Dielectrophoretic Field-flow Fractionation Research Articles

Localized Electroporation With Dielectrophoretic Field Flow Fractionation: Toward Removal of Circulating Tumour Cells From Human Blood.

This paper presents the design and experimental performance of a microelectrode-based device to selectively lyse cells in a flow in a microfluidic channel. Localized cell lysis is achieved by utilizing "irreversible electroporation," in which cells are exposed to high magnitude electric pulses. Localized cell lysis in a flow has research applications and may allow for the removal of harmful cells, such as circulating tumor cells from blood. Due to the dependence of this technique on the magnitude of the applied electric field, lethal electric field regions can be localized in the channel by the calibration of the applied voltage. Dielectrophoresis field flow fractionation is used to levitate target cancer cells in the lethal region of the device microchannel. Experiments are performed to demonstrate the localized lysis of MCF7 cancer cells in a mixture of blood cells. Due to their larger size, these circulating tumor cell analogues levitate to a greater height in the channel than erythrocytes. MCF7 lysis is observed to increase from 4.6% in control experiments to 57.3% in active experiments. Leukocyte viability was unaffected in active experiments. These results demonstrate the feasibility of localizing cell lysis in a microfluidic flow environment.

The potential of a dielectrophoresis activated cell sorter (DACS) as a next generation cell sorter

Originally introduced by H. A. Pohl in 1951, dielectrophoretic (DEP) force has been used as a striking tool for biological particle manipulation (or separation) for the last few decades. In particular, dielectrophoresis activated cell sorters (DACSes) have been developed for applications in various biomedical fields. These applications include cell replacement therapy, drug screening and medical diagnostics. Since a DACS does not require a specific bio-marker, it is able to function as a biological particle sorting tool with numerous configurations for various cells [e.g. red blood cells (RBCs), white blood cells (WBCs), circulating tumor cells, leukemia cells, breast cancer cells, bacterial cells, yeast cells and sperm cells]. This article explores current DACS capabilities worldwide, and it also looks at recent developments intended to overcome particular limitations. First, the basic theories are reviewed. Then, representative DACSes based on DEP trapping, traveling wave DEP systems, DEP field-flow fractionation and DEP barriers are introduced, and the strong and weak points of each DACS are discussed. Finally, for the purposes of commercialization, prerequisites regarding throughput, efficiency and recovery rates are discussed in detail through comparisons with commercial cell sorters (e.g. fluorescent activated and magnetic activated cell sorters).

Isolation of Circulating Tumor Cells by Dielectrophoresis

Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

Correlations between the dielectric properties and exterior morphology of cells revealed by dielectrophoretic field-flow fractionation.

Although dielectrophoresis (DEP) has great potential for addressing clinical cell isolation problems based on cell dielectric differences, a biological basis for predicting the DEP behavior of cells has been lacking. Here, the dielectric properties of the NCI-60 panel of tumor cell types have been measured by dielectrophoretic (DEP) field-flow fractionation, correlated with the exterior morphologies of the cells during growth, and compared with the dielectric and morphological characteristics of the subpopulations of peripheral blood. In agreement with earlier findings, cell total capacitance varied with both cell size and plasma membrane folding and the dielectric properties of the NCI-60 cell types in suspension reflected the plasma membrane area and volume of the cells at their growth sites. Therefore, the behavior of cells in DEP-based manipulations is largely determined by their exterior morphological characteristics prior to release into suspension. As a consequence, DEP is able to discriminate between cells of similar size having different morphological origins, offering a significant advantage over size-based filtering for isolating circulating tumor cells, for example. The findings provide a framework for anticipating cell dielectric behavior on the basis of structure-function relationships and suggest that DEP should be widely applicable as a surface marker-independent method for sorting cells.

