Bioelectronics of The Cellular Cytoskeleton: Monitoring Cytoskeletal Conductance Variation for Sensing Drug Resistance.

Actin and microtubules form cellular cytoskeletal network, which mediates cell shape, motility and proliferation and are key targets for cancer therapy. Changes in cytoskeletal organization dramatically affect mechanical properties of the cells and correlate with proliferative capacity and invasiveness of cancer cells. Changes in the cytoskeletal network expectedly lead to altered nonmechanical material properties including electrical conductivity as well. Here we applied, for the first time, microtubule and actin based electrical measurement to monitor changes in the electrical properties of breast cancer cells upon administration of anti-tubulin and anti-actin drugs, respectively. Semiconductive behavior of microtubules and conductive behavior of actins presented different bioelectrical responses (in similar frequencies) of the cells treated by anti-tubulin with respect to anti-actin drugs. Doped silicon nanowires were applied as the electrodes due to their enhanced interactive surface and compatibility with electronic fabrication process. We found that treatment with Mebendazole (MBZ), a microtubule destabilizing agent, decreases electrical resistance while treatment with Paclitaxel (PTX), a microtubule stabilizing agent, leads to an increase in electrical resistance. In contrast, actin destabilizing agents, Cytochalasin D (CytD), and actin stabilizing agent, Phalloidin, lead to an increased and decreased electrical resistance, respectively. Our study thus provides proof-of-principle of the usage of determining the electrical function of cytoskeletal compartments in grading of cancer as well as drug resistance assays.

An electrochemical biosensor to distinguish between normal and cancer cells based on monitoring their acidosis using gold-coated silicon Nano-roughened electrode.

One of the most interesting fields of research in cancer diagnosis is tracing the relation between extracellular media and cancer progression. Detecting the secreting contents of the cells and translating these molecular identifications into label-free recognizable patterns would open new opportunities in cancer research. Electrochemical responses are in the range of most attractive sensing mechanisms especially in biochemical approaches. Perturbed ionic exchanges as a known biochemical function of cancer cells presented a strong correlation with the pH of the tumor microenvironment. Different ionic activities detected by an electrochemical bio-sensing system in the malignant and normal cells in the presence of acidic ambient were our main results presented in this research. Herein, silicon Nano-roughened substrate as a well-known electrochemical interface was applied in the construction of the biosensor. Viability rate as well as apoptotic factors involving in cancer progression were assessed by biochemical assays in normal (MCF10A) and cancer (MCF7 and MDA-MB468) breast cells. Our findings demonstrated that pH-based electrochemical responses were matched with the results obtained from the biological analyses of both normal and malignant cells. Induction of acidosis in the cells followed by monitoring their electrochemical responses would be a new trend in microenvironment based cancer investigation.

Tracing the pH dependent activation of autophagy in cancer cells by silicon nanowire-based impedance biosensor.

Monitoring the pH dependent behavior of normal and cancer cells by impedimetric biosensor based on Silicon Nanowires (SiNWs) was introduced to diagnose the invasive cancer cells. Autophagy as a biologically activated process in invasive cancer cells during acidosis, protect them from apoptosis in lower pH which presented in our work. As the autophagy is the only activated pathways which can maintain cellular proliferation in acidic media, responses of SiNW-ECIS in acidified cells could be correlated to the probability of autophagy activation in normal or cancer cells. In contrast, cell survival pathway wasn't activated in low-grade cancer cells which resulted in their acidosis. The measured electrical resistance of MCF10, MCF7, and MDA-MB468 cell lines, by SiNW sensor, in normal and acidic media were matched by the biological analyses of their vital functions. Invasive cancer cells exhibited increased electrical resistance in pH 6.5 meanwhile the two other types of the breast cells exhibited sharp (MCF10) and moderate (MCF7) decrease in their resistance. This procedure would be a new trend in microenvironment based cancer investigation.

Nanoelectromechanical Chip (NELMEC) Combination of Nanoelectronics and Microfluidics to Diagnose Epithelial and Mesenchymal Circulating Tumor Cells from Leukocytes.

An integrated nano-electromechanical chip (NELMEC) has been developed for the label-free distinguishing of both epithelial and mesenchymal circulating tumor cells (ECTCs and MCTCs, respectively) from white blood cells (WBCs). This nanoelectronic microfluidic chip fabricated by silicon micromachining can trap large single cells (>12 µm) at the opening of the analysis microchannel arrays. The nature of the captured cells is detected using silicon nanograss (SiNG) electrodes patterned at the entrance of the channels. There is an observable difference between the membrane capacitance of the ECTCs and MCTCs and that of WBCs (measured using SiNG electrodes), which is the key indication for our diagnosis. The NELMEC chip not only solves the problem of the size overlap between CTCs and WBCs but also detects MCTCs without the need for any markers or tagging processes, which has been an important problem in previously reported CTC detection systems. The great conductivity of the gold-coated SiNG nanocontacts as well as their safe penetration into the membrane of captured cells, facilitate a precise and direct signal extraction to distinguish the type of captured cell. The results achieved from epithelial (MCF-7) and mesenchymal (MDA-MB231) breast cancer cells circulated in unprocessed blood suggest the significant applications for these diagnostic abilities of NELMEC.

Monitoring the spreading stage of lung cells by silicon nanowire electrical cell impedance sensor for cancer detection purposes.

We developed a silicon nanowire based electrical cell impedance sensor (SiNW-ECIS) as an instrument that detects cancerous cultured living lung cells by monitoring their spreading state at which the cells stretched and become extended on nanowires. Further current penetration into the extended membrane of malignant cells in respect to normal ones (In the first 6h after cells interaction with surface) are the key mechanism in our diagnosis procedure. The developed device applied to monitor the spreading-induced electrical differences between cancerous and normal lung cells in an integral fashion. Detection was performed so faster than the time required to complete cells mitosis. Morphology and architecture of doped Si nanowires covered microelectrodes observably enhance the contact area between cells and electrodes which support accurate signal recording from stretched cells as indicated by SEM and florescent images.