EDL Gated FET Biosensor Array for the Investigation of Ion Channels and Bioelectric Signals of Circulating Tumor Cells

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This paper demonstrates the applications of novel high sensitive electrical double layer (EDL) gated FET biosensor array in detecting and counting cells, and analyzing their bioelectric signals in different test conditions. We focused on extremely rare cell type such as Circulating Tumor Cells (CTCs) (HCT-8 cell line) derived from Colorectal Cancer (CRC) cell line. CRC is one of the major forms of cancer that affects human population and CTCs have emerged as a clinical biomarker for diagnosis and prognosis of metastatic CRC. Previously, we had shown that our methodology can detect and count CTCs with very high sensitivity, with up to single cell resolution. Simultaneously, we discovered our sensor platform can be used to dynamically monitor the changes in transmembrane potential (Vm) of the cell, which is an important fundamental bioelectric signal of cell. Studies have shown Vm may be useful as a primary parameter in understanding disease progression, cell signaling mechanism and ion channel gating. We demonstrated that the EDL gated FET sensor can dynamically monitor the changes in Vm induced by high concentrations of extracellular KCl. It was also shown that the sensor response changes as extracellular divalent cation concentrations are dynamically increased towards physiological concentrations. The results display the ability of the sensing platform to monitor the cellular response to dynamically changing, very low ion concentrations as well. Furthermore, an interesting application of bioelectric signal study is demonstrated using cadmium ions to block the calcium channels present in the cell. As shown in figure, in low micro molar concentrations, cadmium acts as a permeant channel blocker (electrically, the cell is depolarized and as the Cd2+ concentration increases, it re-polarizes) and in higher concentrations, it accumulates in the intracellular region (the cell is depolarized again), causing induction of apoptotic signals. The sensor response closely follows the cellular response to permeant channel blockers such as cadmium. These results demonstrate that our sensing methodology can replace the conventional electrophysiological methods or optical potentiometric probes to study fundamental cellular mechanisms such as ion channel gating. Our method offers non-invasive means to monitor changes in Vm, with very high sensitivity for individual cells. The cell based studies can be carried out directly in physiological media with high ionic strength, without the use of extensive pre-treatments or additional reagents. Figure 1