Dopamine Self-Polymerization-Assisted Oriented Antibody Immobilization on a Transistor for Alzheimer’s Disease Diagnosis

Antibody transistor biosensors show promise for early Alzheimer's disease (AD) diagnosis due to their single molecule detection capability. However, the random attachment of a payload to antigen-binding fragments (Fab) during biosensor preparation can disrupt target recognition, leading to poor consistency and repeatability. Here, we present a rapid and simple antibody-oriented immobilization method through a dopamine self-polymerization (DASP) process. Experimental and molecular dynamics simulation validation confirms the performance and mechanism of antibody orientation modification, attributed to the different electrostatic and hydrophobic interactions between DA and the various regions of the antibody in the DASP process. Our findings demonstrate that the DASP-based antibody field effect transistor biosensors are capable of accurately quantifying p-tau 217 levels in complex samples, ranging from fg/mL to ng/mL, achieving high recovery rates (96.0-104%) and low relative standard deviations (2.7-4.8%). Coupled with machine learning, the biosensor accurately differentiated between AD patients and healthy individuals in 25 clinical samples with an accuracy rate of 100%. This proposed platform holds potential for developing a nearly single-molecule point-of-care testing method for early AD blood screening in clinical settings. Furthermore, a simple self-assembly approach for antibody orientation fabrication offers broad applications in sensing, diagnostic imaging, and targeted drug delivery.