Charge Polarization-Enhanced Graphene Biosensors for the Attomole Detection of miRNA

)-61-carboxylic acid (MFCA) is used as a linker molecule, replacing the traditional 1-pyrenebutanoic acid succinimidyl ester (PBASE). This modification facilitates the movement of electrons from biomarkers, such as microRNA (miRNA), across the Debye screening layer through a charge attraction effect. This approach achieves a detection limit (LoD) as low as 1 aM for hsa-mir-125b miRNA, a critical biomarker for Alzheimer's disease, and this is an improvement of 2-3 orders of magnitude over previous methods. The enhanced sensitivity is attributed to the efficient electron transfer from miRNA to the graphene surface, demonstrated by density functional theory (DFT) calculation and control experiment with the PBASE linker. Further, this method is also applied in the detection of another miR-34a with an ultralow LoD of 1 aM, showing its generalizability. This work enables the application of charge polarization-enhanced electrical biosensors in the early-stage diagnosis of various diseases with ultrahigh sensitivity.