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Recent Advances in Applications of Droplet Microfluidics Micromachines 2015, 6, 1249-1271; doi:10.3390/mi6091249 OPEN ACCESS micromachines ISSN 2072-666X www.mdpi.com/journal/micromachines Review Recent Advances in Applications of Droplet Microfluidics Wei-Lung Chou 1,:, Pee-Yew Lee 2,:, Cing-Long Yang 1, Wen-Ying Huang 3 and Yung-Sheng Lin 4,* 1 Institute of Occupational Safety and Hazardous Prevention, Hungkuang University, Taichung 43302, Taiwan; E-Mails: [email protected] (W.-L.C.); [email protected] (C.-L.Y.) 2 Institute of Materials Engineering, National Taiwan Ocean University, Keelung 20224, Taiwan; E-Mail: [email protected] 3 Department of Applied Cosmetology, Hungkuang University, Taichung 43302, Taiwan; E-Mail: [email protected] 4 Department of Chemical Engineering, National United University, Miaoli 36003, Taiwan : These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +886-37-382-199; Fax: +886-37-382-189. Academic Editors: Andrew deMello and Xavier Casadevall i Solvas Received: 31 July 2015 / Accepted: 26 August 2015 / Published: 2 September 2015 Abstract: Droplet-based microfluidics is a colloidal and interfacial system that has rapidly progressed in the past decade because of the advantages of low fabrication costs, small sample volumes, reduced analysis durations, high-throughput analysis with exceptional sensitivity, enhanced operational flexibility, and facile automation. This technology has emerged as a new tool for many recently used applications in molecular detection, imaging, drug delivery, diagnostics, cell biology and other fields. Herein, we review recent applications of droplet microfluidics proposed since 2013. Keywords: droplet; microfluidics; applications; detection; imaging; drug delivery; diagnostics; cell 1. Introduction Microfluidics appeared in the early 1980s as a promising interdisciplinary technology and has since received considerable attention. Microfluidics involves volumes of fluid in the range of microliters to Micromachines 2015, 6 1250 picoliters,Micromachines and demonstrates 2015, 6 many advantages such as rapid mass delivery and heat transfer, and reduced2 reagent use and waste generation [1,2]. The reagent use can be reduced to nanoliters or less, and the picoliters, and demonstrates many advantages such as rapid mass delivery and heat transfer, and reduced reaction time can be reduced to mere seconds. Miniaturizing biological assays or processes on a chip reagent use and waste generation [1,2]. The reagent use can be reduced to nanoliters or less, and the has emergedreaction time as a can hopeful be reduced technology to mere [ 3secon–7].ds. Miniaturizing biological assays or processes on a chip has Dropletemerged microfluidics as a hopeful technology entails both[3–7]. continuous-flow emulsion-based droplet microfluidics and electrowetting-basedDroplet microfluidics droplet (alsoentails called both discretecontinuous droplet-flow emulsion or digital-based droplet) droplet microfluidics microfluidics as shownand in Figureelectrowetting1. Droplet- formationbased droplet of (also the continuous-flow called discrete droplet microfluidics or digital isdroplet) the result microfluidics of an emulsion as shown created in usingFigure two immiscible 1. Droplet formation fluids, including of the continuous liduid/liquid-flow microfluidics and gas/liquid is the systems. result of Various an emulsion techniques, created such as channelusing two geometry immiscible (T-junction fluids, including or flow-focusing) liduid/liquid and and gas/liquid dielectrophoresis, systems. Various were techniques, well applied such for as good controlchanne of dropletl geometry generation. (T-junction As or for flow the-focusing) electrowetting-based and dielectrophoresis, droplet, anwere electric well applied field can for change good the control of droplet generation. As for the electrowetting-based droplet, an electric field can change the interfacial tension between the liquid and the surface. Activation of the electrodes leads liquid wetting, interfacial tension between the liquid and the surface. Activation of the electrodes leads liquid wetting, and switching off the electrodes reverses. The change in the interfacial tension is capable of producing and switching off the electrodes reverses. The change in the interfacial tension is capable of producing liquidliquid finger finger and and then then breaking breaking off off from from the the reservoir reservoir toto form a a droplet. droplet. (A) (B) Figure 1. The two major types of droplet microfluidics. (A) Continuous-flow emulsion-based Figure 1. The two major types of droplet microfluidics. (A) Continuous-flow emulsion-based dropletdroplet microfluidics microfluidics from from T-junctionT-junction andand