Dielectrophoresis has broad applicability to marker-free isolation of tumor cells from blood by microfluidic systems

The number of circulating tumor cells (CTCs) found in blood is known to be a prognostic marker for recurrence of primary tumors, however, most current methods for isolating CTCs rely on cell surface markers that are not universally expressed by CTCs. Dielectrophoresis (DEP) can discriminate and manipulate cancer cells in microfluidic systems and has been proposed as a molecular marker-independent approach for isolating CTCs from blood. To investigate the potential applicability of DEP to different cancer types, the dielectric and density properties of the NCI-60 panel of tumor cell types have been measured by dielectrophoretic field-flow fractionation (DEP-FFF) and compared with like properties of the subpopulations of normal peripheral blood cells. We show that all of the NCI-60 cell types, regardless of tissue of origin, exhibit dielectric properties that facilitate their isolation from blood by DEP. Cell types derived from solid tumors that grew in adherent cultures exhibited dielectric properties that were strikingly different from those of peripheral blood cell subpopulations while leukemia-derived lines that grew in non-adherent cultures exhibited dielectric properties that were closer to those of peripheral blood cell types. Our results suggest that DEP methods have wide applicability for the surface-marker independent isolation of viable CTCs from blood as well as for the concentration of leukemia cells from blood.

Preface to Special Topic: Microfluidics in Cancer Research

Preface to Special Topic: Microfluidics in Cancer Research

439 Comparison of Dielectrophoretic Field Flow Fractionation (DEP-FFF) with ApoStream™, an Antibody Independent Platform, with Immunomagnetic Capture Using CellSearch™ for Enumeration of Circulating Tumor Cells in Patients with Metastatic Prostate Cancer

439 Comparison of Dielectrophoretic Field Flow Fractionation (DEP-FFF) with ApoStream™, an Antibody Independent Platform, with Immunomagnetic Capture Using CellSearch™ for Enumeration of Circulating Tumor Cells in Patients with Metastatic Prostate Cancer

Expression of eIF4E relevant biomarkers detected in circulating tumor cells from metastatic NSCLC and prostate cancer patients using antibody-independent ApoStream technology.

e13562 Background: Enumeration of circulating tumor cells (CTCs) is used clinically to monitor disease progression and has previously been shown to be an independent biomarker for predicting survival of metastatic breast, prostate, and colorectal cancer patients. Molecular characterization of CTCs is rapidly emerging as a minimally invasive approach to interrogate the genotype and phenotype of cancers. However, the use of EpCAM-based enrichment platforms relies on the expression of EpCAM thus limiting the type of tumor cells that can be recovered. ApoStream, is a novel, antibody-independent, dielectrophoretic field-flow fractionation based technology that recovers CTCs from cancer patient blood samples. Methods: A side-by-side comparison of EpCAM dependent CellSearch and ApoStream was performed for CTC enumeration in NSCLC and prostate cancer patients. A multiplexed immunofluorescent assay was developed for CTC (cytokeratin+/CD45-/DAPI+ cells) enumeration. CTCs recovered by ApoStream were evaluated for the expression of multiple eIF4E pathway biomarkers using quantitative laser scanning cytometry (LSC). Results: ApoStream isolated a significantly greater number of CTCs in both NSCLC and prostate cancer patients (NSCLC: range 9-1037, mean=407 by ApoStream versus a range of 30-340, mean=118 by CellSearch , p<0.05; prostate cancer: range 12-3490, mean=1472 by ApoStream versus a range of 16-2155, mean=502 by CellSearch , p<0.05). The eIF4E protein expression in CTCs was positively correlated with the CTC count. A trend toward correlation between the eIF4E protein expression level and the expression levels of Cyclin D1, Survivin and Bcl-2 was observed. Conclusions: The ApoStream platform recovers higher numbers of CTCs from the blood of metastatic NSCLC and prostate cancer patients compared to the EpCAM-dependent CellSearch platform. CTCs recovered by ApoStream are suitable for downstream molecular analyses paving the way for broader applications in translational cancer research.

