Current advances and challenges in microfluidic free-flow electrophoresis—A critical review (original) (raw)

High performance microfluidic capillary electrophoresis devices

Biomedical Microdevices, 2007

This paper presents a novel microfluidic capillary electrophoresis (CE) device featuring a double-T-form injection system and an expansion chamber located at the inlet of the separation channel. This study addresses the principal material transport mechanisms depending on parameters such as the expansion ratio, the expansion length, the fluid flow. Its design utilizes a double-L injection technique and combines the expansion chamber to minimize the sample leakage effect and to deliver a highquality sample plug into the separation channel so that the detection performance of the device is enhanced. Experimental and numerical testing of the proposed microfluidic device that integrates an expansion chamber located at the inlet of the separation channel confirms its ability to increase the separation efficiency by improving the sample plug shape and orientation. The novel microfluidic capillary electrophoresis device presented in this paper has demonstrated a sound potential for future use in high-quality, high-throughput chemical analysis applications and throughout the micro-total-analysis systems field.

Bubble-Free Operation of a Microfluidic FreeFlow Electrophoresis Chip with Integrated Pt Electrodes

Analytical Chemistry, 2008

In order to ensure a stable and efficient separation in microfluidic free-flow electrophoresis (FFE) devices, various methods and chips have been presented until now. A major concern hereby is the generation of gas bubbles caused by electrolysis and the resulting disturbances in the position of the separated analyte lanes. Instable lane positions would lead to a decreased resolution in sample collection over time which certainly would be problematic when incorporating a stationary detector system. In contrast to our previous publications, in which we implemented laborious semipermeable membranes to keep bubbles outside the separation region, here we describe an electrochemical approach to suppress the electrolysis of water molecules and therefore bubble formation. This approach allowed a simpler and additionally a closed chip device with integrated platinum electrodes. With the use of this chip, the successful separation of three fluorescent compounds was demonstrated. Quinhydrone, which is a complex of hydroquinone and p-benzoquinone, was added only to the local flow streams along the electrodes, preventing mixing with the separation media and sample. The electrical current was generated via the oxidization and reduction of hydroquinone and p-benzoquinone up to a certain limit of the electrical current without gas formation. The separation stability was investigated for the chip with and without quinhydrone, and the results clearly indicated the improvement. In contrast to the device operating without quinhydrone, a 2.5-fold increase in resolution was achieved. Furthermore, separation was demonstrated within tens of milliseconds. This chemical approach with its high miniaturization possibilities offers an interesting alternative, in particular for low-current miniaturized FFE systems, in which large and open electrode reservoirs are not tolerable.

Microfab-less microfluidic capillary electrophoresis devices

Analytical Methods, 2013

Compared to conventional benchtop instruments, microfluidic devices possess advantageous characteristics including great portability potential, reduced analysis time (minutes), and relatively inexpensive production, putting them on the forefront of modern analytical chemistry. Fabrication of these devices, however, often involves polymeric materials with less-than-ideal surface properties, specific instrumentation, and cumbersome fabrication procedures. In order to overcome such drawbacks, a new hybrid platform is proposed. The platform is centered on the use of 5 interconnecting microfluidic components that serve as either the injector or reservoirs. These plastic units are interconnected using standard capillary tubing, enabling in-channel detection by a wide variety of standard techniques, including capacitively coupled contactless conductivity detection (C 4 D). Due to the minimum impact on the separation efficiency, the plastic microfluidic components used for the experiments discussed herein were fabricated using an inexpensive engraving tool and standard Plexiglas. The presented approach (named 5 2 -platform) offers a previously unseen versatility, enabling the assembly of the platform within minutes using capillary tubing that differs in length, diameter, or material. The advantages of the proposed design are demonstrated by performing the analysis of inorganic cations by capillary electrophoresis on soil samples from the Atacama Desert.

Flow rate independent gradient generator and application in microfluidic free-flow electrophoresis

Analytica Chimica Acta, 2018

Microfluidic gradient generators have been employed in several works in the literature. However, these are typically application specific and especially limited in the range of flow rates that result in the required concentration gradient outputs. Here, a flow rate independent gradient generator designed as a modified Christmas tree-like microfluidic channel network including micromixers at each channel branch is demonstrated. The device was characterized theoretically, modeled using finite element analysis and tested experimentally. Input flow rates up to 200 µl/min, resulting in a maximum speed of about 333 mm/s, for the generation of linear and mirrored linear gradients were demonstrated. As an application example, the gradient generator was monolithically integrated with microfluidic free-flow electrophoresis for the separation/concentration of fluorophores using a novel E-field gradient free-flow electrophoresis mode. The separation of fluorophores, having different charge stages, showed concentration factors of up to 10 fold. In addition, an extended theoretical description of the realizable concentration gradients and the electric field gradient is presented as supplementary information.

