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Micro-engineered capsules for spatial sampling of microbiome in vivo

用于体内微生物组空间采样的微工程胶囊

基本信息

批准号：
10088394
负责人：
Sameer R Sonkusale
金额：
$ 23.63万
依托单位：
TUFTS UNIVERSITY MEDFORD
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10088394
关键词：
3D Print Acidity Aspirate substance Autopsy Bile fluid Chronic Clostridium difficile Collection Complex DNA sequencing Data Development Diagnosis Digestion Disease Distant Ecology Electronics Endoscopy Engineering Enteral Environment Epithelial Euthanasia Extravasation Family suidae Fecal analysis procedure Feces Frequencies Gastrointestinal Contents Gastrointestinal Physiology Gastrointestinal tract structure Health Heating High-Throughput Nucleotide Sequencing Human Immune response Impairment In Situ In Vitro Inflammation Intestines Investigation Large Intestine Liquid substance Location Magnetism Manuals Membrane Metabolic Methods Microbe Microbiology Microcapsules drug delivery system Microfluidics Modeling Operative Surgical Procedures Organ Organ Harvestings Outcome Outcomes Research Oxygen Paraffin Performance Peristalsis Phase Transition Play Polymers Process Production Proteomics Pump Radio Reader Research Research Project Grants Resistance Ribosomal RNA Role Sampling Signal Transduction Silicones Small Intestines Sodium Chloride Spottings Stomach Techniques Technology Testing Waxes Weaning Wireless Technology Work X-Ray Computed Tomography advanced analytics age related bacterial community base biomaterial compatibility body system capsule clinical application design dysbiosis enteric infection enteric pathogen gastrointestinal gut microbiome host microbiota immune function improved in vivo in vivo evaluation innovation innovative technologies meetings metabolomics microbial community microbiome microbiota new technology novel strategies operation opportunistic pathogen pressure prevent radio frequency remote control response sensor technological innovation technology development tool transmission process

项目摘要

Summary Background and rationale: We are proposing exploratory research to develop and test microengineered ingestible capsules designed to sample the content of the gastro-intestinal (GI) tract. The GI tract is known to harbor abundant and diverse microbial communities (microbiome or microbiota) adapted to different acidity, oxygen tension, bile concentration and other conditions found in different organs. These microbes fulfill important metabolic functions essential to digestion and to controlling immune functions of the host. Through the production of metabolites, these microbial communities regulate the immune response and promote the integrity of the epithelium. Abnormal (dysbiotic) microbiomes are known to be associated with certain conditions such as inflammation and impaired resistance to enteric infections. High-throughput sequencing and other advanced analytical techniques enable detailed analyses of complex environments as found in the GI tract. In contrast to the rapid development of high-throughput sequencing and other omics technologies, our ability to non-invasively sample the GI tract is unsatisfactory. Most research uses biomolecules extracted from feces to infer the ecology of the small and large intestine and to detect enteric pathogens. We are proposing to develop microengineered ingestible capsules designed to sample from specific locations in the GI tract. Sampling will be controlled using wirelessly triggered thermally actuated microvalves made from paraffin wax. Sampling will be achieved using an embedded passive osmotic pump capable of sampling at a rate of 100~300 µL/hr without the need for electrical power. External magnetic sensor array will enable tracking of the capsule as it moves through the GI tract due to peristalsis. Specific Aims: The research has two Specific Aims; 1) Design, manufacture and test in vitro and ex vivo micro- engineered ingestible capsules. Ex vivo testing will be performed in intestinal organs dissected from weaned pigs; 2) Using the pig as a model of the human GI tract, capsule designs meeting specific in vitro and ex vivo performance criteria will be tested in vivo. Ribosomal RNA (16S) high-throughput sequencing will be used to profile the bacterial communities sampled by the capsule. Comparing the make-up of sampled microbiota with those collected post-euthanasia from different sections of the pig intestine will reveal the ability of the capsules to sample the content of specific GI organs. Innovation: The research we are proposing aims to develop a new research tool. If successful, the technology will enable a novel approach to studying the physiology of the GI tract and its response to perturbation triggered by enteric infections or other conditions. The technology will facilitate the analysis of gut content collected from various organs in a non-invasive manner. It is anticipated that further development of this technology will lead to clinical application with improved capabilities to diagnose infectious and non-infection GI conditions. !

总结