cience 13 (2008) 206–216www.elsevier.com/locate/cocis

Current Opinion in Colloid & Interface S

Controlled production of emulsions and particles by milli- andmicrofluidic techniques☆

W. Engl a, R. Backov b,1, P. Panizza c,⁎

a Department of Chemical Engineering, Yale University, P.O. Box 208284 New-Haven Connecticut 06520, USAb Centre de Recherche Paul Pascal, UPR CNRS 8641, 115 Avenue A. Schweitzer, 33600, Pessac, France

c Groupe Matière Condensée et Matériaux, UMR CNRS 6626, Université Rennes 1, Campus Beaulieu, 35000, Rennes, France

Received 14 July 2007; received in revised form 10 September 2007; accepted 19 September 2007Available online 26 September 2007

Abstract

The recent developments of soft lithography and microfluidic techniques now permit the manipulation of small quantities of fluids with verygood control and reproducibility. These advances open a new “bottom-up” route to emulsification that paves the way to the fabrication ofcalibrated hierarchically organized emulsions and particles. In this article, we describe the microfluidic techniques elaborated for engineeringemulsions and new dispersed materials and discuss their advantages over “top-down” approaches. We review and comment the high potentialitiesthese techniques offer to emulsion and colloid science, to the development of high-throughput set-ups for chemistry, physics and biology. Weillustrate them through a few examples taken from the current literature.© 2007 Elsevier Ltd. All rights reserved.

1. Introduction

Emulsions are metastable dispersions of one fluid in anotherimmiscible. They are ubiquitous to our daily life since they con-cern many areas, as different as the food, paints, pharmaceutical,polymers, colloids or oil industry, where they occur either as endproducts or during the processing of products [1,2]. As endproducts, emulsions enable to avoid using organic solvents whenprocessing hydrophobic coatings for paints, to vehicle viscousdispersed phases or to encapsulate, transport and vectorize activemolecules. In product processing, emulsion droplets can also beused as reactors to engineer hierarchically organized dispersedmaterials such as for instancemesoporous silica capsules, polymerand ceramic spherical particles. Since most physical properties ofthese materials are size dependent, controlling their monodisper-sity as well as their uniformity in shapes and composition is a

☆ Major recent advances: Microchannel technology is a new “bottom-up”approach for emulsification and colloid science. Recent advances in scaling updroplet production and dimensions of microdevices yield promising prospectsfor transposing this technique into Industry.⁎ Corresponding author. Tel.: +33 223235700; fax: +33 223236717.E-mail addresses: will.engl@yale.edu (W. Engl),

backov@crpp-bordeaux.cnrs.fr (R. Backov), pascal.panizza@univ-rennes1.fr(P. Panizza).1 Tel.: +33 556845630; fax: +33 556845000.

1359-0294/$ - see front matter © 2007 Elsevier Ltd. All rights reserved.doi:10.1016/j.cocis.2007.09.003

necessity. From a practical point of view, monodispersity alsoenhances emulsion stability. As a result of many years of research,several emulsification techniques that produce emulsions withnarrow droplet size distributions now exist. The proper choice ofthe process conditions is dictated by the value of the droplet meansize to reach. Thus, well calibrated fine (50 nm to 1μm) emulsionsare industrially produced by high-pressure microfluidic injection[3], whereas droplets of intermediate sizes (1 to several μm) areobtained using narrowgap shear devices [4]. All these “top-down”techniques handle huge quantity of droplets at the same time. Incontrast, the recent advents made in microtechnologies and inmicrofluidics [5] these last few years, now open a new “bottom-up” approach to emulsification. The goal of this review is to1) describe and understand the numerous advantages such amethodology presents, and 2) discuss the numerous prospects itopens for material science and science. We first describe thevarious microfluidic devices and their flow configurations used toproduce calibrated droplets.

2. Microfluidics: a new “bottom-up” approachto emulsification

The high potentialities of the microfluidic fabrication ap-proach stem from the possibility to generate highly monodisperse

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droplets, one at a time with an incomparable degree of controlover size. This method leads to extremely narrow-sized dis-tribution since no stabilization over coalescence is needed ascollisions between droplets are suppressed during the dropletformation process and the transport in the channels.

