Design of pressure-driven microfluidic networks using electric circuit analogy

This article reviews the application of electric circuit methods for the analysis of pressure-driven microfluidic networks with an emphasis on concentration- and flow-dependent systems. The application of circuit methods to microfluidics is based on the analogous behaviour of hydraulic and electric circuits with correlations of pressure to voltage, volumetric flow rate to current, and hydraulic to electric resistance. Circuit analysis enables rapid predictions of pressure-driven laminar flow in microchannels and is very useful for designing complex microfluidic networks in advance of fabrication. This article provides a comprehensive overview of the physics of pressure-driven laminar flow, the formal analogy between electric and hydraulic circuits, applications of circuit theory to microfluidic network-based devices, recent development and applications of concentration- and flow-dependent microfluidic networks, and promising future applications. The lab-on-a-chip (LOC) and microfluidics community will gain insightful ideas and practical design strategies for developing unique microfluidic network-based devices to address a broad range of biological, chemical, pharmaceutical, and other scientific and technical challenges.     

Surface‐Tension‐Confined Microfluidics and Their Applications

This article is a brief overview of the emerging microfluidic systems called surface‐tension‐confined microfluidic (STCM) devices. STCM devices utilize surface energy that can control the movement of fluid droplets. Unlike conventional poly(dimethylsiloxane)‐based microfluidics which confine the movement of fluids by three‐dimensional (3D) microchannels, STCM systems provide two‐dimensional (2D) platforms for microfluidics. A variety of STCM devices have been prepared by various micro‐/nanofabrication strategies. Advantages of STCM devices over conventional microfluidics are significant reduction of energy consumption during device operation, facile introduction of fluids onto 2D microchannels without the use of a micropump, increased flow rate in a special type of STCM device, among others. Thus, STCM devices can be excellent alternatives for certain areas in microfluidics. In this Minireview, fabrication methods, operating modes, and applications of STCM devices are introduced.     

Optical and electrochemical detection techniques for cell-based microfluidic systems

The ability to fabricate microfluidic systems with complex structures and with compatible dimensions between the microfluidics and biological cells have attracted significant attention in the development of microchips for analyzing the biophysical and biochemical functions of cells. Just as cell-based microfluidics have become a versatile tool for biosensing, diagnostics, drug screening and biological research, detector modules for cell-based microfluidics have also undergone major development over the past decade. This review focuses on detection methods commonly used in cell-based microfluidic systems, and provides a general survey and an in-depth look at recent developments in optical and electrochemical detection methods for microfluidic applications for biological systems, particularly cell analysis. Selected examples are used to illustrate applications of these detection systems and their advantages and weaknesses.     

Microfluidic systems in clinical diagnosis

The use of microfluidic devices is highly attractive in the field of biomedical and clinical assessments, as their portability and fast response time have become crucial in providing opportune therapeutic treatments to patients. The applications of microfluidics in clinical diagnosis and point-of-care devices are continuously growing. The present review article discusses three main fields where miniaturized devices are successfully employed in clinical applications. The quantification of ions, sugars, and small metabolites is examined considering the analysis of bodily fluids samples and the quantification of this type of analytes employing real-time wearable devices. The discussion covers the level of maturity that the devices have reached as well as cost-effectiveness. The analysis of proteins with clinical relevance is presented and organized by the function of the proteins. The last section covers devices that can perform single-cell metabolomic and proteomic assessments. Each section discusses several strategically selected recent reports on microfluidic devices successfully employed for clinical assessments, to provide the reader with a wide overview of the plethora of novel systems and microdevices developed in the last 5 years. In each section, the novel aspects and main contributions of each reviewed report are highlighted. Finally, the conclusions and future outlook section present a summary and speculate on the future direction of the field of miniaturized devices for clinical applications.     

