Graphene-Based Opto-Electronic Platform for Ultra-Sensitive Biomarker Detection at Zeptomolar Concentrations.

A ground-breaking graphene-based biosensor designed for label-free detection of immunoglobulin M (IgM) achieving a remarkable concentration of 100 zeptomolar (10 ^-19 m), is reported. The sensor is a two-terminal device and incorporates a millimeter-wide gold interface, bio-functionalized with ≈10 ¹² anti-IgM antibodies and capacitively coupled to a bare graphene electrode through a water-soaked paper strip. In this configuration, few affinity binding events trigger a collective electrostatic reorganization of the protein layer, leading to an extended surface potential (SP) shift of the biofunctionalized Au surface. The SP shift, mediated by electrolyte capacitive coupling, induces a corresponding shift in the Fermi level of graphene. This shifts the graphene phonon frequencies, which are measured by Raman spectroscopy. Decoupling the sensing interface from the transducing graphene layer provides flexibility in surface chemistry modifications, while preserving the graphene integrity. A key aspect of this biosensor is its ability to precisely determine the graphene charge neutrality point from the voltage dependence of phonon frequency shifts, enabling detections of biomarker at unprecedented low concentrations. The integration of graphene with optical probing demonstrates a proof-of-concept and establishes a ground-breaking approach to in situ biomarker detection, setting the stage for a future generation of portable opto-electronic high-performance diagnostic tools for single-marker detection.
(© 2025 The Author(s). Small Methods published by Wiley‐VCH GmbH.)