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

• 批准号: 9979087
• 负责人: Sameer R Sonkusale
• 金额: $ 19.61万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9979087
• 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; Epithelium; 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; pathogen; pressure; prevent; radio frequency; remote control; response; sensor; technological innovation; technology development; tool; transmission process

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. !

概括 背景和理由：我们正在提出探索性研究以开发和测试微工程 胃肠道（GI）的含量为gi植物的含量。 藏有多种微生物群落（微生物组或微生物群），适合不同的酸度， 这些微生物的氧气张力，胆汁浓度和其他条件 重要的代谢功能对于消化和控制宿主的免疫功能必不可少。 这些微生物群落的代谢产物的生产调节免疫反应，并促进 上皮的完整性。 炎症和对肠道感染的耐药性障碍 其他先进的分析技术可以对GI中发现的复杂环境进行详细的分析 与高通量测序和其他Omics Technics的快速发展相比 gi道的能力不令人满意。 推断小肠和大肠的生态并检测肠道病原体的粪便。 开发微工程的可镶嵌胶囊，旨在从胃肠道特定位置进行采样。 采样将使用由石蜡蜡制成的热触发无线触发的无线触发。 使用能够在Arate的Arate采样的嵌入式无源泵中，将实现采样 100〜300 µL/hr没有电源的下一步 胶囊由于蠕动而穿过胃肠道。 具体目的：研究有两个特定的目的； 1）在体外设计，制造和测试 工程的无胶囊将在肠道内进行一次。 猪; 2）使用猪作为人类胃肠道的模型，胶囊设计特定于体外 性能标准将在体内测试。 配置由胶囊采样的细菌群落。 那些从猪肠的不同之后收集了毛囊的较大的euthanasia 采样特定的胃肠gorgans的含量。 创新：我们提出的研究旨在开发新的研究工具。 将实现研究胃肠道的方法，并恢复到扰动 由肠感染或其他条件触发。 以非侵入性的方式收集了各种器官。 通过Ith Ith Ith改进的CABIONATY进行临床应用的技术 状况。 呢