Recent advances in electric analysis of cells in microfluidic systems

Microfluidics offers an ideal platform to integrate cell-based assays with electric measurements. The technological advances in microfluidics, microelectronics, electrochemistry, and electrophysiology have greatly inspired the development of microfluidic/electric devices that work with a low number of cells or single cells. The applications of these microfluidic systems range from the detecting of cell culture density to the probing of cellular functions at the single-cell level. In this review, we introduce the recent advances in the electric analysis of cells on a microfluidic platform, specifically related to the quantification and monitoring of cells in static solution, on-chip patch-clamp measurement, and examination of flowing cells. We also point out future directions and challenges in this field. Figure Different microfluidic devices applied to electrical analysis of cells     

Optical imaging techniques in microfluidics and their applications

Microfluidic devices have undergone rapid development in recent years and provide a lab-on-a-chip solution for many biomedical and chemical applications. Optical imaging techniques are essential in microfluidics for observing and extracting information from biological or chemical samples. Traditionally, imaging in microfluidics is achieved by bench-top conventional microscopes or other bulky imaging systems. More recently, many novel compact microscopic techniques have been developed to provide a low-cost and portable solution. In this review, we provide an overview of optical imaging techniques used in microfluidics followed with their applications. We first discuss bulky imaging systems including microscopes and interferometer-based techniques, then we focus on compact imaging systems that can be better integrated with microfluidic devices, including digital in-line holography and scanning-based imaging techniques. The applications in biomedicine or chemistry are also discussed along with the specific imaging techniques.     

Surfactants in droplet-based microfluidics

Surfactants are an essential part of the droplet-based microfluidic technology. They are involved in the stabilization of droplet interfaces, in the biocompatibility of the system and in the process of molecular exchange between droplets. The recent progress in the applications of droplet-based microfluidics has been made possible by the development of new molecules and their characterizations. In this review, the role of the surfactant in droplet-based microfluidics is discussed with an emphasis on the new molecules developed specifically to overcome the limitations of 'standard' surfactants. Emulsion properties and interfacial rheology of surfactant-laden layers strongly determine the overall capabilities of the technology. Dynamic properties of droplets, interfaces and emulsions are therefore very important to be characterized, understood and controlled. In this respect, microfluidic systems themselves appear to be very powerful tools for the study of surfactant dynamics at the time- and length-scale relevant to the corresponding microfluidic applications. More generally, microfluidic systems are becoming a new type of experimental platform for the study of the dynamics of interfaces in complex systems.     

Advances in microfluidics for environmental analysis

During the past few years, a growing number of groups have recognized the utility of microfluidic devices for environmental analysis. Microfluidic devices offer a number of advantages and in many respects are ideally suited to environmental analyses. Challenges faced in environmental monitoring, including the ability to handle complex and highly variable sample matrices, lead to continued growth and research. Additionally, the need to operate for days to months in the field requires further development of robust, integrated microfluidic systems. This review examines recently published literature on the applications of microfluidic systems for environmental analysis and provides insight in the future direction of the field.     

Microfluidic generation of barcodes with in situ synthesized perovskite quantum dot encapsulation

Perovskite quantum dots(PQDs) are new class of optoelectronic materials, which have been widely studied for their extraordinary physical properties. Attempts to develop these materials are tending to make their fabrication much controllable and extend their values in different areas. Here, we present a novel strategy for one-step in situ synthesis of PQD-encapsulated barcode particles with the assistance of microfluidic technique. By changing the halide ratio in perovskite precursor solutions that emulsified in microfluidic devices, a series of PQDs with different colors have been successfully fabricated, which made them ideal materials as barcodes. Because of the stable encapsulation of ethyleneglycol dimethacrylate(EGDMA) resin, the PQD-encapsulated barcode particles were with no cytotoxicity and could be anti-quenched. It was demonstrated for the first time that the PQD-encapsutated barcode particles by microfluidics were valuable for multiplex biomolecular encoding and assays.These features indicate that the PQD-encapsutated barcode particles by microfluidics are ideal for many practical applications and have a broad prospect in biomedical field.     

Logic digital fluidic in miniaturized functional devices: Perspective to the next generation of microfluidic lab‐on‐chips

Microfluidics has emerged following the quest for scale reduction inherent to micro‐ and nanotechnologies. By definition, microfluidics manipulates fluids in small channels with dimensions of tens to hundreds of micrometers. Recently, microfluidics has been greatly developed and its influence extends not only the domains of chemical synthesis, bioanalysis, and medical researches but also optics and information technology. In this review article, we will shortly discuss an enlightening analogy between electrons transport in electronics and fluids transport in microfluidic channels. This analogy helps to master transport and sorting. We will present some complex microfluidic devices showing that the analogy is going a long way off toward more complex components with impressive similarities between electronics and microfluidics. We will in particular explore the vast manifold of fluidic operations with passive and active fluidic components, respectively, as well as the associated mechanisms and corresponding applications. Finally, some relevant applications and an outlook will be cited and presented.     

