the size, wall thickness, particle size distribution and physicochemical properties of hollow hydrogel microspheres by controlling parameters such as the concentration of each component (including aqueous phase components and solubility), flow rate, ultraviolet light intensity and irradiation time. It can be used to prepare double negative acoustic metamaterials that can produce negative equivalent mass density and negative equivalent elastic modulus.
[0022] The present invention also provides a hydrogel hollow microsphere obtained according to the above preparation method.
[0023] The diameter of the hollow microspheres in the hydrogel is 50 to 450 μm, and the thickness of the shell is 1 / 10 to 1 / 3 of the diameter of the microspheres.
[0024] The present invention also provides an application of the above-mentioned hydrogel hollow microspheres in the preparation of subwavelength structural units of ultrasonic metamaterials.
[0025] Furthermore, the application is the use of hydrogel hollow microspheres in medical ultrasound imaging, medical ultrasound therapy, or acoustic devices.
[0026] Compared with the prior art, the present invention has the following superior effects:
[0027] The preparation method provided by this invention can take into account the wall thickness, mechanical properties, size uniformity, monodispersity, and preparation difficulty of hollow microspheres, and achieve low-cost batch preparation of monodisperse micron-sized hollow hydrogel microspheres.
[0028] The hydrogel hollow microspheres prepared by this invention can be used as subwavelength structural units of ultrasonic metamaterials. That is, they can be used to prepare double negative acoustic metamaterials that can generate negative equivalent mass density and negative equivalent elastic modulus, and have important application prospects in the fields of medical ultrasound imaging, medical ultrasound therapy, and acoustic devices. Attached Figure Description
[0029] Figure 1 This is a schematic diagram of the mass production of hydrogel hollow microspheres based on microfluidic controllable photocuring technology, including: 1-continuous phase, 2-dispersed phase, 3-droplet generation module, 4-droplet UV curing module, 5-actual microfluidic chip, 6-microsphere collection module, and 7-hollow microsphere.
[0030] Figure 2 This is an optical micrograph of the hollow polyethylene glycol diacrylate (PEGDA) hydrogel microspheres in the examples.
[0031] Figure 3 The following are scanning electron microscope (SEM) images of the hollow polyethylene glycol diacrylate (PEGDA) hydrogel microspheres in the examples: (a) is an SEM image of a single complete hollow polyethylene glycol diacrylate (PEGDA) hydrogel microsphere; (b) is an SEM image of the cross-section of the hollow polyethylene glycol diacrylate (PEGDA) hydrogel microsphere after it has been cut open with a knife. Detailed Implementation
[0032] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be described in detail below with reference to the embodiments and accompanying drawings. It should be noted that the following embodiments are only used to explain and illustrate this invention and are not intended to limit this invention.
[0033] The present invention proposes a method for preparing hydrogel hollow microspheres based on microfluidic controllable photocuring technology. These hydrogel hollow microspheres are mass-produced using droplet microfluidic technology combined with ultraviolet light-controlled curing soft matter technology (e.g.,...). Figure 1 As shown in the figure, the specific preparation method of the hydrogel hollow microspheres is as follows:
[0034] First, prepare the dispersed phase / aqueous phase 2 solution: Add an appropriate amount of micro / nano inorganic particles (titanium dioxide, zinc oxide, iron oxide, cuprous oxide or iron(II,III) oxide), surfactant (sodium poly(4-styrene sulfonate) or sodium dodecyl sulfate) and an appropriate amount of deionized water to a brown glass bottle. Mix evenly using an ultrasonic pulverizer or high-speed homogenizer (5-10 minutes). Then add an appropriate amount of photocurable microsphere gel material (polyethylene glycol diacrylate or methacrylated gelatin) and photoinitiator (2-hydroxy-2-methyl-1-phenylpropanone or 1-hydroxycyclohexylbenzophenone). Mix evenly again using an ultrasonic pulverizer or high-speed homogenizer (1-2 minutes). Then stir magnetically for 15-60 minutes to obtain the dispersed phase solution.
