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: 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
• 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

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：我们提议进行探索性研究来开发和测试微工程技术 众所周知，旨在对胃肠道 (GI) 内容物进行采样的可摄入胶囊。 拥有丰富多样的适应不同酸度的微生物群落（微生物组或微生物群）， 这些微生物满足不同器官中的氧分压、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至关重要。 代谢物的产生，这些微生物群落调节免疫反应并促进 已知上皮细胞的完整性异常（生态失调）与某些微生物有关。 炎症和肠道感染抵抗力受损等情况。 其他先进的分析技术可以对 GI 中的复杂环境进行详细分析 与高通量测序和其他组学技术的快速发展形成鲜明对比。 大多数研究使用从胃肠道中提取的生物分子进行非侵入性采样的能力并不令人满意。 我们建议通过粪便来推断小肠和大肠的生态并检测肠道病原体。 开发微工程可摄入胶囊，旨在从胃肠道的特定位置进行采样。 将使用由石蜡制成的无线触发热驱动微型阀来控制采样。 将使用嵌入式被动渗透泵来实现采样，该泵能够以以下速率采样： 100~300 µL/小时，无需电力即可跟踪外部磁传感器阵列。 胶囊由于蠕动而穿过胃肠道。 具体目标：该研究有两个具体目标；1）设计、制造和测试体外和离体微生物 工程化可摄入胶囊将在断奶后解剖的肠道器官中进行。 2) 使用猪作为人类胃肠道模型，胶囊设计满足特定的体外和离体要求 将使用核糖体 RNA (16S) 高通量测序来测试性能标准。 分析胶囊采样的细菌群落，将采样的微生物群的组成与该样本进行比较。 安乐死后从猪肠道不同部分收集的样本将揭示胶囊的能力 对特定胃肠道器官的内容进行采样。 创新：我们提出的研究旨在开发一种新的研究工具，如果成功的话，该技术。 将为研究胃肠道生理学及其对扰动的反应提供一种新方法 由肠道感染或其他条件触发的技术将有助于对肠道内容物的分析。 以非侵入性方式从各种器官收集的数据预计将得到进一步发展。 技术将导致临床应用，提高诊断感染性和非感染性胃肠道的能力 状况。 ！