Abstract 2374: Performance of a new generation antibody-independent ApoStream™ platform for the enrichment of circulating tumor cells (CTCs)

Abstract Background: Isolation and molecular analysis of Circulating Tumor Cells (CTCs) is technically challenging, but may replace tumor biopsy by providing a minimally-invasive, blood-based, “liquid biopsy” method to monitor metastatic disease progression and guide cancer therapy. The use of currently available EpCAM-based enrichment platforms limits the type of tumor cells that can be recovered. We have developed the first robust CTC isolation device, ApoStream™, which does not rely on specific surface proteins or the size of CTCs. Specific Aims: We demonstrate the performance of a novel antibody-independent dielectrophoretic field-flow fractionation (DEP-FFF) based CTC isolation platform: ApoStream™. Methods: In the ApoStream™ device, DEP-FFF is used to differentially drive cell movement based on different biophysical properties of cells in a continuous flow microfluidic chamber to isolate CTCs from peripheral blood mononuclear cells (PBMCs). To demonstrate performance, pre-labeled SKOV3 ovarian cancer cells (low EpCAM expressing) were spiked into buffer or PBMCs and isolated through ApoStream™ device. Cancer cell recovery, system linearity, and precision were demonstrated. Viability of cancer cells isolated through the ApoStream™ platform, as well as their ability to be propagated in culture, was confirmed. Results: On three different days, the ApoStream™ breadboard device recovered 83.0± 3.0% (mean ± SD), 76.3 ± 2.6%, and 81.5± 1.0% of SKOV3 cells spiked into buffer (average interday recovery of 80.3 ± 3.5%, CV% = 4.3). Additionally, 79.0 ± 1.5%, 81.2 ± 7.8% and 75.2 ± 4.3% of SKOV3 cells spiked into ∼10 million normal PBMCs (average interday recovery 78.5 ± 3.0%, CV% = 3.3) were recovered. When SKOV3 spiking recovery was measured on two different ApoStream™ devices, the CV% was 0.1%. System linearity was evaluated by spiking a range of 4 - 2,600 SKOV3 cells into 10 million PBMCs. The regression analysis for the linearity resulted in a correlation coefficient (R2) of 1.00. Cell viability was not affected by the ApoStream™ device, and was 98.2, 98.8 and 100% of initial viability at 0, 16 and 24 hours after ApoStream™ separation, respectively, as measured by Trypan blue exclusion test conducted on cells propagated in tissue culture. Conclusion: We developed the first antigen-independent and cell size independent device for isolation of CTCs from patient blood with a wide variety of cancers. ApoStream™ technology performance characterization demonstrated high recovery of EpCAM-negative cultured cancer cells over a significant range of spiked cell numbers, as well as excellent linearity performance. Isolation of large numbers of live and unfixed CTCs with the ApoStream™ platform enables downstream molecular characterization of CTCs for the development of personalized treatment options for cancer patients. Acknowledgments: Funded by NCI Contract No. HHSN261200800001E. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2374. doi:1538-7445.AM2012-2374

Abstract 2381: ApoStreamtm, an antibody independent platform, captures circulating tumor cells in patients with hepatocellular carcinoma

Abstract Biopsies of HCC can be technically difficult, given the vascular nature of the liver and underlying liver disease. Many HCC patients do not get biopsies, and molecular characterization of these tumors is not possible. Capture of CTCs from blood allows for analysis of cancer cells in metastatic dissemination. The use of EpCAM-based enrichment platforms limits the type of tumor cells that can be recovered, as it selects only for cells which express the antigen of interest. Nonselective methods of CTC analysis are needed. An ongoing study is evaluating the recovery of CTCs in HCC patients with elevated serum alpha-fetoprotein (AFP) using the novel antibody-independent ApoStream™ platform, which utilizes the principle of dielectrophoretic field-flow fractionation to position cells in a hydrodynamic flow profile for sorting. Paired blood samples from HCC patients were analyzed by CellSearch and ApoStream™. Collected cells were immunophenotyped using antibodies against Cytokeratin (CK), CD45, DAPI, and AFP, and analyzed by quantitative laser scanning cytometry. In comparison with the CellSearch platform, ApoStream™ isolated higher number of CK+/CD45-/DAPI+ CTCs in HCC cancer patients. A majority of the CK+/CD45-/DAPI+ CTCs enriched by the ApoStream™ platform (62-98%) were AFP+. ApoStreamTM also isolated AFP+, putative CTCs with the CK-/CD45-/DAPI+ phenotype (9-85 cells), and cells with CK+/CD45+/DAPI+ phenotype (1-978 cells). Conclusion: The ApoStreamTM CTC enrichment platform successfully isolated a greater number of CTCs from HCC patients. ApoStream™ CTC analysis is also being used for pharmacodynamic analysis in an ongoing phase I study of the combination of sorafenib and vorinostat in patients with advanced HCC. In preclinical models, the combination synergistically induces tumor cell death through activation of CD95. In this study, CTC analysis will compare the expression of CD95 and other markers prior to and after drug combination exposure. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2381. doi:1538-7445.AM2012-2381

Abstract B20: EpCAM-independent ApoStream™ technology isolates circulating tumor cells from blood of patients with various types of cancer.

