Electrophoresis 2014, 00, 1–16 1 Wendell Karlos Tomazelli Coltro 1,2 Chao-Min Cheng 3 Emanuel Carrilho 2,4 Dosil Pereira de Jesus 2,5 1 Instituto de Qu´ ımica, Universidade Federal de Goi ´ as, Goi ˆ ania-GO, Brazil 2 Instituto Nacional de Ci ˆ encia e Tecnologia de Bioanal´ ıtica, Campinas-SP, Brazil 3 Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu, Taiwan 4 Instituto de Qu´ ımica de S ˜ ao Carlos, Universidade de S ˜ ao Paulo, S ˜ ao Carlos-SP, Brazil 5 Institute of Chemistry, University of Campinas, UNICAMP, Campinas-SP, Brazil Received January 6, 2014 Revised March 14, 2014 Accepted March 15, 2014 Review Recent advances in low-cost microfluidic platforms for diagnostic applications The use of inexpensive materials and cost-effective manufacturing processes for mass production of microfluidic devices is very attractive and has spurred a variety of approaches. Such devices are particularly suited for diagnostic applications in limited resource settings. This review describes the recent and remarkable advances in the use of low-cost substrates for the development of microfluidic devices for diagnostics and clinical assays. Thus, a plethora of new and improved fabrication methods, designs, capabilities, detections, and applications of microfluidic devices fabricated with paper, plastic, and threads are covered. Keywords: Bioassays / Clinical assays / Paper-based microfluidic devices / Plastic substrates / Point-of-care / Thread DOI 10.1002/elps.201400006 1 Introduction Using microfluidic devices to perform diagnostic assays is an exciting approach that has gained much attention in the past ten years [1, 2]. This increasing interest may be attributed to the fact that microfluidic devices are portable, require small sample and reagent volumes, and can conveniently integrate the necessary steps for rapid diagnostic assays. Thus, great effort and considerable resources have been focused on the development and evaluation of new substrates, microfabrica- tion techniques, and detection methods to attain inexpensive, robust, disposable, and portable point-of-care (POC) diagnos- tic devices. Recently, microfluidic devices have emerged as a promising diagnostics solution to improve human health in resource-poor and remote settings [3]. In such environments, POC diagnostic devices could provide an adequate solution to be used even by untrained personnel under challenging environmental conditions and limited power. Correspondence: Dr. Dosil Pereira de Jesus, Institute of Chem- istry, University of Campinas, P.O. Box 6154, 13083-970 Campinas, SP, Brazil E-mail: dosil@iqm.unicamp.br Fax: +55-19-3521-3023 Abbreviations: AFP, -fetoprotein; ALP, alkaline phos- phatase; AuNP, gold nanoparticle; CEA, carcinoembryonic antigen; CRP, C-reactive protein; ECL, electrochemilumi- nescense; hCG, human chorionic gonadotropin; ITO, indium tin oxide; PAD, paper-based microfluidic devices; OTS, oc- tadecyltrichlorosilane; PC, polycarbonate; POC, point-of-care; PSA, prostate-specific antigen; PT, polyester-toner; SAW, surface acoustic waves; SERS, surface-enhanced Raman spectroscopy The cost of a POC diagnostic device is also critical and should be as low as possible, particularly if the microde- vice is intended to be used in resource-poor settings [4]. Achieving such cost reduction using inexpensive materials together with cost-effective manufacturing process for mass production of POC microfluidic devices is possible. Despite the low cost, substrates must be biocompatible, easily func- tionalized, adequate for diagnostic detection methods, and non-biohazardous when disposed off. Although silicon, and, to a greater extent, glass, have been primarily used for microfluidic device fabrication, the associated costs and required manufacturing processes are not practical for mass production of POC microfluidic de- vices for communities with limited resources. Currently, plas- tic and paper are considered among the most affordable, easily disposable, and versatile materials for large-scale fab- rication of inexpensive microfluidic devices for diagnostic applications [3, 5–8]. This review covers the primary advances reported in works published from 2011 up to September 2013 regarding fabrication methods, designs, capabilities, and practical ap- plications of microfluidic devices for diagnostic applications fabricated with low-cost materials, such as paper, plastic, and thread. 2 Paper-based microfluidic devices Paper is affordable, abundant, disposable, and compatible with large-scale manufacturing processes for the production of microfluidic devices. Because of these unique features, Colour Online: See the article online to view Figs. 1–3 and 5–11 in colour. C  2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.electrophoresis-journal.com