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Cloth (or fabric) is an omnipresent material that has various applications in everyday life, and has become one of the things people are most familiar with. It has some attractive properties such as low cost, ability to transport fluid by capillary force, high tensile strength and durability, good wet strength, and great biocompatibility and biodegradability. Hence, cloth is an ideal material for the development of economical and user-friendly diagnostic devices for many applications including food detection, environmental monitoring, disease diagnosis and public health. Microfluidic cloth-based analytical devices (μCADs) (or microfluidic fabric-based analytical devices (μFADs)) first emerged in 2011 as a low-cost alternative to conventional laboratory testing, with the goal of improving point of care testing and disease screening in the developing world. In this review, we examine the advances in the development of μCADs from 2011 to 2020, especially highlighting emerging technologies and applications related to the μCADs. First, different fabrication methods for μCADs are introduced and compared. Second, a series of cloth-based microfluidic functional components are discussed, including microvalves, fluid velocity control elements, micromixers, and microfilters. Then, electroanalytical μCADs are described, especially focusing on the use of cloth-based electrodes. Next, various detection methods for μCADs, together with their corresponding applications, are compared and categorized. In addition, the current development of wearable μCADs is also demonstrated. Finally, the future outlook and trends in this field are discussed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This paper introduces a new and simple concept for fabricating low-cost, easy-to-use capillary microchannel (CMC) assisted thread-based microfluidic analytical devices (CMCA-μTADs) for bipolar electrochemiluminescence (BP-ECL) application. The thread with patterns of carbon screen-printed electrodes and bare thread zones (BTZs) is embedded into a CMC. Such CMCA-μTADs can produce a strong and stable BP-ECL signal, and have an extremely low cost ($0.01 per device). Interestingly, the CMCA-μTADs are ultraflexible, and can be bent with a 135° bending angle at the BTZ or with a 150° bending angle at the middle of bipolar electrode (BPE), with no loss of analytical performance. Additionally, the two commonly-used ECL systems of Ru(bpy) 3 2+ /TPA and luminol/H 2 O 2 are applied to demonstrate the quantitative ability of the BP-ECL CMCA-μTADs. It has been shown that the proposed devices have successfully fulfilled the detection of TPA and H 2 O 2 , with detection limits of 0.00432mM and 0.00603mM, respectively. Based on the luminol/H 2 O 2 ECL system, the CMCA-μTADs are further applied for the glucose measurement, with the detection limit of 0.0205mM. Finally, the applicability and validity of the CMCA-μTADs are demonstrated for the measurements of H 2 O 2 in milk, and glucose in human urine and serum. The results indicate that the proposed devices have the potential to become an important new tool for a wide range of applications., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this work, we report the first demonstration of chemiluminescence (CL) detection for microfluidic cloth-based analytical devices (μCADs). Wax screen-printing is used to make cloth channels or chambers, and enzyme-catalyzed CL reactions are imaged using an inexpensive charge coupled device (CCD). We first evaluate the relationship between the wicking rate and the length/width of cloth channel. For our device, the channel length and width between the loading and detection chambers are optimized to be 10mm and 3mm. Thus, the detection procedure can be accomplished in about 15s on a cloth-based device (15 × 30 mm(2)) by using 25-μL sample spotted on it. Next, several parameters affecting cloth-based CL intensity are studied, including exposure time, pH, and concentrations of luminol and enzyme. Under optimal conditions, a linear relationship is obtained between CL intensity and hydrogen peroxide (H2O2) concentrations in the range of 0.5-5mM with a detection limit of 0.46 mM. Finally, the utility of cloth-based CL is demonstrated for determination of H2O2 residues in meat samples. On our device, the chicken meat soaked for 6h with 3% H2O2 can be detected. Moreover, the supernatant of grinded meat sample can be directly applied, without need for other treatments. We believe that μCADs with CL detection could provide a new platform of rapid and low-cost assays for use in areas such as food detection and environmental monitoring., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In this work, we first introduce the fabrication of microfluidic cloth-based analytical devices (μCADs) using a wax screen-printing approach that is suitable for simple, inexpensive, rapid, low-energy-consumption and high-throughput preparation of cloth-based analytical devices. We have carried out a detailed study on the wax screen-printing of μCADs and have obtained some interesting results. Firstly, an analytical model is established for the spreading of molten wax in cloth. Secondly, a new wax screen-printing process has been proposed for fabricating μCADs, where the melting of wax into the cloth is much faster (∼5 s) and the heating temperature is much lower (75 °C). Thirdly, the experimental results show that the patterning effects of the proposed wax screen-printing method depend to a certain extent on types of