Extracellular vesicles-based point-of-care testing for the diagnosis and monitoring of Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is a debilitating condition that affects millions of people worldwide. One promising strategy for detecting and monitoring AD early on is using extracellular vesicles (EVs)-based point-of-care testing; however, diagnosing AD using EVs poses a challenge due to the low abundance of EV-biomarkers. Here, we present a fully integrated organic electrochemical transistor (OECT) that enables high accuracy, speed, and convenience in the detection of EVs from AD patients. We incorporated self-aligned acoustoelectric enhancement of EVs on a chip that rapidly propels, enriches, and specifically binds EVs to the OECT detection area. With our enhancement of pre-concentration, we increased the sensitivity to a limit of detection of 500 EV particles/μL and reduced the required detection time to just two minutes. We also tested the sensor on an AD mouse model to monitor AD progression, examined mouse Aβ EVs at different time courses, and compared them with intraneuronal Aβ cumulation using MRI. This innovative technology has the potential to diagnose Alzheimer’s and other neurodegenerative diseases accurately and quickly, enabling monitoring of disease progression and treatment response.