微流控可控制备液滴、颗粒和胶囊及其应用

doi:10.11949/0438-1157.20231328

化工学报 ›› 2024, Vol. 75 ›› Issue (4): 1455-1468.DOI: 10.11949/0438-1157.20231328

微流控可控制备液滴、颗粒和胶囊及其应用

吉笑盈¹^,²(), 郑园³, 李晓鹏¹^,², 杨振¹^,², 张维⁴, 邱诗蕊⁴, 张倩颖¹^,², 罗沧海³, 孙东鹏³, 陈东³(), 李东亮¹^,²()

^1.四川中烟工业有限责任公司烟草行业雪茄发酵工艺重点实验室，四川成都 610100
^2.四川中烟工业有限责任公司厅市共建国产雪茄烟叶工业高效利用重点实验室，四川成都 610100
^3.浙江大学能源工程学院，浙江杭州 310029
^4.四川中烟工业有限责任公司长城雪茄厂，四川什邡 618400

收稿日期:2023-12-13 修回日期:2024-02-02 出版日期:2024-04-25 发布日期:2024-06-06
通讯作者: 陈东,李东亮
作者简介:吉笑盈（1990—），女，博士，工程师，jixychen@163.com
基金资助:
地市级科研项目(20202303BA530);国家重点研发计划项目(2021YFC3001100)

Controlled preparation of droplets, particles and capsules by microfluidics and their applications

Xiaoying JI¹^,²(), Yuan ZHENG³, Xiaopeng LI¹^,², Zhen YANG¹^,², Wei ZHANG⁴, Shirui QIU⁴, Qianying ZHANG¹^,², Canghai LUO³, Dongpeng SUN³, Dong CHEN³(), Dongliang LI¹^,²()

^1.Cigar Fermentation Technology Key Laboratory of China Tobacco, China Tobacco Sichuan Industrial Co. , Ltd. , Chengdu 610100, Sichuan, China
^2.Industrial Efficient Utilization of Domestic Cigar Tobacco Key Laboratory of Sichuan Province, China Tobacco Sichuan Industrial Co. , Ltd. , Chengdu 610100, Sichuan, China
^3.College of Energy Engineering, Zhejiang University, Hangzhou 310029, Zhejiang, China
^4.The Greatwall Cigar Factory, China Tobacco Sichuan Industrial Co. , Ltd. , Shifang 618400, Sichuan, China

Received:2023-12-13 Revised:2024-02-02 Online:2024-04-25 Published:2024-06-06
Contact: Dong CHEN, Dongliang LI

摘要/Abstract

摘要：

微流控技术在可控制备液滴、颗粒和胶囊方面具有独特优势，能够精确控制液滴、颗粒和胶囊的粒径大小、尺寸分布、形貌结构和材料组成，在生物医药、食品、护肤品等领域具有广泛应用。详细总结了微流控技术可控制备液滴、颗粒和胶囊所用的器件设计、工艺策略及其相关应用。此外，还重点介绍了多相流数值模拟在液滴、颗粒和胶囊制备过程和优化实验参数中的应用，以及微流控器件实现液滴、颗粒和胶囊量产的平行放大策略。将为液滴、颗粒和胶囊的制备和应用提供重要指导。

关键词: 微流控, 液滴, 颗粒, 胶囊, 数值模拟, 平行放大, 微通道

Abstract:

Microfluidics has unique advantages in the controlled preparation of droplets, particles and capsules. Microfluidics could precisely control the size, distribution, structure and composition of droplets, particles and capsules, which are widely used in the field of biomedicine, food and cosmetics. This review comprehensively summarizes the device design, preparation strategy and industrial application for the controlled preparation of droplets, particles and capsules by microfluidics. In addition, the application of multiphase flow numerical simulation of the preparation process of droplets, particles and capsules and the optimization of experimental parameters are also highlighted, as well as the parallel scale-up strategy of microfluidic devices to achieve mass production of droplets, particles and capsules. This review will provide an important guide for the preparation and application of droplets, particles and capsules.

