Microfluidos  

Gerardo  Callegari  &  German  Drazer  Departamento  de  Ingeniería  Mecánica  y  Aeroespacial  

Rutgers,  La  Universidad  de  Nueva  Jersey  

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Contenidos  del  Curso  

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Martes:  0.    Introducción  al  curso.  1.  Introducción.  2.  Física  a  escala  microscópica    Miercoles:  3.  Hidrodinámica  a  escala  microscópica  4.  Transporte  y  régimen  de  Stokes  en  microfluidica.  Jueves:  5.  Difusión  Molecular  y  Transporte  de  Masa  6.  Dispersión  y  mezclado  en  microfluidica  Viernes:  7.  ElectrocinéXca  8.  Aplicaciones:  Separación  de  parZculas  suspendidas  Lunes:  9.  Métodos  de  fabricación  

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Formato  y  Evaluación    

15  hs    Contenidos  teóricos  (martes  15  a  viernes  18  de  10  a  13  y  viernes  18  de  14  a  17).    9  hs    Prác?cas  de  Laboratorio  (martes  22  al  jueves  24,  de  10  a  13)  

 Los  profesores  mostrarán  el  funcionamiento  de  algunos  disposiXvos.  Además  enseñarán  las  técnicas  de  fabricación,  paso  por  paso.  Los  alumnos  dispondrán  de  material  y  aprenderán  las  técnicas  para  elaborar  y  testear  sus  propios  disposiXvos.    4hs  Seminario  (exposición  de  alumnos,  lunes  21,  14-­‐18hs)  

 Los  alumnos  elegirán  una  publicación  de  una  lista  dada  por  los  profesores  y  expondrán  sus  ideas  principales  en  25  minutos  con  5  minutos  para  preguntas.    2  1/2hs  Evaluación  contenidos  teóricos  (martes    10-­‐12:30)    3  1/2hs  Evaluación  Laboratorio:  (martes    29,  13:30-­‐17)  Los  alumnos  habrán  ensamblado  su  propio  disposiXvo,  lo  conectarán  y  demostrarán.  

Breve  repaso  de  la  literatura  y  material  disponible    

impreso,  electrónico,  online…  

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Libro  disponible  online  

hbp://www.kirbyresearch.com/index.cfm/wrap/textbook/microfluidicsnanofluidics.html    Incluye  clases  en  youtube!  

Prof.  Brian  J.  Kirby  Departamento  de  Ingeniería  Mecánica  de  Cornell  

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6  

Libros  (impresos  y  pdfs)  

Clases  también  en  pdf  

7  

Algunas  revistas  interesantes  

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Otros  recursos  online  

Foro  online  donde  discuten  aspectos  experimentales  en  microfabricación    

hbp://blogs.rsc.org/chipsandXps/    

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Guías,  videos,  classes…    Prof.  Yager,  Universidad  de  Washington  hbp://faculty.washington.edu/yagerp/microfluidicstutorial/tutorialhome.htm    Prof.  Wereley,  Purdue  hbps://engineering.purdue.edu/~wereley/fundamentalsofmicrofluidics_files/v3_document.htm    Prof.  Whitesides,  Harvard  hbp://gmwgroup.harvard.edu/index.php    Prof.  Weitz,  Harvard  hbp://weitzlab.seas.harvard.edu/    Prof.  Craighead,  Cornell  hbp://www.hgc.cornell.edu/    Prof.  SanXago,  Stanford  hbp://microfluidics.stanford.edu/    Videos  @  Duke  hbp://microfluidics.ee.duke.edu//    

Microfluidos:  PerspecXvas    

What is microfluidics? It is the science and technology of systems that process or manipulate small (10–9 to 10–18 litres) amounts of fluids, using channels with dimensions of tens to hundreds of micrometres. The first applications of microfluidic technologies have been in analy-sis, for which they offer a number of useful capabilities: the ability to use very small quantities of samples and reagents, and to carry out separations and detections with high resolution and sensitivity; low cost; short times for analysis; and small footprints for the analytical devices1. Microfluidics exploits both its most obvious characteristic — small size — and less obvious characteristics of fluids in microchan-nels, such as laminar flow. It offers fundamentally new capabilities in the control of concentrations of molecules in space and time.

