Innovations in optical microfluidic technologies for point-of-care diagnostics† Frank B. Myers and Luke P. Lee * Received 18th July 2008, Accepted 1st October 2008 First published as an Advance Article on the web 30th October 2008 DOI: 10.1039/b812343h Despite a growing focus from the academic community, the field of microfluidics has yet to produce many commercial devices for point-of-care (POC) diagnostics. One of the main reasons for this is the difficulty in producing low-cost, sensitive, and portable optical detection systems. Although electrochemical methods work well for certain applications, optical detection is generally regarded as superior and is the method most widely employed in laboratory clinical chemistry. Conventional optical systems, however, are costly, require careful alignment, and do not translate well to POC devices. Furthermore, many optical detection paradigms such as absorbance and fluorescence suffer at smaller geometries because the optical path length through the sample is shortened. This review examines the innovative techniques which have recently been developed to address these issues. We highlight microfluidic diagnostic systems which demonstrate practical integration of sample preparation, analyte enrichment, and optical detection. We also examine several emerging detection paradigms involving nanoengineered materials which do not suffer from the same miniaturization disadvantages as conventional measurements. Introduction The potential role of microfluidics in point-of-care (POC) diag- nostics is widely acknowledged, and many reviews have explored its potential applications in clinical diagnostics, 1 personalized medicine, 2 global health, 3,4 and forensics. 5 Despite this, relatively few successful commercial implementations have been demon- strated. 6 To realize the commercialization of microfluidic POC diagnostics, challenges in integrating low-cost, sensitive, and portable optical detection systems must be addressed. Further- more, to demonstrate the practicality of new techniques, an effort should be made to integrate sample preparation from raw clinical samples and compare detection sensitivity to conven- tional methods. Here, we review optical microfluidic systems which address these goals and introduce novel techniques for realizing practical POC diagnostics. Lateral-flow assays (LFAs) and electrochemical sensors dominate the POC diagnostics market today. Immunochroma- tographic LFAs, commonly called ‘‘dipstick tests,’’ rely on capillary flow and qualitative visual readout. LFAs are commercially available for a variety of diagnostic tests (preg- nancy, cardiac markers, infectious diseases, etc.). These devices are successful because they are inexpensive to manufacture, robust, and easy to use. Although sensitivity is relatively poor compared to conventional immunological laboratory assays (such as the enzyme-linked immunosorbent assay, ELISA), LFAs are ideal for applications where analyte abundance is relatively high, complex sample preparation is not needed, and Frank B. Myers is a PhD student in the UCSF/UC Ber- keley Bioengineering graduate program. His research involves the integration of optical and electronic devices into micro- fluidic platforms for medical diagnostics and quantitative cell biology. He obtained BS degrees in Electrical and Computer Engineering from North Caro- lina State University in 2006. Luke P. Lee, PhD is the Lloyd Distinguished Professor of Bioengineering, director of the Biomolecular Nanotechnology Center, and co-director of the Berkeley Sensor and Actuator Center at UC Berkeley. He received his BA in Biophysics and PhD in Applied Physics from UC Berkeley. His current research interests include nano- plasmonics, lab-on-a-chip devices for quantitative biology and diagnostics, molecular biophysics, and integrative translational medicine. Biomolecular Nanotechnology Center, Berkeley Sensor and Actuator Center, Department of Bioengineering, University of California, Berkeley, CA, 94720. E-mail: lplee@berkeley.edu; Fax: +510-642-5835; Tel: +510-642-5855 † Part of a special issue on Point-of-care Microfluidic Diagnostics; Guest Editors—Professor Kricka and Professor Sia. This journal is ª The Royal Society of Chemistry 2008 Lab Chip, 2008, 8, 2015–2031 | 2015 CRITICAL REVIEW www.rsc.org/loc | Lab on a Chip