Yasith S. Nanayakkara

On-Chip Drop-to-Drop Liquid Microextraction Coupled with Real-Time Concentration Monitoring Technique

This paper demonstrates a novel drop-to-drop liquid-liquid micro-extraction (DTD-LLME) device, which is based on an electrowetting on dielectric (EWOD) digital microfluidic chip. Droplets of two immiscible liquids, one of which is an ionic liquid, are formed in nanoliter volumes, driven along electrodes, merged and mixed for extraction, and finally separated upon the completion of the extraction process. All the steps are carried out on a microfluidic chip using combined electrowetting and dielectrophoretic forces, which act on the droplet upon the application of electric potential. Specially, the phase separation of two immiscible nanoliter-scale liquid drops was achieved for the first time on an EWOD digital microfluidic chip. To study the on-chip extraction kinetics, an image-based concentration measurement technique with suitable color parameters was studied and compared with the typical UV absorption based technique. Finally, the effect of applied ac voltage frequency on the extraction kinetics was studied. The observations on DTD-LLME, particularly phase separation, are discussed. The image-based method was found to be applicable for precise concentration measurements with the right choice of the color parameter. Results from experiments on finding the frequency dependence on extraction kinetics demonstrate that the application of higher frequencies can be a factor in accelerating the extraction on the proposed microextraction device.

A fundamental study on electrowetting by traditional and multifunctional ionic liquids: possible use in electrowetting on dielectric-based microfluidic applications.

Water or aqueous electrolytes are the dominant components in electrowetting on dielectric (EWOD)-based microfluidic devices. Low thermal stability, evaporation, and a propensity to facilitate corrosion of the metal parts of integrated circuits or electronics are drawbacks of aqueous solutions. The alternative use of ionic liquids (ILs) as electrowetting agents in EWOD-based applications or devices could overcome these limitations. Efficient EWOD devices could be developed using task-specific ILs. In this regard, a fundamental study on the electrowetting properties of ILs is essential. Therefore electrowetting properties of 19 different ionic liquids, including mono-, di-, and tricationic, plus mono- and dianionic ILs were examined. All tested ILs showed electrowetting of various magnitudes on an amorphous flouropolymer layer. The effects of IL structure, functionality, and charge density on the electrowetting properties were studied. The enhanced stability of ILs in electrowetting on dielectric at higher voltages was studied in comparison with water. Deviations from classical electrowetting theory were confirmed. The physical properties of ILs and their electrowetting properties were tabulated. These data can be used as references to engineer task-specific electrowetting agents (ILs) for future electrowetting-based applications.

The Effect of AC Frequency on the Electrowetting Behavior of Ionic Liquids

This paper presents a study of electrowetting of ionic liquids (ILs) under AC voltages, where nine different ILs (including mono-, di-, and tricationic varieties) with three different AC frequencies (60 Hz, 1 kHz, 10 kHz) were experimentally investigated. The main foci of this study are (i) an investigation of AC frequency dependence on the electrowetting of ILs; (ii) obtaining theoretical relationships between the relevant factors that explain the experimentally achieved frequency dependence; and (iii) a systematic comparison of electrowetting of ILs using AC vs DC voltage fields. The frequency of the AC voltage was found to be directly related to the apparent contact angle change (Deltatheta) of the ILs. This relationship was further analyzed and explained theoretically. The electrowetting properties of ILs under AC voltages were compared to that under DC voltages. All tested ILs showed greater apparent contact angle changes with AC voltage conditions than with DC voltage conditions. The effect of structure and charge density also was examined. Electrowetting reversibility under AC voltage conditions was studied for few ILs. Finally, the physical properties and AC electrowetting properties of ILs were measured and tabulated.

Linear tricationic room-temperature ionic liquids: synthesis, physiochemical properties, and electrowetting properties.

Efficient and facile synthesis of novel linear tricationic room-temperature ionic liquids was performed, and their physiochemical properties were determined. Different physiochemical properties were observed according to the structural variations such as the cationic moiety and the counteranion of the ionic liquid. The electrowetting properties of these ionic liquids were also investigated, and linear tricationic ionic liquids were shown to be advantageous as effective electrowetting materials due to their high structural flexibility.

