Smart Capsule for Targeted Proximal Colon Microbiome Sampling

Authors: NEJATI, SINA - Purdue University; WANG, JIANGSHAN - Purdue University; SEDAGHAT, SOTOUDEH - Purdue University; Long, Amanda; KASI, VENKAT - Purdue University; PARK, KINAM - Purdue University; Johnson, Jay; VERMA, MOHIT - Purdue University; RAHIMI, RAHIM - Purdue University

Submitted to: Acta Biomaterialia
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/19/2022
Publication Date: 9/24/2022
Citation: Nejati, S., Wang, J., Sedaghat, S., Long, A.M., Kasi, V., Park, K., Johnson, J.S., Verma, M., Rahimi, R. 2022. Smart Capsule for Targeted Proximal Colon Microbiome Sampling. Acta Biomaterialia. 154(83-96). https://doi.org/10.1016/j.actbio.2022.09.050.
DOI: https://doi.org/10.1016/j.actbio.2022.09.050

Interpretive Summary: The ability to non-invasively assess colonic microbiome is lacking in both humans and pigs. In humans, non-invasive technologies to assess intestinal health would be beneficial in diagnosing diseases involving enterotoxigenic bacteria. In pigs, this technology would be beneficial for repeated and non-invasive sampling of intestinal contents for microbiome analyses. Traditionally, pigs must be euthanized, and intestinal sections are manually collected to collect intestinal contents in specific sections to assess the microbiome. However, while this process is often a necessary step in swine intestinal health research, it leads to the use of a greater number of animals in research efforts due to an inability to perform repeated non-invasive sampling. To address these issues in both humans and pigs, a battery free non-invasive smart capsule device was designed that can allow for targeted sampling of intestinal microbiome in the colon. The battery free smart capsule is composed of a 3D printed casing with a super absorbent hydrogel inside the capsule, which captures the biomarkers of interest. The capsule is then naturally passed and collected to evaluate the biomarkers and this capsule has been extensively tested in pigs. The capsule has been demonstrated to successfully sampling, preserve, and maintain the bacteria ratio both in vitro and in vivo.

Technical Abstract: The gut microbiome plays a major role in the etiology of numerous diseases and much robust evidence confirms that perturbation to the composition of the colonic microbiota leads to various colonic diseases including colorectal cancer, inflammatory bowel disease, irritable bowel syndrome, and diverticulitis. Extensive efforts have been put forth to monitor the gut microbiome with the aid of sequencing fecal or mucosal biopsy samples that are typically collected via a colonoscopy. However, fecal sampling may not accurately reflect the microbiome composition from the desired region, and colonoscopy is invasive, expensive, time-consuming, requires a skilled medical physician, and a specific regimen that is inappropriate for frequent weekly/monthly observations for host health monitoring. Therefore, for the first time, we designed and developed a novel 3D-printed batteryless sampling device for non-invasive sampling of microbiota from the targeted ascending colon region. The device benefits from the gastrointestinal (GI) tract pH profile to remain inactive in the stomach and small intestine while eventually triggering the opening actuation at the site of interest by employing a double-layer pH-responsive enteric coating. To avoid intermixing of the layers due to the identical solvents, near-infrared (NIR) is exploited to rapidly cure the layers while non-destructively eliminating the trapped solvents supported by various characterization techniques including SEM, ATR-FTIR, Raman, and TGA. The super absorbent hydrogel placed inside the capsule absorbs the colonic microbiota matrix and generates mechanical force during the swelling process to drive the bonded flexible disk for the device closure and sealing mechanism. As a proof of concept, the introduced capsule demonstrated excellent performance in sampling, preserving, and maintaining the bacteria ratio in vitro. Furthermore, the analyzed WideSeq results confirm that Firmicutes/Bacteroidetes ratio extracted from the administered capsule in vivo is consistent with the ratio obtained from the large intestinal content demonstrating the colon targeted sampling capability of the device.