Functional microfluidics:theory,microfabrication,and applications

Microfluidic devices are composed of microchannels with a diameter ranging from ten to a few hundred micrometers.Thus,quite a small(10-9–10-18l)amount of liquid can be manipulated by such a precise system.In the past three decades,significant progress in materials science,microfabrication,and various applications has boosted the development of promising functional microfluidic devices.In this review,the recent progress on novel microfluidic devices with various functions and applications is presented.First,the theory and numerical methods for studying the performance of microfluidic devices are briefly introduced.Then,materials and fabrication methods of functional microfluidic devices are summarized.Next,the recent significant advances in applications of microfluidic devices are highlighted,including heat sinks,clean water production,chemical reactions,sensors,biomedicine,capillaric circuits,wearable electronic devices,and microrobotics.Finally,perspectives on the challenges and future developments of functional microfluidic devices are presented.This review aims to inspire researchers from various fields engineering,materials,chemistry,mathematics,physics,and more—to collaborate and drive forward the development and applications of functional microfluidic devices,specifically for achieving carbon neutrality.

Microfluidic thermotaxic selection of highlymotile sperm and in vitro fertilization

The selection of the most motile and functionally competent sperm is an essential basis for in vitro fertilization(IVF)and normal embryonic development.Widely adopted clinical approaches for sperm sample processing intensely rely on centrifugation and wash steps that may induce mechanical damage and oxidative stress to sperm.Although a few microfluidic sperm sorting devices may avoid these adverse effects by exploiting intrinsic guidance mechanisms of sperm swimming,none of these approaches have been fully validated by clinical-grade assessment criteria.In this study,a microfluidic sperm sorting device that enables the selection of highly motile and functional sperm via their intrinsic thermotaxis is presented.Bioinspired by the temperature microenvironment in the fallopian tube during natural sperm selection,a microfluidic device with controllable temperature gradients along the sperm separation channel was designed and fabricated.This study investigated the optimal temperature conditions for human sperm selection and fully characterized thermotaxis-selected sperm with 45 human sperm samples.Results indicated that a temperature range of 35–36.5℃along the separation channel significantly improves human sperm motility rate((85.25±6.28)%vs.(60.72±1.37)%;P=0.0484),increases normal sperm morphology rate((16.42±1.43)%vs.(12.55±0.88)%;P<0.0001),and reduces DNA fragmentation((7.44±0.79)%vs.(10.36±0.72)%;P=0.0485)compared to the nonthermotaxis group.Sperm thermotaxis is species-specific,and selected mouse sperm displayed the highest motility in response to a temperature range of 36–37.5℃ along the separation channel.Furthermore,IVF experiments indicated that the selected sperm permitted an increased fertilization rate and improved embryonic development from zygote to blastocyst.This microfluidic thermotaxic selection approach will be translated into clinical practice to improve the IVF success rate for patients with oligozoospermia and asthenozoospermia.

Droplet Pattern Formation and Translation in New Microfluidic Flow- Focusing Devices

We conducted experiments on specially designed microfluidic chips that generate droplets through a microfluidic ow-focusing approach. The fluid flow in the microfluidic channel produced a shear flow field at low Reynolds numbers. The droplets in the microfluidic system exhibited special droplet pattern formations similar to periodic crystal-like lattices because of the competition between shear forces and surface tension. By adjusting the flow rate ratio of the water （droplet phase） to oil （continuous phase） phases and changing the outlet channel widths, the droplets formed monolayer dispersion to double-layer formation to monolayer squeezing when the outlet channel widths were 250 or 300 μm. We also obtained droplets with monolayer dispersion, three-layer arrangements, double-layer squeezing, and monolayer squeezing when the outlet channel width was 350 μm. The outlet channel width was increased to 400 μm, and four-layer arrangements were observed. We also studied the translation of droplet formation, which resulted in a detailed strategy to control drop size and droplet pattern formation for emulsi cation in microfluidic devices. We expect that our strategy can provide theoretical guidance to synthesize dispersion or polydisperse colloid particles.

