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 in situ 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 in situ 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.