As a technology, microfluidics seems almost too good to be true: it offers so many advantages and so few disadvantages (at least in its major applications in analysis). But it has not yet become widely used. Why not? Why is every biochemistry laboratory not littered with ‘labs on chips’? Why does every patient not monitor his or her condition using micro-fluidic home-test systems? The answers are not yet clear. I am convinced that microfluidic technology will become a major theme in the analysis, and perhaps synthesis, of molecules: the advantages it offers are too com-pelling to let pass. Having said that, the answers to questions concerning the time and circumstances required for microfluidics to develop into a major new technology are important not just for this field, but also for other new technologies struggling to make it into the big time.

The origins and the future of microfluidicsGeorge M. Whitesides1

The manipulation of fluids in channels with dimensions of tens of micrometres — microfluidics — has emerged as a distinct new field. Microfluidics has the potential to influence subject areas from chemical synthesis and biological analysis to optics and information technology. But the field is still at an early stage of development. Even as the basic science and technological demonstrations develop, other problems must be addressed: choosing and focusing on initial applications, and developing strategies to complete the cycle of development, including commercialization. The solutions to these problems will require imagination and ingenuity.

1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.

The field of microfluidics has four parents: molecular analysis, biodefence, molecular biology and microelectronics. First came analysis. The distant origins of microfluidics lie in microanalytical methods — gas-phase chromatography (GPC), high-pressure liquid chromatography (HPLC) and capillary electrophoresis (CE) — which, in capillary format, revolutionized chemical analysis. These methods (combined with the power of the laser in optical detection) made it possible to simultaneously achieve high sensitivity and high resolution using very small amounts of sample. With the successes of these microanalytical methods, it seemed obvious to develop new, more compact and more versatile formats for them, and to look for other applications of microscale methods in chemistry and biochemistry.

A second, different, motivation for the development of microfluidic systems came with the realization — after the end of the cold war — that chemical and biological weapons posed major military and terrorist threats. To counter these threats, the Defense Advanced Research Projects Agency (DARPA) of the US Department of Defense supported a series of programmes in the 1990s aimed at developing field-deployable microfluidic systems designed to serve as detec-tors for chemical and biological threats. These programmes were the main stimulus for the rapid growth of academic microfluidic technology.

The third motivational force came from the field of molecular biology. The explosion of genomics in the 1980s, followed by the advent of other areas of microanalysis related to molecular biology, such as high-throughput DNA sequencing, required analytical methods with much greater throughput, and higher sensitivity and resolution than had previously been contemplated in biology. Microfluidics offered approaches to overcome these problems.

The fourth contribution was from microelectronics. The origi-nal hope of microfluidics was that photolithography and associated technologies that had been so successful in silicon microelectronics, and in microelectromechanical systems (MEMS), would be directly applicable to microfluidics. Some of the earliest work in fluidic micro-systems did, in fact, use silicon and glass, but these materials have largely been displaced by plastics. For analyses of biological samples in water, devices fabricated in glass and silicon are usually unneces-sary or inappropriate. Silicon, in particular, is expensive, and opaque to visible and ultraviolet light, so cannot be used with conventional optical methods of detection. It is easier to fabricate the components required for microanalytical systems — especially pumps and valves — in elastomers than in rigid materials. Neither glass nor silicon has all the properties (especially permeability to gases) required for work with living mammalian cells.

Figure 1 | A microfluidic chemostat. Microfluidic devices — here, a microfluidic chemostat used to study the growth of microbial populations — now routinely incorporate intricate plumbing. This device includes a high density of pneumatic valves. The colours are dyes introduced to trace the channels. (Image reproduced, with permission, from ref. 65.)

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Nature Publishing Group ©2006

G.  M.  Whitesides:    -­‐  Pionero  en  microfluidos  -­‐  Introdujo  la  idea  de  fabricación  en  PDMS  

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PerspecXvas    

Introduction

The ability to create structures and patterns on micron andsmaller length scales has triggered a wide range of scientif-ic investigations, as well as the development of many

devices to transport and manipulate fluids and pattern surfaces.The engineering paradigm, therefore, turns to design, manipula-tion, and control on length scales that are increasingly approachingthe molecular. These types of investigations involving fluids,broadly identified under the theme of microfluidics, have rekindledinterest in a classical area of fluid dynamics: low-Reynolds-num-ber flows. The objective of this article is to highlight some avenuesof research and development in microfluidics. Given the limitedformat of this article, extensive referencing is not possible, butresearch papers with novel ideas in this field are appearing at arapid pace. One particularly interesting aspect of the research isthe imaginative use of engineering, chemistry and physics toachieve devices with specific functions.

