Highlighting the uniqueness in dielectrophoretic enrichment of circulating tumor cells

Abstract

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.

EMT-Associated Heterogeneity in Circulating Tumor Cells: Sticky Friends on the Road to Metastasis

“…A profusion of recently conceived microfluidic devices also uses the size and/or the deformability parameters [46][47][48][49][50][51][52][53][54][55][56][57][58]. Finally, CTC isolation devices, many also being microfluidic-based [59][60][61][62][63], use dielectrophoresis (DEP) to differentiate tumor cells from normal cells by their electric charges [64].…”

Determination of Dielectric Properties of Cells using AC Electrokinetic-based Microfluidic Platform: A Review of Recent Advances

“…Figure 11 shows the crossover frequencies divided by the liquid conductivity and specific membrane capacitances measured for the four types of cells. The specific membrane capacitances extracted for MOSE-E, MOSE-E/I, MOSE-I, and MOSE-L were 15 (Figure 11b). The specific membrane capacitance increased from a non-malignant stage to the most aggressive stage.…”

“…Additionally, whole cell membrane capacitance serving as a label-free biomarker can be employed to monitor stem cell fate and differentiation, thereby opening new avenues for regulating stem cell fate and continued progress as well as enhancing our understanding of basic stem cell biology [14]. Most importantly, the label-free and non-invasive isolation and enrichment of the circulating tumor cells (CTCs) derived from clinical samples is another application of the extracted cell dielectric properties, which will give valuable prognostic guides for treating malignant diseases and detecting the metastasis and deterioration of tumors [15]. Hence, cell dielectric properties, a type of intrinsic property of cells, can be used as electrophysiological biomarkers that offer a label-free way to characterize cell phenotypes and states, purify clinical samples, and identify target cancer cells.…”

The Fabrication and Application Mechanism of Microfluidic Systems for High Throughput Biomedical Screening: A Review

“…This method is non-destructive for cellular membranes, which is a benefit for the downstream characterization [84][85][86][87][88]. For example, circulating tumor cells (CTCs) are separated due to the capacitances of the malignantly transformed cellular membranes that differ from other cells [85]. So the research of using dielectrophoretic on biological analysis has become a hot lab-on-chip research topic, such as cell manipulation and cell isolation (shown in Figure 4B).…”