A short tutorial contribution to impedance and AC-electrokinetic characterization and manipulation of cells and media: Are electric methods more versatile than acoustic and laser methods?

Abstract Lab-on-chip systems (LOCs) can be used as in vitro systems for cell culture or manipulation in order to analyze or monitor physiological cell parameters. LOCs may combine microfluidic structures with integrated elements such as piezo-transducers, optical tweezers or electrodes for AC-electrokinetic cell and media manipulations. The wide frequency band (<1 kHz to >1 GHz) usable for AC-electrokinetic manipulation and characterization permits avoiding electrochemical electrode processes, undesired cell damage, and provides a choice between different polarization effects that permit a high electric contrast between the cells and the external medium as well as the differentiation between cellular subpopulations according to a variety of parameters. It has been shown that structural polarization effects do not only determine the impedance of cell suspensions and the force effects in AC-electrokinetics but can also be used for the manipulation of media with inhomogeneous temperature distributions. This manuscript considers the interrelations of the impedance of suspensions of cells and AC-electrokinetic single cell effects, such as electroorientation, electrodeformation, dielectrophoresis, electrorotation, and travelling wave (TW) dielectrophoresis. Unified models have allowed us to derive new characteristic equations for the impedance of a suspension of spherical cells, TW dielectrophoresis, and TW pumping. A critical review of the working principles of electro-osmotic, TW and electrothermal micropumps shows the superiority of the electrothermal pumps. Finally, examples are shown for LOC elements that can be produced as metallic structures on glass chips, which may form the bottom plate for self-sealing microfluidic systems. The structures can be used for cell characterization and manipulation but also to realize micropumps or sensors for pH, metabolites, cell-adhesion, etc.

[1]  K. Foster,et al.  Dielectric properties of tissues and biological materials: a critical review. , 1989, Critical reviews in biomedical engineering.

[2]  J. Maczuk,et al.  ON THE LOW-FREQUENCY DIELECTRIC DISPERSION OF COLLOIDAL PARTICLES IN ELECTROLYTE SOLUTION1 , 1962 .

[3]  L. Bousse,et al.  Applying silicon micromachining to cellular metabolism: measuring the rate of acidification induced in the extracellular environment , 1994, IEEE Engineering in Medicine and Biology Magazine.

[4]  J. Gimsa,et al.  A polarization model overcoming the geometric restrictions of the laplace solution for spheroidal cells: obtaining new equations for field-induced forces and transmembrane potential. , 1999, Biophysical journal.

[5]  Ravindra P. Joshi,et al.  Ultrashort electrical pulses open a new gateway into biological cells , 2004, Proceedings of the IEEE.

[6]  H. Morgan,et al.  The dielectrophoretic and travelling wave forces generated by interdigitated electrode arrays: analytical solution using Fourier series , 2001 .

[7]  Martyn Hill,et al.  Acoustofluidics 23: acoustic manipulation combined with other force fields. , 2013, Lab on a chip.

[8]  A. Ramos,et al.  Experiments on ac electrokinetic pumping of liquids using arrays of microelectrodes , 2005, IEEE International Conference on Dielectric Liquids, 2005. ICDL 2005..

[9]  Koji Asami,et al.  Dielectric Approach to Suspensions of Ellipsoidal Particles Covered with a Shell in Particular Reference to Biological Cells , 1980 .

[10]  J. Gimsa,et al.  Introducing phase analysis light scattering for dielectric characterization: measurement of traveling-wave pumping. , 1997, Biophysical journal.

[11]  H Maier,et al.  Electrorotation of colloidal particles and cells depends on surface charge. , 1997, Biophysical journal.

[12]  L. Nie,et al.  An amperometric glucose biosensor based on poly(o-aminophenol) and Prussian blue films at platinum electrode. , 2004, Analytical biochemistry.

[13]  J. Gimsa,et al.  A comprehensive approach to electro-orientation, electrodeformation, dielectrophoresis, and electrorotation of ellipsoidal particles and biological cells. , 2001, Bioelectrochemistry.

[14]  V. Shilov,et al.  Numerical Calculation of the Electrorotation Velocity of Latex-Type Particles , 2002 .

[15]  J. Gimsa.  New Light‐Scattering and Field‐Trapping Methods Access the Internal Electric Structure of Submicron Particles, like Influenza Viruses a , 1999, Annals of the New York Academy of Sciences.

