Abstract
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.
Highlights
Cellular characteristics that can be exploited as biomarkers of cancer are usually categorized according to whether they depend on molecular markers or cell physical properties [1,2,3,4,5]
The most common biomolecular target for the detection and isolation of circulating tumor cells (CTCs) from peripheral blood mononuclear cells (PBMNs) is EpCAM, a cell adhesion molecule present in most epithelial tissues, and methods of exploiting this marker through antibody labeling have played a crucial role in establishing the research and clinical significance of CTCs as prognostic and, potentially, diagnostic indicators for breast, prostate and other cancers [6,7,8]
We demonstrated that the basis for cell DEP crossover frequency differences lay in cell membrane morphology [49,51]
Summary
Cellular characteristics that can be exploited as biomarkers of cancer are usually categorized according to whether they depend on molecular markers or cell physical properties [1,2,3,4,5]. Antibody-conjugation is time consuming and somewhat inefficient, and conjugation and subsequent cell recovery can impact CTC properties and viability For these reasons there is interest in exploring the applicability of cell physical properties for identifying CTCs. Physical markers have the advantage that they can be exploited as the means to discriminate between cancer and normal cells and to create the forces that drive cell separation. In order to make this article as accessible as possible to readers from many backgrounds, we have relegated the supporting theoretical considerations to the appendix
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