**1. Introduction**

804 Mass Transfer - Advanced Aspects

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Luikov, A. V.; (1980). *Heat and Mass Transfer,* Moscow, Mir Publisher.

*Adsorption On Heterogeneous Solid Surfaces*, Elsevier.

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As the development in the microfabrication technology in the last two decades has allowed the easy fabrication of microchannels with low cost, many studies have been conducted on the transport of fluid and the realization of various functions using fluids (Whitesides, 2006; Dittrich et al., 2006). The realization of the microchannel-based fluidic system and the relevant study are called microfluidics. In the scale in which microfluidics is concerned, the surface force is dominant over the body force, since the surface-to-volume ratio is large. The dominant influence of the surface force allows the production as well as the movement and control of micro-sized droplets in a microchannel. This study area is called droplet-based microfluidics (Beebe et al., 2002; Kim, 2004; Stone et al., 2004). Droplet-based microfluidics is expected to enable chemical and biological applications such as particle synthesis (Frenz et al., 2008), microextraction (Mary et al., 2008), and protein crystallization (Zheng et al., 2003). In a general microfluidics system, the Reynolds number (Re) is very small as 0.1-10, and thus the fluid forms a laminar flow. Such a laminar flow makes it difficult for two different fluids to be mixed with each other. However, if droplets are used, different fluids can be mixed with each other, because an internal circulation flow takes place in the droplets (Tice et al., 2003).

This chapter describes the microextraction based on the droplet-based microfluidics. Firstly, we will explain the electrohydrodynamic droplet generation and control technology in the aqueous two-phase system (ATPS) that we employed for the study, and the application of the generated droplets to microextraction. In particular, we were able to control the rate of extraction, which was impossible in the previous extraction methods, and analyzed the microextraction behaviour by simulating the phenomena based on a simple dissolving model.

#### **1.1 Droplet-based microfluidics**

The technology that is firstly required in droplet-based microfluidics is the method to generate droplets in a microchannel. Droplet generation is related with capillary number (Ca), which is the ratio of viscous force to interfacial tension (Squires & Quake, 2005). In a macroscopic system, droplets can be easily generated by vigorously shaking immiscible fluids, but the size distribution is very wide. In a microfluidics system, on the contrary, droplets are generated by various controllable methods so that the size distribution can be limited. Microfluidic methods for forming droplets can be either passive or active. Most methods are passive, relying on the flow field to deform the interface and promote the

Microdroplets for the Study of Mass Transfer 807

electric field, they have the advantages that the electric signals can be easily controlled and there is not a concern for fatigue fracture since there is not a moving part. Electrohydrodynamic methods can be used not only for the generation of droplets but also for their control, and thus there can be many applications of the methods. Several applications of EHD method have been reported in droplet-based microfluidic system. Ozen et al. (Ozen et al., 2006a, 2006b) formed monodisperse droplets using the EHD instability of the interface between two liquids and analyzed the stability in the case where the fluids are assumed to be leaky dielectric. EHD generation of a single droplet in an aqueous two-phase system (ATPS) which has high salt concentrations in both phases was also reported (Song et

Generated droplets should be manipulated properly for further utilization in the same microfluidic system. This includes manipulation of droplets by breakup, sorting and coalescence, etc. Various techniques have been published for the effective manipulations of droplet in the microfluidic systems. For breakup of generated droplets, geometry of the microchannels has been specially designed (Link et al., 2004; Ménétrier-Deremble & Tabeling, 2006) and electrical field has been applied for the control (Choi et al, 2006). Tan et al. reported sorting of droplets through controlling the bifurcating junction geometry and the flow rates of the daughter channels (Tan et al., 2008). Ahn et al. developed dielectrophoretic manipulation of droplets for high-speed microfluidic sorting devices (Ahn et al., 2006). Prakash et al. demonstrated synchronization of bubble movements via planar fluidic resistance ladder network (Prakash & Gershenfeld, 2007). An active method of controlling charged droplets electrically was reported by Link et al (Link et al., 2006). Coalescence of droplets is essential for the reaction of molecules confined in different droplets and thus it has been extensively studied including the mechanism and methodology for microfluidic systems (Bremond et al., 2008; Zagnoni & Cooper, 2009; Tan et

