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 旨在采样胃肠道（GI）含量的可饲养胶囊。胃肠道已知 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， 氧气张力，胆汁浓度和在不同器官中发现的其他条件。这些微生物实现了 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。通过 这些微生物群落的代谢产物的产生调节免疫反应并促进 上皮的完整性。众所周知，异常（失调）微生物组与某些相关 诸如感染和阻力受损的疾病促进感染。高通量测序和 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 道。与高通量测序和其他OMICS技术的快速发展相反，我们 非侵入性采样胃肠道的能力是不令人满意的。大多数研究使用从中提取的生物分子 推断小肠和大肠的生态并检测病原体的粪便。我们正在提议 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无线触发热激活的微欧生牛群来控制。 使用嵌入式的被动渗透泵，能够以速度进行抽样来实现采样 100〜300 µL/hr无需电力。外部磁性传感器阵列将能够跟踪 胶囊由于蠕动而穿过胃肠道。 具体目的：研究具有两个具体目标； 1）设计，制造和测试体外和离体微型 工程化的无胶囊。将在断奶的肠道器官中进行过体内测试 猪； 2）使用猪作为人类胃肠道的模型，胶囊设计符合特定的体外和离体 性能标准将在体内进行测试。核糖体RNA（16S）高通量测序将用于 介绍了由胶囊取样的细菌群落。比较采样微生物群的构成 那些从猪肠的不同部分收集的e酸后者将揭示胶囊的能力 采样特定的胃肠gorgans的含量。 创新：我们提出的研究旨在开发一种新的研究工具。如果成功，技术 将启用一种新的方法来研究胃肠道的生理及其对扰动的反应 由肠道感染或其他疾病触发。该技术将促进肠道内容的分析 以非侵入性方式从各种器官中收集。预计这是进一步的发展 技术将导致临床应用，并具有提高能力来诊断感染性和无感染GI 状况。 呢