Enantiomeric separation of functionalized ethano-bridged Tröger bases using macrocyclic cyclofructan and cyclodextrin chiral selectors in high-performance liquid chromatography and capillary electrophoresis with application of principal component analysis

The enantiomeric separation of a series of racemic functionalized ethano-bridged Tröger base compounds was examined by high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Using HPLC and CE the entire set of 14 derivatives was separated by chiral stationary phases (CSPs) and chiral additives composed of cyclodextrin (native and derivatized) and cyclofructan (derivatized). Baseline separations (Rs≥1.5) in HPLC were achieved for 13 of the 14 compounds with resolution values as high as 5.0. CE produced 2 baseline separations. The separations on the cyclodextrin CSPs showed optimum results in the reversed phase mode, and the LARIHC™ cyclofructan CSPs separations showed optimum results in the normal phase mode. HPLC separation data of the compounds was analyzed using principal component analysis (PCA). The PCA biplot analysis showed that retention is governed by the size of the R1 substituent in the case of derivatized cyclofructan and cyclodextrin CSPs, and enantiomeric resolution closely correlated with the size of the R2 group in the case of non-derivatized γ-cyclodextrin CSP. It is clearly shown that chromatographic retention is necessary but not sufficient for the enantiomeric separations of these compounds.

Enantiomeric separation of isochromene derivatives by high-performance liquid chromatography using cyclodextrin based stationary phases and principal component analysis of the separation data

Isochromene derivatives are very important precursors in the natural products industry. Hence the enantiomeric separations of chiral isochromenes are important in the pharmaceutical industry and for organic asymmetric synthesis. Here we report enantiomeric separations of 21 different chiral isochromene derivatives, which were synthesized using alkynylbenzaldehyde cyclization catalyzed by chiral gold(I) acyclic diaminocarbene complexes. All separations were achieved by high-performance liquid chromatography with cyclodextrin based (Cyclobond) chiral stationary phases. Retention data of 21 chiral compounds and 14 other previously separated isochromene derivatives were analyzed using principal component analysis. The effect of the structure of the substituents on the isochromene ring on enantiomeric resolution as well as the other separation properties was analyzed in detail. Using principal component analysis it can be shown that the structural features that contribute to increased retention are different from those that enhance enantiomeric resolution. In addition, principal component analysis is useful for eliminating redundant factors from consideration when analyzing the effect of various chromatographic parameters. It was found that the chiral recognition mechanism is different for the larger γ-cyclodextrin as compared to the smaller β-cyclodextrin derivatives. Finally this specific system of chiral analytes and cyclodextrin based chiral selectors provides an effective format to examine the application of principal component analysis to enantiomeric separations using basic retention data and structural features.

A liquid drop RC filter apparatus for detection.

AbstractA new analytical detector based on a liquid drop resistor–capacitor (RC) filter is described, in which transformed gain vs. frequency curves are used to analyze compounds. This detector can be used to detect either charged or neutral species (that are dielectrically different) which are dissolved in a liquid (e.g., water, alcohol, solvent mixtures, etc.). This device was fabricated by modifying an electrowetting on dielectric (EWOD)-based experimental setup. When a liquid drop is placed on a dielectric surface, the system acts as a RC filter. At a given frequency, gain is a function of conductivity, surface tension, dielectric constant, double-layer thickness of the solid–liquid drop interface, as well as the applied voltage. Since different liquids and solutions have different physical properties, each liquid/solution has a unique curve (peak) in gain vs. frequency plot. This is the basic principle behind the detector. Different amounts of zinc chloride dissolved in water, benzalkonium chloride in water, 1-methylimidazole in water, cetyltrimethyl-ammonium chloride (CTAC) in water, and CTAC dissolved in ethylene glycol solutions were tested with the detector as proof of principle. The device can be used as a stand-alone detector or can easily be coupled with droplet based microfluidic lab-on-a-chip systems such as EWOD-based microfluidic chips. FigureThe liquid drop RC filter apparatus and obtained curves for CTAC standard solutions

Digital Microfluidic Device Using Ionic Liquids for Electronic Hotspot Cooling

Thermal management in electronics become more challenging as the size of electronics decreases, yet, the heat generated from electronics still increases. To enhance cooling efficiency of conventional cooling schemes such as heat pipes, we experimentally present a use of electrowetting on dielectric (EWOD) digital microfluidic technique to force the cooling liquid medium to move to hot spot area. In this paper, firstly, two different EWOD devices were compared in their cooling performance. One is a system using one plane device and sessile droplet of cooling medium and the other is a system using two parallel planes and liquid is sandwiched in between. Secondly, two types of liquids were used and compared as the cooling medium. De-ionized (DI) water and room temperature ionic liquid (RTIL) have been investigated. RTILs are thermally stable thanks to their low vapor pressure. In addition to thermal stability, RTIL can be tailored task specifically by altering cations and anions. Different experiments were conducted to study the capacity of IL’s to change the surface temperature of the hotspot generated and this was compared with that of DI water. The latter showed higher capacity to remove heat, while evaporation problem was predominant in the sandwiched setup. Three different ionic liquids, 1-butyl-3-methylimidazolium chloride or [BMIM]Cl, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)-imide or [BMIM]Ntf2, and [CMIM]FeCl4 showed less effect on changing the surface temperature compared to water. It is due to generally lower heat conductivity and higher viscosity of ILs than water. However, RTILs showed high thermal stability by resulting in no evaporation during cooling process while water had vigorous evaporation. Nanofluid of RTIL and multiwall carbon nanotubes (MWCNT) mixture has been tested as the first step toward enhancing thermal conductivity of RTIL.Copyright

