Ante-Mortem TSE Diagnosis by Electric Cell-Substrate Impedance Sensing

Transmissible spongiform encephalopathies (TSE) are responsible for fatal neurodegenerative diseases in humans, cattle, and sheep/goats. As TSEs can take many months and even years to present clinical symptoms, it is critical for food and contact safety to diagnose the disease at the earliest possible time point. A cell culture based system can offer the sensitivity and specificity required for anti-mortem diagnosis. In cells, cellular prion protein selectively binds copper to prevent oxidative damage and resulting cell death. Loss of this protein through addition of infective scrapie TSE induces an enhanced sensitivity to copper. Thus, monitoring cell health as copper is added can provide an indicator of the presence of TSEs. Agave BioSystems proposes to detect the change created by infective scrapie TSE through the use of electric cell-substrate impedance sensing (ECIS). Change in electrical impedance is a highly sensitive predictor of the integrity of the cell membranes and of cell viability. Thus, we predict rapid diagnosis of ante-mortem, preclinical samples from this sensitive and specific cell culture impedance detection system. Agave BioSystems, in collaboration with the Cornell University Animal Health Diagnostic Center (AHDC), proposes to develop a scrapie-susceptible cell line for ante-mortem detection of scrapie in real time by ECIS.