Blindly Controlled Magnetically Actuated Capsule for Noninvasive Sampling of the Gastrointestinal Microbiome

The objective of this article is to address the challenges of physical sample retrieval from all locations along patients' gastrointestinal (GI) tracts for studying of interactions between GI microbial communities (microbiomes) and host immune systems. We propose a novel tetherless, blindly controlled, magnetically actuated capsule for noninvasive sampling of GI microbiomes and liquid digesta. The mesoscale capsule, a soft mobile robot platform, is made from two permanent magnets encapsulated in a soft elastomer and actuated remotely by an external magnet. The capsule is controlled blindly using an external magnet to orient and activate the capsule. Following oral administration, capsules transit the GI tract and are activated at specified locations. The capsule is recovered via routine stool passage and collected samples are processed for downstream analyses (e.g., 16S rRNA surveys, metagenomics, metatranscriptomics and/or metabolomics). The localization of the capsule is estimated using the traveling time and the location of collected microbiomes will be confirmed by downstream analyses. A mathematical model of capsule activation is used to predict capsule activation and guide design optimization. We demonstrate the ability of the capsule to collect samples, as well as maintain sample integrity in vitro, ex vivo , and with twelve capsules in in vivo swine models. Eleven capsules successfully collected digesta (in the range of 18 to 61 mg). This sampling apparatus offers a technological advance for the robust sampling of GI tract contents.