Electronic‐Free Traceable Smart Capsule for Gastrointestinal Microbiome Sampling

Abstract Non‐invasive smart electronic‐free sampling capsules have revolutionized the exploration of microbiome‐disease interactions in inaccessible regions of the gastrointestinal (GI) tract. However, a significant impediment to the broader use of electronic‐free capsules is the challenge of reliably tracking and determining their in vivo location. Variability in patient motility introduces uncertainties in capsule position. Thus, there is a critical need for effective solutions that ensure traceability in microbiome studies employing such capsules. While tracking methods are explored in previous smart ingestible capsule designs, most have relied on RF, imaging, and radiation‐based techniques, limiting sampling volume, increasing costs, complicating design, and raising health concerns due to ionizing radiation exposure. To address these challenges, the design of an electronic‐free smart capsule is introduced that integrates a metal tracer for easy metal detection, serving as a reliable tracking mechanism. The capsule is housed in a 3D‐printed casing and includes a superabsorbent hydrogel serving as both a sampling medium and an actuator within the capsule. The capsule's targeted sampling of the GI tract is accomplished by covering the capsule's sampling port with a pH‐responsive coating. Optimal dimensions and material for the cylindrical shaped metal tracer on the capsule are determined through extensive optimizations, considering factors such as gastric flotation, corrosion resistance, read distance, and omnidirectional detectability. The results of these investigations reveal that a 12 mm stainless steel (SS 316L) cylinder offers the necessary detection and tracing capabilities with minimal toxicity and excellent corrosion resistance under relevant physiological conditions in the GI tract. Validation studies, both in vitro and in vivo, confirmed the capsule's trackability using a handheld metal detector. These findings are further validated by X‐ray imaging and CT scans, demonstrating the metal detector's ability to distinguish approximate GI tract regions and determine the time point of excretion. This innovative approach provides a reliable and cost‐effective solution for tracking electronic‐free smart capsules, enhancing their applicability in microbiome research for both human and animal studies.