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Digital microfluidics: A promising technique for biochemical applications

He WANG, Liguo CHEN, Lining SUN

《机械工程前沿（英文）》 2017年 第12卷 第4期   页码 510-525 doi: 10.1007/s11465-017-0460-z

摘要：

Digital microfluidics (DMF) is a versatile microfluidics technology that has significant application potential in the areas of automation and miniaturization. In DMF, discrete droplets containing samples and reagents are controlled to implement a series of operations via electrowetting-on-dielectric. This process works by applying electrical potentials to an array of electrodes coated with a hydrophobic dielectric layer. Unlike microchannels, DMF facilitates precise control over multiple reaction processes without using complex pump, microvalve, and tubing networks. DMF also presents other distinct features, such as portability, less sample consumption, shorter chemical reaction time, flexibility, and easier combination with other technology types. Due to its unique advantages, DMF has been applied to a broad range of fields (e.g., chemistry, biology, medicine, and environment). This study reviews the basic principles of droplet actuation, configuration design, and fabrication of the DMF device, as well as discusses the latest progress in DMF from the biochemistry perspective.

关键词： digital microfluidics     electrowetting on dielectric     discrete droplet     biochemistry    

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Porous ultrathin-shell microcapsules designed by microfluidics for selective permeation and stimuli-triggered

《化学科学与工程前沿（英文）》   页码 1643-1650 doi: 10.1007/s11705-022-2201-z

摘要： Microcapsules are versatile delivery vehicles and widely used in various areas. Generally, microcapsules with solid shells lack selective permeation and only exhibit a simple release mode. Here, we use ultrathin-shell water-in-oil-in-water double emulsions as templates and design porous ultrathin-shell microcapsules for selective permeation and multiple stimuli-triggered release. After preparation of double emulsions by microfluidic devices, negatively charged shellac nanoparticles dispersed in the inner water core electrostatically complex with positively charged telechelic α,ω-diamino functionalized polydimethylsiloxane polymers dissolved in the middle oil shell at the water/oil interface, thus forming a porous shell of shellac nanoparticles cross-linked by telechelic polymers. Subsequently, the double emulsions become porous microcapsules upon evaporation of the middle oil phase. The porous ultrathin-shell microcapsules exhibit excellent properties, including tunable size, selective permeation and stimuli-triggered release. Small molecules or particles can diffuse across the shell, while large molecules or particles are encapsulated in the core, and release of the encapsulated cargos can be triggered by osmotic shock or a pH change. Due to their unique performance, porous ultrathin-shell microcapsules present promising platforms for various applications, such as drug delivery.

关键词： microcapsule     emulsion     microfluidics     selective permeation     stimuli-triggered release    

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医用增材制造领域中的微流控技术 Review

王洁, 邵长敏, 王月桐, 孙凌云, 赵远锦

《工程（英文）》 2020年 第6卷 第11期   页码 1244-1257 doi: 10.1016/j.eng.2020.10.001

摘要：

增材制造是食品、制药、医学和机械加工等领域的一种重要生产技术。得益于增材制造快速、低成本和可定制化的加工特性，医学增材制造推动了医疗器械、医学假体和临床移植物等领域的发展。在此背景下，高通量以及结构和组分把控精准等优势使微流控技术在医用增材制造领域显露头角，且已被应用于药物开发、组织工程和器官芯片的构建。本文综述了近年来微流控技术在医用增材制造领域的研究进展。首先，针对不同结构的液滴和纤维模板的构建，评估了基于微流控技术的医用增材制造的独特优势；其次，介绍了微流控技术在细胞定向、三维细胞培养、体外组织构建和细胞疗法方向的应用现状；最后，讨论了基于微流控技术的医用增材制造面临的挑战及其发展前景。

关键词： 微流控     生物材料     增材制造     液滴     纤维    

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Microfluidic production of liposomes through liquid–liquid phase separation in ternary droplets

