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Lateral Transport of Solutes in Microfluidic Channels Using Electrochemically Generated Gradients in Redox-Active Surfactants Xiaoyang Liu and Nicholas L. Abbott* Department of Chemical and Biological Engineering, University of Wisconsin, 1415 Engineering Drive, Madison, Wisconsin 53706-1691, United States
bS Supporting Information ABSTRACT: We report principles for a continuous flow process that can separate solutes based on a driving force for selective transport that is generated by a lateral concentration gradient of a redox-active surfactant across a microfluidic channel. Microfluidic channels fabricated with gold electrodes lining each vertical wall were used to electrochemically generate concentration gradients of the redox-active surfactant 11-ferrocenylundecyl-trimethylammonium bromide (FTMA) in a direction perpendicular to the flow. The interactions of three solutes (a hydrophobic dye, 1-phenylazo-2-naphthylamine (yellow AB), an amphiphilic molecule, 2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine (BODIPY C5-HPC), and an organic salt, 1-methylpyridinium-3-sulfonate (MPS)) with the lateral gradients in surfactant/micelle concentration were shown to drive the formation of solute-specific concentration gradients. Two distinct physical mechanisms were identified to lead to the solute concentration gradients: solubilization of solutes by micelles and differential adsorption of the solutes onto the walls of the microchannels in the presence of the surfactant concentration gradient. These two mechanisms were used to demonstrate delipidation of a mixture of BODIPY C5-HPC (lipid) and MPS and purification of BODIPY C5-HPC from a mixture of BODIPY C5-HPC and yellow AB. Overall, the results of this study demonstrate that lateral concentration gradients of redox-active surfactants formed within microfluidic channels can be used to transport solutes across the microfluidic channels in a solutedependent manner. The approach employs electrical potentials (0.1M), and offers the basis of continuous processes for the purification or separation of solutes in microscale systems.
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n this paper, we report that spatial gradients in surfactant concentration that are generated electrochemically within a microfluidic channel offer the basis of continuous microscale separations and analytical schemes. Whereas surfactants have been used in many analytical and preparative techniques for the separation of solutes, including liquid chromatography18 and capillary electrophoresis,918 the majority of these approaches are batch processes. Our approach to development of continuous separation processes exploits a redox-active surfactant that contains ferrocene (11-ferrocenylundecyl-trimethylammonium bromide; FTMA) (Figure 1A).1923 Past studies have demonstrated that the ferrocene group of FTMA can be electrochemically reduced and oxidized over numerous cycles within a window of electrochemical potentials that does not lead to substantial electrolysis of water.24 Whereas the reduced state of FTMA (in which the ferrocene is not charged, left side of Figure 1A) exhibits properties that are typical of small amphiphiles (e.g., FTMA exhibits a critical micelle concentration at 0.1 mM in aqueous 0.1 M Li2SO4), oxidized FTMA (in which ferrocene is oxidized to the ferrocenium cation, right side of Figure 1A) is not measurably self-associated over the experimental conditions investigated to date (up to 30 mM in 0.1 M Li2SO4).25 A number of past studies have also demonstrated that changes in the oxidation state of ferrocene-containing surfactants can change the interactions r 2011 American Chemical Society
of the surfactants with organic dyes,2634 biomolecules (e.g., DNA), and semisynthetic polymers.35,36 The principles that we report in this paper rely on the generation of spatial gradients in the concentration of monomeric surfactants and micelles of FTMA across the width of a microfluidic channel, as shown in Figure 1B.37 Aqueous FTMA solutions are pumped through a microfluidic channel while applying a reducing electrical potential to a gold electrode lining one side-wall of the microfluidic channel and an oxidizing potential to a second gold electrode lining the other wall. During transit through the channel, the FTMA molecules are driven through a series of oxidation and reduction cycles, diffusing back and forth between the two electrodes that line the channel. Following an initial transient near the entrance of the channel, steady-state concentration profiles of oxidized and reduced surfactant are thus formed across the microfluidic channel. In the regions of the channel where the concentration of reduced FTMA exceeds the critical micelle concentration (CMC), FTMA micelles form, leading to spatially localized regions of solution containing micelles (as shown in Figure 1B). Recently, Received: December 11, 2010 Accepted: February 26, 2011 Published: March 29, 2011 3033
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Analytical Chemistry
Figure 1. (A) Molecular structures of 11-ferrocenylundecyltrimethylammonium bromide (FTMA) in reduced (left) and oxidized (right) states. (B) Schematic illustration of electrochemically generated gradient in concentration of FTMA across the microfluidic channel. (C) Schematic illustration of top view of the outlet of the microfluidic channel.
