Highlighting the uniqueness in dielectrophoretic enrichment of circulating tumor cells

Circulating tumor cells (CTCs) play an essential role in the metastasis of tumors, and thus can serve as a valuable prognostic factor for malignant diseases. As a result, the ability to isolate and characterize CTCs is essential. This review underlines the potential of dielectrophoresis for CTCs enrichment. It begins by summarizing the key performance parameters and challenges of CTCs isolation using microfluidics. The two main categories of CTCs enrichment-affinity-based and label-free methods-are analysed, emphasising the advantages and disadvantages of each as well as their clinical potential. While the main argument in favour of affinity-based methods is the strong specificity of CTCs isolation, the major advantage of the label-free technologies is in preserving the integrity of the cellular membrane, an essential requirement for downstream characterization. Moving forward, we try to answer the main question: "What makes dielectrophoresis a method of choice in CTCs isolation?" The uniqueness of dielectrophoretic CTCs enrichment resides in coupling the specificity of the isolation process with the conservation of the membrane surface. The specificity of the dielectrophoretic method stems from the differences in the dielectric properties between CTCs and other cells in the blood: the capacitances of the malignantly transformed cellular membranes of CTCs differ from those of other cells. Examples of dielectrophoretic devices are described and their performance evaluated. Critical requirements for using dielectrophoresis to isolate CTCs are highlighted. Finally, we consider that DEP has the potential of becoming a cytometric method for large-scale sorting and characterization of cells.