Review of Microfluidic LiquidâLiquid Extractors - Industrial

Subscriber access provided by UNIV OF NEWCASTLE

Review

Review of Microfluidic Liquid–Liquid Extractors Cong Xu, and Tingliang Xie Ind. Eng. Chem. Res., Just Accepted Manuscript • DOI: 10.1021/acs.iecr.7b01712 • Publication Date (Web): 15 Jun 2017 Downloaded from http://pubs.acs.org on June 21, 2017

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Industrial & Engineering Chemistry Research is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Industrial & Engineering Chemistry Research

Review of Microfluidic Liquid–Liquid Extractors Cong Xu*, Tingliang Xie Institute of Nuclear and New Energy Technology, Collaborative Innovation Center of Advanced Nuclear Energy Technology, Tsinghua University, Beijing, 100084, P.R China, *Email: [email protected] ABSTRACT: During the last few decades, microfluidic liquid–liquid extractors have been developed to address the need for separating solutes in analytical chemistry and efficiently recovering products in microfluidic reactors. This review classifies the various microfluidic liquid–liquid extractors into three major groups based on their flow arrangement—stop-flow microfluidic extractors (MEs), co-current MEs, and countercurrent MEs. Each group is further classified into several subcategories based on flow pattern and/or working principle. The review focuses on how to establish these three groups of microfluidic liquid–liquid extractors, including the difficulties and corresponding solutions for establishing these MEs, as well as their advantages and disadvantages. The review ends with conclusions and the outlook of the field. Keywords: microfluidics, liquid–liquid extractor, microfluidic extraction, stop-flow, co-current flow, countercurrent flow

1. INTRODUCTION Immiscible liquid–liquid extraction is an important operation in chemical, biochemical, and pharmaceutical technology for separating an expected compound from a mixture by relying on the different solubility of the compound. It is well known that the transfer length and the interface area are two key factors influencing the extraction efficiency. A shorter transfer length and larger interface area are expected to enhance the extraction efficiency. In the past few decades, microfluidic technology has been significantly developed because of its small sample volume, fast response time, safety, and low cost. Immiscible liquid–liquid extraction has also been integrated with microfluidic technology to achieve microfluidic liquid–liquid extraction. In 2000, Sato et al.

1

ACS Paragon Plus Environment


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

carried out the first study concerning microfluidic extraction between two immiscible liquids.1 Subsequently, microfluidic liquid–liquid extraction has attracted the attention of many researchers, and has been widely used to separate compounds of interest and prepare samples in analytical chemistry, crystallization, pharmaceutical engineering, etc.2-7 Microfluidic liquid–liquid extraction is performed in various microfluidic liquid–liquid extractors (MLLEs). These microfluidic extractors (MEs) usually have characteristic dimensions of tens to hundreds of micrometers, resulting in a Reynolds number (Re) smaller than 2300, which is the value corresponding to the transition between laminar and turbulent regimes in a round tube. Thus, the flows of liquids in these MEs are laminar, not turbulent, which is not beneficial for liquid–liquid extraction. However, these extremely small dimensions can significantly reduce the transfer length and increase the interface area during liquid–liquid extraction against a weak turbulent flow. It has been proven that liquids flowing through a ME develop large interfacial area-to-volume ratios and short mixing lengths through splitting, folding, and stretching.8 Therefore, MEs enable fast separation of compounds of interest from a mixture with only a small sample volume.

Figure 1 Tree graph of the categories of microfluidic liquid-liquid extractors (MLLEs)

2


Page 2 of 71

Page 3 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


The MEs adopted can be classified into three major groups—stop-flow MEs, co-current MEs, and countercurrent MEs—based on the flow arrangement of two immiscible liquids. To date, no article has compared the three groups of MEs, especially the key factors and methods of establishing these MEs. In addition, some interesting research published during the past decade has not been reviewed, especially for countercurrent MEs. This review summarizes the methodologies used to establish the three groups of MEs, including their merits and drawbacks. Each group is further divided into several subcategories based on the working principle and/or flow pattern. The article is divided into five sections: the first section is this introduction, the second reviews stop-flow MEs, the third reviews co-current MEs, the fourth reviews countercurrent MEs, the fifth gives methods to evaluate extraction performance, and the sixth reviews scale-up of MEs. The article ends with conclusions and the outlook of the field. Figure 1 is a tree graph showing the categories of MEs reviewed in the article, including key problems in establishing these MEs and corresponding solutions (as discussed in detail in the following sections). The aim of this review is to give researchers an overall view of almost all kinds of MEs, including classification, working principles, characteristics, and establishing methodologies, as well as advantages and disadvantages.

2. STOP-FLOW MICROFLUIDIC EXTRACTOR The term “stop-flow” means that one liquid phase (usually the acceptor phase) is stationary, while the other phase (usually the donor phase) is always mobile. This methodology is widely used in chemical and biological analyses. Stop-flow MEs can be divided into three subcategories based on the mechanism used to immobilize the stationary phase: single-drop MEs, membrane liquid-phase MEs, and centrifugal MEs. To date, these three subcategories have not been summarized in a review.

2.1 Single-drop microfluidic extractor In the field of stop-flow MEs, single-drop MEs have been the most widely investigated and applied. This method was first proposed by Liu and Dasgupta in 1995 to overcome some disadvantages of applying liquid–liquid extraction in analytical chemistry.9 In a single-drop ME, the use of several microliters of sample reduces the volumes of valuable or toxic organic solvents, wastes, etc. This is the most significant advantage of this methodology. As shown in Figure 2, this method can be further divided into direct

3



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 2 Schematics of a direct immersion single-drop microfluidic extractor (DI-SDME) and continuous-flow microfluidic extractors (CFMEs): (A) DI-SDME, (B) CFME: drop, and (C) CFME: curved interface and in-line detection.18 (Sun et al., adapted with permission from ref 18. Copyright 2006, Elsevier, Amsterdam.) immersion single-drop MEs (DI-SDMEs) and continuous-flow MEs (CFMEs).10-17 In a DI-SDME (Figure 2-a), a several microliter drop of the extracting solvent (acceptor) is formed at the tip of a micro syringe, relying on the liquid–solid surface tension between the solvent and the tip. The drop is immersed in the aqueous phase (i.e., donor). A magnetic stirrer stirs the aqueous phase to promote mass transfer between the mobile donor phase and the stationary acceptor phase. However, the enrichment factor in a DI-SDME is limited to a theoretical equilibrium stage, which is not high enough. To increase the enrichment factor, the CFME (Figure 2-b) uses a flowing donor phase (usually aqueous phase) to replace the batch-stirred phase in the DI-SDME. This enables the acceptor drop to always be in contact with a fresh donor phase, and a higher enrichment factor can be obtained. After the extraction is finished, whether in the DI-SDME or CFME, the drop is then retracted into the micro syringe and subsequently injected into the analytical instrument. In the DI-SDME and CFME, extraction and analysis are performed as separate steps, and thus there is a time cost. A method similar to the CFME that integrates the extraction and analysis was adopted by Su et al. to detect sodium dodecyl sulfate in real time. As shown in Figure 2-c, instead of a drop, a curved interface of the organic phase is formed at the tip of a Teflon AF liquid-core waveguide capillary.18 The curved interface used in this method is more stable than a drop for mass transfer. A spectrometric detection system with a light emitting diode (LED) as the light source and a photodiode as an absorbance detector was used to detect the analyte concentration in the organic phase in situ. In addition, microfluidic extraction and back-microfluidic extraction can integrated based on the DI-SDME, as shown in Figure 3.19,20 In this method, a drop of an aqueous phase serving as the stripping liquor (acceptor) is formed at the

4


Page 4 of 71

Page 5 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


tip of a needle and then immersed in a thin film of the extracting solvent (extract). The thin film is in direct contact with another aqueous phase consisting of the feeding stock (donor). The analyte in the donor could be transferred into the acceptor through the thin film separating the two aqueous phases. To maintain a stable thin film of the organic phase, a hydrophobic Teflon ring was adopted. This method is suitable for analytical instruments that are compatible with aqueous samples.