Microwave Induced Ethanol Bath Bonding for PMMA Microfluidic Device

High bonding strength,low deformation and convenient procedure are all very important aspects in the microfluidic device fabrication process. In this paper,an improved microwave induced bonding technology is proposed to fabricate microfluidic device based on methyl methacrylate( PMMA). This method employs pure ethanol as the bonding assisted solvent. The ethanol not only acts as the microwave absorbing material,but also works as the organic solvent in bath. The presented research work has shown that the bonding process can be completed in less than 45 s. Furthermore,the convenient bonding only applies microwave oven,beakers and binder clips. Then,we discuss effects of microwave power,bonding time on bonding strength and deformation of microstructures on PMMA microfluidic device. Finally,a 4 layers micro-mixer has been fabricated using the proposed bonding technique which includes 15 trapezoid micro-channels,9 T-type mix units and an X-type mix unit. Experimental results show that the proposed bonding method have some advantages compared with several traditional bonding technologies,such as hot pressing bonding,ultrasonic bonding and solvent assisted bonding methods in respect of bonding strength,deformation and bonding process. The presented work would be helpful for low coat mass production of multilayer polymer microfluidic devices in lab.

Development of PDMS-based Microfluidic Device for Cell-based Assays

In a single step photolithography, muhi-level microfluidic device is fabricated by printing novel architectures on a film photomasks. The whole fabrication process is executed by classical PCB technology without the need to access clean room facilities. Different levels of protruding features on PCB master are produced by exposing a photomask with specifically arranged "windows and rims" architectures, followed by chemical wet etching. Poly(dimethylsiloxane)(PDMS) is then molded against the positive relief master to generate microfluidic device featured with multi-level sandbag structure and peripheral microchannels. This sandbag structure is an analog to traditional dam or weir for particle entrapment. The microstructure does not collapse when subjected to applied pressure, which is suitable for operation on elastic PDMS substrate.Typical immunocytochemcial staining assays were performed in the microdevice to demonstrate the applicability of the sandbag structure for cellular analysis. This simplified microfabrication process employs low-cost materials and minimal specialized equipment and can reproducibly produce mask lines with about 20 μm in width, which is sufficient for most microfluidic applications.

Literature Review of the Use of Zinc and Zinc Compounds in Paper-Based Microfluidic Devices

Zinc and its compounds, alloys and composites play an important role in the modern day world and find application in almost every aspect that can improve the quality of our lives. This ranges from supplements and pharmaceuticals that are meant to improve our health and wellbeing to additives meant to guard or reduce corrosion in metals. However, over the past several years, a new area of technology has been garnering a great deal of attention and has made use of zinc and its compounds. This is with reference to paper-based microfluidic technology that offers several advantages and that keeps expanding in the amount of applications it covers. In this paper, a review is offered for the applications that have used zinc or zinc compounds in paper-based microfluidic devices.

Optofluidics:the interaction between light and flowing liquids in integrated devices

Optofluidics is a rising technology that combines microfluidics and optics.Its goal is to manipulate light and flowing liquids on the micro/nanoscale and exploiting their interaction in optofluidic chips.The fluid flow in the on-chip devices is reconfigurable,non-uniform and usually transports substances being analyzed,offering a new idea in the accurate manipulation of lights and biochemical samples.In this paper,we summarized the light modulation in heterogeneous media by unique fluid dynamic properties such as molecular diffusion,heat conduction,centrifugation effect,light-matter interaction and others.By understanding the novel phenomena due to the interaction of light and flowing liquids,quantities of tunable and reconfigurable optofluidic devices such as waveguides,lenses,and lasers are introduced.Those novel applications bring us firm conviction that optofluidics would provide better solutions to high-efficient and high-quality lab-on-chip systems in terms of biochemical analysis and environment monitoring.