Modern developments in the design and utilization of microflu-idic devices for fluid transport have found many applications, rang-ing from the life sciences industries for pharmaceuticals and bio-medicine (drug design, delivery and detection, diagnostic devices)to industrial applications of combinatorial synthesis (such as rapidchemical analyses and high throughput screening). In other branch-es of medicine, new paradigms for noninvasive diagnostics andsurgery are enabled by small (possibly implanted or ingested)microdevices. As an example of the rapidly increasing demand forbiomedical microdevices, the biochip market was $400M in theyear 2000 and is expected to increase fivefold by 2005 (Jain, 2000).Other areas of applications for microdevices for the transport of liq-uids and gases include the aerospace and automotive industries,microreaction engineering, printing, and optical applications. Novelelectrical devices assembled using microfluidic components arealso a possible area for technological innovation. Two recent arti-cles in the AIChE Journal’s “Perspectives” column provide exam-ples of some of these applications (Jensen, 1999; Langer, 2000).

Generally, microfluidics refers to devices or flow configurationsthat have the smallest design feature on the scale of a micron orlarger. Frequently, this means rectangular channels with cross-sec-tional dimensions on the order of tens or hundreds of microns. Formost cases involving the flow of small molecule liquids like water,

this scale is well suited to the standard continuum description oftransport processes (such equations of change as the Cauchy stressequations supplemented by appropriate constitutive equations andbody forces), even though surface forces play a more important rolethan is usual. The development of mechanical structures on thenanometer length scale is another area of rapid progress. Sincemany of these nanofabrication processes take place in the liquidstate, the understanding of “nanofluidics” is a research challengethat will likely involve contributions from continuum, statistical,and molecular mechanics. In general, the design paradigm faced bythe engineer is scale-down rather than the more familiar scale-up.

Micro- and nanodevices are useful because they allow manipula-tion with fast response times, they can handle small fluid volumes,sense and control flows and pattern substrates on small length scales,and, what promises to be very important, they can selectively addressthe cellular scale. Traditionally, silicon micromachining methodshave been used to make micron-scale electrical and mechanicaldevices from silicon and glass. More recently, elastomeric materialshave been used (McDonald et al., 2000). The latter systems offerpotential advantages of faster design times, low cost, the ability tofabricate nanoscale features, and the possibility of deformable shapes(Quake and Scherer, 2000). Both fabrication techniques will likelycontinue to play important roles in future applications.

Many challenging research and design questions are posed bymicro- and nanofluidic systems. Because the field has seen rapidrecent development, several review articles have already been writ-ten (e.g., Gad-el-Hak, 1999; Ho, 2001). Most of these articles havefocused on specific microdevices (Ho and Tai, 1998; Quake andScherer, 2000; Whitesides and Stroock, 2001), such as the designof valves, pumps, actuators, mixers and reactors, sensors, andthree-dimensional networks of channels. Many of these ideas areimportant in light of the development of the lab-on-a-chip concept(or micro-total-analysis systems), where transport processes,including mixing, reactions, separations, and manipulation of par-ticles, are being applied on smaller scales than traditional engi-neering technologies. Another area of significant interest is inactive control, for example, manipulating the boundary layer inhigh-speed flow; these applications are of less interest to mostchemical engineers and will not be discussed further.

In addition to the design of new devices, there are research ques-tions raised concerning transport processes, in particular the motion

Microfluidics: Basic Issues, Applications, and Challenges

H. A. StoneDiv. of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138

S. KimLilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285

PPeerrssppeeccttiivvee

1250 June 2001 Vol. 47, No. 6 AIChE Journal

Introduction

The ability to create structures and patterns on micron andsmaller length scales has triggered a wide range of scientif-ic investigations, as well as the development of many

devices to transport and manipulate fluids and pattern surfaces.The engineering paradigm, therefore, turns to design, manipula-tion, and control on length scales that are increasingly approachingthe molecular. These types of investigations involving fluids,broadly identified under the theme of microfluidics, have rekindledinterest in a classical area of fluid dynamics: low-Reynolds-num-ber flows. The objective of this article is to highlight some avenuesof research and development in microfluidics. Given the limitedformat of this article, extensive referencing is not possible, butresearch papers with novel ideas in this field are appearing at arapid pace. One particularly interesting aspect of the research isthe imaginative use of engineering, chemistry and physics toachieve devices with specific functions.