Figure 3 Schematic of microfluidic extraction/back-extraction by a single-drop microfluidic extractor.20 (Ma et al., reprinted with permission from ref 20. Copyright 1999, ACS, Washington.)

2.2 Membrane liquid-phase microfluidic extractor The membrane liquid-phase ME can be considered as a development of the single-drop ME. The main drawback of single-drop MEs is that the drop suspended at the tip of the needle is continuously flushed by the mobile phase and consequently, the drop may fall off. To improve the drop stability, a membrane was introduced into the single-drop MEs.17,21,22 As shown in Figure 4, the organic phase (acceptor) is placed in a rod or U-shaped hollow fiber with micro pores and remains stationary owing to the surface tension during extraction. One or two micro syringes are fitted to the hollow fiber to feed in and retract the organic phase before and after the extraction. Part of the hollow fiber is immersed in the aqueous phase (donor) that is continuously stirred, and the solute in the aqueous phase is extracted into the organic phase in the hollow fiber. Similarly, a flat membrane or a bag membrane can be used instead of a hollow fiber to form

5



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

membrane liquid-phase MEs.23,24 Furthermore, the micro pores of the hollow fiber can be filled with the organic phase (extracting solvent), while the chamber in the hollow fiber can be filled with the stripping liquor (acceptor). The solute in the aqueous phase (donor) outside the hollow fiber is extracted into the extracting phase, and then extracted back into the stripping liquor. Consequently, integration of extraction and back-extraction (stripping) is established. This method is also called liquid–liquid–liquid microextraction (LLLME).25 In membrane liquid-phase MEs, no drop exists and therefore the system is rather stable. However, the pressure on each side of the micro pores should be carefully controlled to prevent one phase from penetrating the other phase.

Figure 4 Schematic of membrane liquid-phase microfluidic extractors: (A) rod-shaped hollow fiber and (B) U-shaped hollow fiber

2.3 Centrifugal microfluidic extractor In single-drop and membrane liquid-phase MEs, the stationary phase remains immobile because of surface tension. In contrast, centrifugal MEs use a centrifugal force field to keep the aqueous phase stationary, and droplets of the organic phase can flow through the stationary aqueous phase. A typical example of this methodology, called countercurrent liquid–liquid chromatography (CCC), was invented by Ito.26-30 Because mass transfer between two immiscible liquids was carried out within a narrow tube (e.g., a 1.6 mm I.D. and 130 m long Teflon tube) and Reynolds numbers of the mobile phase is lower than 100 in general, this system can be considered a ME. In CCC, the aqueous phase was used as a stationary phase

6


Page 6 of 71

Page 7 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


instead of the solid phase typically used in liquid chromatography, and the organic liquid was mobile. As shown in Figure 5, CCC can be divided into two types: hydrostatic CCC and hydrodynamic CCC. In hydrostatic CCC, there is a single axis of rotation, which produces a constant centrifugal field (G). Owing to its higher density, the aqueous phase is pushed toward the outside, but at the same time, it is pushed from the outside by the light organic phase fed into the chamber through the conduct. Consequently, in the ideal situation, the aqueous phase remains in place and the organic phase is dispersed as droplets into the stationary phase. In hydrodynamic CCC, variable and cyclic centrifugal fields (G) are produced by the planetary rotation of the bobbin around its own axis and the central rotor axis. The rotation of the bobbin around its own axis can provide a larger force to promote movement of the light organic phase and keep the heavy aqueous phase immobile. There is contact between the two liquid phases throughout the tubing.

Figure 5 Schematic of a countercurrent liquid–liquid chromatography (CCC) (blue: mobile phase, light organic phase; green: stationary phase, heavy aqueous phase): (A) hydrostatic design and (B) hydrodynamic design The major challenge of CCC is maintaining a stable liquid stationary phase. Although the term CCC includes “countercurrent”, these MEs are not operated in the countercurrent flow mode. As Berthod et al.

7



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

pointed out, “the very name of the technique, countercurrent chromatography, is inappropriate since the two liquid phases do

not flow countercurrent to

each other.”31

In

an important branch of

microfluidics—centrifugal microfluidics on a round polycarbonate disc—a ME using a mechanism almost identical to that of the hydrostatic CCC was designed to separate mixtures. Figure 6-a shows the typical structure of this design, and Figure 6-b shows its mechanism.32,33

Figure 6 Schematic of a centrifugal microfluidic extractor: (A) structure32 (Kazarine et al., adapted with permission from ref 32. Copyright 2012, ACS, Washington.) and (B) mechanism.

2.4 Brief summary The key for establishing a stop-flow ME is keeping one phase immobile. This can be realized by liquid–solid surface tension (single-drop and membrane liquid-phase methods) and external centrifugal force (centrifugal force-assisted methods). In all these MEs, the maximum mass transfer that can be achieved only corresponds to the phase equilibrium. In addition, owing to the micro volumes of samples used, these MEs are used in analytical chemistry, but not in high-throughput extraction process. Thus, the precise control of sample volumes and/or flow rates of both liquid phases are parameters that need to be addressed. A significant branch of single-drop MEs, the head-space single-drop ME (HS-SDME), is not included in this review because this method actually involves gas–liquid extraction, not liquid–liquid extraction. For information on HS-SDMEs, readers can refer to references 14 and 17.

3. CO-CURRENT MICROFLUIDIC EXTRACTOR

8


Page 8 of 71

Page 9 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Co-current MEs are different from stop-flow MEs in that they have no stationary liquid phase. In a co-current ME, both immiscible liquids flow in the same direction, allowing continuous extraction to be realized. Thus, co-current MEs can be used not only in analytical chemistry with maximum fluxes of tens of microliters per minute, but also in high-throughput extraction processes with tens to hundreds of milliliters per minute. As early as 2001, the company BASF investigated the feasibility of two types of static MEs developed at IMM GmbH for use in high-throughput extraction processes.5 As a result, static MEs were proven to have potential for high-throughput extraction processes.

Figure 7 Schematics of four kinds of co-current microfluidic extractors (MEs): (A) laminar flow ME, (B) droplet flow ME, (C) slug flow ME, and (D) chaotic flow ME In the field of microfluidic liquid–liquid extraction, co-current MEs have been more widely and deeply investigated than stop-flow MEs and countercurrent MEs. To date, there have been several reviews of co-current microextraction.34-36 The review by Zhao and Middelberg is mainly concerned with the transition of flow patterns, ordered manipulation of droplets, and the effects of hydrodynamics on mixing performance in co-current MEs.34 In addition, the definitions and applications of some dimensionless numbers common to the field of microfluidics, such as the Bond number Bo (gravitational force/interfacial tension force), capillary number Ca (viscous force/interfacial tension force), Ohnesorge number Oh

9



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 71

(viscous force/inertial and interfacial tension force), and Weber number We (inertial force/interfacial tension force), can be found in this review. The review by Assmann et al. is mainly concerned with flow patterns and phase separation, including scaling-up of MEs for high throughput.35 The review by Ciceri et al. is mainly concerned with the applications of microfluidic extraction in analytical chemistry.36 In distinction from these previous reviews, this section of our review is focused on methods of establishing co-current MEs. In this section, the ways to establish co-current MEs and the corresponding difficulties are analyzed and summarized. In the following section, co-current MEs are divided into four groups based on flow pattern, as shown in Figure 7: laminar flow MEs, droplet flow MEs, slug flow MEs, and chaotic flow MEs. This categorization of co-current MEs is more detailed and clear than that previously presented in the literature. In addition, recent developments in co-current MEs are also discussed.

3.1 Laminar flow microfluidic extractor In the literature, laminar flow MEs are also called parallel flow MEs.35 In laminar flow MEs, both immiscible liquids flow continuously and side-by-side in the same direction, and neither one is dispersed. One continuous and stable interface is formed between immiscible liquid lamellas, and the solute is transferred by molecular diffusion from one liquid to the other. There are two key components for establishing a laminar flow ME: the inlet structure and the interface stability.

