Applications of microfluidic systems in environmental analysis

During the past few decades, rapid growth in the applications of microfluidic systems to environmental analysis or environmentally related species has been observed. This review presents and critically discusses the published literature on the applications of microfluidic systems to real environmental samples or samples simulating environmental conditions. The subjects covered include integrated pretreatments, separation modes, detection methods and monitoring sensors used in these platforms. The main challenges in this field and the author’s perspectives on future directions for environmental analysis based on microfluidic systems are also proposed.     

Droplet microfluidics

Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of "digital fluidic" operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as microreactors ranging from the nano- to femtoliter range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. This review will focus on the various droplet operations, as well as the numerous applications of the system. Due to advantages unique to droplet-based systems, this technology has the potential to provide novel solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics.     

A multi-functional electrochemical sensing system using microfluidic technology for the detection of urea and creatinine

This study presents a new microfluidic system capable of precise measurements of two important biomarkers, urea and creatinine, automatically. In clinical applications, high levels of these two biomarkers are early indicators of nephropathy or renal failure and should be monitored on a regular basis. The microfluidic system is composed of a microfluidic chip, a control circuit system, a compressed air source and several electromagnetic valves to form a handheld system. The microfluidic chip is fabricated by using micro-electromechanical systems and microfluidic techniques comprising electrochemical sensor arrays and polydimethylsiloxane-based microfluidic structures such as micropumps/micromixers, normally closed valves and microchannels. The microfluidic system performs a variety of critical processes including sample pretreatment, mixing, transportation and detection on a single chip. The experimental results show that the entire procedure takes approximately 40 min, which is much faster than the traditional method (more than 6 h). Furthermore, the total sample volume consumed in each operation is only 0.1 mL, which is significantly less than that required in a large system (5 mL). The developed automatic microfluidic system may provide a powerful platform for further clinical applications.     

SmartBuild-a truly plug-n-play modular microfluidic system

In this Technical Note, for the first time, a truly "plug-n-play" modular microfluidic system (SmartBuild Plug-n-Play Modular Microfluidic System) is presented for designing and building integrated modular microfluidic systems for biological and chemical applications. The modular microfluidic system can be built by connecting multiple microfluidic components together to form a larger integrated system. The SmartBuild System comprises of a motherboard with interconnect channels/grooves, fitting components, microchannel inserts with different configurations and microchips/modules with different functionalities. Also, heaters, micropumps and valving systems can be designed and used in the system. Examples of an integrated mixing system and reaction systems are presented here to demonstrate the versatility of the SmartBuild System.     

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.     

Dielectrophoresis in microfluidics technology

Dielectrophoresis (DEP) is the movement of a particle in a non-uniform electric field due to the interaction of the particle's dipole and spatial gradient of the electric field. DEP is a subtle solution to manipulate particles and cells at microscale due to its favorable scaling for the reduced size of the system. DEP has been utilized for many applications in microfluidic systems. In this review, a detailed analysis of the modeling of DEP-based manipulation of the particles is provided, and the recent applications regarding the particle manipulation in microfluidic systems (mainly the published works between 2007 and 2010) are presented.     

On the recent developments of insulator‐based dielectrophoresis: A review

Insulator‐based dielectrophoresis (iDEP), also known as electrodeless DEP, has become a well‐known dielectrophoretic technique, no longer viewed as a new methodology. Significant advances on iDEP have been reported during the last 15 years. This review article aims to summarize some of the most important findings on iDEP organized by the type of dielectrophoretic mode: streaming and trapping iDEP. The former is primarily used for particle sorting, while the latter has great capability for particle enrichment. The characteristics of a wide array of devices are discussed for each type of dielectrophoretic mode in order to present an overview of the distinct designs and applications developed with iDEP. A short section on Joule heating effects and electrothermal flow is also included to highlight some of the challenges in the utilization of iDEP systems. The significant progress on iDEP illustrates its potential for a large number of applications, ranging from bioanalysis to clinical and biomedical assessments. The present article discusses the work on iDEP by numerous research groups around the world, with the aim of proving the reader with an overview of the state‐of‐the‐art in iDEP microfluidic systems.     

Engineered alginate hydrogels for effective microfluidic capture and release of endothelial progenitor cells from whole blood

Microfluidic adhesion-based cell separation systems are of interest in clinical and biological applications where small sample volumes must be processed efficiently and rapidly. While the ability to capture rare cells from complex suspensions such as blood using microfluidic systems has been demonstrated, few methods exist for rapid and nondestructive release of the bound cells. Such detachment is critical for applications in tissue engineering and cell-based therapeutics in contrast with diagnostics wherein immunohistochemical, proteomic, and genomic analyses can be carried out by simply lysing captured cells. This paper demonstrates how the incorporation of four-arm amine-terminated poly(ethylene glycol) (PEG) molecules along with antibodies within alginate hydrogels can enhance the ability of the hydrogels to capture endothelial progenitor cells (EPCs) from whole human blood. The hydrogel coatings are applied conformally onto pillar structures within microfluidic channels and their dissolution with a chelator allows for effective recovery of EPCs following capture.     

