Dual‐Functional Ingestible Passive Capsules for High‐Throughput Intestinal Sampling with Sealed Containment and Targeted Drug Delivery

Abstract

Gut biological information, including microbiota and metabolites, shows increasing associations with diseases such as inflammatory bowel disease, obesity, and diabetes. Precise sampling and modulation of biological information have become critical in medical research, health assessments, and interventions. Although various intestinal sampling and drug delivery capsules have been developed independently, achieving multifunctional passive capsules within a swallowing size remains a challenge. Here, we have designed a dual‐functional passive capsule that integrates intestinal sampling and drug delivery capabilities through a dual‐control mechanism based on pH responsiveness and mechanical actuation and meets the standard requirements for oral ingestion (Ø10.5 mm × L26 mm). It is engineered to target specific regions of the gut, activating the sampling function in response to pH values (≥5.5). The system enables high‐throughput collection of intestinal juice (>300 μL) while effectively resisting gas interference. An integrated, spring‐driven actuation mechanism provides a sealing force exceeding 0.78 N, ensuring secure encapsulation of collected samples even under the mechanical stresses posed by high‐viscosity intestinal contents (1 × 10 6 mPa s). The capsule's dual functionality was successfully validated in‐vivo using Bama miniature pigs, demonstrating efficient, contamination‐sealed sample collection suitable for downstream sequencing analysis and highlighting its strong potential for biomedical applications.