Inlet structure The mechanism by which mass transfer is enhanced in laminar flow MEs is described by the following

equation:37

t =

Where

t

L2 Dm

(1)

is the time required for complete mixing of the molecules by diffusion, L is the characteristic

length of mass transfer for the molecule, and Dm is the diffusion coefficient of the molecule. As

t

is

proportional to the square of L, the characteristic length of microchannels should always be reduced as

10


Page 11 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


much as possible. Obviously, the extraction efficiency of laminar flow MEs can be significantly enhanced by splitting both immiscible liquids into as many thin lamellas as possible. This is realized by the inlet configuration.

Figure 8 Various inlet structures: (A) T-/Y-junction, (B) Ψ-junction, (C) crossflow T-junction, and (D) interdigital pattern inlet.52 (Kriel et al., reprinted with permission from ref 52. Copyright 2017, WILEY, Weinheim.) A straight microchannel with a T- or Y-junction is the most common co-current ME, as shown in Figure 8-a.38-46 Each immiscible liquid generates a lamella, which flows through the T- or Y-junction in the straight microchannel. Three lamellas can be generated through a Ψ-junction or crossflow T-junction, as shown in Figure 8-b and 8-c, respectively.39,45,47-51 The three lamellas can be arranged as W/O/W to perform an in situ extraction-strip (back extraction) process, in which the center organic phase is the extracting solvent, and the aqueous phases on either side are the feeding and stripping liquors.47 Figure 8-d shows an interdigital pattern inlet with 49 microchannels, which feed 24 aqueous and 25 organic streams to the contact zone where extraction takes place.52

11



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 71

Interface stability Continuous and stable interfaces are essential for laminar flow MEs. However, such interfaces can be

ruined by two factors: Kelvin-Helmholtz (KH) instability and pressure imbalance.

Figure 9 Rupture of interfaces in co-current flow microfluidic extractors: (A) Kelvin-Helmholtz instability and (B) pressure imbalance of the interface As shown in Figure 9-a, the KH instability causes the interfaces moving horizontally at different velocities to form waves.53,54 Eq. (2) can be used to predict the interface instability,53 where ρ1 and ρ2, and U1 and U2 are the densities and average velocities of the two phases, respectively, and σ is the interfacial tension between the phases. When the relatively velocity between the phases is below a threshold value, the interfacial tension can stabilizes the interface. In contrast, waves with a small wavelength become unstable and grow until droplets are formed. Thus, the interfacial tension can suppress the KH instability.

(U

− U 2 ) < 2 gσ (ρ1 − ρ2 ) 2

1

ρ1 + ρ2 ρ1ρ2

(2)

However, Eq. (2) does not consider the velocity distribution across the direction vertical to the interface and the wall surface tension (liquid–solid tension). Figure 10-d and 10-e show that even if the velocities of both phases are identical and Eq. (2) is satisfied, the interface between water and kerosene may become unstable.55 This phenomenon may be caused by the velocity distribution.

12


Page 13 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 10 Flow patterns for a water-kerosene system in a rectangular microchannel,55 (A) Oil slugs, q = 20, WeKS = 5.94 × 10-6, WeWS = 3.04 × 10-3, (B) monodisperse droplets, q = 20, WeKS = 5.94 × 10-4, WeWS = 3.04 × 10-1, (C) drop populations, q = 40, WeKS = 1.34 × 10-1, WeWS = 2.74, (D) parallel flows with a smooth interface, q = 1, WeKS = 5.35 × 10-1, WeWS = 6.85 × 10-1, (E) parallel flows with a wavy interface, q = 1, WeKS = 5.94, WeWS = 7.61, and (F) chaotic thin striation flows, q = 0.5, WeKS = 53.50, WeWS = 17.12 (q: volumetric flux ratio of water to kerosene; WeWS and WeKS: Weber numbers of water and kerosene). (Zhao et al., adapted with permission from ref 55. Copyright 2006, John Wiley & Sons, Hoboken.) A pressure imbalance can also ruin a continuous and stable interface.56,57 As shown in Figure 9-b, when the pressure difference across the interface exceeds the interfacial tension, i.e., Laplace pressure, the phase with the larger pressure can intrude into the other phase. Consequently, the interface is ruined. To date, although clear mathematic criteria are rarely available for accurately predicting the interface instability, some qualitative conclusions on maintaining a stable interface have been confirmed in practice. Three methods can be adopted to maintain a stable interface.

13



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 71

Figure 11 Methods for maintaining a stable interface in co-current flow microfluidic extractors: (A) surface-tension-assisted method,58 (Zhao et al., reprinted with permission from ref 58. Copyright 2001, Science, Washington.) (B) guide structure: ridge,47 (Tokeshi et al., reprinted with permission from ref 47. Copyright 2002, ACS, Washington.) (C) guide structure: partition wall,40 (Rea=0.69, Reo=1.67, Ca=2.5× 10-4; Maruyam et al., reprinted with permission from ref 40. Copyright 2004, RSC, Cambridge.) (D) guide structure: pillar,50 (Rea=0.10; Berthier et al., adapted with permission from ref 50. Copyright 2009, Elsevier, Amsterdam.) and (E) membrane-assisted method (Rea=0.53) Rea and Reo: Reynolds numbers of the aqueous phase and organic phase; Ca: Capillary number (1) Surface-tension-assisted method Selectively

patterned

hydrophobic/hydrophilic

microchannels

can

enhance

the

interface

instability.47,49,58-60 In this method, the organic and aqueous phases flow while adhering to hydrophobic and hydrophilic walls, respectively. A recent review by Hibara et al gave a clear explanation on the method.61 For the aqueous phase to encroach the hydrophobic side, the aqueous phase should advance over the

14


Page 15 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


hydrophobic surface, replacing the wetting organic phase. The advancing contact angle becomes very larger, consequently. A similar phenomenon also occurs for the organic phase to encroach the hydrophilic side. These phenomena greatly increase the Laplace pressure window. Namely, the extra liquid–solid surface tensions provided by the wall wettability can protect the interface from KH instability and pressure imbalance to some extent. This method has also been adopted to establish continuous countercurrent MEs, as mentioned in the following section “Countercurrent flow microfluidic extractor”. Figure 11-a shows an example of using this method to construct two and three lamella,47 where Zhao et al. patterned surface free energies inside glass channel networks by combining multi-stream liquid laminar flow and self-assembled monolayer (SAM) chemistry. In an important branch of microfluidics, paper microfluidics, this method has also been used to construct a co- and countercurrent flow arrangements in an open microchannel.49,62 By selectively patterning surfaces with different wetting properties, liquid–liquid interfaces can be pinned and multiphase flows essentially decoupled into single-phase subsystems. (2) Guide-structure-assisted method There are three kinds of guide structures used in the literature for maintaining stable interfaces: ridge, partition wall, and pillar, as shown in Figure 11-b, 11-c, and 11-d, respectively.40,42,45-48,50 These guide structures are placed at the interface between the phases. Although their geometric structures are different, the mechanism of enhancing the interface stability is the same, as shown schematically in Figure 12 for a ridge guide structure. The Laplace pressure caused by the interfacial tension is expressed by Eq. (3).

 1 1   ∆PLap = σ  + R⊥   R=

(3)

Where σ is the interfacial tension, and R= and R⊥ are the orthogonal radiuses of the curved interface at point A. A stable interface has to satisfy Eq. (4).

P1 − P2 ≤ ∆PLap

(4)

The guide structure can decrease R= (approaching infinity in Figure 12) and/or R⊥, and consequently

15



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

increase the Laplace pressure. Thus, Eq. (4) can be satisfied for a wider range of operating conditions, such as flow rate and driving pressure, which means that the interface stability is enhanced. In addition, the guide structure also reduces the interface area compared with the design without the guide structure. Consequently, the influence of the KH instability on the interface is reduced.