《化学科学与工程前沿（英文）》 2022年 第16卷 第6期   页码 1017-1022 doi: 10.1007/s11705-021-2118-y

摘要： Liposomes, the self-assembled phospholipid vesicles, have been extensively used in various fields such as artificial cells, drug delivery systems, biosensors and cosmetics. However, current microfluidic routes to liposomes mostly rely on water-in-oil-in-water double emulsion droplets as templates, and require complex fabrication of microfluidic devices, and tedious manipulation of multiphase fluids. Here we present a simple microfluidic approach to preparing monodisperse liposomes from oil-in-water droplets. For demonstration, we used butyl acetate-water-ethanol ternary mixtures as inner phase and an aqueous solution of surfactants as outer phase to make oil-in-water droplets, which can evolve into water-in-oil-in-water double emulsion droplets by liquid–liquid phase separation of ternary mixtures. Subsequently, the resultant water-in-oil-in-water droplets underwent a dewetting transition to form separated monodisperse liposomes and residual oil droplets, with the assistance of surfactants. The method is simple, does not require complex microfluidic devices and tedious manipulation, and provides a new platform for controllable preparation of liposomes.

关键词： microfluidics     liposomes     ternary droplets     phase separation    

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基于微流控工程的高强力学性能蛋白纤维 Review

孙静, 陈静思, 刘凯, 曾洪波

《工程（英文）》 2021年 第7卷 第5期   页码 615-623 doi: 10.1016/j.eng.2021.02.005

摘要：

21世纪以来，研究者对轻质和高强力学性能的天然蜘蛛丝、蚕丝纤维投入了大量研究。受此研究启发，诸多人工纺丝技术（湿法纺丝、干法纺丝、电纺等）被先后开发，并用以制造坚固的蛋白纤维。然而，传统纺丝手段对所制纤维的控制能力较差。针对此问题，微流控技术已与这些技术完成良好的结合，实现了以精心设计的方式制造生物纤维，且具有操作简单和成本效益的特点。通过控制微流体通道的类型、大小、流速和剪切力，可以精确调节所制造纤维的机械行为。该技术已成功用于制造广泛的蛋白纤维，并推进了蛋白纤维的生产效率及其在各个领域的应用。本文综述了基于微流控技术的蛋白纤维的设计及制造的最新进展。首先简要讨论了天然蜘蛛丝的纺丝过程和微流控技术的纺丝过程。进而，着重讨论了通过微流控技术再生的蛋白纤维的制造及其力学性能，接着讨论了重组蛋白纤维。此外，对其他来源的蛋白纤维也进行了详细回顾。最后，对制造蛋白纤维的微流控技术的发展进行了简要总结与展望。

关键词： 蛋白纤维     微流控     软材料     生物材料    

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Microfluidics for cell-cell interactions: A review

Rui Li,Xuefei Lv,Xingjian Zhang,Omer Saeed,Yulin Deng

《化学科学与工程前沿（英文）》 2016年 第10卷 第1期   页码 90-98 doi: 10.1007/s11705-015-1550-2

摘要： Microfluidic chip has been applied in various biological fields owing to its low-consumption of reagents, high throughput, fluidic controllability and integrity. The well-designed microscale intermediary is also ideal for the study of cell biology. Particularly, microfluidic chip is helpful for better understanding cell-cell interactions. A general survey of recent publications would help to generalize the designs of the co-culture chips with different features. With ingenious and combinational utilization, the chips facilitate the implementation of some special co-culture models that are highly concerned in a different spatial and temporal way.