2.1. Droplet production

Several microchannel techniques exist to generate calibrateddroplets depending on the type of technology used for thefabrication of the microfluidic devices. They are depicted inFig. 1. With planar chips, designed using soft lithography orlaser etching fabrication methods, two main configurationsare now commonly used. Periodic trains of monodispersedroplets can form by colliding two immiscible fluids streams ata T-shaped junction (Fig. 1a) [6,7] or by using a flow focusingmicrodevice (FFD) where a 2D planar co-axial stream is forcedto flow through a small orifice (Fig. 1b) [8]. With both con-figurations, experiments can be performed either by imposingthe flow rates or the pressure drop of the various streams. Ineach case, the mechanism of droplet formation which resultsfrom a subtle interplay between confinement, viscous andcapillary stresses leads to the production of periodic trains madeof monodisperse droplets with extremely narrow size distribu-tion. The mean droplet size can be fine-tuned by adjusting theflow parameters of the various streams from 10 μm, typicallythe lateral size of the channels used for the experiment, up to afew hundreds of microns. It decreases with the flow rate and

Fig. 1. Shown are different strategies used to generate monodisperse emulsions dropjunction in planar microfluidic devices, b) flow focusing microfluidic device and c)

viscosity of the continuous phase and increases with the flowrate of the dispersed phase [9–11]. The dispersion in dropletsize is extremely low as the coefficient of variation (CV) de-fined as the ratio of the standard deviation of the droplet sizeover the mean size is typically lower than 5%. To decrease thedroplet size, one may break the drops into controlled daughterdroplets at a simple T junction [12] or at a junction of anyarbitrary angle [13]. This passive method of break-up is verypowerful since the size ratio of daughter droplets can be ad-justed by modifying the hydrodynamic resistances of the twojunction's outlets. It can be carried out in succession withoutincreasing the polydispersity of the droplets until their dimen-sions are larger than the channel dimensions.

A drawback of planar devices is that prior to droplet for-mation, both the to-be-dispersed and the continuous phases arein contact with the channel walls. It follows that the wettingproperties of the materials constituting the channels play a keyrole since they control the nature and stability of the dropletswith respect to phase inversion [14,15]. Thus, when oil pref-erentially wets the channels, as for instance with polydimethyl-siloxane (PDMS) based microdevices, stable O/W dropletscannot be prepared. To avoid this problem, it is necessary tomodify the wetting properties of the channels at the locationwhere droplet are formed for instance by applying a specificsurface treatment [16,17].

Droplets with comparable narrow size distribution can also begenerated with non-planar microfluidic devices which do notnecessitate any expensive technologies such as soft lithography

lets one by one and images of the droplets obtained with these techniques: a) Tdouble capillary millifluidic set-up.

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or laser etching techniques for their design. One may thus extendthe flow focusing method to 3D, by injecting the disperse fluidwith a syringe pump through a capillary tube with an innerdiameter of typically a hundred microns, inside a chamberpressurized by a continuous supply of another immiscible fluid[18,19]. When the tip of the feeding capillary tube faces thesmall exit orifice of the chambers, the outer fluid stream focusesand forces the injected disperse fluid to exit the chamber throughthe orifice producing a microjet. As a result of a capillaryinstability, the microjet then breaks up into a chain of nearlymonodisperse droplets, much smaller than the exit orifice.

Monodisperse drops in larger sizes can also be generatedusing double capillary devices, by injecting the disperse phasethrough the co-flowing matrix fluid (Fig. 1c) [20–23]. The set-up consists of a blunt calibrated needle with a diameter φ oftypically a few hundreds of micrometers, centred to a cylindricalglass capillary with a diameter of D≥φ.Using independentsyringe pumps, two immiscible fluids are respectively infusedthrough both the needle and the annular gap between it and theinternal capillary wall. The flow rates are independently con-trolled and adjusted in order to form monodisperse droplets ofthe dispersed phase in the continuous one. Both W/O and O/Wdroplets can be prepared provided that the wetting properties ofthe internal capillary wall are compatible with the continuousphase. With glass surfaces, this can easily be done. Such devices