Figure 12 Laplace pressure with and without the guide ridge (R= → ∞) (3) Membrane-assisted method The membrane-assisted method can be considered a further enhancement of the guide-structure-assisted method. Several studies have used this method to construct co-current flow microextrators.63-66 This method inserts a membrane with many micro pores between the immiscible liquids. As in the guide-structure-assisted method, the Laplace pressure caused by the micro pores is key for maintaining a stable interface. As shown in Figure 11-e, the liquid phase that wets the membrane intrudes into the micro pores to form curved interfaces, across which mass transfer to the other phase occurs. However, owing to the micro pores, the curved interface has a much smaller radius than that in the guide-structure method. Therefore, the Laplace pressure is significantly enhanced so as to more effectively maintain a stable interface. Moreover, it should be noted that the membrane results in a significant decrease of the interface between the phases, and the extraction efficiency is not enhanced. However, owing to the significant decrease in the contact area, the KH instability has little influence on the interface stability. Overall, when Eq. (4) is satisfied, steady co-current flow microfluidic extraction can be performed using the membrane-assisted method.

3.2 Droplet flow and slug flow microfluidic extractors

16


Page 16 of 71

Page 17 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Owing to the difficulty in maintaining a stable interface between two immiscible liquids, it is hard to establish laminar flow MEs with a long microchannel. In published works, all of the microchannels without membranes are less than 7 cm.38-51, 55-60 Thus, the contacting time between the two liquids is limited. In addition, mass transfer within every bulk phase in laminar flow MEs is dominated by molecular diffusion caused by the molecules thermal motion. When the overall mass transfer is dominated by the bulk phase mass transfer, the overall mass transfer rate in laminar flow MEs is lower compared with that in other MEs with the chaotic advection. These issues restrict the potential applications of laminar flow MEs. However, droplet and slug flow MEs can overcome these issues to an extent. A number of studies concerning droplet and slug flow MEs have been published.67-78 Droplet and slug flow MEs have advantages such as decreased solvent consumption, easy control, and excellent repeatability. The key to establishing a droplet or slug flow ME is the dispersion of one phase (dispersed phase) in the other phase (continuous phase) to generate suitable droplets or slugs. In fact, the mechanisms of generating droplets and slugs are similar. The only difference between the two is that droplets have diameters that are smaller than the microchannel dimensions and no deformation occurs, whereas slugs are larger than the microchannel depth or width and have to deform to fit the microchannel, as shown in Figure 7-b and 7-c. Usually, if droplets can be formed, droplet flow can be turned into slug flow by appropriately increasing the dispersed phase flux and decreasing the continuous phase flux. For transition criteria between the two flow patterns, refer to reference 55. In droplet flow in a straight microchannel, mass transfer is dominated by molecular diffusion across the interface. However, droplet flow in a meandering microchannel achieves better mass transfer because of chaotic internal recirculation in each droplet caused by secondary flows.79 In a slug flow, there is a thin film of the continuous phase between the wall and each deformed slug, which significantly increases the interface area between the phases. Furthermore, the shear force between the thin film and the slug induces an internal vortex flow in the top half of the slug and an opposite vortex in the bottom half of the slug. At the same time, the shear force between the wall and the continuous phase neighboring the slug induces two internal recirculating vortex flows with opposite recirculating directions. These internal vortex flows are all chaotic. Consequently, even if mass transfer across the interfaces is still dominated by molecular diffusion, the overall mass transfer is significantly enhanced.80 For details of the

17



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

dynamics of droplets in microchannels, refer to the excellent reviews by Baroud et al. and Seemann et al.81,82 The following discussion is concerned with the focus of this review—methods of establishing droplet and slug flow MEs, i.e., how to generate droplets. To date, four methods have been adopted to generate droplets in microchannels: crossflow, co-flow, focusing-flow, and step emulsification, as shown in Figure 13.

Figure 13 Methods of droplet generation: (A) crossflow, (B) co-flow, (C) focusing-flow, (D) hydrodynamic focusing-flow, and (E) step emulsification

Crossflow method A T-junction is the typical device used to generate droplets in microchannels, as shown in Figure

13-a.83-91 The dispersed phase fed in through the branch inlet is sheared by the continuous phase fed in through the horizontal inlet. There are two main mechanisms for generating droplets: the dripping regime and the squeezing regime.83,84,90 Two dimensionless parameters, the ratio of the width of the branch inlet to that of the horizontal inlet λ and the capillary number Ca, are used to distinguish the two regimes.83 In the dripping regime, λ is much lower than 1.0 and Ca is high enough so that the shear force caused by the shear flow overcomes the surface tension, breaking up the dispersed phase into droplets. In the squeezing regime, λ is about 1.0 and the Ca value is lower, so that the droplet enlarges bit-by-bit to block the microchannel.

18


Page 18 of 71

Page 19 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Consequently, the pressure drop across the surface of the droplet increases, pinching off the droplet. That is, droplet generation is dominated by the shear force in the dripping regime and by the pressure drop in the squeezing regime. The transition from the squeezing to dripping regime occurs at a value of the capillary number of the order of 10-2. In the squeezing regime, the droplet/slug size is determined by the fluxes of both phases and is little influenced by the liquid properties, as expressed in Eq.(5);83,90 in the dripping regime, the droplet/slug size is strongly dependent on the Capillary number Ca, as expressed in Eq. (6).84 1/ 3

Q  L Q ∝  dis  , for droplet generation; ∝ dis , for slug generation Dh  Qcont  W Qcont dp

dp Dh

∝ Cacont

−1

(5)

(6)

Where dp is the mean diameter of droplets, Dh is the hydrodynamic diameter of the microchannel, L is the length of slugs, and W is the width of the microchannel. Qdis and Qcont are the fluxes of the dispersed phase and continuous phase, respectively. Cacont is the Capillary number of the continuous phase.

Co-flow method Figure 13-b shows the structure of a co-flow device. Figure 14 shows three typical flow patterns

observed in such devices: dripping regime, narrowing jet regime and widening jet regime.92,93 The flow pattern is determined by the combined action of the shear force, interfacial tension, and inertial force. The transitions between the flow patterns can be characterized using the capillary number Ca of the outer liquid and the central liquid.92-95 Utada et al. pointed out that droplet generation in a co-flow device can be attributed to the Rayleigh-Plateau instability—the absolute instability and the convective instability.92,93 In the dripping regime, the droplet size is determined by the ratio of fluxes of the phases, which is similar to the above crossflow device. In the narrow jetting mode, the droplet size is determined by (Qdis/Qcont)0.5 and can be expressed as Eq.(7), where Qdis and Qcont are the fluxes of the central dispersed phase and the outer continuous phase, respectively; in the widened jetting mode, the droplet size is in proportion to (Qdis/ucont)0.5 and can be expressed as Eq.(8), where ucont is the velocity of the continuous phase.92

19



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

0 .5

 Q  ≈  2 dis  , for narrow jetting mode Dh  Qcont  dp

Page 20 of 71

(7)

0.5

Q  d p ∝  dis  , for widened jetting mode  ucont 

(8)

Figure 14 Typical flow patterns in a co-flow device: (A) dripping flow, (B) narrow jetting flow (Inner Reynolds number Rein=～7–70, Outer Reynolds number Reout=～15–50), and (C) widened jetting flow (Rein=～60–200, Reout=～1–60).92 (Utada et al., adapted with permission from ref 92. Copyright 2007, APS, Washington.)

Focusing-flow method In 2003, Anna et al. proposed a new method to generate microfluidic droplets, as shown in Figure

13-c.96,97 Figure 13-d shows another device, which is similar to that in Figure 13-c, except for the focusing orifice.98-100 In these device, the continuous phase vertically squeezes the dispersed phase from two sides, and both phases then pass through the focusing orifice together. The shear force and interfacial tension are two main factors that control the droplet size. In addition, the shape and dimensions of the focusing orifice also influence the droplet size. The Rayleigh-Plateau instability is the essential mechanism of droplet generation. In contrast to the crossflow and co-flow devices, the focusing-flow device with a focusing orifice can generate smaller and more monodisperse droplets.96,97 There are two methods for controlling droplet size.101 First, the droplet size and generation rate increase with increases in the flux of the dispersed phase when the flux of the continuous phase is constant. Second, increasing the driving pressure of the

20


Page 21 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


dispersed phase significantly increases the droplet size, but when a threshold value of the pressure is exceeded, the droplet size becomes constant. The flow patterns can mainly be divided into five groups: threading, jetting, dripping, tubing, and viscous displacement, as shown in Figure 15, of which, the jetting and dripping regimes are widely adopted in practice.99,100 The mean diameter of droplets in the two regimes can be determined by Eqs. (9) and (10). The flow patterns can be characterized using the capillary number of each phase as shown in the left of Figure 15. −1   Qcont −3  2.2 × 10  Cacont  , d > 2.5 Dh dp  Qdis + Qcont   ≈ , for dripping regime, Cadis and Cacont < 0.1 − 0.17 Dh   Qcont   0.5 Q + Q Cacont  , d < 2.5 Dh cont  dis  

0.5

 Q  ≈ 3.1 dis  , for jetting regime, Cadis < 0.1 Dh  2Qcont  dp

(9)

(10)

Figure 15 Flow pattern map and typical flow patterns in a focusing-flow device:100 (A) threading, (B) jetting, (C) dripping, (D) tubing, and (E) viscous displacement. (Cubaud et al., adapted with permission from ref 100. Copyright 2008, AIP, Melville.)

