Stamp-Imprinted Polymer EIS Biosensor for Amyloid-Beta Detection: A Novel Approach Towards Alzheimer's Screening.

Surface-imprinted polymers (SIPs) represent an exciting and cost-effective alternative to antibodies for electrochemical impedance spectroscopy (EIS)-based biosensing. They can be produced using simple printing techniques and have shown high efficacy in detecting large biomolecules and microorganisms. Stamp imprinting, a novel SIP method, creates the target analyte's imprint using a soft lithography mask of the analyte matrix, thereby reducing material complexities and eliminating the need for cross-linking, which makes the process more scalable than the conventional SIPs. In this work, we demonstrate a stamp-imprinted EIS biosensor using a biocompatible polymer, polycaprolactone (PCL), for quantifying amyloid beta-42 (Aβ-42), a small peptide involved in the pathophysiology of Alzheimer's disease. The evaluated SIP-EIS biosensors showed a detection limit close to 10 fg/mL, and a detection range covering the physiologically relevant concentration range of the analyte in blood serum (from 10 fg/mL to 10 μg/mL). The device sensitivity, which is found to be comparable to antibody-based EIS devices, demonstrates the potential of SIP-EIS biosensors as an exciting alternative to conventional antibody-based diagnostic approaches. We also evaluate the viability of analyzing these proteins in complex media, notably in the presence of serum albumin proteins, which cause biofouling and non-specific interactions. The combination of high sensitivity, selectivity, and ease of fabrication makes SIP-EIS biosensors particularly suited for portable and point-of-care applications.