Designer substrates and devices for mechanobiology study

Both biological and engineering approaches have contributed significantly to the recent advance in the field of mechanobiology.Collaborating with biologists,bio-engineers and materials scientists have employed the techniques stemming from the conventional semiconductor industry to rebuild cellular milieus that mimic critical aspects of in vivo conditions and elicit cell/tissue responses in vitro.Such reductionist approaches have help to unveil important mechanosensing mechanism in both cellular and tissue level,including stem cell differentiation and proliferation,tissue expansion,wound healing,and cancer metastasis.In this mini-review,we discuss various microfabrication methods that have been applied to generate specific properties and functions of designer substrates/devices,which disclose cell-microenvironment interactions and the underlying biological mechanisms.In brief,we emphasize on the studies of cell/tissue mechanical responses to substrate adhesiveness,stiffness,topography,and shear flow.Moreover,we comment on the new concepts of measurement and paradigms for investigations of biological mechanotransductions that are yet to emerge due to on-going interdisciplinary efforts in the fields of mechanobiology and microengineering.

Microfluidics-based assay on the effects of microenvironmental geometry and aqueous flow on bacterial adhesion behaviors

Abstract A new microfluidic system with four different microchambers （a circle and three equilateral concave polygons） was designed and fabricated using poly（dimethylsiloxane） （PDMS） and the soft lithography method. Using this microfluidic device at six flow rates （5, 10, 20, 30, 40, and 50 μL/h）, the effects of microenvironmental geometry and aqueous flow on bacterial adhesion behaviors were investigated. Escherichia coli HB101 pGLO, which could produce a green fluorescent protein induced by L-arabinose, was utilized as the model bacteria. The results demonstrated that bacterial adhesion was significantly related to culture time, microenvironment geometry, and aqueous flow rates. Adhered bacterial density increased with the culture time. Initially, the adhesion occurred at the microchamber sides, and then the entire chamber was gradually covered with increased culture time. Adhesion densities in the side zones were larger than those in the center zones because of the lower shearing force in the side zone. Also, the adhesion densities in the complex chambers were larger than those in the simple chambers. At low flow rates, the orientation of adhered bacteria was random and disorderly. At high flow rates, bacterial orientation became close to the streamline and oriented toward the flow direction; All these results implied that bacterial adhesion tended to occur in complicated aqueous flow areas.The present study provided an on-chip flow system for physiological behavior of biological cells, as well as provided a strategic cue for the prevention of bacterial infection and biofilm formation.

Simulating Experiment and Circuit Simulation of RTD/HPT Photo-Controlled MOBILE

The MOBILE is a logic element realizing the monostable-bistable transition of a circuit that consists of two resonant tunneling transistors—the resonant tunneling diodes (RTDs) connected in series. It has several advantages including multiple inputs and multiple functions. In this paper, by connecting a heterojunction phototransistor (HPT) with the MOBILE, a novel optoelectronic functional device can be got, which presents the function of both photocurrent switching and photocurrent latching. These behaviors have been demonstrated for the first time by simulating experiments and circuit simulations, with RTDs firstly manufactured in China. Research indicates that the novel photo-controlled MOBILE has the same logic functions as conventional electrical MOBILE except for with light as an input signal.

The Development of the Heparin Monitoring System Based on Microfluidics Technology

Heparin monitoring is widely used to measure the anticoagulant effect of unfractionated heparin and adjust the dose to keep within the target treatment range. This technology has applications in many fields and also prospects in the future. Its application has the advantages of rapidity, high throughput and minimum sample consumption. Many point of care devices for heparin monitoring are available. The CoaguChek device only requires a small sample size, which is obtained through a fingerstick. Over the last few years, the point-of-care (POC) testing was used widely for its convenience, efficiency, and faster turnaround times.

Cell Segmentation and Tracking in Microfluidic Platform

In this research, we have concentrated on trajectory extraction based on image segmentation and data association in order to provide an economic and complete solution for rapid microfluidic cell migration experiments. We applied region scalable active contour model to segment the individual cells and then employed the ellipse fitting technique to process touching cells. Subsequently, we have also introduced a topology based technique to associate the cells between consecutive frames. This scheme achieves satisfactory segmentation and tracking results on the datasets acquired by our microfluidic platform.