Step emulsification method The step emulsification method was first proposed by Priest et al. in 2006 and then further

investigated.102-104 The microfluidic device for this method is shown in Figure 13-e. In this method, the aspect ratio of the microchannel sharply decreases along the flow direction. This sharp change of the aspect ratio makes the confined co-flowing stream unstable, causing it to break up into monodisperse droplets.102

21



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The essential mechanism is as follows. In the upstream and shallow microchannel, the interface between the phases in a thread co-flowing stream is confined and stabilized by the walls. However, the thread flow is anisotropically elongated at the step, which causes the Rayleigh-Plateau instability to affect the elongated thread flow, and the instability is transferred to the downstream droplets.103 Droplets can be generated before the step, at the step (expected), and after the step by using different dispersed phase to continuous phase ratios, as shown the left of Figure 16, which can be characterized using a 2-D map (the right of Figure 16) of the capillary number Ca (=0–0.035) for the dispersed phase and the ratio of the width of the thread flow to the microchannel depth.102

Figure 16 Typical flow patterns in a step emulsification device.102 (Priest et al., adapted with permission from ref 102. Copyright 2006, AIP, Melville.) In addition to these above methods, another method named as drop-on-demand has been widely used to produce monodispersed droplets with picoliter to nanoliter volumes and high frequencies.105-111 The drop-on-demand technology has potential in biological studies, chemical analysis, and materials fabrication. A piezoelectric jet technology has been used widely to generate droplets on demand.105-107 Xu and Attinger proposed the piezoelectric jet technology to dispensing fine droplets on demand directly in the liquid-filled channel.105 In the technology, a 25-100 µm nozzle was connected to a µl-volume reagent chamber and the opposite orifice was connected to a main channel. The whole chip was sealed by a membrane, and a piezoelectric actuator was placed on top of each chamber. Aqueous picoliter to nanoliter droplets, on demand, could be produced at frequencies up to 2.5 KHz, in which the actuator driven the aqueous phase in the chamber into the main channel through the nozzle. Electrowetting is another available way for generating droplets on demand.108,109 5-50µm droplets could be produced through integrating

22


Page 22 of 71

Page 23 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


electrowetting into a microfluidic flow focusing device as shown in Figure 13-C. In addition, Moon et al. devised a robust way to generate picoliter droplets out of a single microliter droplet.111 In the method, a single aqueous droplet was placed between two hydrophilic substrates and then immersed in silicone oil. Consequently, an aqueous liquid bridge was formed. When one substrate was drawn away, the bridge became unstable and generated fine droplets.

3.3 Chaotic flow microfluidic extractor Chaotic flow MEs for two immiscible liquids are developed based on chaotic advection micromixers for two miscible liquids. In fact, the above laminar flow MEs also originate from laminar micromixers available for miscible liquids. In contrast with laminar micromixers, chaotic advection micromixers are more suitable for adaptation to extraction processes as chaotic flow MEs. In chaotic advection micromixers, secondary flows that contain a velocity component vertical to the main flow direction can be generated. These secondary flows destroy regular parallel flows and enable microfluidic masses to be split, stretched, folded, and broken up.112-121 Consequently, the interfacial area is greatly increased, and the required mixing length is reduced. When adapted for use in extraction processes, these advantages are retained and enhance the extraction performance. Because almost all chaotic flow MEs can be operated at Reynolds numbers in the hundreds, which is much larger than those for laminar flow and drop/slug flow MEs (in general, Re < 100), they are much more suitable for the requirements of extraction processes. In chaotic flow MEs, droplets are irregular, disordered, and uncontrollable. Thus, unlike laminar and droplet/slug flow MEs, they cannot be used in analytical chemistry, but is suitable for high-throughput extraction processes. The key to establishing a chaotic flow MEs is the same as that for chaotic advection micromixers, involving generation of secondary flows in microchannels under the laminar flow regime. The modes to generate secondary flows can be divided into active and passive modes.122 The active mode uses external forces, e.g., stirring, ultrasonic wave, and electronic and magnetic field forces, to generate secondary flows. As it is hard to integrate these external force sources with MEs, chaotic advection micromixers and chaotic flow MEs operated in the passive mode have more potential.123 In the passive mode, secondary flows are induced by specially designed microchannels, in which

23



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

transverse mixing occurs. The methods of inducing secondary flows in MEs are identical to those of micromixers for miscible liquids. To induce secondary flows, five types of channels have been implemented in micromixers for miscible liquids: 2-D tortuous microchannels, 3-D twisted microchannels, barrier-embedded microchannels, groove/ridge-machined microchannels, and cylindrical (or semispherical) microchannels, as shown in Figure 17. Alternating curved channels, Tesla microchannels, and zigzag channels are typical 2-D tortuous microchannels, in which secondary flows and transverse transport are produced (Figure 17-a).113,114,116,124 3-D twisted microchannels, such as a wavelike channel, modify the smooth wall of a straight channel to form a wavelike shape (Figure 17-b).125,126 Kim et al. developed barrier-embedded micromixers, in which a Kenics structure was used to induce chaotic flow.117 In addition, Bertsch et al.118 investigated the intersecting and helical barrier (Figure 17-c), and Cheri et al.127 investigated four obstacle geometries embedded in the chamber. Groove/ridge- machined microchannels are built by cutting grooves or placing ridges on the walls of a straight channel to induce transverse flows (Figure 17-d).112,119,128 Cylindrical (or semispherical) microchannels force fluids into a cylindrical or semispherical chamber along the tangential or perpendicular channel to generate vortices with transverse flows (Figure 17-e).120,121,126 These methods can be directly used in chaotic flow MEs. Although chaotic micromixers for miscible liquids have been widely investigated, few passive chaotic MEs have been used for extractions to date.129-132 This may be because during the first stage of development for microfluidic extraction, applications in analytical chemistry (µTAS) have attracted the attention of most researchers. Therefore, laminar and drop/slug flow MEs, with ordered and controllable flow patterns, have been addressed. However, chaotic flow MEs are now gradually attracting interest because they are suitable for high-throughput extraction processes. Xu et al. proposed an oscillating feedback ME using the Coanda effect.129-132 As shown in Figure 18, the recirculating channels could promote generation of an oscillating flow in the mixing chamber. The oscillating flow contains a velocity component vertical to the main flow direction, which enhances mass transfer between the two phases. For a liquid–liquid system consisting of an aqueous phase containing 1076 mg/L of Zr ions and a 30% TBP (Tri-Butyl-Phosphate)-kerosene organic phase, the phase equilibrium was reached in 0.0188 s at a total flux of 60 mL/min.

24


Page 24 of 71

Page 25 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 17 Passive chaotic flow microfluidic extractors: (A) 2-D serpentine microchannel: alternatively curved channel,113,114,116 (Reynolds number Re=0–800; Jang et al., reprinted with permission from ref 113. Copyright 2004, John Wiley & Sons, Hoboken. Hong et al., reprinted with permission from ref 114. Copyright 2004, RSC, Cambridge. Mengeaud et al., reprinted with permission from ref 116. Copyright 2002, ACS, Washington.) (B) 3-D twisted microchannel,126 (Re =～0–10; Lee et al., reprinted with permission from ref 126. Copyright 2005, Springer, Berlin.) (C) barrier-embedded microchannel: Intersecting and helical structure,118 (Re=12; Bertsch et al., reprinted with permission from ref 118. Copyright 2001, RSC, Cambridge.) (D) groove/ridge-machined microchannel,112 (Re=0–100; Stroock et al., reprinted with permission from ref 112. Copyright 2002, Science, Washington.) (E) cylindrical (or semispherical) microchannel121 (Fu et al., adapted with permission from ref 121. Copyright 2013, Elsevier, Amsterdam.)