A novel 3D mammalian cell perfusion-culture system in microfluidic channels

Mammalian cells cultured on 2D surfaces in microfluidic channels are increasingly used in drug development and biological research applications. These systems would have more biological or clinical relevance if the cells exhibit 3D phenotypes similar to the cells in vivo. We have developed a microfluidic channel based system that allows cells to be perfusion-cultured in 3D by supporting them with adequate 3D cell-cell and cell-matrix interactions. The maximal cell-cell interaction was achieved by perfusion-seeding cells through an array of micropillars; and 3D cell-matrix interactions were achieved by a polyelectrolyte complex coacervation process to form a thin layer of matrix conforming to the 3D cell shapes. Carcinoma cell lines (HepG2, MCF7), primary differentiated (hepatocytes) and primary progenitor cells (bone marrow mesenchymal stem cells) were perfusion-cultured for 72 hours to 1 week in the microfluidic channel, which preserved their 3D cyto-architecture and cell-specific functions or differentiation competence. This transparent 3D microfluidic channel-based cell culture system also allows direct optical monitoring of cellular events for a wide range of applications.     

Acoustofluidics 17: Theory and applications of surface acoustic wave devices for particle manipulation

In this paper, number 17 of the thematic tutorial series "Acoustofluidics-exploiting ultrasonic standing waves, forces and acoustic streaming in microfluidic systems for cell and particle manipulation", we present the theory of surface acoustic waves (SAWs) and some related microfluidic applications. The equations describing SAWs are derived for a solid-vacuum interface before generalisations are made about solid-solid and solid-fluid interfaces. Techniques for SAW generation are discussed before an overview of applications is presented.     

An integrated microfluidic biochemical detection system for protein analysis with magnetic bead-based sampling capabilities

This paper presents the development and characterization of an integrated microfluidic biochemical detection system for fast and low-volume immunoassays using magnetic beads, which are used as both immobilization surfaces and bio-molecule carriers. Microfluidic components have been developed and integrated to construct a microfluidic biochemical detection system. Magnetic bead-based immunoassay, as a typical example of biochemical detection and analysis, has been successfully performed on the integrated microfluidic biochemical analysis system that includes a surface-mounted biofilter and electrochemical sensor on a glass microfluidic motherboard. Total time required for an immunoassay was less than 20 min including sample incubation time, and sample volume wasted was less than 50 microl during five repeated assays. Fast and low-volume biochemical analysis has been successfully achieved with the developed biofilter and immunosensor, which is integrated to the microfluidic system. Such a magnetic bead-based biochemical detection system, described in this paper, can be applied to protein analysis systems.     

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.     

Urine analysis in microfluidic devices

Microfluidics has attracted considerable attention since its early development in the 1980s and has experienced rapid growth in the past three decades due to advantages associated with miniaturization, integration and automation. Urine analysis is a common, fast and inexpensive clinical diagnostic tool in health care. In this article, we will be reviewing recent works starting from 2005 to the present for urine analysis using microfluidic devices or systems and to provide in-depth commentary about these techniques. Moreover, commercial strips that are often treated as chips and their readers for urine analysis will also be briefly discussed. We start with an introduction to the physiological significance of various components or measurement standards in urine analysis, followed by a brief introduction to enabling microfluidic technologies. Then, microfluidic devices or systems for sample pretreatments and for sensing urinary macromolecules, micromolecules, as well as multiplexed analysis are reviewed, in this sequence. Moreover, a microfluidic chip for urinary proteome profiling is also discussed, followed by a section discussing commercial products. Finally, the authors' perspectives on microfluidic-based urine analysis are provided. These advancements in microfluidic techniques for urine analysis may improve current routine clinical practices, particularly for point-of-care (POC) applications.     

Microfluidic electronics

Microfluidics, a field that has been well-established for several decades, has seen extensive applications in the areas of biology, chemistry, and medicine. However, it might be very hard to imagine how such soft microfluidic devices would be used in other areas, such as electronics, in which stiff, solid metals, insulators, and semiconductors have previously dominated. Very recently, things have radically changed. Taking advantage of native properties of microfluidics, advances in microfluidics-based electronics have shown great potential in numerous new appealing applications, e.g. bio-inspired devices, body-worn healthcare and medical sensing systems, and ergonomic units, in which conventional rigid, bulky electronics are facing insurmountable obstacles to fulfil the demand on comfortable user experience. Not only would the birth of microfluidic electronics contribute to both the microfluidics and electronics fields, but it may also shape the future of our daily life. Nevertheless, microfluidic electronics are still at a very early stage, and significant efforts in research and development are needed to advance this emerging field. The intention of this article is to review recent research outcomes in the field of microfluidic electronics, and address current technical challenges and issues. The outlook of future development in microfluidic electronic devices and systems, as well as new fabrication techniques, is also discussed. Moreover, the authors would like to inspire both the microfluidics and electronics communities to further exploit this newly-established field.     

