The field of electrophoresis encompasses separations of molecules or particles based on their migration in an applied electric field. Electrophoresis now includes a wide variety of techniques including isoelectric focusing (IEF), isotachophoresis (ITP), 2-D gel electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), capillary electrophoresis (CE), free-flow electrophoresis (FFE), dielectrophoresis (DEP), as well as other forms of electrokinetics or movement directed by an applied electric field.
Figure 1 – A schematic of the microfluidic sorter for nanoparticles and nanocrystals is shown on the left. An inlet channel leads to a constriction, where dielectrophoretic forces focus larger particles into the center outlet channel. Smaller particles are deflected in the upper and lower outlet channels. Electric potentials are applied to the end of the channel through corresponding reservoirs (not depicted) to evoke electrokinetic transport of sample from the inlet (left) and generate electric field gradients at the constriction for dielectrophoresis.Research in electrokinetics now intersects the interdisciplinary fields of microfluidics and microdevices, biotechnology, and material synthesis. Fundamental and applied research characterizing electrokinesis and electrophoresis impacts scientific investigations in clinical, basic, and applied disciplines from cancer research to molecular biology. Toward this end, the AES Electrophoresis Society annual meeting is dedicated to the development and refinement of electrophoretic and detection technologies by sharing high-quality science and techniques from scientists and engineers from many disciplines to facilitate peer-to-peer training, communication, and the training of AES Electrophoresis Society members and scientists worldwide. For this reason, over 100 scientists from all over the world attended the AES Electrophoresis Society Annual Meeting hosted at the 2013 fall meeting of the Association for Industrial Chemical Engineers (AIChE) (November 3–8) as a special topic of the AIChE conference.
Critical topics in electrophoresis and electrokinetics include:
1. Advances in electrokinetics and electrophoresis
- Behavior and assembly of micro- and nanoparticles
- Nonpolar media
- Nanoscale
- Theory
2. Advances in bioanalytical, biosensing, and biomedical applications
- Microfluidics
- Sample preparation
- Electroporation, electrophysiology, and cell electrokinetics
- Electrophoretic protein separation, and analysis
3. Ionic fluxes at interfaces
The small audience and topic focus encouraged discussion. The AES 2013 annual meeting attracts in-depth discussion as scientists and engineers try to understand and apply new ideas, models, phenomena, and tools to their own research areas. Despite the small size, it was still possible to hold 14 sessions and a poster session with parallel sessions each afternoon of the three-day meeting.
AES 2013 meeting highlights
Advances in electrokinetics and electrophoresis
Nanoscale electrokinetics presents both challenging and intriguing physics due to feature dimensions that are on the same length scale as the electrical double layer. Toward this end, Dr. David Davidson from Stanford University (Stanford, CA) presented a numerical analysis of electric double layers. The model was applied to predict conditions for chaotic flow behavior. It was shown that the electrokinetic instability leads to chaotic transport, otherwise unheard of at the low Reynolds numbers seen in micro- and nanodevices.
Another highlight was representative of the quality of the numerous international contributors. From the Institute of Chemical Technology in Prague, Czech Republic, Jiří Hrdlička presented a mathematical model describing traveling-wave electroosmotic micropumps to explain their rather poor ability to work against pressure loads. Hrdlička’s group took an unusual approach, using a combination of the Poisson-Nernst-Planck and the Navier-Stokes equations, without common simplifications for dynamic simulations to study the energy transformations and the charging of the electric double layers. According to their findings, the alternating current (AC) electroosmosis is only suitable at the submicrometer scale, since the pump’s ability to work against pressure loads diminishes rapidly when increasing the channel diameter.
Insulator-based dielectrophoresis (iDEP) dominated the workshop. iDEP is a phenomenon in which a nonlinear electric field is created between two electrodes of the same geometry in an electrolyte-filled microfluidic channel by using the geometry of barriers etched in the channel to create an electric field gradient. Highlights included labs from Arizona State University (Phoenix, AZ) and Rochester Institute of Technology (Rochester, NY) showing the simulation and testing of the impact of geometries and patterns of insulator posts etched into the channel on the trapping of particles.
Electrokinetics at the micro- and nanoscale is heavily influenced by surface effects, particularly surface charge. Glass and polymethyl methylacrylate (PMMA) surfaces were analyzed and compared to better understand how to translate electrokinetic behavior originally observed in glass to polymer substrates. Comparison of electrophoretic, dielectrophoretic, and electroosmotic forces were presented. Influence of proteins in the membrane on electrical properties was shown.
