Surface Reaction-Mediated Nanomolar Detection of Chemically Activated Plant Metabolite Biomarkers with Field Effect Sensors

Abstract Among potent psychedelic drugs derived from plant metabolites, N,N-dimethyltryptamine (DMT) is a known endogenous tertiary amine alkaloid that can be harmful to brain activity even when present in biological fluids at nanomolar concentrations. Conventional electrochemical detection methods reach only micromolar limits, far above the physiological window, while full mass-spectrometric analysis needed for practical nanomolar detection depends on centralized medical facilities. Here, we present a three-step sensing strategy combining selective chemical activation with a self-assembled monolayer (SAM)-functionalized surface in order to facilitate nanomolar detection with extended-gate field-effect transistor (EGFET) sensors. Initially, the target tertiary amine is selectively oxidized to its N-oxide and rearranged to the corresponding amide, introducing a reactive handle absent from the native molecule. As a next step, the activated analyte is captured by an amino-terminated SAM on the gate electrode of the FET device. Finally, the resulting shift in gate surface potential is transduced by the EGFET into a detectable electrical output. Using gramine as a DMT surrogate, the fabricated sensory device achieves a limit of detection of 7 nM, well within the required physiological window. The surface-bound amount was independently confirmed by ellipsometry measurements of dried samples. This chemistry-driven activation strategy bypasses the need for complex biosensors and offers a general route to small-molecule metabolite targets that are difficult to address with antibody- or aptamer-based recognition.