25



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 18 Oscillating feedback microfluidic extractor: 130 (A) mechanism and (B) flow patterns. (Reynolds number of aqueous phase Rea=100–600; Xu et al., adapted with permission from ref 130. Copyright 2014, Elsevier, Amsterdam.)

3.4 Brief summary Co-current MEs enable continuous microfluidic liquid–liquid extraction. Therefore, they can be used in continuous high-throughput extraction processes. However, there are two issues that should be addressed in practice. First, mass transfer is limited by the thermodynamic phase equilibrium, which makes the extraction efficiency of co-current MEs lower than that of countercurrent MEs. Thus, for a high-throughput

26


Page 26 of 71

Page 27 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


extraction process, it is necessary to integrate several co-current MEs with the same number of phase separators, e.g., settlers, and interstage pumps or check valves to construct a multistage countercurrent flow arrangement. This is further discussed in the subsequent section “Countercurrent flow microfluidic extractor”. Second, as laminar, droplet, and slug flow MEs usually have ordered and controlled flow patterns and monodisperse droplets, they are often used in analytical chemistry. In contrast, chaotic flow MEs usually have polydisperse and disordered droplets, and are difficult to precisely control flow patterns, but they have higher throughputs than the other three types of co-current MEs. Consequently, the chaotic flow MEs are suitable for high-throughput extraction processes. In a co-current flow ME, the transitions between slug flow, droplet flow, laminar flow, and unstable flow are related to the ratio of the inertial force to the surface tension, i.e., the Weber number We. Reference 55 gives a detailed description of experimental results for such systems. In short, as shown in Figure 10, when the surface tension is dominant, slug flow and droplet flow occur, whereas when the inertial force is dominant, laminar flow readily occurs.55 In addition, other aspects are also important for co-current flow MEs, including mass transfer and its modelling, as well as CFD simulation. However, to avoid deviating from the subject of this review and a too long article, these aspects are summarized only briefly here. Some reviews and critical references are also given here to help readers to rapidly locate these critical articles. For modeling of mass transfer in laminar flow MEs, readers can refer to references 133–137; for modeling of mass transfer in droplet/slug flow MEs, readers can refer to references 67, 68, 138, and 139. To date, there has been little research on modeling of mass transfer in chaotic flow MEs because the disordered droplet flow (size distribution, coalescence rate, break-up rate, turbulence, and so on) is too complex. As an excellent review concerning with mass transfer in co-current flow MEs, Kashid et al. reviewed mass transfer models (the stagnant film model, penetration model, and film-penetration model), mass transfer coefficients in different extraction systems, and so on.140 As for the determination of the mass transfer coefficients, instantaneous neutralization (acid-base) reaction is available. Dessimoz et al. determined the mass transfer coefficients in a laminar flow ME and a slug flow ME using a aqueous solution containing NaOH from 0.1 to 0.3 M and a toluene (or hexane) solution containing trichloroacetic acid of 0.6 M, and the global volumetric mass transfer coefficients were both in the range of 0.2-0.5 s-1.67 Similarly, the mass transfer coefficient in a

27



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

droplet flow ME was also determined by monitoring the extraction of succinic acid from n-butanol to aqueous drops containing NaOH.69 Due to the complexity of the flow field, computational fluid dynamics (CFD) has often been adopted to simulate mixing and flow field in co-current flow MEs. Kashid et al. used PIV to visualize the internal circulation in the slug flow in a straight microchannel, and used CFD to predict the internal circulation. The effects of the flow velocity and slug length on the velocity profile and stagnant zones of the internal circulations within a slug with and without a wall film were discussed.141 More CFD simulations for droplets in straight microchannels can refer to references 142-145. In addition, Muradoglu et al. used the finite-volume (FV)/front-tracking (FT) method to study the effects of various non-dimensional parameters on the chaotic mixing in the droplets through a serpentine microchannel.146 During the simulation, the molecular mixing caused by diffusion was ignored, and only the mixing caused by the chaotic advection was considered. It was found that the chaotic mixing is little influenced by the Reynolds number, but significantly depends on the capillary number, the viscosity ratio, and the ratio of the drop size to the microchannel width. Through CFD simulations, Wang et al. confirmed that the best mixing in the droplets moving through a serpentine microchannel occurs when the drop size is comparable with the microchannel width.147

4. COUNTERCURRENT MICROFLUIDIC EXTRACTOR As mentioned above, the extraction efficiency in stop-flow MEs and co-current MEs are limited by the phase equilibrium and thus are rather low. However, countercurrent MEs can overcome this difficulty. In countercurrent extraction, the light liquid phase (usually the organic phase, i.e., solvent) and the heavy liquid phase (usually the aqueous phase, i.e., feed) must be arranged to flow countercurrently. This is easy on the macroscale, but difficult on the microscale, as the viscous force and surface tension force are dominant over the inertial force and gravity on the microscale. Therefore, to date, only a few studies have examined countercurrent microfluidic extraction and extractors.52,148-157,159,160 These studies can be classified as those related to multistage countercurrent MEs, those related to continuous countercurrent MEs, and those related to hybrid countercurrent MEs, on the basis of the mass transfer mode and details of the flow arrangement.

28


Page 28 of 71

Page 29 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 19 Micromixer-settler activated by a driven rod

4.1 Multistage countercurrent microfluidic extractor 4.1.1 Development Owing to the difficulties caused by working on the microscale, including difficulty in completing phase separation, only a few of studies have utilized multistage countercurrent microfluidic extraction. The studies in this field began by determining an appropriate small-volume platform for evaluating a liquid–liquid extraction process in a radioactive environment. In 1955, Wall presented the micromixer-settler shown in Figure 19 to conserve valuable materials and achieve phase equilibrium possible in a reasonably short time.151 The micromixer-settler consisted of a number of stages, with every stage containing one micromixer and one settler. In the micromixer, a central driving rod with perforated discs is reciprocated at a certain frequency to mix two immiscible liquids. In cooperation with the ball used as a check valve at the bottom of the mixer, the driving rod simultaneously lifts the mixed phases to the settler, from which the two phases are separated by gravity flow into adjacent mixing stages in opposite directions. In 2012, Li et al. proposed a bionic device to perform multistage countercurrent microfluidic extraction, as shown in Figure 20.152,153 Every stage consists of a multi-parallel channel section as the mixer

29



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

and a phase separator acting under gravity. In the mixing channels, the aqueous phase is dispersed as droplets in the organic phase (extractant) for mass transfer, in which the two liquids are fed in alternately and flow in parallel (co-current flow). The important feature of this design is the check valves between each two neighboring stages. As a result of these check valves, the two liquids can flow countercurrently.

