An impedimetric microelectrode-based array sensor for label-free detection of tau hyperphosphorylation in human cells

Abstract

Tauopathies such as Alzheimer's disease (AD) belong to the group of neurodegenerative diseases that are characterised by hyperphosphorylation of the protein tau. Hyperphosphorylation of tau is one of the salient events leading to neuronal cytotoxicity and cognitive impairments. In this context, inhibition of tau hyperphosphorylation by specific tau kinase inhibitors can provide an excellent drug target for the treatment of AD and other tau-related neurodegenerative diseases. To improve the identification, optimisation and validation during the high-cost hit-to-lead cycle of AD drugs, we established a fast and sensitive label-free technique for testing the efficacy of tau kinase inhibitors in vitro. Here, we report for the first time that microelectrode-based impedance spectroscopy can be used to detect the pathological risk potential of hyperphosphorylated tau in the human neuroblastoma cell line SH-SY5Y. Our findings provide a novel real-time recording technique for testing the efficiency of tau kinase inhibitors or other lead structures directed to tau hyperphosphorylation on differentiated SH-SY5Y cells.

Direct Chemosensitivity Monitoring Ex Vivo on Undissociated Melanoma Tumor Tissue by Impedance Spectroscopy

“…Using our unique MCA technology, we applied impedance spectroscopy for the labelfree and noninvasive characterization of the TMF composition. On the basis of the correlative immunocytochemical analysis, we established an equivalent circuit model allowing to retrieve more cell and tissue-specific information out of the complex impedance spectra (30,31). So additional impedance spectra-derived parameters could be used for analyzing the heterogeneity of the isolated tumor tissue and included in the standard chemotherapeutic sensitivity analysis in the manner of an impedimetric multiparameter-derived principal component analysis.…”

Induced Tauopathy in a Novel 3D-Culture Model Mediates Neurodegenerative Processes: A Real-Time Study on Biochips

“…In this context, we have developed a novel 3D in vitro cell culture model, which is based on the human neuroblastoma cell line SH-SY5Y that have been previously used in several tau pathology studies [8], [9], [10]. However, the use of spheroid cultures, instead of monolayer cultures, might be preferred, since 3D cultures recapitulate the in vivo situation likely better than 2D cell cultures [11], [12].…”

Array‐Based Sensors

“…Typically, these optical properties observed are change in color (absorption spectra) and luminescence emission intensity. Needless to say, there are also array sensors that utilize other modes of signal transduction such as luminescence lifetime [44], conductivity [45,46], potentiometry [47,48], impedance [49,50], radiofrequency [51], or polarographic [52] methods.…”