Microfluidics in macro-biomolecules analysis: macro inside in a nano world

Use of microfluidic devices in the life sciences and medicine has created the possibility of performing investigations at the molecular level. Moreover, microfluidic devices are also part of the technological framework that has enabled a new type of scientific information to be revealed, i.e. that based on intensive screening of complete sets of gene and protein sequences. A deeper bioanalytical perspective may provide quantitative and qualitative tools, enabling study of various diseases and, eventually, may offer support for the development of accurate and reliable methods for clinical assessment. This would open the way to molecule-based diagnostics, i.e. establish accurate diagnosis and disease prognosis based on identification and/or quantification of biomacromolecules, for example proteins or nucleic acids. Finally, the development of disposable and portable devices for molecule-based diagnosis would provide the perfect translation of the science behind life-science research into practical applications dedicated to patients and health practitioners. This review provides an analytical perspective of the impact of microfluidics on the detection and characterization of bio-macromolecules involved in pathological processes. The main features of molecule-based diagnostics and the specific requirements for the diagnostic devices are discussed. Further, the techniques currently used for testing bio-macromolecules for potential diagnostic purposes are identified, emphasizing the newest developments. Subsequently, the challenges of this type of application and the status of commercially available devices are highlighted, and future trends are noted.     

New advances in microfluidic flow cytometry

In recent years, researchers are paying the increasing attention to the development of portable microfluidic diagnostic devices including microfluidic flow cytometry for the point‐of‐care testing. Microfluidic flow cytometry, where microfluidics and flow cytometry work together to realize novel functionalities on the microchip, provides a powerful tool for measuring the multiple characteristics of biological samples. The development of a portable, low‐cost, and compact flow cytometer can benefit the health care in underserved areas such as Africa or Asia. In this article, we review recent advancements of microfluidics including sample pumping, focusing and sorting, novel detection approaches, and data analysis in the field of flow cytometry. The challenge of microfluidic flow cytometry is also examined briefly.     

Microfluidic Device： A Miniaturized Platform for Chemical Reactions

Microfluidic devices, as a new miniaturized platform stemming from the field of micro-electromechanical sys-tems, have been used in many disciplines. In the field of chemical reactions, microfluidic device-based microreac-tors have shown great promise in building new chemical technologies and processes with increased speed and reli- ability and reduced sample consumption and cost. This technology has also become a new and effective tool for precise, high-throughput, and automatic analysis of chemical synthesis processes. Compared with conventional chemical laboratory batch methodologies, microfluidic reactors have a number of features, such as high mixing ef- ficiency, short reaction time, high heat-transfer coefficient, small reactant volume, controllable residence time, and high surface-to-volume ratio, among others. Combined with recent advances in microfluidic devices for chemical reactions, this review aims to give an overview of the features and applications of microfluidic devices in the field of chemical synthesis. It also aims to stimulate the development of microfluidic device applications in the field of chemical reactions.     

Research progress on pesticide residue detection based on microfluidic technology

The problem of pesticide residue contamination has attracted widespread attention and poses a risk to human health. The current traditional pesticide residue detection methods have difficulty meeting rapid and diverse field screening requirements. Microfluidic technology integrates functions from sample preparation to detection, showing great potential for quick and accurate high-throughput detection of pesticide residues. This paper reviews the latest research progress on microfluidic technology for pesticide residue detection. First, the commonly used microfluidic materials are summarized, including silicon, glass, paper, polydimethylsiloxane, and polymethyl methacrylate. We evaluated their advantages and disadvantages in pesticide residue detection applications. Second, the current pesticide residue detection technology based on microfluidics and its application to real samples are summarized. Finally, we discuss this technology's present challenges and future research directions. This study is expected to provide a reference for the future development of microfluidic technology for pesticide residue detection.     

Particles and microfluidics merged: perspectives of highly sensitive diagnostic detection

There is a growing need for diagnostic technologies that provide laboratories with solutions that improve quality, enhance laboratory system productivity, and provide accurate detection of a broad range of infectious diseases and cancers. Recent advances in micro- and nanoscience and engineering, in particular in the areas of particles and microfluidic technologies, have advanced the “lab-on-a-chip” concept towards the development of a new generation of point-of-care diagnostic devices that could significantly enhance test sensitivity and speed. In this review, we will discuss many of the recent advances in microfluidics and particle technologies with an eye towards merging these two technologies for application in medical diagnostics. Although the potential diagnostic applications are virtually unlimited, the most important applications are foreseen in the areas of biomarker research, cancer diagnosis, and detection of infectious microorganisms.

