Smart Sampling Capsule for Capture and Detection of Enteric Pathogens in the Small Intestine

Abstract Early and accurate detection of enteric pathogens is critical for addressing global health challenges, including timely diagnosis of infections, prevention of zoonotic disease transmission, and mitigation of widespread foodborne outbreaks. However, many pathogens can evade immune detection by entering a dormant state in the small intestine and may only reactivate under immune‐compromised conditions. This latent behavior, particularly in the upper gastrointestinal (GI) tract, necessitates targeted sampling from the small intestine to enable timely intervention and administration of appropriate prophylaxis. Conventional stool‐based diagnostics often fall short in this regard, as they do not accurately reflect microbial communities in upstream regions, where microbiota profiles differ substantially from fecal samples. To address this gap, a smart, noninvasive capsule platform capable of site‐specific microbial sampling from the small intestine is developed and evaluated. The capsule comprises a superabsorbent hydrogel enclosed in a nonbiodegradable 3D‐printed casing, with a pH‐responsive enteric coating on its aperture. This coating selectively dissolves under small intestinal pH conditions, allowing luminal fluid containing microbial content to enter the capsule. The hydrogel then swells, capturing the sample and simultaneously sealing the capsule to prevent contamination as it transits downstream. As a proof‐of‐concept, systematic in vitro and in vivo experiments are conducted to evaluate the capsule's ability to sample and detect Listeria monocytogenes , a model enteric pathogen, in the small intestine. Postsampling analyses assess the stability of the microbial composition and its viability within the capsule. Results demonstrate that the capsule preserved microbial viability ( p < 0.05) and genetic integrity (UniFrac similarity: 89%) for up to three days after sampling. Additionally, in vivo studies in pig models confirm the capsule's safe passage through the GI tract without causing obstruction or irritation. Importantly, L. monocytogenes is successfully detected in capsule‐retrieved samples using both 16S rRNA sequencing and standard culturing methods, whereas it is frequently undetectable in matched fecal samples. This study highlights a new, minimally invasive strategy for detecting low‐abundance, spatially localized pathogens in the upper GI tract and provides a foundational step toward developing more precise diagnostic tools, personalized antibiotic regimens, and early‐stage prophylactic interventions.