Epitope-Imprinted Field-Effect Transistors Overcome Debye Length Limitations for Label-Free Protein Detection

Graphene-based field-effect transistor (GFET) biosensors face limitations in detecting charged analytes due to ionic screening (Debye screening effect). This limitation restricts their ability to detect charged target analytes <i>in situ</i> in physiological solutions. To overcome this challenge, we present a non-destructive van der Waals (vdW) integration of an epitope molecular-imprinted membrane (EMIM) with a GFET biosensor. This innovative vdW-heterostructured biosensor, termed the EMIM-Chip, features a 3.3 ± 1.7 nm thin EMIM dielectric layer self-assembled on the graphene surface. The EMIM layer, featuring specifically imprinted cavities, replaces antibodies and effectively mitigates ionic screening. This innovation enables rapid <i>in situ</i> detection of Alzheimer's disease (AD) biomarker Aβ proteins (50 aM-5 pM) in purified samples and patient plasma/urine within minutes. Notably, these sensors retain their functionality even after 30 days of environmental storage, positioning our approach as a promising foundation for future medical tool development.