Microextraction has been developed and widely applied as an efficient tool for molecular transport in microfluidic devices, taking the advantages of small dimension such as stable and continuous operation without the need of shaking and settling as in conventional extraction system and enhanced separation caused by large interfacial distance and short diffusion time. Several research results on microfluidic extraction of metal ion complexes within organic-aqueous two-phase system have been published by Kitamori's group (Tokeshi et al., 2000a, 2000b; Surmeian et al., 2002; Hisamoto et al., 2003). Kitamori's group realized microextraction in the microfluidic system by forming a laminar flow with two or more fluids in a microchannel and using the interfaces between different fluids. When the microextraction is realized in a droplet-based microfluidic system, a more rapid mass transfer can be expected than in a laminar flow-based system because the ratio of the interfacial area between the different fluids per the unit volume is larger. As an example of the droplet-based microextraction, Xu et al. (Xu et al., 2008) demonstrated extraction of succinic acid from *n*-butanol to aqueous droplets containing sodium hydroxide. Mary et al. studied the extraction of a solute from the continuous phase and purification where the solute transport was in the opposite direction (Mary et al., 2008). Castel et al. (Castell et al., 2008, 2009) reported continuous molecular enrichment in a microfluidic system aided by the vortex within segmented droplets and developed liquid-liquid phase separator which turns segmented flow to continuous flow. These examples of droplet-based microfluidics indicate

al., 2007; Choi et al., 2008). The results are considered in Section 2.1.

al., 2007; Ahn et al., 2006).

**1.2 Microextraction in microfluidic systems** 

natural growth of interfacial instability (Christopher & Anna, 2007). Specially designed geometries that affect the streams or externally applied forces are used to generate droplets in the microfluidic systems depending on the characteristics of the immiscible fluids such as viscosity, interfacial tension, wettability to the material surface and other electric properties. Flow rates of the dispersed phase (Qd), continuous phase flows (Qc) and their ratio (Qd/ Qc) are the parameters that can be controlled during the droplet formation operation. Three common techniques that are often used for generation of droplet in microfluidic system are dispersing fluid in a continuous phase with the configuration of co-flowing stream, crossflowing in T-junction and flow-focusing as shown in Figure 1 (Anna et al., 2003). These techniques are feasible particularly for fast generation of droplets of oil/water two-phase system with uniform size distribution.

Fig. 1. Illustrations of the three main microfluidic geometries of methods used for droplet formation. (a) Co-flowing streams, (b) crossflowing streams in a T-shaped junction, and (c) elongational flow in a flow focusing geometry. In each case the widths of the inlet and outlet streams are indicated. It is assumed that the device is planar with a uniform depth h. (Anna et al., 2003)

Different from the passive methods, the active methods generate droplets by applying various external forces. Electrohydrodynamic methods are the most frequently used for the active generation. Although electrohydrodynamic methods require electrodes to apply an

natural growth of interfacial instability (Christopher & Anna, 2007). Specially designed geometries that affect the streams or externally applied forces are used to generate droplets in the microfluidic systems depending on the characteristics of the immiscible fluids such as viscosity, interfacial tension, wettability to the material surface and other electric properties. Flow rates of the dispersed phase (Qd), continuous phase flows (Qc) and their ratio (Qd/ Qc) are the parameters that can be controlled during the droplet formation operation. Three common techniques that are often used for generation of droplet in microfluidic system are dispersing fluid in a continuous phase with the configuration of co-flowing stream, crossflowing in T-junction and flow-focusing as shown in Figure 1 (Anna et al., 2003). These techniques are feasible particularly for fast generation of droplets of oil/water two-phase

Fig. 1. Illustrations of the three main microfluidic geometries of methods used for droplet formation. (a) Co-flowing streams, (b) crossflowing streams in a T-shaped junction, and (c) elongational flow in a flow focusing geometry. In each case the widths of the inlet and outlet streams are indicated. It is assumed that the device is planar with a uniform depth h. (Anna

Different from the passive methods, the active methods generate droplets by applying various external forces. Electrohydrodynamic methods are the most frequently used for the active generation. Although electrohydrodynamic methods require electrodes to apply an

system with uniform size distribution.

et al., 2003)

electric field, they have the advantages that the electric signals can be easily controlled and there is not a concern for fatigue fracture since there is not a moving part. Electrohydrodynamic methods can be used not only for the generation of droplets but also for their control, and thus there can be many applications of the methods. Several applications of EHD method have been reported in droplet-based microfluidic system. Ozen et al. (Ozen et al., 2006a, 2006b) formed monodisperse droplets using the EHD instability of the interface between two liquids and analyzed the stability in the case where the fluids are assumed to be leaky dielectric. EHD generation of a single droplet in an aqueous two-phase system (ATPS) which has high salt concentrations in both phases was also reported (Song et al., 2007; Choi et al., 2008). The results are considered in Section 2.1.