Figure 20 Bionic multistage countercurrent microextractors:152 (A) the human cardiovascular system, (B) a simulated cardiovascular system, (C) an asymmetrical countercurrent microextraction system, (D) configuration of one stage of the microextractor, including a microcontactor, a phase separator, and two check valves, (E) a symmetrical countercurrent microextraction system, and (F) a four-stage countercurrent microextraction setup. (Reynolds number of organic phase Reo=12–24; Li et al., adapted with permission from ref 152. Copyright 2012, RSC, Cambridge.) In 2013, Holbach and Kockmann proposed another method to realize multistage countercurrent microfluidic extraction (Figure 21).149 This method has two distinguishing features. First, a pump is used to replace the check valve between neighboring stages, as shown in Figure 21-a. Second, phase separation is performed by relying on different surface wettability, i.e., a hydrophobic PEEK tube and a hydrophilic steel sieve (Figure 21-b). An N-stage countercurrent microfluidic extraction requires N + 1 interstage pumps and one pressure control valve for the dispersed phase outlet. The pumps function as pressure balance components and one-way valves. In 2015, Hereijgers et al. proposed a membrane-assisted method.161 The key feature of this method was the use of a membrane to partition the two liquid phases. Owing to the surface tension, the micro pores of the membrane could generate a Laplace pressure to compensate for the pressure loss in every stage. Thus, the valves and/or pumps between neighboring stages in the multistage countercurrent microextraction could be removed. In addition, the two liquid phases in the multistage

30


Page 30 of 71

Page 31 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


countercurrent microfluidic extraction flow co-currently on both sides of the membrane, in which no phase was dispersed, as droplets or slugs, which distinguishes this method from the others described above. However, it should be noted that when a membrane is used to partition the phases, a direct and continuous countercurrent flow arrangement is obviously more suitable than a multistage countercurrent flow arrangement with a co-current flow arrangement in every stage. Thus, multistage countercurrent MEs relying on membranes are not discussed in the section. In addition, Kriel et al. proposed a two-stage countercurrent microextraction process, in which two identical co-current MEs consisting of 24 aqueous and 25 organic phase interdigital inlets were integrated with interstage phase separators (the collection vessels between stages) by gravity to form a complete countercurrent SX circuit.52

Figure 21 A multistage countercurrent microextractor using a number of pumps and a valve: (A) countercurrent arrangement and pressure profile over the stages and (B) schematic of the phase separator (Reynolds number of organic phase Reo=11–400, Capillary number Ca=9.0×10-3–2.5×10-2, Weber number We=0.01–10; based on ref 149.)

31



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

In fact, any co-current ME can be used to establish multistage countercurrent microfluidic extraction, as long as a phase separator is integrated with the co-current ME (micromixer) to form one complete stage and interstage pumps and/or check valves are added between two such neighboring stages. Although only the above four methods are found in the literature to date, we can still conclude that there are two key factors for establishing a multistage countercurrent ME: how to compensate for pressure loss over each stage and how to complete phase separation following mixing of two immiscible liquids.

Figure 22 Schematic of a multistage and continuous countercurrent extractor

Figure 23 Flow arrangement of a multistage countercurrent microfluidic extractor 4.1.2 Pressure compensation

32


Page 32 of 71

Page 33 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


It is clear that a multistage countercurrent ME should be constructed as shown in the top of Figure 22. In fact, the schematic is identical to a macroscale system, in which every stage of the ME consists of one co-current micromixer and one phase separator. In every co-current micromixer, two liquid phases flow co-currently, called parallel flow. Thus, in a multistage countercurrent ME, the flow in every stage is co-current, but the flow is countercurrent from a global standpoint. The necessity of pressure compensation in such systems can be explained by Figure 23, which shows the schematic of a multistage countercurrent ME with two stages. Taking the organic phase as an example, it is necessary to enable the organic phase to flow from point A in the micromixer to point B in the phase separator to maintain pressure PA larger than PB. To establish the countercurrent flow arrangement, the organic phase separated in the phase separator in the second stage must flow into the micromixer of the first stage. Thus, pressure PB should be larger than pressure PC at point C in the inlet of the micromixer in the first stage. Similar to the second stage, the flow of the organic phase in the first stage necessitates that PC is larger than pressure PD at point D in the phase separator of the first stage. Thus, PA is larger than PD. This pressure difference has two consequences. First, the organic phase can flow backward into the phase separator of the first stage from the micromixer of the second stage. Second, regular flow of the aqueous phase from the phase separator of the first stage to the micromixer of the second stage is prevented. Consequently, no countercurrent flow arrangement can be established owing to the pressure loss over every stage, which is caused by the flow resistance of each liquid phase. Two methods can be used to solve these problems by compensating for the pressure loss. Figure 24-a depicts the method adopted by Li et al.,152,153 in which both phases are fed into micromixers alternately and periodically. Each check valve is inserted into the inlet of the respective liquid phase. When one liquid phase flows into the micromixer through its check valve, the other check valve is closed to compensate for the pressure loss and prevent the liquid from flowing backward. This method may be summarized as “alternate feeding and two check valves”. Figure 24-b shows the method adopted by Holbach and Kockmann.149 This method use pumps between two neighboring stages to compensate for the pressure loss. Each pump is simultaneously a check valve. In contrast with the method shown in Figure 24-a, both liquid phases can be continuously fed in, thus enabling higher throughput. This method can be summarized as

33



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

“continuous feeding and interstage pumps”. However, it should be noted that check valves and pumps are typical devices with moving parts, which means that these methodologies are not passive and that their miniaturization and integration with the micromixer and phase separator are difficult.

Figure 24 Two methods to compensate for pressure loss: (A) 2N + 1 interstage check valves and two feeding pumps, and (B) N + 1 interstage pumps and one outlet check valve 4.1.3 Interstage phase separation In a multistage countercurrent ME, it is essential to completely separate the two phases in a phase separator following each micromixer. This is necessary to enable a countercurrent flow arrangement, i.e., turning the co-current flow in every local stage into a countercurrent flow from the overall standpoint. On the macroscale, phase separation, i.e., droplet coalescence, usually relies on density differences between the both phases. Gravity or a centrifugal force is generally used to promote the coalescence of

34


Page 34 of 71

Page 35 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


droplets. However, droplet coalescence on the microscale is very difficult because it is difficult to exert a centrifugal field on a phase separator on the microscale. Moreover, the gravitational force is much smaller than the surface forces that prevent droplets from coalescing. This can be attributed to the increase in the inner pressure caused by the liquid–liquid interfacial tension. It is well known that the interfacial tension gives rise to a pressure drop across the droplet surface, i.e., the Laplace pressure, calculated as 2σ/r, where σ is the interfacial tension and r is the radius of the droplet. Thus, the pressure drop increases with a decrease in the droplet diameter. In comparison to droplets on the macroscale, those on the microscale have very small diameters. This means that the droplets on the microscale experience larger pressure drops across the interface. For the same pressure in the bulk phase, a droplet on the microscale has an inner pressure that is greater than that of a macroscale droplet (inner pressure = bulk pressure + Laplace pressure). As a result, the microscale droplet is more rigid. To coalesce, two droplets undergo the following three steps: approach, shape deformation and film drainage, and film rupture and fusion.34,162 Easy deformation and fast film drainage are important for the coalescence of droplets. However, small rigid droplets are difficult to deform and have low film drainage rates. Thus, on the microscale, coalescence does not occur readily. Here, we give a short summary of interstage phase separation methods to give researchers a quick and clear understanding of the problem. These phase-separating methods (or droplet coalescence methods) to be published in the literature can be classified into three groups by the mechanism of droplet coalescence: gravity separation, surface-wettability separation, and retarding separation.

Figure 25 Settlers adopted by BASF AG:5 (A) 15 mL mini settler, (B) 150 mL settler, and (C) 150 mL settler with a heating jacket. (Benz et al., reprinted with permission from ref 5. Copyright 2001, WILEY, Weinheim.)

35



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Gravity separation Gravity separation can be used to achieve droplet coalesce in a phase separator with larger dimensions,

from several millimeters to several centimeters, by reducing the surface tension. In a larger phase separator, gravity, i.e., the difference between the densities of the two liquid phases, is a dominant factor for promoting droplet coalescence. Such phase separators can also be called settlers. Microfluidic extraction devices that integrate a settler with a micromixer are called Micromixer-settlers in the literature. In 1986, Halperin et al. constructed a micromixer-settler with only one stage, in which a settler of about 1 mL was fitted into a vibration micromixer to perform rapid solvent extraction of radioactive nuclides.154 Kumar et al. integrated a settler of about 1.2 mL with a helical tube micromixer to form a single-stage passive micromixer-settler for nuclear solvent extraction.163,164 In 2001, Benz et al. at BASF AG evaluated interdigital micromixers for extraction processes, in which mini settlers with volumes of 15 and 150 mL were adopted, as shown in Figure 25.5 Overall, the gravity separation method can be easily realized, but the phase separator is larger than the micromixer, and consequently, it is difficult to miniaturize. To overcome the barrier caused by the differences between the microscale and macroscale, the settler and the micromixer are usually manufactured separately and connected by a tube.