[16]  J. L. Griffin.  Orientation of human and avian erythrocytes in radio-frequency fields. , 1970, Experimental cell research.

[17]  R Ehret,et al.  Online monitoring of BALB/3T3 metabolism and adhesion with multiparametric chip-based system. , 2007, Analytical biochemistry.

[18]  S G Shirley,et al.  Dielectrophoretic sorting of particles and cells in a microsystem. , 1998, Analytical chemistry.

[19]  W. Benecke,et al.  Microfabricated electrohydrodynamic (EHD) pumps for liquids of higher conductivity , 1992 .

[20]  G. Gradl,et al.  A 3-D microelectrode system for handling and caging single cells and particles , 1999 .

[21]  J. Gimsa,et al.  A new working principle for ac electro-hydrodynamic on-chip micro-pumps , 2007 .

[22]  Julian P.H. Burt,et al.  A combined travelling wave dielectrophoresis and electrorotation device: applied to the concentration and viability determination of Cryptosporidium , 1997 .

[23]  Aaron R Wheeler,et al.  Digital microfluidics with impedance sensing for integrated cell culture and analysis. , 2013, Biosensors & bioelectronics.

[24]  F F Becker,et al.  Separation of human breast cancer cells from blood by differential dielectric affinity. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Fred Lisdat,et al.  A label-free DNA sensor based on impedance spectroscopy , 2008 .

[26]  Traveling wave dielectrophoresis micropump based on the dispersion of a capacitive electrode layer , 2009 .

[27]  J. Gimsa,et al.  Experimental verification of an equivalent circuit for the characterization of electrothermal micropumps: High pumping velocities induced by the external inductance at driving voltages below 5 V , 2013, Electrophoresis.

[28]  T. Laurell,et al.  Review of cell and particle trapping in microfluidic systems. , 2009, Analytica chimica acta.

[29]  Nicolas G Green,et al.  Numerical simulation of travelling wave induced electrothermal fluid flow , 2004 .

[30]  J. Gimsa,et al.  A unified resistor-capacitor model for impedance, dielectrophoresis, electrorotation, and induced transmembrane potential. , 1998, Biophysical journal.

[31]  G. Gross,et al.  The use of neuronal networks on multielectrode arrays as biosensors. , 1995, Biosensors & bioelectronics.

[32]  Yucheng Ding,et al.  A theoretical and numerical investigation of travelling wave induction microfluidic pumping in a temperature gradient , 2014 .

[33]  Hywel Morgan,et al.  Single-cell microfluidic impedance cytometry: a review , 2010 .

[34]  Luc J. Bousse,et al.  Micromachined multichannel systems for the measurement of cellular metabolism , 1994 .

[35]  Thomas Laurell,et al.  Chip integrated strategies for acoustic separation and manipulation of cells and particles. , 2007, Chemical Society reviews.

[36]  R. Peri,et al.  High-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology , 2008, Nature Reviews Drug Discovery.

[37]  Stefan Schinkinger,et al.  Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. , 2005, Biophysical journal.

[38]  Damijan Miklavcic,et al.  Electroporation of Intracellular Liposomes Using Nanosecond Electric Pulses—A Theoretical Study , 2013, IEEE Transactions on Biomedical Engineering.

[39]  J. Gimsa,et al.  On the field distribution in electrorotation chambers—Influence of electrode shape , 2006 .

[40]  H. Schwan.  Biophysics of the Interaction of Electromagnetic Energy with Cells and Membranes , 1983 .

[41]  G. Fuhr,et al.  Living cells in opto-electrical cages , 2000 .

[42]  Aviad Hai,et al.  On-chip electroporation, membrane repair dynamics and transient in-cell recordings by arrays of gold mushroom-shaped microelectrodes. , 2012, Lab on a chip.

[43]  Ronald Pethig,et al.  Enhancing traveling-wave dielectrophoresis with signal superposition. , 2003, IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society.

[44]  W Baumann,et al.  A decrease of intracellular ATP is compensated by increased respiration and acidification at sub-lethal parathion concentrations in murine embryonic neuronal cells: measurements in metabolic cell-culture chips. , 2011, Toxicology letters.

[45]  Martin Z. Bazant,et al.  Fast ac electro-osmotic micropumps with nonplanar electrodes , 2006 .