Passive electrophoresis in microchannels using liquid junction potentials

ELECTROPHORESIS, 2002

The formation of the liquid junction potential (LJP) is a well-studied phenomenon that occurs in the presence of ionic concentration gradients. Although the LJP has been well characterized, its impact has generally been overlooked in microfluidic applications. The characteristics of flow in microfluidic channels cause this phenomenon to be particularly important, both as a source of deviation from anticipated results and as a tool capable of being harnessed to perform useful tasks. It is demonstrated that LJPs formed in microchannels can induce appreciable electrophoretic transport of charged species without the use of electrodes or an external power supply. This process is demonstrated in an H-filter (an H-shaped microfluidic channel used to bring two fluids into contact allowing extraction of diffusing species from one stream to another) by generating junction potentials between two flowing streams containing different concentrations of strong electrolytes and observing the mass transport of the charged dye fluorescein between those streams. It is shown that the LJP can be controlled to either accelerate or decelerate mass transport across a fluid interface in the absence of an interposed membrane. A preliminary mathematical description of the phenomena is offered to support the hypothesis that the observed mass transport is a result of the LJP. Possible practical microfluidic applications of electrophoretic transport without electrodes are discussed.

Miniaturizing free-flow electrophoresis - A critical review

Electrophoresis, 2008

Free-flow electrophoresis (FFE) separation methods have been developed and investigated for around 50 years and have been applied not only to many types of analytes for various biomedical applications, but also for the separation of inorganic and organic substances. Its continuous sample preparation and mild separation conditions make it also interesting for online monitoring and detection applications. Since 1994 several microfluidic, miniaturized FFE devices were developed and experimentally characterized. In contrast to their large-scale counterparts microfluidic FFE (μ-FFE) devices offer new possibilities due to the very rapid separations within several seconds or below and the requirement for sample volumes in the microliter range. Eventually, these μ-FFE systems might find application in so-called lab-on-a-chip devices for real-time monitoring and separation applications. This review gives detailed information on the results so far published on μ-FFE chips, comprising its four main modes, namely free-flow zone electrophoresis (FFZE), free-flow IEF (FFIEF), free-flow ITP (FFITP), and free-flow field-step electrophoresis (FFFSE). The principles of the different FFE modes and the basic underlying theory are given and discussed with special emphasis on miniaturization. Different designs as well as fabrication methods and applied materials are discussed and evaluated. Furthermore, the separation results shown indicate that similar separation quality with respect to conventional FFE systems, as defined by the resolution and peak capacity, can be achieved with μ-FFE separations when applying much lower electrical voltages. Furthermore, innovations still occur and several approaches for hyphenated, more integrated systems have been proposed so far, some of which are discussed here. This review is intended as an introduction and early compendium for research and development within this field.

Free Flow Electrophoresis Separation of Proteins and DNA Using Microfluidics and Polycarbonate Membranes

Procedia Engineering, 2016

Microfluidic free flow electrophoresis (FFE) enables several advantages directly related to size reduction, however at the cost of difficult fabrication strategies that compromise either the device's efficiency or shelf-time. We circumvent these limitations by integrating polycarbonate sheets as ionic permeable membranes to separate electrolyte and separation chamber compartments. The membrane effectively blocks hydrodynamic flow while no additional electrical resistance between fluidic compartments could be measured. We performed isoelectric focusing (IEF) experiments to separate a series of proteins with different pI values in the 3.5-9.3 range. We also demonstrate the separation of DNA according to its size in zone electrophoresis (ZE) mode.

Modelling the Operational Limits of a Separation Enhancement Method for Capillary Electrophoresis: a Designer's Tool

Procedia Engineering, 2012

We report on a model giving new insight into electrokinetic fluid flow in microfluidic devices, and demonstrate its use as a tool for designing capillary electrophoresis (CE) systems; particularly lab-on-a-chip applications. The electroosmotic flow (EOF) is directly related to the zeta-potential which can be dynamically modified by applying a potential to a zeta-potential modification (ZPM) electrode close to the channel wall [1]. We investigate the effect on EOF where the zeta-potential is modified along a single channel wall, rather than complete channel coverage. We consider the effect for a single channel wall because it makes the fabrication process simpler. The EOF affects the amount of separation attainable in CE systems for a given channel length. We show that with control of the EOF, separations can be achieved in channels of shorter length. The use of a single electrode introduces peak broadening; we investigate the effect this has on the separation and the limits it places on the separation enhancement method.