Abstract Introduction: Referred to as a “liquid tumor biopsy”, the ability to enrich Circulating Tumor Cells (CTCs) from blood samples allows for the analysis of cancer cells undergoing metastatic dissemination and has been a hallmark of biomarker discovery. However, the use of EpCAM-based enrichment platforms limits the type of tumor cells that can be recovered, which subsequently limits the use of CTCs as surrogates for the classical tumor biopsy. Therefore an EpCAM-independent enrichment platform is critically needed. Specific Aims: The performance of a novel antibody-independent dielectrophoretic field-flow fractionation based CTC isolation technology ApoStream was demonstrated in spiked cell model and cancer patient blood. Experimental Procedures: We used ApoStream, a novel antibody-independent technology, to enrich CTCs from prostate and breast cancer patient blood (high EpCAM expression), non-small cell lung cancer patient blood (NSCLC, low EpCAM expression) and melanoma (no EpCAM expression). Cells isolated from ApoStream were stained for cytokeratin (CK), CD45, and DAPI, and melanoma CTCs with tumor marker S100, CD45 and DAPI. Imaging and CTC enumeration were done using laser scanning cytometry (LSC). CTC morphology in lung cancer specimens was confirmed with H&E staining. To further demonstrate performance of ApoStream platform, EpCAM-negative ovarian cancer cells SKOV3 were spiked into peripheral blood mononuclear cells (PBMCs) from normal donor blood and isolated using the ApoStream device. Results: High CTC recovery from cancer patient blood samples was achieved with counts ranging from 0 − 2104 (lung, n=33), 0 − 3490 (prostate, n=15), 176 − 968 (breast, n=3), and 4 − 3120 (melanoma, n=11) CTCs per 7.5 ml blood. Positive CTC counts were obtained in ninety percent of NSCLC samples, 93% of prostate cancer samples, 100% breast cancer and melanoma specimens. There were no false-positive CTCs from normal donor blood controls demonstrating ApoStream's specificity. In cell spiking experiments, 80 ± 3% cells were recovered by ApoStream after spiking of EpCAM-negative ovarian cancer cells (SKOV3) into human peripheral blood mononuclear cells (PBMCs). EpCAM-negative CTCs were also recovered in all tested breast cancer patient specimens, confirming that ApoStream isolates cancer cells independent on their EpCAM status. Conclusions: Our data demonstrate that the ApoStream platform recovers large numbers of CTCs from the blood of patients with metastatic NSCLC, prostate, breast cancer and melanoma. Thus, the ApoStream CTCisolation platform provides a new effective tool with broad applications in cancer biomarker discovery and personalization of cancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B20.

Dynamic physical properties of dissociated tumor cells revealed by dielectrophoretic field-flow fractionation

Metastatic disease results from the shedding of cancer cells from a solid primary tumor, their transport through the cardiovascular system as circulating tumor cells (CTCs) and their engraftment and growth at distant sites. Little is known about the properties and fate of tumor cells as they leave their growth site and travel as single cells. We applied analytical dielectrophoretic field-flow fractionation (dFFF) to study the membrane capacitance, density and hydrodynamic properties together with the size and morphology of cultured tumor cells after they were harvested and placed into single cell suspensions. After detachment, the tumor cells exhibited biophysical properties that changed with time through a process of cytoplasmic shedding whereby membrane and cytoplasm were lost. This process appeared to be distinct from the cell death mechanisms of apoptosis, anoikis and necrosis and it may explain why multiple phenotypes are seen among CTCs isolated from patients and among the tumor cells obtained from ascitic fluid of patients. The implications of dynamic biophysical properties and cytoplasmic loss for CTC migration into small blood vessels in the circulatory system, survival and gene expression are discussed. Because the total capacitance of tumor cells remained higher than blood cells even after they had shed cytoplasm, dFFF offers a compelling, antibody-independent technology for isolating viable CTCs from blood even when they are no larger than peripheral blood mononuclear cells.