纳米材料中的界面现象

在课程教学中融入科学前沿实例不仅可以阐明所学基本原理的实际意义,还可以为基本原理的灵活应用提供范例,启发学生独立思考能力。界面化学是物理化学课程中的重要学习内容,但由于在常规尺度的多相体系中界面现象并不显著,学生对该部分知识常有忽视。近年来纳米材料已成为国内外研究的热点。纳米材料由于其高界面分子比例而表现出更为显著的界面现象。将界面化学的基本原理应用于纳米材料的研究中,已取得了一系列令人瞩目的成果。本文首先对附加压力、接触角等相关界面现象的基本原理进行梳理,然后分别介绍根据这些基本原理所发展出的分子马达、光控微流控器件、液体门控技术以及超疏水表面四项科技突破。

基于水动力空化的微通道设备研究进展

针对微通道设备中的水动力空化现象,从限流元件的几何形状及尺寸、工作流体和通道粗糙度3个方面分析了其影响规律.限流元件的常见形状主要有微孔、微文丘里、微隔膜和微柱,不同几何形状的限流元件具有不同的空化流动特性;限流元件自身的尺寸参数以及尺寸缩小引起的尺度效应都对空化流型起着重要作用.常用的工作流体包含去离子水、乙醇、磷酸盐缓冲盐水(PBS)、制冷剂(R-123)、聚乙烯醇(PVA)微泡(MBs)悬浮液、全氟戊烷(PFC5)悬浮液、二氧化钛(TiO_(2))纳米颗粒悬浮液、多元液体混合物等;与水相比,其余工作流体均不同程度地提高了空化强度.粗糙度的引入主要体现于通道的表面粗糙元件和侧壁粗糙元件,其空化强度相较于光滑表面得到明显提高.微通道水动力空化设备主要应用于能量收集、液相剥离和生物医学领域.基于近年来国内外对微尺度水动力空化的研究现状,设想了微通道设备中的水动力空化现象的潜在研究方向及应用趋势.

胆甾相液晶微球光子禁带的动态调控及其应用

胆甾相液晶微球是空间结构高度对称的三维光子晶体,能够全方位地选择性反射特定波长的圆偏振光,具有无角度依赖性的光子禁带,作为一种新兴的光学材料在全向激光器、反射式显示和微传感器等领域展现出广阔的应用前景。近年来,毛细管微流控技术的蓬勃发展为连续、可控、高通量地制备结构复杂且分子规则取向的单分散胆甾相液晶微球提供了强有力的支持。本综述重点关注利用毛细管微流控技术制备胆甾相液晶微球的相关研究工作,首先分析了毛细管微流控装置在设计微球结构中的决定性作用,阐明了溶液体系的选择与液晶分子取向间的关系以及边界效应对微球尺寸的影响;随后,从胆甾相液晶微球的光学特性切入,介绍了利用温度、溶剂和光等外界刺激调控螺旋结构自组装的原理和策略以及微球之间独有的“光子交叉通讯”现象;最后,总结了现阶段胆甾相液晶微球的潜在应用方向并讨论了该材料体系未来面临的挑战。

不互溶体系中HMX基PBX微球的制备及性能表征

为了探索球形奥克托今(HMX)的制备方法,以二甲亚砜为溶剂,二甲基硅油/四氯化碳(体积比为1∶2)为非溶剂,硝化棉为黏结剂,采用液上滴落成球、液下扰动成球和微流控成球3种方法研究了HMX在不互溶体系中的制备及性能;通过扫描电镜、X-射线衍射仪、热分析、摩擦感度仪和撞击感度仪等,表征了样品的形貌、晶型、活化能、摩擦感度和撞击感度。结果表明,液上滴落成球法可以制备出球形HMX,其粒径在1500μm左右;液下扰动法同样可以制备出球形HMX,其粒径在950μm左右;微通道法制备的HMX球形度偏低,粒径在300μm左右。3种方法制备HMX晶型均与原料HMX的一致,为β晶型;液上滴落成球方法制备的HMX活化能相比原料值提高了141.22kJ/mol,撞击感度降低了2J,摩擦感度由原来的120N降至240N;液下扰动成球和微流控方法制备的球形HMX活化能比原料分别提高了5kJ/mol和21kJ/mol, HMX撞击感度没有明显改变,摩擦感度由原来的120N降低至216N,表明该微球结构取得了良好的降感效果。