screens, wax melting temperatures and melting time. Under optimized conditions, the minimum printing width of hydrophobic wax barrier and hydrophilic channel is 100 μm and 1.9 mm, respectively. Importantly, the developed analytical model is also well validated by these experiments. Fourthly, the μCADs fabricated by the presented wax screen-printing method are used to perform a proof-of-concept assay of glucose or protein in artificial urine with rapid high-throughput detection taking place on a 48-chamber cloth-based device and being performed by a visual readout. Overall, the developed cloth-based wax screen-printing and arrayed μCADs should provide a new research direction in the development of advanced sensor arrays for detection of a series of analytes relevant to many diverse applications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A handheld flow genetic analysis system (FGAS) is proposed for rapid, sensitive, multiplex and real-time quantification of nucleic acids at the point-of-care (POC) level. The FGAS includes a helical thermal-gradient microreactor and a microflow actuator, as well as control circuitry for temperature, fluid and power management, and smartphone fluorescence imaging. All of these features are integrated into a field-portable and easy-to-use molecular diagnostic platform powered by lithium batteries. Due to the unique design of the microreactor, not only steady temperatures for denaturation and annealing/extension but also a linear thermal gradient for spatial high-resolution melting can be achieved through simply maintaining a single heater at constant temperature. The smartphone fluorescence imaging system has a wide field of view that captures all PCR channels of the microreactor in a single snapshot without the need for any mechanical scanning. By these designs, the FGAS enables real-time monitoring of the temporal and spatial fluorescence signatures of amplicons during continuous-flow amplification. On the current FGAS, visual detection of as little as 10 copies per μL of genomic DNA of Salmonella enterica was achieved in 15 min, with real-time quantitative detection of the DNA over 6 orders of magnitude concentration from 10(6) to 10(1) copies per μL also completed in 7.5-15 min. In addition, multiple pathogenic DNA targets could be simultaneously discriminated with direct bar-chart readout or multiplex spatial melting in serial flow. We anticipate that the FGAS has great potential to become a next-generation gene analyzer for POC molecular diagnostics.

The development of microfluidic tools for nucleic acid analysis has become a burgeoning area of research during the postgenome era. Here we have developed a microfluidic device that integrates reverse transcription (RT) and polymerase chain reaction (PCR) with online fluorescence detection to realize a rapid detection system for performing both genetic amplification and product analysis. The microfluidic device mainly comprises a grooved copper heating block for RT and a heated cylinder for amplification. To expedite the analysis process, we combined the continuous-flow PCR with an online fluorescence detection system that allows analysis of amplification products within 1 min. Rotaviruses are worldwide enteric pathogens in humans and animals responsible for a significant burden of disease through person-to-person transmission and exposure to contaminated foods and water. In this study, rotavirus from stool specimens was successfully amplified and detected using the RT-PCR microfluidic system within 1 h, and the limit of detection of the RNA concentration was estimated to be 3.6×10(4) copies μl(-1). Compared with a large-scale apparatus, the integrated microfluidic system presented here can perform rapid nucleic acid amplification and analysis, possibly making it a crucial platform for future diagnosis application., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This study develops a new microfluidic DNA amplification strategy for executing parallel DNA amplification in the microfluidic gradient polymerase chain reaction (MG-PCR) device. The developed temperature gradient microfluidic system is generated by using an innovative fin design. The device mainly consists of modular thermally conductive copper flake which is attached onto a finned aluminum heat sink with a small fan. In our microfluidic temperature gradient prototype, a non-linear temperature gradient is produced along the gradient direction. On the copper flake of length 45 mm, width 40 mm and thickness 4 mm, the temperature gradient easily spans the range from 97 to 52 degrees Celsius. By making full use of the hot (90-97 degrees Celsius) and cold (60-70 degrees Celsius) regions on the temperature gradient device, the parallel, two-temperature MG-PCR amplification is feasible. As a demonstration, the MG-PCR from three parallel reactions of 112-bp Escherichia coli DNA fragment is performed in a continuous-flow format, in which the flow of the PCR reagent in the closed loop is induced by the buoyancy-driven nature convection. Although the prototype is not optimized, the MG-PCR amplification can be completed in less than 45 min. However, the MG-PCR thermocycler presented herein can be further scaled-down, and thus the amplification times and reagent consumption can be further reduced. In addition, the currently developed temperature gradient technology can be applied onto other continuous-flow MG-PCR systems or used for other analytical purposes such as parallel and combination measurements, and fluorescent melting curve analysis.

