Electrochemical sensors for the detection and tracking of Alzheimer’s disease

Project Summary Electrochemical sensors for the detection and tracking of Alzheimer’s disease Alzheimer’s disease (AD) is the most prevalent form of dementia. Despite recent advances in biosensing, early detection and continuous monitoring of disease progression/regression remains technically challenging. Current methods for detecting AD biomarkers in plasma or blood are either too costly to be performed routinely or lack sensitivity and/or specificity. It is well recognized that early therapeutic interventions can slow down the progression of the disease before irreversible neuronal damages occur, thereby managing symptoms and improving quality of life. Herein, we propose to develop organic electrochemical transistors (OECTs) for the detection of biomarkers of AD in plasma or blood. The OECT devices act as amplifiers for electrochemical signals resulting, for example, from changes in analyte concentration, and have therefore been previously used as electrochemical biosensors with very limits of detection. To fabricate OECT biosensors, the surface of a metal electrode is commonly functionalized with a redox enzyme specific to the analyte. This strategy, however, is not applicable to sensing Amyloid-β monomers (biomarkers for AD), because large proteinaceous species, such as Amyloid-β oligomers, fibrils and aggregates dominate the electronic response of the devices. We will explore a novel approach to solve this problem by synthesizing porous conducting polymers that are functionalized with specific antibodies for Amyloid-β monomers, and use these as the active material in OECTs for electrochemical sensing (Aim 1). We will also develop size-specific OECT sensors to discriminate small molecule biomarkers from larger aggregates, by preparing conductive molecularly imprinted polymers (MIPs) with controllable pore size for size-screening (Aim 2). This dual chemo- and size-specific platform will enable us to track the progress of AD, characterized by an increase in Amyloid-β morphology or size (e.g., monomeric, oligomeric, fibrillar or aggregated), which is currently not possible with existing sensing technologies. Without these low-cost, scalable, and reliable biosensors for the routine detection of the onset of AD, it will be allowed to progress beyond the possibility of treatment. This project will be achieved in synergy with RPL Alperstein and Kwee for cross-validation of the biosensing approach. It will also leverage a collaboration with RPL Messina and the technical cores of the COBRE to ultimately provide a powerful biosensing platform for the detection and tracking of a range of disorders displaying protein heterogeneity.