非洲猪瘟检测方法研究进展

非洲猪瘟(ASF)是由非洲猪瘟病毒(ASFV)引起的猪的一种急性、热性、高度接触性传染病。ASF疫情的暴发,严重威胁全球生猪养殖业安全,给全球造成巨大的经济损失。目前尚未开发出安全有效的ASF疫苗,因此,及时、准确的ASF实验室诊断成为疫情防控的重要手段。ASF现有检测方法包括血清学检测、聚合酶链式反应(PCR)、等温扩增技术和规律成簇的间隔短回文重复序列及其相关系统(CRISPR/Cas)等,其中,血清学检测、PCR检测和CRISPR/Cas都需要专业人员和设备,而等温扩增技术受限于单一类型的检测样品,且灵敏度较低,因此ASF现有检测方法无法同时达到灵敏度高,又快速、简便、可用于现场检测的要求。相较之下,ASF新型检测方法可以达到便捷、高效、省时省力以及可以在现场实现快速检测的优势,其中,生物传感器无需专业人员操作,人工智能(AI)可减少人员成本,并可用于疫情的早期监测,基于磁珠的技术无需复杂的设备,微流体技术可实现高通量快速检测,磁流体装置可解决核酸污染的问题。随着科技的进步,基于免疫层析试纸条和各类传感器的ASF新型检测方法将蓬勃发展。本文总结了ASF现有检测方法,并综述了近5年ASF新型检测方法的发展情况,以期对ASF疫情的科学防控提供参考。

基于双电场叠加效应的诱导电荷电渗调控方法

为了从多种细胞群体中提取纯净细胞群或者从复杂的样本中提取所需成分,提出了一种基于双电场叠加效应的诱导电荷电渗调控新方法,研究诱导电荷电渗漩涡的重塑机理及其颗粒操控性能.首先,建立多物理场耦合仿真模型并研究双电场叠加作用下诱导电荷电渗漩涡的非对称演变机理.其次,设计并加工颗粒操控器件,搭建颗粒操控实验系统.然后,研究不同电压下非对称诱导电荷电渗漩涡对单种颗粒的聚集和纵向偏移特性.最后,研究非对称诱导电荷电渗漩涡对不同颗粒的聚集和分离特性.结果表明:此方法能够以简单的控制方式实现微尺度颗粒的聚集、偏移和分离,其在环境检测、疾病诊断领域方面具有巨大的应用潜力.

微流控技术在卵巢癌疾病建模、药物评估、精准医疗中的应用

卵巢癌是全球第三大常见的女性生殖系统恶性肿瘤,5年生存率仅为40%,早期诊断手段的缺乏和化疗耐药是目前卵巢癌诊疗面临的巨大的挑战。微流控技术(microfluidic technology)作为一种利用微芯片调控流体流动实现的集成化分析技术,具有高敏感度、高通量和低成本等显著优势,而且,该技术能在微纳尺度下模拟肿瘤微环境,有利于研究肿瘤细胞与免疫系统的交互作用。近年来微流控技术已广泛用于医学研究、药物研发、精准医疗等生命健康领域。在卵巢癌研究方面,微流控技术可用于肿瘤建模、早期肿瘤生物标志物的检测和抗肿瘤药物的筛选等,为卵巢癌早期诊断和精准治疗提供了创新视角与未来导向。

In vitro engineered models of neurodegenerative diseases

Neurodegeneration is a catastrophic process that develops progressive damage leading to functional andstructural loss of the cells of the nervous system and is among the biggest unavoidable problems of our age.Animalmodels do not reflect the pathophysiology observed in humans due to distinct differences between the neuralpathways,gene expression patterns,neuronal plasticity,and other disease-related mechanisms in animals andhumans.Classical in vitro cell culture models are also not sufficient for pre-clinical drug testing in reflecting thecomplex pathophysiology of neurodegenerative diseases.Today,modern,engineered techniques are applied to developmulticellular,intricate in vitro models and to create the closest microenvironment simulating biological,biochemical,and mechanical characteristics of the in vivo degenerating tissue.In THIS review,the capabilities and shortcomings ofscaffold-based and scaffold-free techniques,organoids,and microfluidic models that best reflect neurodegeneration invitro in the biomimetic framework are discussed.