Fig. 2. Shown are illustrations of the different microfluidic techniques used to producstand respectively for the inner, middle and outer fluids. a) The two steps drop break-uare reprinted from “Production of monodisperse double emulsions by two steps drop bwith permission from ACS. b) 3D equivalent of the double step drop break-up tech“Controlled production of hierarchically organized large emulsions and particles usinPhysicochem. Eg. Aspects (2007), doi:10.1016/j.colsurfa.2007.06.026 with permissioand form monodisperse double emulsions or core-shells (images are reprinted from “A.S. et al., Science, 2005, 308:537–541 with permission from AAS.

then allow the extension of the preparation of well calibratedemulsions up to sizes of a few millimeters. Emulsions withsmaller sizes (typically a few tens micrometers) can be generatedby using a double capillary device which consists of a cylindricalcapillary tubes co-axially nested within a square glass [24••].

2.2. Fabrication of double emulsions

Microfluidic emulsification techniques offer a promisingroute to the fabrication of monodisperse double emulsions and tothe tailoring of complex architecture. It is the only techniquewhich enables to encapsulate 100% of an active product in asingle step and to control the nature of the encapsulated objects.To illustrate this, let us consider the fabrication of double emul-sions, which consists of emulsion drops containing smallerdroplets inside. In batches, the fabrication process usually re-quires two step processes: an emulsification of the inner dropletsin the middle fluid followed by a second emulsification fordispersion [2]. In microfluidic planar devices, calibrated doubleemulsions can be generated with a mere succession of two Tjunctions as depicted in Fig. 2a [25••]. Aqueous droplets ofuniform size are formed at a T junction by colliding water andoily flows. The resulting periodic train of W/O droplets is thendirected towards another T junction placed downstream, to formmonodisperse organic drops containing aqueous droplets within

e double emulsions and corresponding images of emulsion droplets. I, M and Op method using a planar device. Photograph of the droplet formation mechanismreak-up in microfluidic devices”, Okushima S., Langmuir, 2004, 20:9905–9908.nique using double capillary devices. Images of the droplets are reprinted fromg assemblies on line of co-axial flow devices”, Panizza P. et al., Colloids Surf. A:n from Elsevier and c) microcapillary device used to break-up concentric streamsMonodisperse double emulsions generated from a microcapillarydevice”, Utada

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an external aqueous phase. The sizes of drops and inner dropletscan be fine-tuned independently by adjusting the flow ratevalues of the various streams. Moreover, the number of en-capsulated droplets can also be monitored independentlyfrom their size and that of the drops. This can be achievedby performing an additional injection or withdrawing of thecontinuous phase between the two T junctions using another Tjunction. This enables to dilute or concentrate the initial W/Odroplet train before its encapsulation without altering the dropletsize. From a practical point of view, double W/O/W emulsionscan only be prepared provided that the upstream anddownstream T junctions, used to form droplets and drops arerespectively hydrophobic and hydrophilic. O/W/O emulsionsare prepared by inverting the wetting properties of these twojunctions. This method is very versatile. It can successfully betransposed to 3D as shown in Fig. 2b and extended to morethan two steps [26••]. W/O/W/O macroemulsions can then beprepared using an assembly of glass double capillary devicesconnected to each other by means of Plexiglas home-mademodules. A promising feature of this multiple steps emulsifica-tion technique is the possibility to encapsulate in a same drop,droplets of various compositions and to control their sizes andrespective ratio (Fig. 2a). When two droplet trains having thesame continuous phase but droplets of different compositionmeet at a T junction, they form a periodic alternated train [27].Monodisperse drops containing droplets of different composi-tion are generated by injecting this droplet train through theneedle of another double capillary device placed downstream.The size of the internal droplets, their respective number as wellas the size of the drops can be tuned continuously and in-dependently by changing the flow conditions [25••, 26••].