Modern developments in the design and utilization of microflu-idic devices for fluid transport have found many applications, rang-ing from the life sciences industries for pharmaceuticals and bio-medicine (drug design, delivery and detection, diagnostic devices)to industrial applications of combinatorial synthesis (such as rapidchemical analyses and high throughput screening). In other branch-es of medicine, new paradigms for noninvasive diagnostics andsurgery are enabled by small (possibly implanted or ingested)microdevices. As an example of the rapidly increasing demand forbiomedical microdevices, the biochip market was $400M in theyear 2000 and is expected to increase fivefold by 2005 (Jain, 2000).Other areas of applications for microdevices for the transport of liq-uids and gases include the aerospace and automotive industries,microreaction engineering, printing, and optical applications. Novelelectrical devices assembled using microfluidic components arealso a possible area for technological innovation. Two recent arti-cles in the AIChE Journal’s “Perspectives” column provide exam-ples of some of these applications (Jensen, 1999; Langer, 2000).

Generally, microfluidics refers to devices or flow configurationsthat have the smallest design feature on the scale of a micron orlarger. Frequently, this means rectangular channels with cross-sec-tional dimensions on the order of tens or hundreds of microns. Formost cases involving the flow of small molecule liquids like water,

this scale is well suited to the standard continuum description oftransport processes (such equations of change as the Cauchy stressequations supplemented by appropriate constitutive equations andbody forces), even though surface forces play a more important rolethan is usual. The development of mechanical structures on thenanometer length scale is another area of rapid progress. Sincemany of these nanofabrication processes take place in the liquidstate, the understanding of “nanofluidics” is a research challengethat will likely involve contributions from continuum, statistical,and molecular mechanics. In general, the design paradigm faced bythe engineer is scale-down rather than the more familiar scale-up.

Micro- and nanodevices are useful because they allow manipula-tion with fast response times, they can handle small fluid volumes,sense and control flows and pattern substrates on small length scales,and, what promises to be very important, they can selectively addressthe cellular scale. Traditionally, silicon micromachining methodshave been used to make micron-scale electrical and mechanicaldevices from silicon and glass. More recently, elastomeric materialshave been used (McDonald et al., 2000). The latter systems offerpotential advantages of faster design times, low cost, the ability tofabricate nanoscale features, and the possibility of deformable shapes(Quake and Scherer, 2000). Both fabrication techniques will likelycontinue to play important roles in future applications.

Many challenging research and design questions are posed bymicro- and nanofluidic systems. Because the field has seen rapidrecent development, several review articles have already been writ-ten (e.g., Gad-el-Hak, 1999; Ho, 2001). Most of these articles havefocused on specific microdevices (Ho and Tai, 1998; Quake andScherer, 2000; Whitesides and Stroock, 2001), such as the designof valves, pumps, actuators, mixers and reactors, sensors, andthree-dimensional networks of channels. Many of these ideas areimportant in light of the development of the lab-on-a-chip concept(or micro-total-analysis systems), where transport processes,including mixing, reactions, separations, and manipulation of par-ticles, are being applied on smaller scales than traditional engi-neering technologies. Another area of significant interest is inactive control, for example, manipulating the boundary layer inhigh-speed flow; these applications are of less interest to mostchemical engineers and will not be discussed further.

In addition to the design of new devices, there are research ques-tions raised concerning transport processes, in particular the motion

Microfluidics: Basic Issues, Applications, and Challenges

H. A. StoneDiv. of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138

S. KimLilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285

PPeerrssppeeccttiivvee

1250 June 2001 Vol. 47, No. 6 AIChE Journal

H.  A.  Stone:  -­‐  Mecánica  de  fluidos  -­‐  Muchas  contribuciones  en  temas  variados  

11  

S.  Kim:  -­‐  Mecánica  de  fluidos.  Libro:  Microhydrodynamics  

Microfluidos/Lab  on  a  chip:  Reviews  

13 Dec 2003 18:58 AR AR203-FL36-15.tex AR203-FL36-15.sgm LaTeX2e(2002/01/18) P1: IBD10.1146/annurev.fluid.36.050802.122124

Annu. Rev. Fluid Mech. 2004. 36:381–411doi: 10.1146/annurev.fluid.36.050802.122124

Copyright c� 2004 by Annual Reviews. All rights reserved

ENGINEERING FLOWSIN SMALLDEVICES:Microfluidics Toward a Lab-on-a-Chip

H.A. Stone,1 A.D. Stroock,2 and A. Ajdari31Division of Engineering and Applied Sciences, Harvard University, Cambridge,Massachusetts 02138; email: has@deas.harvard.edu2School of Chemical and Biomolecular Engineering, Cornell University, Ithaca,New York 14853; email: ads10@cornell.edu3Physico-Chimie Theorique, UMR CNRS-ESPCI 7083, ESPCI, 10 rue Vauquelin,75005 Paris, France; email: armand@turner.pct.espci.fr