flow-focusing;flow-focusing; (B ()B )Electrowetting Electrowetting-based-based dropletdroplet microfluidics. microfluidics. TheThe microchannels microchannels in in continuous-flow continuous-flow microfluidic microfluidic devices devices have have at least at one least dimension one dimension smaller than smaller 1 mm. Droplets acting as individual compartments in the fluid are comparable in size with the apparatus than 1 mm. Droplets acting as individual compartments in the fluid are comparable in size with itself. In contrast to that in macroscale channels, the capillary force in microchannels dominates the the apparatus itself. In contrast to that in macroscale channels, the capillary force in microchannels inertial effects, and capillary action dramatically alters system behavior. For obtaining fine control over dominatesthe size the and inertial shape of effects, droplets, and several capillary active action and passive dramatically methods alters involving system various behavior. techniques For obtaininghave fine controlbeen proposed over the [8,9] size. As and shown shape in ofFigure droplets, 2, droplet several microfluidic active ands is passivea rapidly methods growing involvingfield, and the various techniquesnumber have of publications been proposed (according [8,9]. to As ISI shown Web of in Knowledge) Figure2, droplet has increased microfluidics substantially is a rapidly since 20 growing10. field,Droplet and the microfluidics number of publicationsnot only has (accordingmost conventional to ISI Webmicrofluidic of Knowledge) characteristics has increased but also provides substantially sincenumerous 2010. Droplet superior microfluidics advantages such not as ultrahigh only has-throughput most conventional generation and microfluidic manipulation characteristics of microreactors, but also providesimplementation numerous of superior ultrasmall advantages reactors, expulsion such as of ultrahigh-throughput Taylor diffusion and sample generation dilution, and minimization manipulation of of sample absorption on channel walls, and enhanced mixing and mass transfer inside droplets [2]. microreactors, implementation of ultrasmall reactors, expulsion of Taylor diffusion and sample dilution, minimization of sample absorption on channel walls, and enhanced mixing and mass transfer inside droplets [2]. Micromachines 2015, 6 1251 Micromachines 2015, 6 3 600 500 400 300 Publications 200 100 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Year Figure 2. Number of publications on droplet microfluidics in the past 15 years. Figure 2. Number of publications on droplet microfluidics in the past 15 years. DropletDroplet microfluidics microfluidics exhibits exhibits great great promise promise forfor various applications applications in a in broad a broad spectrum spectrum of fields of. fields. Droplet-basedDroplet-based platforms platforms have have been been employedemployed in inchemical chemical reactions, reactions, molecule molecule synthesis, synthesis,imaging, drug imaging, delivery, drug discovery, diagnostics, food, cell biology, and other applications. For example, they can drug delivery, drug discovery, diagnostics, food, cell biology, and other applications. For example, be applied in polymerase chain reaction (PCR)-based analyses, enzyme kinetics and protein they cancrysta bellization applied studies, in polymerase cell cultures, chain functional reaction component (PCR)-based encapsulation analyses,, and enzyme small kineticsmolecule and and protein crystallizationpolymeric studies, particle cellsynthesis cultures, [10–15] functional. The fundamental component features encapsulation, of these droplet and-based small microfluidic molecule and polymericplatforms particle with synthesishigh-level integration [10–15]. include The fundamental fine control of featuressmall sample of thesevolumes, droplet-based reduced amounts microfluidic of platformsreagents with and high-level samples,integration reduced analysis include times, fine improved control sensitivity, of small lowered sample detection volumes, limits, reduced increased amounts of reagentshigh and-throughput samples, screening, reduced enhanced analysis operational times, improved flexibility sensitivity, [9]. lowered detection limits, increased Many researchers have conducted fundamental studies on droplet microfluidics [16]. Sarvothaman et al. high-throughput screening, enhanced operational flexibility [9]. developed a strategy that involves using fluoroalkyl polyethylene glycol copolymers to reduce protein Manyadhesion, researchers which have causes conducted droplet movements fundamental to fail studies [17]. Seiffert on droplet et al. proposed microfluidics faster [droplet16]. Sarvothaman production et al. developedby delayed a strategy
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