Double emulsions can also be generated in a single stepprocess using a different strategy. The idea consists of desta-bilizing a liquid thread of two or more parallel co-flowingstreams in order to form monodisperse drops containingdroplets (Fig. 2c). This can be achieved for instance in planarmicrofluidic devices by forcing this liquid thread through thesmall orifice of a flow focusing geometry [28••]. A similarapproach has successfully been transposed to 3D by Utada etal. Their device consists of two cylindrical glass capillarytubes co-axially nested within an outer square glass tube andtapered at their facing ends as depicted in Fig. 2c [24••]Three different fluids are simultaneously injected in the sys-tem at controlled flow rates. The innermost fluid is pumpedthrough one of the inner tube, whereas the middle fluid isinjected through the outer square capillary region, in the samedirection. Since the outermost fluid is pumped through theouter co-axial region of the opposite direction, all fluids areforced through the exit orifice formed by the other innercylindrical tube. The thread breaks up to produce doubleemulsion in the collecting tube. The size of the inner andouter droplets as well as the number of inner droplets can bemonitored and varied with a very good degree of control.This technique offers an incomparable step forward for theproduction of core-shell droplets with a control over bothdroplet size and shell thickness [29]. For instance, core-shelldroplets with a ratio of shell over size as low as 3% have been

prepared. By photopolymerizing a polymer in the interme-diate fluid, these structures can be used to form capsules.They can also be transformed into polymer vesicles by usingfor the middle phase a volatile fluid where diblock co-poly-mers are dissolved [30].

2.3. Towards the tailoring of complex dispersed materials

Synthesis of solid particles in planar microfluidic reactors isan excellent route to particles with unconventional shape andmorphologies. In batches, dispersed materials obtained by usingdroplets as microreactors are generally spherical systems sincethe minimization of interfacial energy leads to spherical shapesduring most syntheses, whether they are polymer latexes formedthrough emulsion polymerization or droplets formed using shearflows in microfluidic devices. This inherent difficulty canhowever be circumvented by using a microfluidic scheme whichpermits good controls of the droplets geometrical and concen-tration environments. In 2004–2005, several papers have thusdemonstrated the possibility to generate non-spherical particles,such as disks, ellipsoids or rods by photopolymerizing monomerdroplets on the “fly” while flowing in constrained geometries asillustrated in Fig. 3 [31–33]. Monodisperse monomer dropletswith different volume are first produced using a flow focusingdevice by varying the flow rates of the continuous and dropletphases. These droplets are then forced to flow through a narrowchannel in which polymerization takes place. Because ofconfinement, droplets adopt a non-spherical shape, dictated bya relationship between w and h, the two lateral dimensions of thechannel and d, the diameter of an undeformed droplet. At lowcapillary numbers, for wNd and hNd, the droplets minimizetheir surface energy by taking a spherical shape whereas forhNdNw, and for situations where dNw and dNh, confinementsuppresses the relaxation of their shape into spheres, and thedroplets respectively deform into discoid or rod shapes. Withthis approach, the aspect ratio of the non-spherical droplets canbe conveniently monitored by changing the ratio between thedroplet volume and the dimensions of the microchannels.

The fabrication of solid particles using continuous micro-fluidic reactors exhibit many features that distinguish it frombatch polymerization of monodisperse emulsions produced by“top-down” emulsification methods [2–4]. The polydispersityof the solid particles obtained using microfluidic tools is com-parable to that of the droplets prior to hardening, typically below3%. This value is therefore much narrower than in the batchmethods, where coalescence and Oswald ripening occur. Inmicrofluidic reactors, no stabilization against coalescence ofmonomer droplets is necessary since their collisions aresuppressed. Furthermore, polymerization in a confined geom-etry allows for the production of non-spherical shapes such asdisks, rods or tubes with an independent and very good controlover volume, shapes and aspect ratio. The ability to generate andto control composition gradients with microfluidic devicesoffers a unique route to synthesize colloids with complex archi-tectures. A good illustrative example of this concept concernsthe production of Janus particles obtained by breaking up aliquid thread of two parallel co-flowing streams of monomer

Fig. 3. Schematic (a–c) and optical microscopy (a′–c′) images of particles obtained from with polymerization of deformed monomer droplets with different shapes:microspheres (a, a′), disks (b, b′) and rods (c, c′). Reprinted from “Continuousmicrofluidic reactors for polymer particles”, SeoM. et al., Langmuir, 2005, 11614–11622with permission from ACS.

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of two immiscible polymer solutions that is forced through anarrow orifice (Fig. 4). The resulting droplets present a Janus-like structure, with an approximate flat interface between theadjacent polymer phases that can be solidified with an UVexposition, performed downstream [34•]. This synthesis methodgives a precise control over the volume ratio of the constituent ofthe particles as well as their size. It can also be extended togenerate ternary particles by breaking up a three parallel co-flowing monomer streams.

