Bioimpedance Sensing Capsule for Measuring Intestinal Permeability

About This Grant

PROJECT SUMMARY Crohn's disease and ulcerative colitis, known collectively as inflammatory bowel disease (IBD), exhibit distinct and progressive patterns of inflammation in the gastrointestinal (GI) tract, sharing overlapping symptoms with other illnesses and complicating diagnosis. Although endoscopy provides visualization useful for diagnostics, it has limited reach within the GI tract and cannot provide explicit physiological measurements. Bioimpedance, a surrogate for epithelial barrier integrity, is a promising technique for quantifying dielectric tissue properties relevant to the state of inflammation in the gastrointestinal tract. However, research studying the physiological implications of bioimpedance is limited beyond the esophagus due to variations in inflammatory response and inconsistent sensor contact in the GI tract, obfuscating the real-time correlation between tissue impedance and inflammatory state. To address this, we propose to adapt a previously developed ingestible capsule platform to collect real-time measurements of pH, pressure, and bioimpedance of epithelial tissues. In prior work, we have successfully demonstrated capsule-embedded bioimpedance sensors for wireless monitoring of tissue permeability of excised colonic tissue from mice and in a cecum using a rat colitis model to evaluate the potential of bioimpedance for disease assessment. We hypothesize that a multimodal sensing approach utilizing ingestible capsule technology will enable access to barrier integrity information in local tissues throughout the GI tract, expanding the toolbox of approaches for early detection of inflammatory GI diseases. Through two distinct aims, the proposed capsule device will correlate changes in bioimpedance and intestinal permeability in the GI tract—phenomena not easily detected by traditional capsule endoscopy—and demonstrate safe GI transit using animal models. Aim 1 will focus on benchtop evaluation. Bioimpedance data will be collected from freshly excised ex vivo tissues of adult pigs with altered intestinal barrier integrity. Additionally, we will enhance measurement reliability while reducing the capsule size by integrating an array of bioimpedance and pressure sensors around the capsule to confirm tissue contact and microfabricating a pH sensor for capsule localization. The capsule will be evaluated in simulated intestinal fluids, and by ex vivo peristaltic simulators (i.e., modified organ chamber) to characterize the device under interferent GI conditions such as motion and acidic pH levels. In Aim 2, we will collect bioimpedance, contact pressure, and pH data in vivo during two animal studies in healthy adult pigs. One study will feature surgically implanted capsules fixed at stationary locations during measurement to ensure sensor contact and separate measurements by tissue type. Additionally, a small-scale pig study will be performed to understand capsule motility and ensure the safe passage of the capsule throughout GI transit while validating the reliability of the measurement. This aim will unveil measurement variability in vivo, generate datasets for statistical interpretation, and assist with determining feasibility of our technology toward future studies of permeability as an early-stage biomarker for inflammation.