Abstract: Embodiments include an ingestible capsule comprising a housing including a therapeutic payload carrying compartment; a power supply; a release mechanism; and a sensing mechanism, the sensing mechanism being sensitive to an environment external to the housing; the ingestible capsule being configured for passage through a GI tract of a subject mammal, during which passage: the sensing mechanism is configured to output a signal varying according to a GI tract environment, wherein the sensing mechanism comprises one or more sensors from among: a VOC gas sensor; a TCD gas sensor; a reflectometer formed by a transmission antenna of the ingestible capsule connected in series with a directional coupler configured to measure a reflected signal from the transmission antenna; and an accelerometer; the release mechanism is configured to cause a therapeutic payload to be released into the GI tract from the therapeutic payload carrying compartment at a release timing determined according to the output signal.