The need for low-cost microfluidic devices for studying electrokinetics was evident in multiple presentations and was particularly emphasized in two fabrication and new materials characterization papers. Karen Bengtsson from Linköping University (Linköping, Sweden) characterized the materials used in microfluidic devices made by 3-D printing. In their method, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) was used as a conductive material, polyethylene glycol (PEG) was used as 3-D mask to form channels and was later dissolved in water, and polydimethylsiloxane (PDMS) sealed the channel. The effect on free zone electrophoresis was described.
Advances in bioanalytical, biosensing, and biomedical applications
Contract clinical labs, hospitals, and biomedical researchers depend on the tools available for measuring everything from small molecules to cells. Of particular importance is the detection and quantitation of a wide variety of biomarkers. In the Advances in Electrophoretic Protein Separation and Analysis session, Nancy Kendrick of Kendrick Labs (Madison, WI) described the detection of phosphothyrosine in thawed lung cancer cells Western blotting duplexing.
Exciting for those in this emerging field, the theory and application of iDEP dominated many sessions, including the applied biology session. In one example, the constriction of a channel connected to five output channels in an applied electric field was used for separation of 0.1- and 1-μm particles by Alexandra Ros of Arizona State University (ASU) (see Figure 1). Ryan Yanashima, also of ASU, described iDEP devices in which the gap between the electrodes was decreasing along the channel filled with triangular saw tooth features used for the separation of proteins.
Zachary Gagnon of Johns Hopkins University (Baltimore, MD) presented the use of high-permittivity media for fluidic routing and chemical sensing with DEP. Samuel Kilchenmann from École Polytechnique Fédérale de Lausanne (Lausanne, Switzerland) presented a new microfluidic device with thick metal electrodes to be used for electrorotation studies. Alireza Salmanzadeh described work done at Virginia Tech (Blacksburg, VA) showing the effect of sphyngolipids on contactless DEP response.
Figure 2 – Finding the crossover frequency of mouse ovarian surface epithelium (MOSE) cells based on cells’ movement in a microfluidic channel using contactless dielectrophoresis (cDEP). Cells move toward the top of the channel at frequencies higher that their crossover frequency, or toward the bottom of the channel at frequencies higher that their crossover frequency (this work is published in Integr. Biol.
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, 843).Nathan Swami of the University of Virginia (Charlottesville, VA) presented an insulator constriction iDEP device to isolate pathogens with persistence resistance to antibiotics. Zdeněk Slouka of the University of Notre Dame (Notre Dame, IN) presented a device that uses cation exchange membranes to isolate charged molecules. From industry, Sean Parlia and Andrei Dukhin of Dispersion Technology (Bedford Hills, NY) presented a commercial device to measure the zeta potentials of proteins and other particles (see Figure 2).
Electroporation is a phenomenon that increases the permeabilization of the cell membrane by exposing the cell to electric pulses. This can be applied therapeutically to introduce anything from a small-molecule drug, a therapeutically active biopolymer, to DNA for gene therapy.
Critical and interrelated paths of inquiry in electroporation remain as follows:
1. How to predict efficient electroporation conditions for a wide variety of cells.
2. How to measure the effectiveness of electroporation in introducing material into a cell.
3. The design and manufacture of devices for electroporation.
Mohammad Bonakdar of the Davalos research group at Virginia Tech described how a microfluidic model of the blood–brain barrier could be used as a platform to study electroporation-enhanced drug delivery to the central nervous system. Jaka Čemažar of Virginia Tech addressed the measurement of electroporation in cell populations with his description of a dielectrophoretic field flow fractionation method to separate electroporated cells from nonelectroporated cells. Related to creating tools and devices for efficient electroporation, work from the same group described a microfluidic device. Similarly, Shegnian Wang of Louisiana Tech University (Ruston, LA) presented a strategy for enhancing electroporation of cells by gold nanoparticles using noncontact fluidic electrodes to enhance the electroporation of cells in a high-frequency electric field.
Electrophysiology can give important information about the health of a cell under different conditions, useful for understanding cell environment toxicity as well as normal cell communication and environmental interaction. The movement of whole cells in an applied electric field, or cell electrokinetics, is an emerging field of study as scientists seek to use electric force to move particles in the way it has been previously applied to molecules. In work that married both electrophysiology and cell electrokinetics, Fatima Labeed of the University of Surrey (Guildford, U.K.) described how the dielectrophoresis effect could be used to measure human samples taken from a mouth swab and was applied to the early detection of oral cancer.
