Raman spectroscopy of graphene for ultrasensitive protein detection

We report a novel graphene-based biosensor designed for the label-free detection of immunoglobulin M (IgM), showing a Limit of Detection (LOD) of 100 zepto-molar (10-19 M). The sensor features a two-terminal device with a millimetric gold sensing surface, bio-functionalized with a densely packed monolayer of anti-immunoglobulin M (anti-IgMs) capturing sites and capacitively coupled to a bare graphene electrode through a water-soaked paper strip. In this setup, bio-recognition events induce a surface potential shift of the sensing interface due to a collective electrostatic rearrangement of the recognition layer, which is effectively transduced by the graphene electrode. Specifically, the carrier density and Fermi level of the graphene electrode changes, affecting the phonon frequencies. A Raman spectrometer allows the in-situ monitoring of the graphene phonon frequency shifts, triggered by the incubation with few molecules of analyte (~ 10 IgMs in 0.1 mL). The combination of a graphene transducer with optical probing provides a proof-of-concept biosensor and introduces a pioneering method for in-situ biomarker detection, setting the stage for the development of portable, high-performance opto-electronic diagnostic tools suited for point-of-care applications.