The possibility to perform independent operations on indi-vidual dispersed objects and to integrate them opens incom-parable broad prospects for engineering newmaterials. Complexarchitectures prepared along these lines are now flourishing inliterature. They include the fabrication of colloid-filled hydrogelJanus granules of tunable size, geometry and composition, theencapsulation of solid particles in liquid drops or the productionof non-spherical objects with liquid compartments. Consider forinstance, the fabrication of colloid-filled non-spherical Janusgranules reported by Shepherd et al. [35]. It necessitates severaloperations. To start, monodisperse colloid-filled hydrogel Janusdroplets are produced with a flow focusing device according tothe method previously described, the two hemispheres of thedroplets differing by their composition in colloids. These spher-ical droplets are then deformed, by flowing through a con-strained geometry, while being photopolymerized.

2.4. Turning microfluidic emulsion technology into an industrialtool

Microfluidic technology paves the way to a bottom-up ap-proach to emulsion science that offers numerous prospectscompared to the “top-down” techniques that handle large pop-ulations of droplets at each step of an industrial process.However, its impact in industry relies on the ability to generatehigh throughput. So far, it is limited because of the extremelysmall flow rates involved (typically of the order of 0.1 ml/h) insuch devices. The formation rate of monodisperse droplets in asingle FFD is only a few tens of droplets/s. The necessity toparallelize droplets generators such as FFD or T junctions istherefore the central issue for potential industrial applications.From a practical point of view, this issue turns out to be a realdifficult task which raises numerous theoretical questions. Byparallelizing devices with multiple nodes, branches and cross-flows, one couples non-linear fluidic oscillators. At low Reynoldnumbers, monophasic flows of Newtonian fluids in a networkmade of channels are governed by linear equations since the flowrate of a fluid flowing through a channel is proportional to thepressure drop applied to the extremities of this channel. Suchinterconnected flows can be solved using an analogy withresistors electrical circuits and do not present any difficulty. Incontrast, multiphase flows of immiscible fluids are highly non-

Fig. 4. (a) Sheath-flow microfluidic device used to produce monodisperse colloid-filled hydrogel granules. b) Schematic representation of the granules shapes andcomposition. c) View of the parallel two streams prior to their dispersion in droplets. d) Formation of Janus droplets. Reprinted from “Microfluidic assembly ofhomogeneous and Janus colloid-filled hydrogel granules”, Shepherd R.F., Langmuir 2006, 22:8618–8622 with permission from ACS.

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linear. Understanding such flows in hydrodynamic networks is achallenging problem in the field of hydrodynamics and non-linear physics. Take for instance, a situation where a train ofdroplets or bubbles is directed towards a T junction and ask howthe droplets and carrier phase divide between the two outlets[23]. When a droplet reaches the junction, two directions arepossible if it does not break. The selection is triggered by thedominant stream so that the droplet flows into the outletcharacterized by the lower hydrodynamic resistance. Since thepresence of droplets in conducts increase the resistance to flow,there is a hydrodynamic feedback between choices of successivedroplets. The outcome turns out to be a complex non-lineardynamical problemwhich may lead to chaos or quasiperiodicity.With such effects, producing droplets in parallel microfluidicdevices yields to emulsions with large polydispersity [36].

A possible way to circumvent this difficulty of paralleliza-tion is to generate droplets without applying cross-flows. In thelast two years, large efforts have been undertaken along thisline by Nakajima's group in Japan [37••,38]. They haveconceived and developed two different microchannel arraydevices able to generate monodisperse droplets with a pro-duction rate increased by a factor 100 and more with respect tosingle channel devices. The first device is a silicon micro-channel (MC) array plate with a multilevel structure. Themethod consists of forcing the to-be-dispersed phase throughan array made of several hundreds of parallel channels into ashallow well, filled with the continuous phase as depicted inFig. 5 [37••]. This MC array plate is capable of generatingmonodisperse discoid droplets of O/W or W/O types withoutapplying a forced cross-flow of the continuous phase, up to athousand droplets per second. The other device consists of asilicon array of about 104 asymmetric straight through-holes

