Addressing of LnCaP Cell Using Magnetic Particles Assisted Impedimetric Microelectrode.

In this study, we provide a facile, effective technique for a simple isolation and enrichment of low metastatic prostate tumor cell LNCaP using biocompatible, magnetic particles asissted impedimetric sensing system. Hydrophobic cell membrane anchors (BAM) were generated onto magnetic particles which diameters vary from 50 nm to 5 µm and were used to capture LNCaP cells from the suspension. Finally, magnetic particle-LNCaP complex were addressed onto the surface of the interdigitated microelectrode (IDM). Cell viability was monitored by our laboratory developed-technique Electrical Cell Substrate Impedance Sensing (ECIS). The results reavealed that 50 nm-magnetic particles showed best performance in terms of cell separation and cell viability. This technique provides a simple and efficient method for the direct addressing of LNCaP cell on the surface and enhances better understanding of cell behavior for cancer management in the near future.

Electric Cell-Substrate Impedance Sensing (ECIS) with Microelectrode Arrays for Investigation of Cancer Cell-Fibroblasts Interaction.

The tumor microenvironment, including stromal cells, surrounding blood vessels and extracellular matrix components, has been defined as a crucial factor that influences the proliferation, drug-resistance, invasion and metastasis of malignant epithelial cells. Among other factors, the communications and interaction between cancer cells and stromal cells have been reported to play pivotal roles in cancer promotion and progression. To investigate these relationships, an on-chip co-culture model was developed to study the cellular interaction between A549-human lung carcinoma cells and MRC-5-human lung epithelial cells in both normal proliferation and treatment conditions. In brief, a co-culture device consisting of 2 individual fluidic chambers in parallel, which were separated by a 100 µm fence was utilized for cell patterning. Microelectrodes arrays were installed within each chamber including electrodes at various distances away from the confrontation line for the electrochemical impedimetric sensing assessment of cell-to-cell influence. After the fence was removed and cell-to-cell contact occurred, by evaluating the impedance signal responses representing cell condition and behavior, both direct and indirect cell-to-cell interactions through conditioned media were investigated. The impact of specific distances that lead to different influences of fibroblast cells on cancer cells in the co-culture environment was also defined.

Electrical dual-sensing method for real-time quantitative monitoring of cell-secreted MMP-9 and cellular morphology during migration process.

MMP-9 (92 kDa gelatinease), which is member of matrix metalloproteinases (MMPs) family, plays a crucial role in the breakdown of extracellular matrix (ECM) by degrading the major components of ECM that lead to tumor cell invasion and metastasis through the basement membrane. Our study presents the on-chip dual-sensing device for rapid detection of cell-secreted MMP-9 and corresponding cell morphology changes in real-time domain. The device consists of 2 sensing platforms (both are interdigitated array microelectrodes - IDAMs) within 1 common fluidic chamber: one detects the cell morphology responses via Electric Cell-substrate Impedance Sensing (ECIS) technique, meanwhile the other records the cleavage effect between cell-secreted MMP-9 and the surface immobilized peptide via the capacitance-based sensing method. Thanks to the selectivity of designed peptide, this approach allows the rapid and specific detection of MMP-9. In comparison with gold standard ELISA assay, the detection time was significantly reduced from over 4h to within 30 min with the wide detection range from 10 pM to 10nM. Finally, this study provides the novel model for MMP-9 protease direct detection from living cell and new insights in multi-purpose detection of cancer associated enzyme and cell migration behavior.

Hydrogel-based diffusion chip with Electric Cell-substrate Impedance Sensing (ECIS) integration for cell viability assay and drug toxicity screening.

In this study, we have provided a novel analytical integration between hydrogel-based cell chip and Electric Cell-substrate Impedance Sensing (ECIS) technique to apply to a high-throughput, real-time cell viability assay and drug screening. For simulating the drug diffusion model, we have developed a hydrogel-based tissue-mimicking structure with microfluidic channel, without unwanted flow, to generate a gradient concentration with long-term stability. Along the gradient line, four individual micro-electrodes were installed to record the impedance signal changes, which result from the cell viability under drug effects. By watching for cellular impedance changes, we successfully estimated the cytotoxicity of the treatment corresponding to the various concentration values of stimuli, generated by the diffusion process along the channel. Reliable IC50 values and time-dose relationships were also achieved. With the feature of real-time monitoring capability, the advantages of non-invasion, label-free detection, time saving and simple manipulation, our integrative device has become a promising high throughput cell-based on-chip platform for cell viability assay and drug screening.

Real-time monitoring in vitro cellular cytotoxicity of silica nanotubes using electric cell-substrate impedance sensing (ECIS).

An electrical measurement known as Electric Cell-substrate Impedance Sensing (ECIS) has become increasingly applied to the study of cellular viability, proliferation and cytotoxicity with the advantages of label-free, non-invasion and real-time monitoring capability in comparison with other conventional methods (MTS, MTT). With this technique, cells are grown on the micro-sized gold electrodes where the micro-ampere alternative current is applied to measure the impedance changes due to the physiological changes caused by internal or external stimuli. In another field, Silica Nanotubes (SNTs) are a novel class of inorganic structures with promising potentials in bio-separation, drug delivery, imaging and other biomedical applications. In this study, by using ECIS-based self-fabricated cell chip, Cells were cultured on the working electrodes and separately exposure to the 0, 2 microm, 2 microm and 10 microm long at the varying concentrations of SNTs to evaluate the cellular responses such as viability, multiplication time and cytotoxicity. Final results were additionally compared with the MTS method as a reference to review the reliability