Dielectrophoretic-Field Flow Fractionation Analysis of Dielectric, Density, and Deformability Characteristics of Cells and Particles

Dielectrophoretic field-flow fractionation (DEP-FFF) has been used to discriminate between particles and cells based on their dielectric and density properties. However, hydrodynamic lift forces (HDLF) at flow rates needed for rapid separations were not accounted for in the previous theoretical treatment of the approach. Furthermore, no method was developed to isolate particle or cell physical characteristics directly from DEP-FFF elution data. An extended theory of DEP-FFF is presented that accounts for HDLF. With the use of DS19 erythroleukemia cells as model particles with frequency-dependent dielectric properties, it is shown that the revised theory accounts for DEP-FFF elution behavior over a wide range of conditions and is consistent with sedimentation-FFF when the DEP force is zero. Conducting four elution runs under specified conditions, the theory allows for the derivation of the cell density distribution and provides good estimates of the distributions of the dielectric properties of the cells and their deformability characteristics that affect HDLF. The approach allows for rapid profiling of the biophysical properties of cells, the identification and characterization of subpopulations, and the design of optimal DEP-FFF separation conditions. The extended DEP-FFF theory is widely applicable, and the parameter measurement methods may be adapted easily to other types of particles.

Isolation of rare cells from cell mixtures by dielectrophoresis.

The application of dielectrophoretic field-flow fractionation (depFFF) to the isolation of circulating tumor cells (CTCs) from clinical blood specimens was studied using simulated cell mixtures of three different cultured tumor cell types with peripheral blood. The depFFF method can not only exploit intrinsic tumor cell properties so that labeling is unnecessary but can also deliver unmodified, viable tumor cells for culture and/or all types of molecular analysis. We investigated tumor cell recovery efficiency as a function of cell loading for a 25 mm wide x 300 mm long depFFF chamber. More than 90% of tumor cells were recovered for small samples but a larger chamber will be required if similarly high recovery efficiencies are to be realized for 10 mL blood specimens used CTC analysis in clinics. We show that the factor limiting isolation efficiency is cell-cell dielectric interactions and that isolation protocols should be completed within approximately 15 min in order to avoid changes in cell dielectric properties associated with ion leakage.

DYNAMICS OF DIELECTROPHORETIC FIELD-FLOW FRACTIONATION (DEP-FFF) BASED MICRO SORTER FOR CELL SEPARATION

Dielectrophoretic Field-Flow Fractionation (DEP-FFF) is a technique that selects particles of interest from a mixture of many samples. Conventional DEP-FFF technique used DEP force to levitate particles to different heights according to their dielectric properties. Levitated particles are then separated by their velocity difference in a microchannel. Numerical simulation and experimental results found that particles become wavy trajectory when the ratio of levitation height (hp) and average of electrode width and spacing (d) is below 0.6 (hp/d<0.6). In the mean time, sorted particles disperse randomly in Y-direction, too. The wavy trajectory and random distribution cause cell separation imprecisely. A novel MEMS-fabricated DEP-FFF based micro sorters is designed to improve these problems. The experimental results show that the particles can be levitated to a constant height and focus into a single particle stream along the centerline in the new micro sorter design. One can conclude that the new design leads to better cell separation in a DEP-FFF based micro sorter.

Dielectrophoretic field-flow fractionation system for detection of aquatic toxicants.

