In Operando Observation of Neuropeptide Capture and Release on Graphene Field-Effect Transistor Biosensors with Picomolar Sensitivity

Transmission electron microscopy (TEM) is being pushed to new capabilities which enable studies on systems that were previously out of reach. Among recent innovations, TEM through liquid cells (LC-TEM) enables in operando observation of biological phenom-ena. This work applies LC-TEM to the study of biological compo-nents as they interact on an abiotic surface. Specifically, biological recognition elements (BREs) based on biopanned peptides with affinity to neuropeptide Y are observed in operando on functional graphene field-effect transistor (GFET) biosensors. On working devices capable of achieving picomolar responsivity to neuropep-tide Y, LC-TEM reveals translational motion, stochastic positional fluctuations due to constrained Brownian motion, and rotational dynamics of captured analyte. Coupling these observations with the electrical responses of the GFET biosensors in response to analyte capture and/or release will potentially enable new insights leading to more advanced and capable biosensor designs.