EWOD based liquid-liquid extraction and separation

Liquid-liquid extraction techniques are one of the major tools in chemical engineering, analytical chemistry, and biology, especially in a system where two immiscible liquids have an interface solutes exchange between the two liquid phases along the interface up to a point where the concentration ratios in the two liquids reach their equilibrium values [1]. Solutes including nucleic acids and proteins of interests can be extracted from one liquid phase to the other immiscible liquid phase as a preparation step for many analytical processes.There are several advantages in miniaturizing the liquid-liquid extraction methods to on-chip level extraction. Usual advantages of miniaturization are the reduction in the sample size and portability. In addition, transport phenomena is faster in Micro-systems than in ordinary size systems, and therefore, one may expect that liquid-liquid extraction takes less time to achieve in miniaturized devices. It is due to shorter diffusion time in micro scale as well as high surface to volume ratio of Microsystems.Electrowetting on dielectric (EWOD) digital microfluidics is an efficient platform to process droplet based analytical processes [2]. Nanoliter (nL) or smaller volume of aqueous liquid droplets can be generated and transported on a chip by EWOD process. In addition to the high surface to volume ratio, high chemical potential can be expected in droplet based extraction when the droplets are in motion.In this paper, we propose to use room temperature ionic liquid (RTIL) as a second liquid phase for extraction, which forms immiscible interface with aqueous solutions. Properties of RTIL can be tailored by choice of cation, anion and substituents. RTIL has been investigated as replacements for the organic solvents and various “task-specific” ionic liquid are being developed which exhibit many attractive properties such as very low vapor pressure, high thermal stability [3]. We recently published EWOD properties of various RTILs toward microfluidic applications [4]. To demonstrate liquid-liquid micro extraction on chip, we fabricated and tested EWOD digital microfluidic devices. Fig. 1 shows (a) top and (b) cross sectional views of EWOD device. Two model extraction systems were tested. One is organic dye extracted from RTIL (1-butyl-3-methylimidazolium bis(trifluoromethanesulfonylimide or BMIMNTf2) to water and the other is iodine (I2) extracted from water to BMIMNTf2. The later model experiment is demonstrated in Fig. 2. Droplets of aqueous solution and BMIMNTf2 solution were generated on chip reservoir then transported for extraction and separated by EWOD actuation. When an aqueous solution and BMIMNTf2 solution join together, they created an interface, since water and BMIMNTf2 are immiscible. Extraction of I2 was done along the interface. After successful extraction, two immiscible liquid phases were separated by EWOD actuation and formed two separate droplets. From the result shown in Fig 2 (g), it is expected that extraction performance at the interface of moving droplet would be enhanced compared to the stationary droplet, because a moving interface prevent the chemical equilibrium, thus more chemical extraction potential can be provided with a moving interface than at a stationary interface.This demonstration is the first step toward total analysis system. The presented result opens the way to on-chip micro extraction, which will be readily integrated with other sample preparation microfluidic components and detection components. Currently, micro extraction systems for larger molecules such as nucleic acids, proteins and biological cells are being developed for further analytical applications.Copyright

Liquid-Liquid Extraction Based on Digital Microfluidics

Liquid-liquid extraction techniques are one of the major tools in chemical engineering, analytical chemistry, and biology, especially in a system where two immiscible liquids have an interface solutes exchange between the two liquid phases along the interface up to a point where the concentration ratios in the two liquids reach their equilibrium values [1]. In this paper, we propose to use room temperature ionic liquid (RTIL) as a second liquid phase for extraction, which forms immiscible interface with aqueous solutions. We demonstrate liquid-liquid extraction with the EWOD digital microfluidic device, two model extraction systems were tested. One is organic dye extracted from RTIL(1-butyl-3-methylimidazolium bis(trifluoromethanesulfonylimide or BMIMNTf2) to water and the other is iodine (I2 ) extracted from water to BMIMNTf2. Droplets of aqueous solution and BMIMNTf2 solution were generated on chip reservoir then transported for extraction and separated by EWOD actuation successfully.Copyright