Generated droplets should be manipulated properly for further utilization in the same microfluidic system. This includes manipulation of droplets by breakup, sorting and coalescence, etc. Various techniques have been published for the effective manipulations of droplet in the microfluidic systems. For breakup of generated droplets, geometry of the microchannels has been specially designed (Link et al., 2004; Ménétrier-Deremble & Tabeling, 2006) and electrical field has been applied for the control (Choi et al, 2006). Tan et al. reported sorting of droplets through controlling the bifurcating junction geometry and the flow rates of the daughter channels (Tan et al., 2008). Ahn et al. developed dielectrophoretic manipulation of droplets for high-speed microfluidic sorting devices (Ahn et al., 2006). Prakash et al. demonstrated synchronization of bubble movements via planar fluidic resistance ladder network (Prakash & Gershenfeld, 2007). An active method of controlling charged droplets electrically was reported by Link et al (Link et al., 2006). Coalescence of droplets is essential for the reaction of molecules confined in different droplets and thus it has been extensively studied including the mechanism and methodology for microfluidic systems (Bremond et al., 2008; Zagnoni & Cooper, 2009; Tan et al., 2007; Ahn et al., 2006).

#### **1.2 Microextraction in microfluidic systems**

Microextraction has been developed and widely applied as an efficient tool for molecular transport in microfluidic devices, taking the advantages of small dimension such as stable and continuous operation without the need of shaking and settling as in conventional extraction system and enhanced separation caused by large interfacial distance and short diffusion time. Several research results on microfluidic extraction of metal ion complexes within organic-aqueous two-phase system have been published by Kitamori's group (Tokeshi et al., 2000a, 2000b; Surmeian et al., 2002; Hisamoto et al., 2003). Kitamori's group realized microextraction in the microfluidic system by forming a laminar flow with two or more fluids in a microchannel and using the interfaces between different fluids. When the microextraction is realized in a droplet-based microfluidic system, a more rapid mass transfer can be expected than in a laminar flow-based system because the ratio of the interfacial area between the different fluids per the unit volume is larger. As an example of the droplet-based microextraction, Xu et al. (Xu et al., 2008) demonstrated extraction of succinic acid from *n*-butanol to aqueous droplets containing sodium hydroxide. Mary et al. studied the extraction of a solute from the continuous phase and purification where the solute transport was in the opposite direction (Mary et al., 2008). Castel et al. (Castell et al., 2008, 2009) reported continuous molecular enrichment in a microfluidic system aided by the vortex within segmented droplets and developed liquid-liquid phase separator which turns segmented flow to continuous flow. These examples of droplet-based microfluidics indicate

Microdroplets for the Study of Mass Transfer 809

(about 4-5 dyne/cm) compared to that of common ATPS formed with poly(ethylene glycol) and dextran (10-4 to 0.1 dyne/cm). Thus the interface readily responds to the external electric field in microchannels. The fabricated microfluidic device has a T-junction at which the two-phase flow may have the configuration that can generate dispersed droplets by the electric potential difference applied. The threshold voltage necessary for the electrohydrodynamic droplet generation depends on pH due to the degree of dissociation and charge accumulation. Electrokinetic control of droplet break-up and switching of droplet movement direction were also demonstrated based on the same electrophoretic mobility of ATPS droplets. Volume of broken droplets and the direction of droplet movement were effectively controlled by the applied DC electric field. In addition, simple manipulatin of ATPS droplets was demonstrated in the microchannels that are branched at the end.

The ATPS for the droplet generation was prepared by dissolving TBAB and AS in water by 15 and 30%, respectively, by stirring the solution well. The prepared solution is left still for more than 12 hours so that it can be divided into two phases by the difference in the specific gravity. After separating the stable phases, TBAB-rich phase and AS-rich phase were individually introduced at the inlets of the microfluidic system by syringe pump, which controlled the flow rates of each phase independently. The microfluidic system in Figure 2 was fabricated by using the general PDMS replica. The ratios of flow rate of TBAB-rich phase to AS-rich phase were fixed at 0.133 and 0.156 in which the two streams were laminar as shown in figure. In these ratios, the more viscous TBAB-rich phase occupied about half of the channel width, but from T-junction one branched channel was totally occupied by TBAB-rich phase and the other branched channel by TBAB-rich phase and AS-rich phase together. Application of an electric field in this state through the electrodes shown in Figure 2 causes the change in the interface as in Figure 3, as the AS-rich phase is drawn in the direction toward the positive electrode. The interface at the center of T-junction was deformed to the positive electrode, which is located at the outlet where only TBAB-rich phase was flowing out. At the same time, the interface in the part of the channel connected to the negative electrode was also deformed due to the temporary change in volumetric flow

Fig. 2. Schematic illustration of the device for electrohydrodynamic generation of droplets

**2.1 Electrohydrodynamic generation of droplets** 

and the dimensions of the channels

that droplets not only help mass transfer through the droplet surface but also mix the fluids be means of the circulation flow inside them and serve as carriers of fluids by themselves. These properties show that droplets can be used for microextraction as well as microreaction.