Ionic fluxes at interfaces
Ionic fluxes at interfaces create varied phenomena rich in complex physics. Understanding and harnessing the force field gradients that can be created by ion fluxes at interfaces is a challenge. Dr. Gagnon presented remarkable work highlighting how manipulating ion fluxes at solution interfaces in an applied electric field in microchannels creates electric field gradients that can be harnessed in ways analogous to physical interfaces used in insulator-based dielectrophoresis.
Plenary session
The quality of the presentations at this conference was remarkable. The plenary session offered among the most compelling examples of the depth and range of work in electrophoresis.
An examination of droplet generation and dehydration of liquid in droplets was presented by Shelley Anna of Carnegie Mellon University (Pittsburgh, PA). Focusing on the power of fabrication techniques as applied to electrophoresis structures, Cindy Harnett from the University of Louisville (Louisville, KY) presented a fabrication technique of 3-D electrodes: lithography over topography, lift-up and thin film patterning, ion milling, and shadow evaporation, then illustrated their power with examples of electric field effects produced by these structures. Marc Madou of the University of California-Irvine presented electrochemical reactors that can be integrated on a compact disk, with the radial pumping of fluid toward the CD edge or CD center.
Don Arnold of Eksigent Technologies (Redwood City, CA) presented a number of microfluidic techniques for generating high pressures and discussed the application to HPLC. Steve Quake of Stanford University demonstrated the power of microfluidic devices as a platform that lends itself to both integration of function and very large scale of integration (VLSI) with its application to single-cell genome sequencing.
Awards session
The awards session honors people who have made significant contributions to electrophoresis in both the engineering and biology communities and to the AES Society. Awardees receive a commemorative plaque and lifetime membership to AES.
The 2013 AES Electrophoresis Society Career Award was presented to David E. Garfin, former AES President, for his contribution and service to the field of electrophoresis. The awards session, honoring Dr. Garfin, included five invited speakers from academia and industry speaking about diverse topics in electrophoresis from engineering and bioanalysis. Dr. Garfin closed the session with a thought-provoking lecture that summarized decades of developments he has witnessed and especially the current trend toward miniaturization in the field of electrophoresis.
Poster session
Twenty posters, almost all authored by students, comprised the poster session, and featured many late-breaking posters with results hot off the presses. These posters were of outstanding quality and eligible for a best poster award. Three posters were selected, with third place awarded to Nan Shih of Texas A&M (College Station, TX), second place to Yuchen Pan of the University of California-Berkeley, and first prize to Augusto M. Tentori of the University of California-Berkeley.
AES 2013 exhibition
Controlling lab-on-a-chip experiments
Technology for controlling all aspects of a microfluidic experiment was shown at the booth of LabSmith, Inc. (Livermore, CA). This Bay Area company offers a complete line of instrumentation to control a microfluidic experiment, including pumps, valves, sensors, connectors, chips, high-voltage power supplies, and a microscope. For pressure-driven flow-based microfluidic experiments, Elveflow (San Francisco, CA) made its debut appearance at AES and AIChE. This company, headquartered in Paris, France, provides tools for microfluidics experiments that rely on pressure-driven flow. Applications targeted are life sciences applications adapted for a microfluidic chip format.
Dielectrophoresis for cell physiology characterization
DEPTECH (East Sussex, U.K.) described its dielectrophoresis system for electrophysiology. Applications include general use for cell assays, diagnostics, and cell separation and patterning to address novel cell biology applications in the key areas of cancer research, drug discovery, in vitro toxicology, and stem cell development.
Microfluidic chips
Trianja Technologies (Allen, TX) is a new name in glass and fused-silica microfluidic chips. Its particular focus is on designing chips for biological applications spanning education to OEM production for biomedical and diagnostics applications.
Credits
The AES Electrophoresis Society meeting organizers and executive director deserve special recognition for organizing and planning an outstanding symposium.
Dr. Yolanda Fintschenko is with LabSmith, Inc., 61111 Southfront Rd., Livermore, CA 94551, U.S.A.; tel.: 925-292-5161; e-mail: yfintschenko@labsmith com; www.labsmith.com. Dr. Alireza Salmanzadeh is with the University of California, Berkeley, CA, U.S.A. Dr. Rafael Davalos is with Virginia Technical University, Blacksburg, VA, U.S.A.