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.     

Integration of spore-based genetically engineered whole-cell sensing systems into portable centrifugal microfluidic platforms

Bacterial whole-cell biosensing systems provide important information about the bioavailable amount of target analytes. They are characterized by high sensitivity and specificity/selectivity along with rapid response times and amenability to miniaturization as well as high-throughput analysis. Accordingly, they have been employed in various environmental and clinical applications. The use of spore-based sensing systems offers the unique advantage of long-term preservation of the sensing cells by taking advantage of the environmental resistance and ruggedness of bacterial spores. In this work, we have incorporated spore-based whole-cell sensing systems into centrifugal compact disk (CD) microfluidic platforms in order to develop a portable sensing system, which should enable the use of these hardy sensors for fast on-field analysis of compounds of interest. For that, we have employed two spore-based sensing systems for the detection of arsenite and zinc, respectively, and evaluated their analytical performance in the miniaturized microfluidic format. Furthermore, we have tested environmental and clinical samples on the CD microfluidic platforms using the spore-based sensors. Germination of spores and quantitative response to the analyte could be obtained in 2.5–3 h, depending on the sensing system, with detection limits of 1 × 10⁻⁷ M for arsenite and 1 × 10⁻⁶ M for zinc in both serum and fresh water samples. Incorporation of spore-based whole-cell biosensing systems on microfluidic platforms enabled the rapid and sensitive detection of the analytes and is expected to facilitate the on-site use of such sensing systems.     

Droplet‐based microfluidics systems in biomedical applications

Microfluidics has made a very impressive progress in the past decades due to its unique and instinctive advantages. Droplet‐based microfluidic systems show excellent compatibility with many chemical and biological reagents and are capable of performing variety of operations that can implement microreactor, complex multiple core–shell structure, and many applications in biomedical research such as drug encapsulation, targeted drug delivery systems, and multifunctionalization on carriers. Droplet‐based systems have been directly used to synthesize particles and encapsulate many biological entities for biomedicine applications due to their powerful encapsulation capability and facile versatility. In this paper, we review its origin, deviation, and evolution to draw a clear future, especially for droplet‐based biomedical applications. This paper will focus on droplet generation, variations and complication as starter, and logistically lead to the numerous typical applications in biomedical research. Finally, we will summarize both its challenge and future prospects relevant to its droplet‐based biomedical applications.     

Direct immobilization of DNA probes on non-modified plastics by UV irradiation and integration in microfluidic devices for rapid bioassay

DNA microarrays have become one of the most powerful tools in the field of genomics and medical diagnosis. Recently, there has been increased interest in combining microfluidics with microarrays since this approach offers advantages in terms of portability, reduced analysis time, low consumption of reagents, and increased system integration. Polymers are widely used for microfluidic systems, but fabrication of microarrays on such materials often requires complicated chemical surface modifications, which hinders the integration of microarrays into microfluidic systems. In this paper, we demonstrate that simple UV irradiation can be used to directly immobilize poly(T)poly(C)-tagged DNA oligonucleotide probes on many different types of plastics without any surface modification. On average, five- and fourfold improvement in immobilization and hybridization efficiency have been achieved compared to surface-modified slides with aminated DNA probes. Moreover, the TC tag only costs 30% of the commonly used amino group modifications. Using this microarray fabrication technique, a portable cyclic olefin copolymer biochip containing eight individually addressable microfluidic channels was developed and used for rapid and parallel identification of Avian Influenza Virus by DNA hybridization. The one-step, cost-effective DNA-linking method on non-modified polymers significantly simplifies microarray fabrication procedures and permits great flexibility to plastic material selection, thus making it convenient to integrate microarrays into plastic microfluidic systems.     

Development of a low-cost microfluidic capillary-electrophoresis system coupled with flow-injection and sequential-injection sample introduction (review)

Microfabrication techniques used for the production of MEMS (micro electro-mechanical systems) have been successfully used to produce highly efficient microfluidic capillary electrophoresis chip systems. A limitation of this approach are the difficulties associated with the creation of the micrometer-sized structures in glass or other substrates, which currently involve specialized and expensive lithographic and etching processes. A further limitation is that hitherto most microfluidic chips are not designed for continuous introduction of a series of different samples, which limits the overall throughput of such systems. This article reviews the development of a microfluidic system for rapid CE separations, produced at a low cost of less than a dollar each, using equipment and materials readily available in the ordinary laboratory. Applications of the system, after coupling to flow-injection and/or sequential-injection sample introduction, for the determination of FITC-labeled amino acids by laser-induced fluorescence, trace metals by chemiluminescence, carbohydrates by amperometry, and inorganic and organic anions by indirect UV absorbance are exemplified to illustrate the performance and versatility of the microfluidic system.