AptaMod: Modular Biosensing for Alzheimer’s Disease Detection

Project Video

Abstract

Early detection of Alzheimer’s disease (AD) remains a critical unmet need. Current diagnostic methods are often invasive, costly, slow, and are often implemented too late in disease progression. To meet this need, the development of AptaMod, a novel detection method for Alzheimer’s disease, was created. The proposed biosensor design integrates a DNA aptazyme with a lateral flow assay (LFA) for rapid, minimally invasive detection of AD biomarkers. The biosensor targets a blood-based biomarker, beta-amyloid, which is elevated in early AD. The DNA aptazyme has a specific binding site for the biomarker. Upon biomarker binding, the aptazyme undergoes a conformational change that brings horseradish peroxidase (HRP) and its substrate, 3,3’,5,5’-tetramethylbenzidine (TMB) into close proximity. The enzyme HRP then oxidizes TMB, producing a visible blue colorimetric signal within minutes. In order to reduce waste, a toehold-mediated strand displacement (TMSD) mechanism enables reusability by replacing the aptazyme component without discarding the entire device. The DNA aptazyme is immobilized on a LFA platform, a porous nitrocellulose membrane strip, which draws the sample across the control and test lanes via capillary action, allowing on-strip binding and signal generation without expensive and complex instrumentation for detection. The integration of our developed DNA aptazyme into an LFA platform allows for portability, rapid readout, and potential adaptation to multiple biomarkers. This design offers a low-cost, modular, and sensitive diagnostic tool that could be incorporated into routine check-ups, enabling earlier intervention and detection, improving patient outcomes, and significantly reducing diagnostic turnaround time from weeks to minutes.