Key Words low-Reynolds-number hydrodynamics, electro-osmosis, nanofluidics,microdevices, mixing

■ Abstract Microfluidic devices formanipulating fluids arewidespread andfindinguses in many scientific and industrial contexts. Their design often requires unusualgeometries and the interplay of multiple physical effects such as pressure gradients,electrokinetics, and capillarity. These circumstances lead to interesting variants ofwell-studied fluid dynamical problems and some new fluid responses. We provide anoverviewof flows inmicrodeviceswith focus on electrokinetics,mixing and dispersion,and multiphase flows. We highlight topics important for the description of the fluiddynamics: driving forces, geometry, and the chemical characteristics of surfaces.

1. INTRODUCTION

Microfluidics refers to devices and methods for controlling and manipulating fluidflows with length scales less than a millimeter. Studies of such fluid-related phe-nomena have long been part of the fluid mechanical component of colloid science(e.g., Russel et al. 1989) and plant biology (Canny 1977) and draw on many clas-sical features of the dynamics of viscous flows (e.g., Happel & Brenner 1965,Batchelor 1977). However, the subject has received enormous recent attention be-cause of (a) the availability of methods for fabricating individual and integratedflow configurations with length scales on the order of tens and hundreds of micronsand smaller (e.g., Ho&Tai 1998, Stone&Kim 2001,Whitesides& Stroock 2001),(b) rapid developments in biology and biotechnology for which manipulations onthe cellular length scale (and below) and the ability to detect small quantitiesand manipulate very small volumes (typically less than 1 microliter) offer advan-tages (Voldman et al. 1999, Jain 2000, Beebe et al. 2002), (c) the quest for cheapportable devices able to perform simple analytical tasks, and (d) the potential use of

0066-4189/04/0115-0381$14.00 381

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Reviews  

Microfluidics: Fluid physics at the nanoliter scale

Todd M. Squires*

Departments of Physics and Applied & Computational Mathematics, California Institute ofTechnology, Pasadena, California 91125, USA

Stephen R. Quake†

Departments of Applied Physics and Physics, California Institute of Technology,Pasadena, California 91125, USA

!Published 6 October 2005"

Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor,and time required for calculations. Microfluidic systems hold similar promise for the large-scaleautomation of chemistry and biology, suggesting the possibility of numerous experiments performedrapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a visionwill be realized, significant progress has been achieved, and various applications of significant scientificand practical interest have been developed. Here a review of the physics of small volumes !nanoliters"of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relativeimportance of various physical phenomena. Specifically, this review explores the Reynolds numberRe, addressing inertial effects; the Péclet number Pe, which concerns convective and diffusivetransport; the capillary number Ca expressing the importance of interfacial tension; the Deborah,Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformablemicrostructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describingdensity-driven flows; and the Knudsen number, describing the importance of noncontinuum moleculareffects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherentin microfluidics mean that the influence of boundaries is typically significant. A variety of strategieshave been developed to manipulate fluids by exploiting boundary effects; among these areelectrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe thephysics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simplescaling arguments, with the hopes of developing an intuitive sense for this occasionallycounterintuitive world.

CONTENTS

I. Introduction 978II. Dimensionless Numbers in Microfluidics 979

A. The Reynolds number: Inertial irrelevance 981B. The Péclet number and the problem of mixing 982

1. Sensing, filtering, and fabricating withparallel laminar flows 983

a. T sensor 983b. Filtration without membranes 983c. Fabricating and interrogating using multiple

laminar streams 9842. Fighting diffusion: Particle separations 9853. Beating diffusion: When mixing matters 985a. Taylor dispersion 986b. Rotary mixer 987c. Mixing by chaotic advection 988

C. The capillary number: Free-surface deformations 9891. Droplet formation in two-phase flows 989

2. Fluid control using patterned surfaces 9903. Fluid manipulation with capillary forces 991a. Solid-liquid interfacial energy manipulation 991b. Surfaces with wettability gradients 992

i. Thermal gradients #Fig. 19!a"$ 992ii. Reactive fluids #Fig. 19!b"$ 992

iii. Self-propelling liquid bi-slugs #Fig. 19!c"$ 992iv. Optowetting #Fig. 19!d"$ 992v. Electrowetting 993

vi. Dielectrophoresis 994c. Liquid-liquid surface tension manipulation 994

D. The Weissenberg and Deborah numbers: Let themountains flow 995

1. Microfluidic single-polymer studies 9982. Elastic instabilities 9983. Controlled polymer deformation for

separations 1000E. The Grashof and Rayleigh numbers: Tracer-driven

flows 10011. Protein crystallization 10022. Polymerase chain reaction !PCR" 10043. Electrohydrodynamic instabilities 1004

