Swallowable expandable fibrous capsules for nonendoscopic sampling of esophageal cells

Esophageal adenocarcinoma is a highly lethal malignancy with a 5-year survival rate of only 18.8%, largely due to late-stage diagnosis in the absence of effective population-wide screening. Survival improves to 42.9% when detected at a localized stage (I/II). More than 90% of esophageal adenocarcinoma cases are diagnosed without prior identification of Barrett's esophagus, its only known precursor. We present a swallowable, string-tethered capsule that expands in the stomach to enable atraumatic retrieval of esophageal epithelial cells without sedation or endoscopic guidance, completing the procedure in under 3 minutes. Capsules are fabricated via gas-foamed expansion of nanofiber mats or hybrid aerogel formation, enabling rapid in situ reexpansion upon gastric fluid exposure and safe retrieval. In swine studies, capsules dissolved within 2 minutes, reexpanded within seconds, required minimal retrieval force, and consistently captured intact epithelial layers without injury. This platform could enable low-cost, high-throughput esophageal sampling in primary care and resource-limited settings.