A digital microfluidic method for multiplexed cell-based apoptosis assays

Digital microfluidics (DMF), a fluid-handling technique in which picolitre-microlitre droplets are manipulated electrostatically on an array of electrodes, has recently become popular for applications in chemistry and biology. DMF devices are reconfigurable, have no moving parts, and are compatible with conventional high-throughput screening infrastructure (e.g., multiwell plate readers). For these and other reasons, digital microfluidics has been touted as being a potentially useful new tool for applications in multiplexed screening. Here, we introduce the first digital microfluidic platform used to implement parallel-scale cell-based assays. A fluorogenic apoptosis assay for caspase-3 activity was chosen as a model system because of the popularity of apoptosis as a target for anti-cancer drug discovery research. Dose-response profiles of caspase-3 activity as a function of staurosporine concentration were generated using both the digital microfluidic method and conventional techniques (i.e., pipetting, aspiration, and 96-well plates.) As expected, the digital microfluidic method had a 33-fold reduction in reagent consumption relative to the conventional technique. Although both types of methods used the same detector (a benchtop multiwell plate reader), the data generated by the digital microfluidic method had lower detection limits and greater dynamic range because apoptotic cells were much less likely to de-laminate when exposed to droplet manipulation by DMF relative to pipetting/aspiration in multiwell plates. We propose that the techniques described here represent an important milestone in the development of digital microfluidics as a useful tool for parallel cell-based screening and other applications.     

基于液滴技术的微流控芯片实验室

液滴微流控系统是微流控芯片领域的一个新的分支,由于其诸多独特的优势而得到了广泛的研究和报道。本文对液滴的制备和相关的操控技术,包括液滴的分裂、融合、混合、分选、存储和编码等进行了介绍,对液滴技术近年来在化学与生物化学分析等领域中的应用进行了综述,并展望了液滴微流控技术的发展前景。     

Microfluidic technologies for MALDI-MS in proteomics

The field of microfluidics continues to offer great promise as an enabling technology for advanced analytical tools. For biomolecular analysis, there is often a critical need to couple on-chip microfluidic sample manipulation with back-end MS. Though interfacing microfluidics to MS has been most often reported through the use of direct ESI-MS, there are compelling reasons for coupling microfluidics to MALDI-MS as an alternative to ESI-MS for both online and offline analysis. The intent of this review is to provide a summary of recent developments in the integration of microfluidic systems with MALDI-MS, with an emphasis on applications in proteomics. Key points are summarized, followed by a review of relevant technologies and a discussion of outlook for the field.     

Miniaturizing free-flow electrophoresis - a critical review

Free-flow electrophoresis (FFE) separation methods have been developed and investigated for around 50 years and have been applied not only to many types of analytes for various biomedical applications, but also for the separation of inorganic and organic substances. Its continuous sample preparation and mild separation conditions make it also interesting for online monitoring and detection applications. Since 1994 several microfluidic, miniaturized FFE devices were developed and experimentally characterized. In contrast to their large-scale counterparts microfluidic FFE (mu-FFE) devices offer new possibilities due to the very rapid separations within several seconds or below and the requirement for sample volumes in the microliter range. Eventually, these mu-FFE systems might find application in so-called lab-on-a-chip devices for real-time monitoring and separation applications. This review gives detailed information on the results so far published on mu-FFE chips, comprising its four main modes, namely free-flow zone electrophoresis (FFZE), free-flow IEF (FFIEF), free-flow ITP (FFITP), and free-flow field-step electrophoresis (FFFSE). The principles of the different FFE modes and the basic underlying theory are given and discussed with special emphasis on miniaturization. Different designs as well as fabrication methods and applied materials are discussed and evaluated. Furthermore, the separation results shown indicate that similar separation quality with respect to conventional FFE systems, as defined by the resolution and peak capacity, can be achieved with mu-FFE separations when applying much lower electrical voltages. Furthermore, innovations still occur and several approaches for hyphenated, more integrated systems have been proposed so far, some of which are discussed here. This review is intended as an introduction and early compendium for research and development within this field.