关键词： microfluidic chip     co-culture     cell-cell interactions     review    

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基于液滴微流控的分级结构反蛋白石多孔支架用于仿生三维细胞共培养 Article

邵长敏, 刘羽霄, 池俊杰, 叶方富, 赵远锦

《工程（英文）》 2021年 第7卷 第12期   页码 1778-1785 doi: 10.1016/j.eng.2020.06.031

摘要：

三维（3D）细胞培养具有更好地模拟天然组织特异性的优势，在药物开发、毒性测试和组织工程中发挥着重要作用。然而，现有的3D细胞培养的支架或微载体通常尺寸有限，并且在模拟生物体内血管复合体方面表现不佳。因此，本研究提出了一种通过简单的微流控方法制备的新型分级结构反蛋白石多孔支架，用于促进3D细胞共培养。该支架是基于微流控乳液液滴模板和惰性聚合物聚合的复合概念构建的。研究结果表明，该支架能够保证细胞培养过程中的营养供给，从而实现大面积的细胞培养。此外，通过在该支架中连续种植不同的细胞，本文还开发了内皮细胞包裹肝细胞的3D细胞共培养系统，用于构建功能化组织。研究结果表明，该支架用于细胞共培养系统，有助于维持肝细胞特定的体内功能。该分级结构反蛋白石多孔支架为3D细胞培养甚至仿生组织的构建奠定了基础。

关键词： 微流控     反蛋白石     细胞培养     液滴     生物材料    

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Modeling and simulation of droplet translocation and fission by electrowetting-on-dielectrics (EWOD)

Nathan HOWELL, Weihua LI

《机械工程前沿（英文）》 2010年 第5卷 第4期   页码 376-388 doi: 10.1007/s11465-010-0104-z

摘要： This paper discusses methods of microfluidic droplet actuation by means of electrowetting-on-dielectrics (EWOD) and provides a technique for modeling and simulating a microfluidic device by using the computational fluid dynamics (CFD) program, Flow3D. Digital or droplet microfluidics implies the manipulation of droplets on a scale of nanoliters (10 L) to femtoliters (10 L), as opposed to continuous microfluidics that involve the control of continuous fluid within a channel. The two operations in focus here are droplet translocation (moving) and droplet fission (splitting), in which the pressures and velocities within the droplet are analyzed and compared to existing works, both theoretical and experimental. The variation in the pressure of the leading and trailing faces of a droplet indicates the variation in surface energy—an important parameter that explains how a droplet will move toward a region of higher electric potential. The higher voltage on one side of a droplet reduces surface energy, which leads to an induced pressure drop, thus resulting in fluid motion. Flow3D simulations are for both water and blood droplets at voltages between 50 V and 200 V, and the droplet size, surface properties (Teflon coated), and geometry of the system are kept constant for each operation. Some peculiarities of the simulation are brought to light, such as instabilities of the system to higher voltages and fluids with higher dielectric constants, as well as the creation of a tertiary droplet when the applied voltage causes a large enough force during fission. The force distribution across the droplet provides a general understanding of the electrowetting effect and more specifically allows for a comparison between the effects that different voltages have on the forces at the droplet surface. The droplet position and mean kinetic energy of the droplet are also investigated and compared to other works, proving the dynamics of a droplet motion found here.

关键词： electrowetting-on-dielectrics (EWOD)     electrowetting     microfluidics     droplet translocation     droplet fission     Flow3D     dielectric constant    

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生物细胞的旋转——基本原理及应用 Review

Tao Tang, Yoichiroh Hosokawa, Takeshi Hayakawa, Yo Tanaka, Weihua Li, Ming Li, Yaxiaer Yalikun

《工程（英文）》 2022年 第10卷 第3期   页码 110-126 doi: 10.1016/j.eng.2020.07.031

摘要：

细胞旋转是现代生物科学中最重要的细胞操作技术之一，不仅允许从任意角度观察细胞，而且还简化了分析细胞力学特性、表征细胞生理学和进行显微手术的程序。在广泛的学术和工业应用中，已经报道了许多细胞旋转的方法。其中，最受欢迎的是基于微型机器人的直接接触控制和基于场的非接触方法（如光场、磁场、电场、声场和流体动力场方法）。本文首先总结了这六大类方法的基本机制、优点和缺点，然后详细讨论了它们的区别和局限性。本文旨在缩短每种方法之间的差距，并说明细胞旋转领域目前的研究进展及未来前景。