The ability to perform DNA amplification on a microfluidic device is very appealing. In this study, a compact continuous-flow polymerase chain reaction (PCR) microfluidics was developed for rapid analysis of genetically modified organisms (GMOs) in genetically modified soybeans. The device consists of three pieces of copper and a transparent polytetrafluoroethylene capillary tube embedded in the spiral channel fabricated on the copper. On this device, the P35S and Tnos sequences were successfully amplified within 9min, and the limit of detection of the DNA sample was estimated to be 0.005 ng microl(-1). Furthermore, a duplex continuous-flow PCR was also reported for the detection of the P35S and Tnos sequences in GMOs simultaneously. This method was coupled with the intercalating dye SYBR Green I and the melting curve analysis of the amplified products. Using this method, temperature differences were identified by the specific melting temperature values of two sequences, and the limit of detection of the DNA sample was assessed to be 0.01 ng microl(-1). Therefore, our results demonstrated that the continuous-flow PCR assay could discriminate the GMOs in a cost-saving and less time-consuming way.

This review surveys the advances of microvalves, micropumps, and micromixers within PCR microfluidic chips over the past ten years. First, the types of microvalves in PCR chips are discussed, including active and passive microvalves. The active microvalves are subdivided into mechanical (thermopneumatic and shape memory alloy), non-mechanical (hydrogel, sol-gel, paraffin, and ice), and external (modular built-in, pneumatic, and non-pneumatic) microvalves. The passive microvalves also include mechanical (in-line polymerized gel and passive plug) and non-mechanical (hydrophobic) microvalves. The review then discusses mechanical (piezoelectric, pneumatic, and thermopneumatic) and non-mechanical (electrokinetic, magnetohydrodynamic, electrochemical, acoustic-wave, surface tension and capillary, and ferrofluidic magnetic) micropumps in PCR chips. Next, different micromixers within PCR chips are presented, including passive (Y/T-type flow, recirculation flow, and drop) and active (electrokinetically-driven, acoustically-driven, magnetohydrodynamical-driven, microvalves/pumps) micromixers. Finally, general discussions on microvalves, micropumps, and micromixers for PCR chips are given. The microvalve/micropump/micromixers allow high levels of PCR chip integration and analytical throughput.

The possibility of performing fast and small-volume nucleic acid amplification and analysis on a single chip has attracted great interest. Devices based on this idea, referred to as micro total analysis, microfluidic analysis, or simply 'Lab on a chip' systems, have witnessed steady advances over the last several years. Here, we summarize recent research on chip substrates, surface treatments, PCR reaction volume and speed, architecture, approaches to eliminating cross-contamination and control and measurement of temperature and liquid flow. We also discuss product-detection methods, integration of functional components, biological samples used in PCR chips, potential applications and other practical issues related to implementation of lab-on-a-chip technologies.