vertically microfabricated on a plate surface of a liquid cham-ber to supply the to-be dispersed phase [38]. Each asymmetricthrough-hole is composed of a slit (with typical length, widthand depth values of respectively 100, 10 and 20 μm) and acylindrical channel (typically 10 μm in diameter and 5 μm indepth). These through-holes are uniformly arranged with in-tervals of typically 100 μm across the asymmetric straight-through MC. The phase to disperse is injected through thearray of vertical channels into the horizontal module filled withthe continuous phase. This device can be applied to thepreparation of monodisperse emulsions as well as micropar-ticles and microcapsules. Since the formation rate of dropletsfrom each active through-hole is typically a few tens ofdroplets/s, this apparatus can produce up to 105 droplets persecond.

2.5. Scaling up microfluidics

Scaling up these microdevices into millimetric ones presentssome considerable advantages. Recently, a continuous co-axialflow scheme to engineer and industrially produce at low costhierarchically organized structures of larger sizes with an in-comparable degree of control over their size, shape and internalstructure has been developed (Fig. 6) [26••]. The method con-sists of using an assembly of capillaries or flexible tubes (withdiameters ranging from 50 μm to a few mm) put together withelementary home-made modules. This synthesis method isbased on the association of three different elements able toachieve the basic following four functions used in microfluidicdevices: (1) form periodic trains of monodisperse dropletswith very good control over their size, (2) dilute–concentratethese trains while keeping the volume of droplets unchanged,

Fig. 5. Schematic illustrations of the two techniques based on microchannel arrays developed by M. Nakajima's group to scale up production of monodisperse dropletsand photographs of produced emulsions. a) The two level structures conceived to scale up droplet production is made of an array of several hundreds of parallelchannels. The to-be-dispersed phase is injected through the microchannels into the shallow well filled with the continuous phase. (Left) Images of successfullygenerated O/W discoid droplets. Reprinted from “Controlled generation of monodisperse discoid droplets using microchannel arrays”, Kobayashi I. et al., Langmuir,2006, 22:10893–10897 with permission from ACS. b) Mechanism of droplet formation using an asymmetric straight through-holes MC plate. (Right) An microscopicphotographs of the resultant droplets. Reprinted from “Novel asymmetric through-hole array microfabricated on a silicon plate for formulating monodisperseemulsions”, Kobayashi I. et al., Langmuir, 2005, 21:7629–7632 with permission from ACS.

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(3) generate periodic trains made of alternated droplets and(4) deform droplets in a controlled manner. Modular millifluidicset-ups can then be designed to produce newly controlled in-tegrated architectures limited only by the number of combina-tions possible and one's creativity. The great versatility of thismethod is already illustrated through the encapsulation of drop-lets or solid particles of various shapes, composition and size, inliquid or solidified drops, the formation of large organic orinorganic cylindrical particles as well as the generation of doubleand triple emulsions. This strategy presents several advantagesover microfluidic synthesis while keeping its specificities. Sinceno lithography, glass etching techniques or specific equipmentare necessary for the design of the devices, their fabrication costsare low. The connecting capillary tubes and the various modulescan assemble and disassemble easily so that modular set-ups canbe designed on demand in a short time. This modularity is alsoconsiderable advantage from a practical point of view sincemodifying a hydrodynamic circuit on a planar microfluidic chipdemands starting over at the lithography or glass etching level.Combined with the ability to modify very simply the wettingproperties of the glass capillary tubes used for connectionit offers the opportunity to fabricate multiple emulsions of

different nature with a same device. The use of such devices pavethe way to an industrial integrative formulation of dispersedmaterials with very large characteristic sizes ranging fromtypically 100 μm to several mm and new complex architectures[39]. This should lead to the rapid emergence of new products incosmetics or food where the texture and visual aspect plays a keyrole for sale.

