ß-Amyloid as a Novel Target Biomarker for the OEGFET Biosensor, Revolutionizing Noninvasive Alzheimer's Screening

Early detection of neurodegenerative diseases has the potential to slow disease progression by timely interventions and effective management. Alzheimer's disease (AD), the most common form of dementia globally, has a preclinical phase that lasts decades prior to the prodromal stage. Preclinical stage neurological changes are accompanied by changes in biomarker concentrations, such as amyloid beta (Aß) peptides; however, at present, there are no cost-effective and noninvasive biomarker quantification methods suitable for population screening. To meet this need, we have tailored our proven organic electrolyte-gated field effect transistor (OEGFET) biosensor for the detection of Aß in serum and saliva samples. This was achieved by incorporating a covalently bound Aß antibody (AB) within the soft-fluidic microchannel of the biosensor: a significant advancement that demonstrates the robustness of our sensor system toward different types of bioreceptors and target biomarkers. Furthermore, the AB-OEGFET was created using flexible substrates and polymers due to their impressive biocompatibility. We observed the characteristic OEGFET device current to Aß concentration correlation behavior in all tested media, including serum and saliva specimens. The response of AB-OEGFET in buffer was recorded from 10µg/ml to 100 fg/ml, and the limit of detection of Aß was achieved in the range of 100 ng/ml for the spiking tests in saliva and serum specimens. The device specificity was investigated in serum samples spiked with a nonbinding protein analyte, α-synuclein. The predictable behavior of the sensor in targeting the Aß was observed in all tested solutions including saliva and serum that are crowded with numerous other proteomic biomarkers. The background ionic concentration in higher concentration serum and saliva was observed to promote some nonspecific binding to the bioreceptor adding a competing matrix effect. Irrespective of these exceptions, our first demonstration of the integration of AB receptors with OEGFET electronics, as explored in our study, holds substantial promise for the advancement of disposable, noninvasive biosensors for AD.