Ghodssi, Reza

Abstract Hydrogen sulfide (H 2 S) is a gaseous inflammatory mediator and important signaling molecule for maintaining gastrointestinal (GI) homeostasis. Excess intraluminal H 2 S in the GI tract has been implicated in inflammatory bowel disease and neurodegenerative disorders; however, the role of H 2 S in disease pathogenesis and progression is unclear. Herein, an electrochemical gas‐sensing ingestible capsule is developed to enable real‐time, wireless amperometric measurement of H 2 S in GI conditions. A gold (Au) three‐electrode sensor is modified with a Nafion solid‐polymer electrolyte (Nafion‐Au) to enhance selectivity toward H 2 S in humid environments. The Nafion‐Au sensor‐integrated capsule shows a linear current response in H 2 S concentration ranging from 0.21 to 4.5 ppm ( R 2 = 0.954) with a normalized sensitivity of 12.4% ppm −1 when evaluated in a benchtop setting. The sensor proves highly selective toward H 2 S in the presence of known interferent gases, such as hydrogen (H 2 ), with a selectivity ratio of H 2 S:H 2 = 1340, as well as toward methane (CH 4 ) and carbon dioxide (CO 2 ). The packaged capsule demonstrates reliable wireless communication through abdominal tissue analogues, comparable to GI dielectric properties. Also, an assessment of sensor drift and threshold‐based notification is investigated, showing potential for in vivo application. Thus, the developed H 2 S capsule platform provides an analytical tool to uncover the complex biology‐modulating effects of intraluminal H 2 S.