关键词： 细胞旋转     细胞重新定向     显微操作     微流控技术    

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Microfluidic dual loops reactor for conducting a multistep reaction

Si Hyung Jin, Jae-Hoon Jung, Seong-Geun Jeong, Jongmin Kim, Tae Jung Park, Chang-Soo Lee

《化学科学与工程前沿（英文）》 2018年 第12卷 第2期   页码 239-246 doi: 10.1007/s11705-017-1680-9

摘要： Precise control of each individual reaction that constitutes a multistep reaction must be performed to obtain the desired reaction product efficiently. In this work, we present a microfluidic dual loops reactor that enables multistep reaction by integrating two identical loop reactors. Specifically, reactants A and B are synthesized in the first loop reactor and transferred to the second loop reactor to synthesize with reactant C to form the final product. These individual reactions have nano-liter volumes and are carried out in a stepwise manner in each reactor without any cross-contamination issue. To precisely control the mixing efficiency in each loop reactor, we investigate the operating pressure and the operating frequency on the mixing valves for rotary mixing. This microfluidic dual loops reactor is integrated with several valves to realize the fully automated unit operation of a multistep reaction, such as metering the reactants, rotary mixing, transportation, and collecting the product. For proof of concept, CdSeZn nanoparticles are successfully synthesized in a microfluidic dual loops reactor through a fully automated multistep reaction. Taking all of these features together, this microfluidic dual loops reactor is a general microfluidic screening platform that can synthesize various materials through a multistep reaction.

关键词： microfluidics     multistep reaction     rotary mixing     nanoparticle    

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A review on emulsification via microfluidic processes

Yichen Liu, Yongli Li, Andreas Hensel, Juergen J. Brandner, Kai zhang, Xiaoze Du, Yongping Yang

《化学科学与工程前沿（英文）》 2020年 第14卷 第3期   页码 350-364 doi: 10.1007/s11705-019-1894-0

摘要： Emulsion is a disperse system with two immiscible liquids, which demonstrates wide applications in diverse industries. Emulsification technology has advanced well with the development of microfluidic process. Compared to conventional methods, the microfluidics-based process can produce controllable droplet size and distribution. The droplet formation or breakup is the result of combined effects resulting from interfacial tension, viscous, and inertial forces as well as the forces generated due to hydrodynamic pressure and external stimuli. In the current study, typical microfluidic systems, including microchannel array, T-shape, flow-focusing, co-flowing, and membrane systems, are reviewed and the corresponding mechanisms, flow regimes, and main parameters are compared and summarized.

关键词： microfluidics     emulsification     capillary number     droplet breakup    

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Ionically Imprinting-Based Copper (Ⅱ) Label-Free Detection for Preventing Hearing Loss Article

Huan Wang, Hui Zhang, Xiaoli Zhang, Hong Chen, Ling Lu, Renjie Chai

《工程（英文）》 doi: 10.1016/j.eng.2023.09.001

摘要：

Copper is a microelement with important physiological functions in the body. However, the excess copper ion (Cu2+) may cause severe health problems, such as hair cell apoptosis and the resultant hearing loss. Therefore, the assay of Cu2+ is important. We integrate ionic imprinting technology (IIT) and structurally colored hydrogel beads to prepare chitosan-based ionically imprinted hydrogel beads (IIHBs) as a low-cost and high-specificity platform for Cu2+ detection. The IIHBs have a macroporous microstructure, uniform size, vivid structural color, and magnetic responsiveness. When incubated in solution, IIHBs recognize Cu2+ and exhibit a reflective peak change, thereby achieving label-free detection. In addition, benefiting from the IIT, the IIHBs display good specificity and selectivity and have an imprinting factor of 19.14 at 100 lmol∙L–1. These features indicated that the developed IIHBs are promising candidates for Cu2+ detection, particularly for the prevention of hearing loss.