[46]  F. Barnes,et al.  Handbook of biological effects of electromagnetic fields , 2007 .

[47]  M. Mowlem,et al.  Simultaneous high speed optical and impedance analysis of single particles with a microfluidic cytometer. , 2012, Lab on a chip.

[48]  D. Jayus Nor Salim,et al.  Cell to aperture interaction in patch‐clamp chips visualized by fluorescence microscopy and focused‐ion beam sections , 2011, Biotechnology and bioengineering.

[49]  J. Gimsa,et al.  On the analytical description of transmembrane voltage induced on spheroidal cells with zero membrane conductance , 2001, European Biophysics Journal.

[50]  Jan Gimsa,et al.  Modular glass chip system measuring the electric activity and adhesion of neuronal cells--application and drug testing with sodium valproic acid. , 2010, Lab on a chip.

[51]  Martin Stelzle,et al.  Accumulation and trapping of hepatitis A virus particles by electrohydrodynamic flow and dielectrophoresis , 2006, Electrophoresis.

[52]  M. Brischwein,et al.  Lab-on-a-Chip Systems for Cellular Assays , 2006 .

[53]  A. Ajdari,et al.  Pumping liquids using asymmetric electrode arrays , 2000, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[54]  T. Tsong,et al.  Schwan equation and transmembrane potential induced by alternating electric field. , 1990, Biophysical journal.

[55]  H. Morgan,et al.  Pumping of liquids with traveling-wave electroosmosis , 2005 .

[56]  G. Fuhr,et al.  Traveling‐wave dielectrophoresis of microparticles , 1992, Electrophoresis.

[57]  B Wolf,et al.  Monitoring of cellular behaviour by impedance measurements on interdigitated electrode structures. , 1997, Biosensors & bioelectronics.

[58]  K. Jensen,et al.  Cells on chips , 2006, Nature.

[59]  R. Hölzel,et al.  Electrorotation of single yeast cells at frequencies between 100 Hz and 1.6 GHz. , 1997, Biophysical journal.

[60]  H. Pauly,et al.  Über die Impedanz einer Suspension von kugelförmigen Teilchen mit einer Schale , 1959 .

[61]  Jan Gimsa,et al.  Cellular absorption of electric field energy: influence of molecular properties of the cytoplasm. , 2002, Bioelectrochemistry.

[62]  Jan Gimsa,et al.  Estimating the subcellular absorption of electric field energy: equations for an ellipsoidal single shell model. , 2002, Bioelectrochemistry.

[63]  H Kiesewetter,et al.  Low frequency electrorotation of fixed red blood cells. , 1998, Biophysical journal.

[64]  Jan Gimsa,et al.  Recording electric potentials from single adherent cells with 3D microelectrode arrays after local electroporation. , 2010, Biosensors & bioelectronics.

[65]  Thomas B. Jones,et al.  Electromechanics of Particles , 1995 .

[66]  Hans Bäumler,et al.  Alpha- and beta-dispersion of fixed platelets: comparison with a structure-based theoretical approach , 2002 .

[67]  Thomas Schnelle,et al.  Combined dielectrophoretic field cages and laser tweezers for electrorotation , 2000 .

[68]  U. Lei,et al.  Quasistatic force and torque on ellipsoidal particles under generalized dielectrophoresis , 2007 .

[69]  Thomas Schnelle,et al.  Travelling wave-driven microfabricated electrohydrodynamic pumps for liquids , 1994 .

[70]  Adrian Neild,et al.  Strategies for single particle manipulation using acoustic radiation forces and external tools , 2010 .

[71]  N. Allbritton,et al.  Micro total analysis systems for cell biology and biochemical assays. , 2012, Analytical chemistry.

[72]  H. Fricke,et al.  Relation of the Permittivity of Biological Cell Suspensions to Fractional Cell Volume , 1953, Nature.

[73]  M. Stelzle,et al.  Microdevices for manipulation and accumulation of micro‐ and nanoparticles by dielectrophoresis , 2003, Electrophoresis.

[74]  N F de Rooij,et al.  Multi-layer microfluidic glass chips for microanalytical applications , 2001, Fresenius' journal of analytical chemistry.

[75]  Ronald Pethig,et al.  Dielectrophoretic forces on particles in travelling electric fields , 1996 .