An ingestible bioelectronic capsule for in vivo DNA monitoring in the gastrointestinal tract

Early detection of gastrointestinal pathogens and disease-associated DNA sequences is critical for timely clinical intervention, yet current diagnostic workflows rely on ex vivo stool analysis or invasive biopsy, which delays diagnosis and compromises trace DNA integrity. Here, we report an ingestible bioelectronic capsule embedded with a paper-based CRISPR/Cas system for in vivo sampling, on-board lysis, sequence-specific DNA sensing, and wireless signal readout. By performing thoroughly in situ, the capsule mitigates the degradation and dilution of target DNA that occur during ex vivo handling. It enables detection of the Salmonella invA gene in simulated gastric fluid, real gastric samples, and the stomachs of large animal models (canine and porcine). We further validate the capsule strategy for detecting Helicobacter pylori DNA in human volunteer samples. This CRISPR/Cas-embedded bioelectronic capsule offers a non-invasive, point-of-care approach for in vivo monitoring of specific DNA sequences in the gastrointestinal tract, with potential for personalized health management.