关键词： Structural color     Microfluidics Ionic imprinting     Label-free detection     Hearing loss    

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Characterization of particle deposition during crossflow filtration as influenced by permeate flux and crossflow velocity using a microfluidic filtration system

Hongzhan Di, Gregory J. O. Martin, Dave E. Dunstan

《化学科学与工程前沿（英文）》 2021年 第15卷 第3期   页码 552-561 doi: 10.1007/s11705-020-1962-5

摘要： Particle deposition during crossflow filtration is significantly influenced by the operating conditions, in particular the permeate flux and crossflow velocity. However, there is a lack of detailed knowledge about how deposit layer structures and distributions depend on operating parameters. This study uses a microfluidic visualisation filtration system to examine the influence of operating conditions on the deposition process during crossflow ultrafiltration from a microscopic perspective. Increasing the permeate flux caused an increasing amount of deposition and a thicker deposit layer. Higher crossflow velocities reduced the extent of deposition. The degree of deposition varied over a range of operating conditions due to the altered hydrodynamic forces exerted on the particles, which can be examined by the deposition probability according to an existing model. Building on this, an empirical correlation between the deposition probability and volume of deposition as function of filtration time was developed, which gave good agreement with experimental results. The effect of solution conditions was also involved in this correlation as a interaction energies. This could be useful for predicting the dynamic deposition process during crossflow filtration over a range of operating and solution conditions.

关键词： particle deposition     crossflow filtration     microfluidics     confocal microscopy    

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标题 作者 时间 类型 操作

Digital microfluidics: A promising technique for biochemical applications

He WANG, Liguo CHEN, Lining SUN

期刊论文

Porous ultrathin-shell microcapsules designed by microfluidics for selective permeation and stimuli-triggered

期刊论文

医用增材制造领域中的微流控技术

王洁, 邵长敏, 王月桐, 孙凌云, 赵远锦

期刊论文

Microfluidic production of liposomes through liquid–liquid phase separation in ternary droplets

期刊论文

基于微流控工程的高强力学性能蛋白纤维

孙静, 陈静思, 刘凯, 曾洪波

期刊论文

Microfluidics for cell-cell interactions: A review

Rui Li,Xuefei Lv,Xingjian Zhang,Omer Saeed,Yulin Deng

期刊论文

基于液滴微流控的分级结构反蛋白石多孔支架用于仿生三维细胞共培养

邵长敏, 刘羽霄, 池俊杰, 叶方富, 赵远锦

期刊论文

Modeling and simulation of droplet translocation and fission by electrowetting-on-dielectrics (EWOD)

Nathan HOWELL, Weihua LI

期刊论文

生物细胞的旋转——基本原理及应用

Tao Tang, Yoichiroh Hosokawa, Takeshi Hayakawa, Yo Tanaka, Weihua Li, Ming Li, Yaxiaer Yalikun

期刊论文

Microfluidic dual loops reactor for conducting a multistep reaction

Si Hyung Jin, Jae-Hoon Jung, Seong-Geun Jeong, Jongmin Kim, Tae Jung Park, Chang-Soo Lee

期刊论文

A review on emulsification via microfluidic processes

Yichen Liu, Yongli Li, Andreas Hensel, Juergen J. Brandner, Kai zhang, Xiaoze Du, Yongping Yang

期刊论文

David A.Weitz：Soft Functional Materials Prepared by Microfluidics（2019年6月15日）

David A.Weitz(院士)

2021年01月20日

会议视频

Ionically Imprinting-Based Copper (Ⅱ) Label-Free Detection for Preventing Hearing Loss

Huan Wang, Hui Zhang, Xiaoli Zhang, Hong Chen, Ling Lu, Renjie Chai

期刊论文

Characterization of particle deposition during crossflow filtration as influenced by permeate flux and crossflow velocity using a microfluidic filtration system

Hongzhan Di, Gregory J. O. Martin, Dave E. Dunstan

期刊论文

Leong：Can Microfluidics Address the Biomanufacturing Challenge of Drug-Gene-Celltherap（2019年6月15日）

Kam. W. Leong(院士)

2021年01月20日

会议视频