3. Miniaturizing the laboratory using droplet-basedmicrofluidic devices

Monodisperse droplets generated by microfluidic devicescan serve as microreactors to compartmentalize reactions andcontrol the reaction time precisely [40]. One of the keyproperties of droplet-based high-throughput microfluidicdevices stems from the uniform constant speed motion ofdroplets in the channel allowing equivalence between distanceand reaction so that one can perform a stationary measurementof a kinetic process along the flow. Using this property,microfluidic platforms to perform kinetic measurements offast and very fast reactions with better than millisecondresolution using very small volumes of reagents have recently

Fig. 6. (a) Sketches of the different elementary tubular millifluidic modules and their corresponding basic functions. b) Shown are schematic representations of thedifferent modular set-ups used to fabricate triple and double emulsions and images of emulsions produced with different number of internal droplets reprinted from“Controlled production of hierarchically organized large emulsions and particles using assemblies on line of co-axial flow devices”, Panizza P. et al., Colloids Surf. A:Physicochem. Eng. Aspects (2007), doi:10.1016/j.colsurfa.2007.06.026 with permission from Elsevier.

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been developed [40]. This microreactor technology is a veryefficient alternative to batch chemical procedure, because of therapidity of analysis and the low consumption of reagents.Furthermore, other advantages results from the high heat andmass transfer rates provided by microfluidic reactors whichinduce safe and fast syntheses and therefore may open newchemical reactions [41]. Briefly, the droplets are usually formedat a T junction by using the to-be-disperse phase, streams of thevarious reagents separated from each other by buffer streams inorder to avoid premixing. Rapid mixing of the reagent inside thedroplet is necessary since it determines the starting time of thereaction. This is achieved by chaotic advection when thedroplets flow through a winding channel [42]. The compositionof the reaction mixture at the reaction time, t, is then determinedwith spectroscopic techniques (UV–vis, Raman or Flurores-cence) by analyzing the composition inside the droplets at thedistance d= tU (where U is the velocity of the droplet) withinthe channel. Since the composition of reagents within eachdroplet carrier can be changed by simply varying the flow ratesof the reagent streams, this technique can be used for screeningof a target. Using droplets as microreactors is not limited tochemical reactions, but can apply to other fields such as forinstance enzyme kinetics, DNA analysis, synthesis of nano-particles or protein crystallization. We advise the reader to referto the reviews written by R.F. Ismagilov to get more informationand precision on the use of droplets in these various fields[43••].

Another interesting specificity of droplet-based microfluidicdevices is the possibility to rapidly carry out many experiments(typically a few hundred per second) under the samecontrollable conditions. These features are well suited tostudy stochastic processes where many experiments arenecessary to accurately measure the probability of a singleevent. A good example of this approach concerns, a droplet-based set-up recently developed by Laval et al. to investigatecrystal nucleation kinetics [44•]. Monodisperse droplets of asolution are produced, convected along a channel and thenrapidly submitted to a temperature quench so that nucleationmay occur. The nucleation rate is then determined by measuringthe probability that a droplet contains a nucleus at differentpositions along the channel on a large number of droplets. Thistechnique presents numerous advantages over the classicaldroplet methods using emulsions. They include the productionof monodisperse droplets of tunable size with no surfactantmolecule which may induce heterogeneous nucleation, therapidity of the temperature quench, the possibility to eliminateinteractions between multiple nuclei by choosing small enoughdroplets and a fast and direct measurement of the proportionof crystallized droplets. This continuous method yields torapid and reliable statistical measurements of the nucleationkinetics, and offers the opportunity to carry out high-throughputcrystallization conditions [45].

The ability of microfluidic technology to produce, handleand manipulate single droplet in a very controlled way opensnew prospects to study the physical properties and stabilityof emulsions, at the scale of an individual or two droplets.Along this line, a microfluidic interfacial tensiometer has been

conceived [46]. The method is based on quantitative real timeobservation and analysis of drop shape dynamics in micro-channels. Drops of controlled diameter and spacing areproduced at a T junction of two immiscible fluids and injectedin a wider downstream channel where they become spherical.They are then deformed by flow constrictions. Measurementsare performed at the exit or entrance of a constriction where theflow is respectively accelerating or decelerating, producing anextensional flow that deform the drops. This tensiometer givesvery accurate and precise results, with very low reagentconsumption and rapidity. Because of the equivalence betweentime and position along the channel, the age of the interface isknown, so that information on the dynamic surface tension andkinetics of adsorption surfactant at the interface can be gainedby using multiple constrictions along the channel. With nodoubt, in the near future, microfluidic tools will be used toinvestigate the coalescence between two droplets. Such a studycould for instance be performed by forming in a capillary tubean alternating train of small and large droplets using a Tjunction. Since in the downstream channel, the small dropletsare convected faster than the large ones, coalescence eventscould therefore be observed and quantified.