Key words: microfluidics, droplet, particle, capsule, numerical simulation, parallel scale-up, microchannel

中图分类号:

TQ 050

吉笑盈, 郑园, 李晓鹏, 杨振, 张维, 邱诗蕊, 张倩颖, 罗沧海, 孙东鹏, 陈东, 李东亮. 微流控可控制备液滴、颗粒和胶囊及其应用[J]. 化工学报, 2024, 75(4): 1455-1468.

Xiaoying JI, Yuan ZHENG, Xiaopeng LI, Zhen YANG, Wei ZHANG, Shirui QIU, Qianying ZHANG, Canghai LUO, Dongpeng SUN, Dong CHEN, Dongliang LI. Controlled preparation of droplets, particles and capsules by microfluidics and their applications[J]. CIESC Journal, 2024, 75(4): 1455-1468.

图/表 6

图1 微流控可控制备液滴、颗粒、胶囊[3, 28-30]

Fig.1 Controlled preparation of droplets, particles and capsules by microfluidics[3, 28-30]

图2 微流控可控制备液滴及其应用：(a) PDMS和玻璃微管微流控器件可控制备单组分、双组分和三组分单乳液滴[41-42]；(b) 微流控构建水包油食品乳液，通过微流控将葵花籽油乳化成液滴，并利用大豆蛋白稳定液滴[30]；(c) 微流控3D液滴打印可控制备液滴阵列，通过将液滴阵列嵌入弹性体，实现刺激触发的多形状、多模式、多步骤变形[48]；(d) 微流控构建均匀分布的悬浮液滴和微流控3D液滴打印构建有序排列的悬浮液滴[49,51]

Fig.2 Controlled preparation of droplets by microfluidics and their applications: (a) Controlled preparation of one-, two- and three-component droplets by PDMS and glass-capillary microfluidic devices[41-42]; (b) Oil-in-water food emulsions prepared by microfluidics， sunflower oil is emulsified into droplets and stabilized by soybean proteins[30]; (c) Microfluidic 3D droplet printing for the controlled preparation of droplet arrays[48]（droplet arrays are embedded in the elastomer matrix as functional units）, multi-shape, multi-mode and multi-step deformations can be achieved by different stimuli; (d) Randomly distributed droplet suspension prepared by microfludics and ordered droplet suspension prepared by microfluidic 3D droplet printing[49,51]

图3 以单乳液滴为模板可控制备颗粒及其应用：(a) 以单乳液滴为模板，溶剂挥发制备包裹胡萝卜素的颗粒，用于食品天然色素添加[57]；(b) 离子交联制备包裹细胞的水凝胶颗粒，用于细胞封装培养[59]；(c) 光交联制备负载抗炎药双氯芬酸钠的水凝胶颗粒，用于关节炎缓释治疗[60]；(d) 光交联制备用于负载骨髓干细胞的多孔颗粒，用于骨骼再生[61]；(e) 化学交联制备包裹抗癌药物5-氟尿嘧啶的颗粒，用于肿瘤治疗[29]；(f) 化学交联制备作为细胞生长支架的水凝胶颗粒，用于组织再生[62]

Fig.3 Controlled preparation of particles using single-emulsion droplets as templates and their applications: (a) Preparation of carotenoid-loaded particles by solvent evaporation and their applications as natural colorants for food[57]; (b) Preparation of cell-loaded hydrogel particles by ionic crosslinking and their applications for cell culture[59]; (c) Preparation of drug-loaded hydrogel particles by photo-triggered crosslinking and their applications for arthritis treatment[60]; (d) Preparation of stem cell-loaded porous particles by photo-triggered crosslinking and their applications for bone regeneration[61]; (e) Preparation of drug-loaded particles by chemical crosslinking and their applications for oncology therapy[29]; (f) Preparation of hydrogel particles as cell growth scaffolds by chemical crosslinking and their applications for tissue regeneration[62]