The miniaturization of biological and chemical analytical devices by micro-electro-mechanical-systems (MEMS) technology has posed a vital influence on such fields as medical diagnostics, microbial detection and other bio-analysis. Among many miniaturized analytical devices, the polymerase chain reaction (PCR) microchip/microdevices are studied extensively, and thus great progress has been made on aspects of on-chip micromachining (fabrication, bonding and sealing), choice of substrate materials, surface chemistry and architecture of reaction vessel, handling of necessary sample fluid, controlling of three or two-step temperature thermocycling, detection of amplified nucleic acid products, integration with other analytical functional units such as sample preparation, capillary electrophoresis (CE), DNA microarray hybridization, etc. However, little has been done on the review of above-mentioned facets of the PCR microchips/microdevices including the two formats of flow-through and stationary chamber in spite of several earlier reviews [Zorbas, H. Miniature continuous-flow polymerase chain reaction: a breakthrough? Angew Chem Int Ed 1999; 38 (8):1055-1058; Krishnan, M., Namasivayam, V., Lin, R., Pal, R., Burns, M.A. Microfabricated reaction and separation systems. Curr Opin Biotechnol 2001; 12:92-98; Schneegabeta, I., Köhler, J.M. Flow-through polymerase chain reactions in chip themocyclers. Rev Mol Biotechnol 2001; 82:101-121; deMello, A.J. DNA amplification: does 'small' really mean 'efficient'? Lab Chip 2001; 1: 24N-29N; Mariella, Jr. R. MEMS for bio-assays. Biomed Microdevices 2002; 4 (2):77-87; deMello AJ. Microfluidics: DNA amplification moves on. Nature 2003; 422:28-29; Kricka, L.J., Wilding, P. Microchip PCR. Anal BioAnal Chem 2003; 377:820-825]. In this review, we survey the advances of the above aspects among the PCR microfluidic devices in detail. Finally, we also illuminate the potential and practical applications of PCR microfluidics to some fields such as microbial detection and disease diagnosis, based on the DNA/RNA templates used in PCR microfluidics. It is noted, especially, that this review is to help a novice in the field of on-chip PCR amplification to more easily find the original papers, because this review covers almost all of the papers related to on-chip PCR microfluidics.

The rising need for low-cost diagnostic devices has led to the search for inexpensive matrices that allow performing alternative analytical assays. Cloth is a viable material for the development of analytical devices due to its low material and manufacture costs, ability to wick assay fluids by capillary forces, and potential for patterning multiplexed channel geometries. In this paper, we describe the construction of low-cost, ultraflexible microfluidic cloth-based analytical devices (μCADs) for wireless electrochemiluminescence based on closed bipolar electrodes (C-WL-ECL), employing extremely cheap materials and a manufacturing process. The C-WL-ECL μCADs are built with wax-screen-printed cloth channels and carbon ink screen-printed electrodes, and the estimated cost per device is only $0.015. To demonstrate the performance of C-WL-ECL μCADs, the two most commonly used ECL systems – tris(2,2′-bipyridyl)ruthenium(ii)/tri-n-propylamine (Ru(bpy)32+/TPA) and 3-aminophthalhydrazide/hydrogen peroxide (luminol/H2O2) – are applied. Under optimized conditions, the C-WL-ECL method has successfully fulfilled the quantitative determination of TPA with a detection limit of 0.085 mM. In addition, on the bent μCADs (bending angle (ϑ) = 180°), the luminol/H2O2-based ECL system can detect H2O2 as low as 0.024 mM. Based on such an ECL system, the bent μCADs are further used for determination of glucose in a phosphate buffer solution (PBS), with the detection limit of 0.195 mM. Finally, the applicability and validity, anti-interference ability, and storage stability of the C-WL-ECL μCADs are investigated. The results indicate that the proposed device has shown potential to extend the use of microfluidic analytical devices, due to its simplicity, low cost, ultraflexibility, and acceptable analytical performance. [ABSTRACT FROM AUTHOR]