Dielectrophoretic field-flow fractionation (dFFF) was applied as a contact-free way to sense changes in the plasma membrane capacitances and conductivities of cultured human HL-60 cells in response to toxicant exposure. A micropatterned electrode imposed electric forces on cells in suspension in a parabolic flow profile as they moved through a thin chamber. Relative changes in the dFFF peak elution time, reflecting changes in cell membrane area and ion permeability, were measured as indices of response during the first 150 min of exposure to eight toxicants having different single or mixed modes of action (acrylonitrile, actinomycin D, carbon tetrachloride, endosulfan, N-nitroso- N-methylurea (NMU), paraquat dichloride, puromycin, and styrene oxide). The dFFF method was compared with the cell viability assay for all toxicants and with the mitochondrial potentiometric dye assay or DNA alkaline comet assay according to the mode of action of the specific agents. Except for low doses of nucleic acid-targeting agents (actinomycin D and NMU), the dFFF method detected all toxicants more sensitively than other assays, in some cases up to 10 (5) times more sensitively than the viability approach. The results suggest the dFFF method merits additional study for possible applicability in toxicology.

Enrichment of putative stem cells from adipose tissue using dielectrophoretic field-flow fractionation.

We have applied the microfluidic cell separation method of dielectrophoretic field-flow fractionation (DEP-FFF) to the enrichment of a putative stem cell population from an enzyme-digested adipose tissue derived cell suspension. A DEP-FFF separator device was constructed using a novel microfluidic-microelectronic hybrid flex-circuit fabrication approach that is scaleable and anticipates future low-cost volume manufacturing. We report the separation of a nucleated cell fraction from cell debris and the bulk of the erythrocyte population, with the relatively rare (<2% starting concentration) NG2-positive cell population (pericytes and/or putative progenitor cells) being enriched up to 14-fold. This work demonstrates a potential clinical application for DEP-FFF and further establishes the utility of the method for achieving label-free fractionation of cell subpopulations.

AC electrokinetic characterisation and separation of cells with high and low embryogenic potential in suspension cultures of carrot (Daucus carota)

Suspension cultures of Daucus carota L. were established, and cells with embryogenic potential were separated from those without by density gradient centrifugation in Ficoll at different stages in the growth curve. In order to obtain information about the electrical properties of individual cells, electrorotation spectra of single plant cells from different fractions were measured before and after induction of embryogenesis. The data were analysed using models based on Maxwell–Wagner's theories of interfacial polarisation. It was found that the denser cells had a higher embryogenic potential, a darker appearance and a higher internal conductivity (>1 S m−1) than the less dense cells, which had less or no embryogenic potential and a lower internal conductivity (<1 S m−1). Modelling the dielectrophoretic (DEP) response on the basis of the electrorotation data suggested that separation of cells with high embryogenic potential may be achievable in the frequency range 1–10 MHz. Actual dielectrophoretic separation of cells with high embryogenic potential from suspensions in which embryogenesis had not yet been induced was achieved using steric as well as hyperlayer dielectrophoretic Field-Flow Fractionation (DEP-FFF).

Numerical solution of the dielectrophoretic and travelling wave forces for interdigitated electrode arrays using the finite element method

AC electrokinetics is the study of the movement of polarisable particles under the influence of AC electric fields. The fields are applied to a suspension of particles by planar microelectrode structures and one particular design, the interdigitated bar electrode has been used in both dielectrophoretic (DEP) field flow fractionation and travelling wave dielectrophoresis. This paper presents, numerical solutions of the DEP and travelling wave forces for an interdigitated electrode array energised with either a 2- or 4-phase signal. The electrorotational torque experienced by the particle in the 4-phase travelling wave array is also calculated. The solutions are compared with previous results.

The dielectrophoretic and travelling wave forces generated byinterdigitated electrode arrays: analytical solution using Fourierseries

In alternating current electrokinetics, electric fields are used togenerate forces on particles. Techniques have been applied for themanipulation of particles and the measurement of their dielectric properties.The fields are typically generated by microelectrode structures fabricated onplanar surfaces. One particular design, using interdigitated bar electrodes,is used both in dielectrophoretic field flow fractionation and travelling wavedielectrophoresis. This paper presents a Fourier series analysis of thedielectrophoretic force on a particle generated by this type of electrodearray, for both dielectrophoresis and travelling wave dielectrophoresis.Simple expressions are derived for the force at a distance of the order of theelectrode spacing from the electrodes. A full analytical expression is givenfor the dielectrophoretic force in two dimensions. Comparisons are made withpreviously published experimental observations.