F. The Knudsen number: When molecules matter 10051. Molecular effects in gases 10052. Fluid slip over nonwetting surfaces 1006

III. Driving Flows at the Boundaries 1007A. Electrokinetic effects 1007

1. Electrostatics in ionic solutions 1007

*Present address: Department of Chemical Engineering,University of California, Santa Barbara, CA 93106. Electronicaddress: squires@engineering.ucsb.edu

†Present address: Department of Bioengineering, StanfordUniversity, Stanford, CA 94305. Electronic address:quake@stanford.edu

REVIEWS OF MODERN PHYSICS, VOLUME 77, JULY 2005

0034-6861/2005/77!3"/977!50"/$50.00 ©2005 The American Physical Society977

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IOP PUBLISHING REPORTS ON PROGRESS IN PHYSICS

Rep. Prog. Phys. 75 (2012) 016601 (41pp) doi:10.1088/0034-4885/75/1/016601

Droplet based microfluidicsRalf Seemann1,2, Martin Brinkmann2, Thomas Pfohl2,3 andStephan Herminghaus2

1 Experimental Physics, Saarland University, D-66123 Saarbrucken, Germany2 Max Planck Institute for Dynamics and Self-Organization, D-37018 Gottingen, Germany3 Department of Chemistry, University of Basel, CH-4056 Basel, Switzerland

E-mail: ralf.seemann@physik.uni-saarland.de

Received 1 November 2010, in final form 22 September 2011Published 22 December 2011Online at stacks.iop.org/RoPP/75/016601

AbstractDroplet based microfluidics is a rapidly growing interdisciplinary field of research combiningsoft matter physics, biochemistry and microsystems engineering. Its applications range fromfast analytical systems or the synthesis of advanced materials to protein crystallization andbiological assays for living cells. Precise control of droplet volumes and reliable manipulationof individual droplets such as coalescence, mixing of their contents, and sorting incombination with fast analysis tools allow us to perform chemical reactions inside the dropletsunder defined conditions. In this paper, we will review available drop generation andmanipulation techniques. The main focus of this review is not to be comprehensive andexplain all techniques in great detail but to identify and shed light on similarities andunderlying physical principles. Since geometry and wetting properties of the microfluidicchannels are crucial factors for droplet generation, we also briefly describe typical devicefabrication methods in droplet based microfluidics. Examples of applications and reactionschemes which rely on the discussed manipulation techniques are also presented, such as thefabrication of special materials and biophysical experiments.

(Some figures may appear in colour only in the online journal)

This article was invited by C F Schmidt.

Contents

1. Introduction 22. Device fabrications 3

2.1. Standard device fabrication technique inscience and research 3

2.2. Special device properties for droplet basedmicrofluidics 3

2.3. Alternative device materials 43. Droplet formation 5

3.1. Carrier phases and surfactants 53.2. From bulk emulsification to microfluidic

droplet production 63.3. T-junction 63.4. Flow focusing 73.5. Step emulsification 83.6. Unconventional techniques and fluids 9

4. Interfacial instabilities and energetics of dropletproduction 94.1. Energy assessment of droplet generation 104.2. Droplet formation 10

4.3. Droplet formation in microfluidic devices 124.4. Hydrodynamic models and droplet size scaling 14

5. Droplet manipulation and sorting 155.1. Confinement and hydraulic resistance 155.2. Dielectrophoresis 165.3. Magnetic fields 175.4. Thermocapillary effect 175.5. Electrorheological fluids 185.6. Mechanical valves 185.7. Surface acoustic streaming 185.8. Droplet detecting and sensing 185.9. Static and dynamic droplet packings 19

6. Droplet coalescence, splitting, and mixing 206.1. Droplet coalescence using special channel

geometries and flow conditions 206.2. Droplet coalescence using particular

properties of liquids 216.3. Droplet coalescence using the

thermocapillary effect 21

0034-4885/12/016601+41$88.00 1 © 2012 IOP Publishing Ltd Printed in the UK & the USA