图4 微流控可控制备双乳液滴和胶囊及其应用：(a) PDMS和玻璃微管微流控器件可控制备单核和多核的双乳液滴[42, 65]；(b) 微流控3D液滴打印可控制备单核和多核的双乳液滴[71]；(c) 以单乳液滴为模板，溶剂挥发使聚合物在油/水界面沉积，包裹油滴形成胶囊[73]；(d) 以双乳液滴为模板，离子交联制备水核包裹肝细胞、水凝胶壳层包裹成纤维细胞的水凝胶胶囊，构建肝脏类器官模型[75]；(e) 以薄壁双乳液滴为模板，制备通过渗透压控制释放的薄壁水核胶囊[76]

Fig.4 Controlled preparation of core-shell droplets and capsules and their applications: (a) Controlled preparation of single- and multi-core droplets by PDMS and glass-capillary microfluidic devices[42, 65]; (b) Controlled preparation of single- and multi-core droplets by microfluidic 3D droplet printing[71]; (c) Oil-core capsules prepared using single droplets as templates and by solvent evaporation[73]; (d) Hydrogel capsules with hepatocytes in the core and fibroblasts in the shell prepared using core-shell droplets as templates and by ionic crosslinking, which are used as liver organoids[75]; (e) Thin-shell water-core capsules prepared using thin-shell core-shell droplets as templates and by solvent evaporation, whose release could be triggered by osmotic pressure[76]

图5 两相流与三相流数值模拟单乳和双乳液滴的形成：(a) 空气剪切水相形成液滴的两相流数值模拟[83],水相为分散相，空气为连续相；(b) 空气流速和内管尺寸影响液滴直径的模拟与实验比较[83],流体模拟采用与实验相同的内外管直径、水相黏度、水相密度、水相流速、空气黏度、空气密度、空气流速等参数；(c) 水包油胶囊的三相流数值模拟[84],油相为内相，水相为中间相，空气为连续相；(d) 油/水和水/空气界面张力影响胶囊直径、内核直径和壁厚的模拟结果[84],流体模拟采用与实验相同的内外管直径、油相黏度、油相密度、油相流速、水相黏度、水相密度、水相流速、空气黏度、空气密度等参数

Fig.5 Two- and three-phase computational fluid dynamics (CFD) simulations of the formation of single droplets and core-shell droplets: (a) Two-phase CFD simulations of the droplet formation by shearing water with air[83], water is the dispersed phase and air is the continuous phase; (b) Comparison of CFD and experimental results on droplet diameter as a function of air flow rate and inner tube size[83], CFD simulations use the same parameters as those of experiments, such as inner and outer tube diameters, water viscosity, water density, water flow rate, air viscosity, air density and air flow rate; (c) Three-phase CFD simulations of the formation of core-shell droplets[84], the oil phase is the inner phase, the aqueous phase is the middle phase, and air is the continuous phase; (d) CFD results on capsule diameter, core diameter and shell thickness as a function of oil/water and water/air interfacial tensions[84], CFD simulations use the same parameters as those of experiments, such as inner and outer tube diameters, oil viscosity, oil density, oil flow rate, water viscosity, water density, water flow rate, air viscosity and air density

图6 微流控乳化单元的平行放大：(a) 基于平行树枝状的放大设计[87]；(b) 基于发散树枝状的放大设计[88]；(c) 基于主枝干结构的平行放大设计[24]

Fig.6 Scale-up by parallelization of microfluidic emulsification units: (a) Scale-up design based on parallel dendrites[87]; (b) Scale-up design based on divergent dendrites[88]; (c) Scale-up design based on main-branch structures[24]

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微流控可控制备液滴、颗粒和胶囊及其应用

Controlled preparation of droplets, particles and capsules by microfluidics and their applications

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