An important research field now deals with developingactive techniques and new tools to handle droplets inmicrofluidic devices.

4. Conclusion and prospects

Microfluidic technology offers a new “bottom-up” approachto emulsification which shows much promise in the emulsionfield. By contrast to the “top-down” approach of otheremulsification techniques, which operate on a very largenumber of droplets at each step, microfluidic generates onesingle droplet at a time with incomparable results in terms ofsize control. Its abilities to create chemical gradient and tohandle each produced droplet individually lay the foundation ofa new concept in colloidal science, that of ContinuousIntegrative Chemistry. The novelty and originality of thisapproach consists of using monodisperse droplet as individualchemical reactor and operating “on line” on each reactor tosuccessively add a chemical or physical function at each step ofa process. This integrative approach is based on severalelementary functions that microfluidic tools can accomplish.These basic operations include formation of parallel streamswith different composition, generation of monodisperse droplettrains, dilution and concentration of these trains, formation ofalternated trains with droplet of different compositions,asymmetric droplet breaking-up, fusion of two droplets,controlled deformation of the droplets, and encapsulation. Bycombining and integrating these various functions withpolymerization, solidification or any other chemical process,it then becomes possible to synthesize new dispersed materialswith complex architecture. This methodology yields to a verygood control of the size, shape, and internal structure of themanipulated objects, at each step of the process. It is for instancethe only technique that can ensure encapsulation of an activeproduct at 100% in a single step. Illustrative examples of the

• Of special interest.•• Of outstanding interest.

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high potentialities of this approach are now numerous inliterature. They concern for instance double emulsions withinternal droplets of different composition, triple emulsions, non-spherical particles, Janus or ternary particles and core-shells.With no doubt, the further step to make is to combinemicrofluidic and millifluidic formulation methods to generatemultiscale structured materials. By integrating these tools withclassical emulsification techniques, the fabrication of multipleemulsions with four or five degrees of multiplicity andhierarchical sizes ranging from the micrometer for theinnermost droplets up to typically a millimeter for the size ofthe outer drops should in principle be feasible. However, despiteits numerous advantages, the microfluidic technology is not yetsuitable as a production tool for industry because of the verysmall flow rate involved (typically of the order of a fewhundreds of microliters per hours) in this type of devices.Consequently, a very important and active research work mustnow be devoted to overcome this limitation since both industrialand financial stakes are tremendous.

Generatingmonodisperse droplets with controllable sizes andshapes and being able to manipulate them individually andreproductively in networks of small channels give the oppor-tunity to miniaturize a laboratory down to a few inches persquare [47, 48•]. This is the lab-on chip concept. Using dropletsas individual microcarriers and reactors in such devices is verypromising for developing high-throughput applications sincereaction conditions can easily be compartmentalized and ad-dressable [44•]. This approach enables to considerably increaseand accelerate the number of tests up to a few tens per seconds,using very small amounts of materials. The prospects are nu-merous for many scientific fields where one target must be testedagainst a large number of reaction conditions. In chemicalengineering, this continuous screening approach permits forinstance to explore the conditions of a reaction, to optimize it andconsequently to orientate the synthesis of new materials. Forbiology, it permits to efficiently and rapidly test the effect of adrug on viruses.

The possibility with droplet-based microdevices to rapidlyperform many experiments (typically a few hundred per second)under the same controllable conditions also opens many op-portunities to address fundamental issues. These tools are thuswell suited to study stochastic processes which necessitate astatistical analysis such as for instance coalescence phenomenaor crystallization nucleation. In biology, such a digital high-throughput technique may give access to the statistical dis-tribution of a population as a function of a stress [49]. Finally, onanother level, flows of droplets occurring in microfluidic devicesraise challenging questions in the field of hydrodynamics andnon-linear physics [23,50].

To conclude, the recent progresses made in the productionof droplets of controllable size and in their individual manipula-tion lead to novel approaches of emulsification and synthesisof complex materials, and the foundation of new scientificmethods and applications in many different fields. Recentadvances in scaling up droplet production and the dimensionsof microdevices now allow to transpose these promising tech-niques into industry.

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