[0035] Preparation of continuous phase / oil phase 1 solution: Add oil (silicone oil, liquid paraffin or n-hexadecane) and 1-5 wt% Span series surfactant to a beaker, stir until completely dissolved to obtain continuous phase solution.
[0036] A droplet microfluidic platform (droplet generation module 3 and its actual microfluidic chip 5) and a UV curing module 4 were constructed. The dispersed phase and continuous phase solutions were respectively drawn into 5 mL syringes, which were then fixed to a micro-injection pump. The pump parameters were adjusted (continuous phase flow rate 10–200 μL / min, dispersed phase flow rate 1–40 μL / min, dispersed phase flow rate to continuous phase flow rate ratio 1:1–10). The droplet microfluidic chip was mounted on a fixture. The chip inlet was connected to the needle via a tubing, and the outlet tubing led into a collection bottle. The outlet tubing was positioned at the same level as the droplet microfluidic chip. The outlet tubing included a section of curved tubing channel. A UV lamp (365 nm) was installed at the curved tubing channel, with the UV light intensity at the curved tubing channel being 30–80 mW / cm². 2 The illumination time is 20-60 seconds, and the outlet hose is connected to the collection bottle.
[0037] Turn on the syringe pump and UV lamp. Adjust the flow rates of the dispersed phase and the continuous phase to ensure uniform generation of microdroplets. As the microdroplets flow through the curved tubing channel, they solidify into microspheres under UV irradiation. The microsphere collection module 6 collects the solution containing the dispersed hydrogel hollow microspheres 7.
[0038] The collected hydrogel hollow microspheres were washed and filtered with deionized water and anhydrous ethanol, and the process was repeated three times. Then, they were soaked in concentrated hydrochloric acid for 6-10 hours, washed and filtered with deionized water and anhydrous ethanol, and the process was repeated several times. The microspheres were then frozen with liquid nitrogen and dried in a freeze dryer for 36 hours to obtain hydrogel hollow microspheres.
[0039] Non-essential improvements and adjustments made by those skilled in the art based on the above-described invention are still within the scope of protection of this invention.
[0040] Example
[0041] The hydrogel hollow microspheres prepared in this embodiment based on droplet microfluidics technology are mainly composed of polyethylene glycol diacrylate (PEGDA) and zinc oxide powder. The detailed process is as follows:
[0042] First, prepare a dispersed phase (aqueous phase) solution. Dry zinc oxide nanopowder under vacuum at 45°C for 10 hours. Then, add 3% by volume of zinc oxide nanopowder, 1% by volume of poly(4-styrene sulfonate), and an appropriate amount of deionized water to a brown glass bottle. Mix thoroughly using an ultrasonic pulverizer (3 minutes). Then, add 20% by volume of PEG(400)DA and 2% by volume of photoinitiator 2-hydroxy-2-methyl-1-phenylpropanone. Mix thoroughly again using an ultrasonic pulverizer (3 minutes). Finally, stir magnetically for 20 minutes to obtain the dispersed phase solution.
[0043] Then, prepare a continuous phase (oil phase) solution by adding liquid paraffin and 2 wt% Span80 surfactant to a beaker and stirring until completely dissolved to obtain a continuous phase solution.
[0044] Then, the droplet microfluidic platform was set up using a flow-focusing chip with a minimum channel diameter of 200 μm. The syringe pump was turned on, and the pump parameters were adjusted to achieve a continuous phase flow rate of 150 μL / min and a dispersed phase flow rate of 15 μL / min. After the microdroplets were stably and continuously generated, the UV lamp was turned on to ensure that the UV light intensity received by each microdroplet was 30 mW / cm². 2 The illumination time was 15 seconds. When the microdroplets flowed through the curved flexible tube channel, they solidified into microspheres under the irradiation of the ultraviolet lamp. The solution of the solidified hydrogel hollow microspheres was collected.
[0045] The microspheres were then washed and filtered with deionized water and anhydrous ethanol, and the process was repeated three times. They were then soaked in concentrated hydrochloric acid for 6 hours, and washed and filtered again with deionized water and anhydrous ethanol, and the process was repeated several times. The microspheres were then frozen with liquid nitrogen and dried in a freeze dryer for 36 hours to obtain hydrogel hollow microspheres.
