An Edible H2O2 Biosensor for Gastrointestinal Metabolites and Peroxidase Enzyme Quantification

ABSTRACT. Gastrointestinal (GI) fluids are a rich source of diagnostic biomarkers, yet access to these analytes remains limited to specialized clinical settings due to the rigidity, potential toxicity and environmental burden of conventional ingestible devices. Here, we present an edible biosensor for metabolite and enzyme activity quantification in gastric fluid, designed to be safely ingested and partially metabolized after use. The biosensor is validated for H2O2 quantification, a key reactive oxygen species associated with GI inflammations, via a controlled redox reaction involving caffeic acid and horseradish peroxidase. Following spectrophotometric and electrochemical validation, the redox system is integrated into an edible extended-gate electrolyte-gated field-effect transistor that uses a toothpaste pigment as the semiconductor. The device is tested in vitro and detects H2O2 in the 0–3 mM range, with a limit of detection of ∼143.7 µM and sensitivity of 2.7 µC mM−1. As a proof-of-application, we demonstrate the use of the edible biosensor to detect metabolites (glucose and cholesterol) and biomarkers (gastric peroxide enzyme activity) by minimal modifications of the biorecognition elements, and we validate the sensing mechanism in simulated physiological environment. This work moves toward direct in vivo biosensing for the GI tract, which is safe and accessible at the point-of-care.