we characterized lateral concentration profiles of FTMA formed in microfluidic channels and demonstrated that it was possible to manipulate the lateral concentration profiles by changing the potentials applied to the electrodes lining the walls of the channel.37 The interactions of solutes (analytes) with the
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electrochemically generated concentration gradients of FTMA, however, have not been reported. This paper is focused on the interactions of solutes with gradients in concentration of FTMA, generated as described above, and the use of these interactions to drive the selective transport of analytes across microfluidic channels. Past studies have shown that a wide range of solutes will interact with surfactants through solute-specific, physical mechanisms.2628,3436,38,39 For example, small organic molecules can be solubilized within the hydrophobic interior or palisade layer of a micelle.38 Alternatively, polyelectrolyes and DNA interact with surfactants through electrostatic and hydrophobic forces in a manner that is dependent upon the extent of self-association of the surfactants.35,36 We hypothesized, therefore, that solutes, when fed into a microfluidic channel in the presence of a gradient in concentration of FTMA, would experience a driving force that leads to lateral partitioning of the solutes across the channel as a consequence of concentration-dependent interactions between the solutes and FTMA. We hypothesized that such lateral transport processes would depend on the structure and properties of the solutes and, thus, might offer the basis of principles for continuous microscale separations and analytical processes. In this paper, we report an investigation of three model solutes: a hydrophobic dye (1-phenylazo-2-naphthylamine, referred as yellow AB; Figure S1A, Supporting Information), an amphiphilic molecule (the lipid 2-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4adiaza-s-indacene-3-pentanoyl)-1-hexadecanoyl-sn-glycero-3phosphocholine, referred as BODIPY C5-HPC; Figure S1B, Supporting Information), and a hydrophilic molecule (the organic salt 1-methylpyridinium-3-sulfonate, referred as MPS; Figure S1C, Supporting Information) The approach described in this paper can be viewed as a fieldflow fractionation (FFF), of which there are various types, including electric field flow fractionation (EFFF), isoelectricfocusing (IEF) FFF,4044 transverse IEF,45,46 and free-flow electrophoresis.47 All these FFF methods employ an external electric field that is applied perpendicular to the direction of flow of a mobile phase. Our approach, however, is distinguished from these past examples of FFF by several attributes: (i) The driving force. The driving force underlying the transport processes involved in EFFF is derived from the interaction of the charges of the solutes with the external electric field. In contrast, in our approach, the driving force for the lateral transport of solutes is a gradient in solute chemical potential that arises from the abovementioned interactions of the solutes and surfactants. (ii) The magnitude of applied electrical potentials. Whereas EFFF requires the use of large potentials (>1 V) to generate a field that extends across the channel, our approach requires the use of only small potentials (00.3 V vs Ag|AgCl) to oxidize and reduce FTMA at the electrodes, thus minimizing changes in pH, Joule heating, bubble generation, and convective disturbances that are associated with the fields and potentials required for EFFF.48 (iii) The concentration of electrolyte. EFFF requires the use of low concentrations of electrolyte because high concentrations screen the applied electrical fields, thus resulting in low rates of migration of solutes. In contrast, the Faradaic electrode processes that lead to the generation of the lateral gradients in FTMA concentration are readily performed in the presence of high concentrations of electrolyte (0.1 M Li2SO4). (iv) Range of applicable solutes. Whereas EFFF can be applied to the separation of solutes that are readily dissolved in water, the principles reported here are not constrained to water-soluble molecules. As 3034
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demonstrated in this study, molecules that are only sparingly soluble in aqueous solutions can also be separated using FTMA.
’ MATERIALS AND METHODS The sources of all materials and detailed experimental methods are described in Supporting Information. In brief, microfluidic channels were fabricated with depths of 80 μm, widths of 80 μm, and lengths of 40 mm. A detailed description of the design and fabrication of the microfluidic channels (with electrodes lining each of the two vertical walls of the channels) can be found elsewhere.37 Aqueous solutions of FTMA and solutes were fed to the microfluidic system from an upstream reservoir via a Micro-Line tube (inner diameter of 0.51 mm, Thermoplastic Processes, Stirling, NJ). The electrical potentials of the electrodes were controlled using a bipotentiostat. Downstream of the microfluidic channel, the flow was equally split into four channels (Figure 1C). Each outlet channel was connected to a separate syringe of a 10 channel syringe pump (KDS230, KD Scientific Inc., Holliston, MA) in order to draw FTMA solutions through the microfluidic channel at a desired flow rate and collect and analyze the compositions of the outlet streams. In preliminary experiments, yellow AB was measured to adsorb onto the tubes that connected the microfluidic channel with the upstream reservoir and (downstream) syringe pumps. To address this issue, we preadsorbed yellow AB onto the surfaces of the tubes by filling the tubes with a methanolic solution of yellow AB (2 106 mol/g), evaporating the methanol under vacuum, and then feeding a 1 mM reduced FTMA aqueous solution at a flow rate of 0.04 mL/h until the concentration of yellow AB at the outlet of the tube was very low (