[0046] The optical micrograph of the hollow polyethylene glycol diacrylate (PEGDA) gel microspheres prepared in this embodiment is shown below. Figure 2 The scanning electron microscope (SEM) image is shown below. Figure 3 As shown ( Figure 3 (a) in the image represents a single, intact hollow polyethylene glycol diacrylate (PEGDA) gel microsphere. Figure 3 (b) is a cross-sectional view of hollow polyethylene glycol diacrylate (PEGDA) gel microspheres after being cut open with a knife.
[0047] The hollow hydrogel microspheres prepared in this embodiment have a diameter of 300–450 μm and a shell thickness of 1 / 5–1 / 3 of the microsphere diameter.
Claims
1. A method for preparing hydrogel hollow microspheres based on microfluidic controllable photocuring technology, characterized in that, The preparation method includes: (1) After mixing micro-nano inorganic oxide particles with water, gel material and photoinitiator are added to prepare an aqueous solution; the micro-nano inorganic oxide particles are selected from titanium dioxide, zinc oxide, iron oxide, cuprous oxide or iron(II,III) oxide; (2) Prepare oil phase solution; (3) The aqueous solution and the oil solution are injected into the aqueous microchannel and the oil microchannel of the droplet microfluidic chip respectively by an external pump to generate microdroplets; (4) When the microdroplets flow through the curved flexible tube channel, they are irradiated with ultraviolet light and solidified to obtain hydrogel hollow microspheres; In step (1), the gel material includes photocurable microsphere gel material and photoinitiator, the mass-volume fraction of the micro-nano inorganic oxide particles in the aqueous phase is 1~6 w / v%, the volume fraction of the photocurable microsphere gel material in the aqueous phase is 8~50%, and the volume fraction of the photoinitiator in the aqueous phase is 1~3%. In step (3), the radii of the aqueous microchannel and the oil microchannel in the microfluidic chip are 50~500μm, the flow rates of the aqueous phase and the oil phase are independently 10~200μL / min, and the ratio of the aqueous phase flow rate to the oil phase flow rate is 1:1~10; in step (4), the ultraviolet light intensity received by each microdroplet is 30~80mW / cm. 2 The illumination time is 20~60s; In step (4), inorganic oxide particles with good ultraviolet light absorption capacity cause microdroplets to roll continuously at the curved tube channel due to friction with the tube wall, so that only the outer layer is cured under ultraviolet light while the inside is not cured, thus producing hydrogel hollow microspheres.
2. The method for preparing hydrogel hollow microspheres based on microfluidic controllable photocuring technology according to claim 1, characterized in that, In step (1), the gel material includes a photocurable microsphere gel material and a photoinitiator, wherein the photocurable microsphere gel material is selected from polyethylene glycol diacrylate or methacrylated gelatin.
3. The method for preparing hydrogel hollow microspheres based on microfluidic controllable photocuring technology according to claim 1, characterized in that, In step (2), the oil phase is selected from silicone oil, liquid paraffin or n-hexadecane, and contains 1-5 wt% Span series surfactants.
4. The method for preparing hydrogel hollow microspheres based on microfluidic controllable photocuring technology according to claim 1, characterized in that, In step (2), the external pump is selected from a micro-injection pump or a micro-pressure peristaltic pump; the microfluidic chip includes a T-shaped chip, a flow focusing chip or a coaxial flow chip, a PDMS chip or a metal droplet generator.
5. A hydrogel hollow microsphere obtained by the preparation method according to any one of claims 1-4.
6. The hydrogel hollow microspheres according to claim 5, characterized in that, The diameter of the hollow microspheres in the hydrogel is 50~450μm, and the thickness of the shell layer is 1 / 10~1 / 3 of the diameter of the microspheres.
7. The application of the hydrogel hollow microspheres of claim 5 in the preparation of subwavelength structural units of acoustic and ultrasonic metamaterials.
8. The application according to claim 7, characterized in that, The application refers to the use of hydrogel hollow microspheres in medical ultrasound imaging, medical ultrasound therapy, or acoustic devices.