The Role of Dielectrophoresis for Cancer Diagnosis and Prognosis

Abstract

Liquid biopsy is emerging as a potential diagnostic tool for prostate cancer (PC) prognosis and diagnosis. Unfortunately, most circulating tumor cells (CTC) technologies, such as AdnaTest or Cellsearch^®, critically rely on the epithelial cell adhesion molecule (EpCAM) marker, limiting the possibility of detecting cancer stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) that are present during PC progression. In this context, dielectrophoresis (DEP) is an epCAM independent, label-free enrichment system that separates rare cells simply on the basis of their specific electrical properties. As compared to other technologies, DEP may represent a superior technique in terms of running costs, cell yield and specificity. However, because of its higher complexity, it still requires further technical as well as clinical development. DEP can be improved by the use of microfluid, nanostructured materials and fluoro-imaging to increase its potential applications. In the context of cancer, the usefulness of DEP lies in its capacity to detect CTCs in the bloodstream in their epithelial, mesenchymal, or epithelial-mesenchymal phenotype forms, which should be taken into account when choosing CTC enrichment and analysis methods for PC prognosis and diagnosis.

Keywords: circulating tumor cells; detection; dielectrophoresis; prognosis; prostate cancer.

Figure 1

Polarization, induced net dipole and dielectrophoretic force direction for a particle that is (left) more polarizable than the surrounding medium and (right) less polarizable. Top and bottom are two opposite arrangements of the background electric field (adapted from ref. [14]).

Figure 2

Clauss−Mosotti function for MDA, a CTC derived from breast cancer, as compared to healthy cell types in pheripheral blood.

Figure 3

The DEP responses of cancer and normal blood cells expressed in terms of first crossover frequency $f_{CO1}$ (Adapted from ref [24]).

Figure 4

Side view of an interdigitated electrode channel, with indication of particle response depending on the sign of the DEP force.

Figure 5

Schematic, side-view, of the ApoStream^TM device, showing the complex multi-inlet, multi-outlet, and microfluidic system. (Adapted from [30]).

Figure 6

Schematic representation of the metastatic process. Metastasis is a multi-stage process starting with the formation and growth in situ of the primary tumor (A). Some tumors can become invasive due to the detachment of cells (CTCs) that are able to enter blood or lymph vessels, a process known as intravasation, and migrate to sites far from the starting point (B). The following step is the dissemination of cancer occurring when “traveling cells” extravasate (exit blood or lymph vessels) and colonize new sites forming secondary tumors (C). Once in the new sites, cancerous cells are able to proliferate and recruit the blood vessels (angiogenesis) needed for trophic support. (Created with https://smart.servier.com, accessed on 15 December 2021).