Label-Free Enrichment of Circulating Tumor Plasma Cells: Future Potential Applications of Dielectrophoresis in Multiple Myeloma

Abstract

In multiple myeloma (MM), circulating tumor plasma cells (CTPCs) are an emerging prognostic factor, offering a promising and minimally invasive means for longitudinal patient monitoring. Recent advances highlight the complex biology of plasma cell trafficking, highlighting the phenotypic and genetic signatures of intra- and extra-medullary MM onset, making CTPC enumeration and characterization a new frontier of precision medicine for MM patients, requiring novel technological platforms for their standardized and harmonized detection. Dielectrophoresis (DEP) is an emerging label-free cell manipulation technique to separate cancer cells from healthy cells in peripheral blood samples, based on phenotype and membrane capacitance that could be successfully tested to enumerate and isolate CTPCs. Herein, we summarize preclinical data on DEP development for CTPC detection, as well as their clinical and research potential.

Keywords: acute leukemia; lymphoma; minimal residual disease; multiple myeloma.

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.

Figure 2

Clauss-Mosotti function for MDA, a CTC derived from breast cancer, versus healthy cells in peripheral blood.

Figure 3

DEP responses of cancer and normal blood cells expressed in terms of first crossover frequency.

Figure 4

Side view schematic of the ApoStreamTM device showing the complex multi-inlet, multi-outlet and microfluidic system.