Surface-wettability separation Surface-wettability separation uses surface wettability (i.e., surface tension or capillary force) to promote

droplet coalescence. The method can further be divided into membrane-wettability separation and outlet-wettability separation. For the former, Skarnemark et al. used three filter units with Teflon membranes (0.5 µm pore size) to separate an aqueous phase from an emulsion generated in an interdigital micromixer. The hydrophobic Teflon membrane enables the organic phase to pass through its pores, but prevents the aqueous phase from passing through the pores.165 A similar method was used by Kralj et al., in which a hydrophobic PTFE (Polytetrafluoroethylene) membrane (0.1–1.0 µm pore size) was used.166 The mechanism of membrane-wettability separation is schematically depicted in Figure 26. The hydrophobic micro pores are wetted by the organic phase, allowing it to pass through. However, the micro pores are not wetted by the aqueous phase, as the capillary force caused by the surface tension prevents the aqueous

36


Page 36 of 71

Page 37 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


phase entering the pores, and consequently, the two phases are separated. In membrane-wettability separation, only one hydrophobic or hydrophilic material is adopted. In contrast, to completely separate the aqueous phase and the organic phase, outlet-wettability separation uses both hydrophobic and hydrophilic materials to separate the two phases. These materials separately guide the aqueous and organic phases into different outlet channels, thus achieving separation.149,167-169 Here, we introduce two applications of this separation system. As shown in Figure 21-b, Holbach and Kockmann used a hydrophobic PTFE tube and a hydrophilic steel sieve to achieve interstage phase separation.149 Okubo et al. used a similar method for rapid separation of two phases, in which hydrophobic glass and hydrophilic aluminum foil siding were used to direct the phases into different outlet channels.167 Surface-wettability separation is a passive process, and the phase separator can readily be miniaturized and fitted into the micromixer.

Figure 26 Schematic of membrane-wettability separation

Figure 27 Schematic of droplet coalescence by retardation in specially designed microchannels: (A) section variation-induced coalescence170 (Reynolds number of aqueous phase Rea=0.07–0.15, Capillary number Ca=4.37×10-5–8.79×10-5; Bremond et al., reprinted with permission from ref 170. Copyright 2008, APS, Washington.) and (B) pillar-induced coalescence.171 (Rea=0.07–0.76, Ca=2.08×10-5–2.21×10-4; Niu et al., reprinted with permission from ref 171. Copyright 2008, RSC, Cambridge.)

Retarding separation

37



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Figure 28 Schematic structure of a phase separator using both outlet-wettability separation and retarding separation.167 (Reynolds number of aqueous phase Rea=0.25–1.67; Okubo et al., adapted with permission from ref 167. Copyright 2004, Elsevier, Amsterdam.) Retarding separation relies on specially designed microchannels to enable retardation of a leading droplet, which then comes into contact with the following droplet to coalesce.80,167,169 Figure 27 shows two examples of droplet coalesce through retardation. In these specially designed microchannels, the approach of the droplets, drainage of the thin liquid film, rupture of the thin liquid film, and fusion of the two droplets occurs in sequence.170,171 In practice, retarding separation is frequently adopted together with outlet-wettability separation. The outlet-wettability separation approaches by Okubo et al. and Kashid et al. mentioned in the above section simultaneously used retarding separation to promote phase separation.80,167 In the apparatus shown in Figure 28, the distance between the top glass panel and the bottom aluminum foil is 5 or 12 µm, and the width of the microchannel is 10 mm. Experiments proved that complete separation of two phases requires oil droplets with a minimum size of at least the channel depth to allow deformation and

38


Page 38 of 71

Page 39 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


retardation by the hydrophobic PTFE surface.167 If the droplets were smaller than the microchannel dimensions or the bottom panel was replaced with a glass panel, no retardation occurred, and consequently, complete phase separation could not be achieved. 4.1.4 Brief summary In this section, we summarized and analyzed multistage countercurrent MEs. Three issues should be addressed for these systems. First, it should be noted that the three methods of phase separation—gravity, surface-wettability, and retarding—are often adopted collectively to enhance droplet coalescence. As mentioned above, surface-wettability separation integrates retarding separation.

117,167,169

Similarly, in

gravity separation, the settler can be divided into two sections, where the top section is hydrophobic and the bottom section hydrophilic, which can enhance phase separation.152 Second, the phase separation time is a significant factor influencing the performance of a multistage countercurrent ME, and shorter separation times are always preferable. Thus, although electric-field separation (i.e., electric-field coalescence) is not currently available for countercurrent MEs, it should be addressed as a promising method of rapid separation in the future172-175 This is because the coalescence time of this method is very short and it is available for emulsion separation, which is difficult using the above three methods. The performance of these phase separation methods are compared and summarized in Table S1. Third, owing to the interstage pumps and/or valves, multistage countercurrent MEs are active, not passive, which makes it difficult to miniaturize the whole extraction process on a small chip. The modelling of mass transfer in the micromixer in each stage of a multistage countercurrent flow ME is identical with that of a co-current flow ME as long as the micromixer is the same.

4.2 Continuous countercurrent microfluidic extractor 4.2.1 Development Continuous countercurrent MEs have various features that distinguish them from multistage countercurrent MEs, and have an equally important role in microfluidic extraction. The bottom of Figure 22 shows a schematic diagram of a continuous countercurrent extraction arrangement. Multistage countercurrent MEs operate in the stage-wise contact mode, in which mass transfer occurs at every contact

39



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

stage, but not at the cross section between the two stages. In contrast, continuous countercurrent MEs operate in the differential contact mode, in which mass transfer occurs in the cross section where the phases meet. A distinguishing feature of continuous countercurrent MEs is that a continuous and stable interface between the two liquids is required, but complete phase separation does not occur. Owing to this lack of phase separation, all the interstage pumps and/or check valves required in a multistage co-current ME can be removed in a continuous countercurrent ME. This enables continuous countercurrent MEs to have simple structures that are easy to be fabricated, miniaturized, and operated in the passive mode. However, the development and application of continuous countercurrent MEs is hindered by the problem of maintaining a continuous and stable interface between two liquids against the shear force caused by the countercurrent flow.176 Owing to the countercurrent flow, the shear force at the interface is intensified, and consequently, the interface is easily ruined, resulting in one phase is dispersed as droplets in the other phase. To date, only a few research groups have conducted studies in this field. These studies can be divided into two categories: the surface-tension-assisted method and the membrane-assisted method. 4.2.2 Surface-tension-assisted method The mechanism of the surface-tension-assisted method is similar to that of surface-tension-assisted method for co-current MEs. The key is to modify the surface wettability to enhance the surface tension, which contributes to maintaining a stable interface against the shear force and interface instability. In this method, the flows in a microchannel are controlled by patterning surface free energies, as mentioned in 2002 by Zhao et al.59 The Kitamori group carried out numerous investigations in this field.57,148,155-157 In a ME containing top and bottom glass microchannels, they used octadecyltrichlorosilane (ODS) to modify one glass microchannel to change its wettability to hydrophobic from hydrophilic. Figure 29 shows a typical schematic of their work. A continuous interface between the two phases could be maintained for a short length with the enhanced hydrophobic wettability.148 In addition, the interface shape of countercurrently flowing immiscible liquids was investigated, and a curved shape was confirmed. The Laplace pressure caused by the interfacial tension has an important role in maintaining a continuous and stable interface against the shear force.57,156,157, 158 The critical condition maintaining a stable interface is the

40


Page 40 of 71

Page 41 of 71

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


pressure drop △PFlow between the two liquids should be in the range of the Laplace pressure △PLap as follows.158

Figure 29 Schematic of the continuous countercurrent microextraction used by Kitamori et al.:148 (A) a microchip that has undergone selective surface modification, (B) fluorescence microscope images of the countercurrent microflow, and (C) phase-separation conditions at various aqueous (Vaq) and butylacetate (Vbutyl) flow rates. (Reynolds numbers of two phases Rea and Reo:

Review of Microfluidic LiquidâLiquid Extractors - Industrial

Recommend Documents

Review of Microfluidic LiquidâLiquid Extractors - Industrial