Ingestible Pill for spatially targeted sampling of gut microbiome

用于肠道微生物组空间靶向采样的可摄入药丸

• 批准号: 10642791
• 负责人: Sameer R Sonkusale
• 金额: $ 19.29万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-13 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10642791
• 关键词: 3D Print; Adult; Aging; Anatomy; Animal Model; Animals; Architecture; Automobile Driving; Bioinformatics; Cells; Clinical Trials; Coin; Colon; Cross-Over Trials; Custom; Data; Development; Devices; Diet; Disease; Distal; Electronics; Engineering; Ensure; Environment; Extravasation; Family suidae; Female; Food; Future; Gastrointestinal Contents; Gastrointestinal tract structure; Harvest; Health; Human; In Situ; In Vitro; Individual; Ingestion; Intervention Trial; Intestinal Content; Intestines; Location; Magnetism; Measures; Meat; Methods; Microfabrication; Motor; Nutritional; Nutritional Study; Osmosis; Outcome; Oxygen; Particulate; Performance; Phase; Plants; Play; Population; Process; Pump; Randomized; Research; Research Personnel; Resolution; Role; Running; Safety; Sampling; Schools; Scientist; Site; Specific qualifier value; Stomach; System; Taxonomy; Technology; Testing; Therapeutic; Time; United States Department of Agriculture; Universities; Validation; Veterinary Medicine; Veterinary Schools; Viscosity; Weight; aspirate; cell motility; design; efficacy evaluation; experience; falls; fecal microbiota; flexibility; gastrointestinal; gut microbiome; gut microbiota; improved; in vitro testing; in vivo; innovation; male; metabolome; microbial; microbiota; microbiota profiles; miniaturize; nano; nanofabrication; nutrition; pill; preservation; prototype; response; sensor; tomography; wireless

Project Summary This R21/R33 proposal is submitted in response to PAR-20-133. The proposal focuses on the development of an ingestible device termed “micro-pill”. The micro-pill will be designed to autonomously sample intestinal content from predetermined anatomical sites in the gastrointestinal (GI) tract, a process which currently requires invasive methods. The development of the micro-pill benefits from the applicants' experimentation with an earlier version of the pill that utilizes an osmotic pump for sampling. To ensure accurate sampling of GI luminal content from specific anatomical sites, the micro-pill will be fitted with a miniaturized motor controlled by pH and pO2 sensors. The concept takes advantage of the proximal-to-distal rising pH and falling oxygen gradient, such that the micro-pill will sample autonomously based on pre-programmed pH and O2 thresholds. This innovative control mechanism is optimal for this application because it dispenses with the need for tomography or built-in camera that may be needed to track the pill's location for spatially selective sampling. The new micro-pill will run on power from a coin cell battery and will also support wireless magnetic activation in individuals where pH/pO2 levels may be altered due to atypical GI tract conditions. The architecture of the micro-pill is optimized to enable sampling of viscous intestinal content and reduce leakage and contamination, while maximizing the volume of sample collected and maintaining low specific weight for improved buoyancy and motility through the GI tract. During the R21 phase micro-pill prototypes will be built and tested in vitro in conditions simulating the viscosity of the GI lumen and ex vivo in pig intestines. Optimized designs will be tested in live pigs. The R21 phase is organized in 3 specific aims: (1), To design, fabricate and validate in vitro a motorized micro-pill; (2) To design, integrate and test pH/pO2 sensors in vitro and ex vivo using electronics integrated in the micro-pill; (3) To test the ingestible micro-pill in live pigs in vivo. The aims of the R33 phase are to assess the efficacy of the micro- pill (4) and conducting a 2-phase randomized controlled cross-over diet trial in humans (5). In Specific aim 4 the feasibility of sampling human adults' luminal content from pre-determined GI tract regions will be tested in a clinical trial. The trial will not only assess the micro-pill's function, but also compare the effects of a plant-based and a meat-based diet on the GI tract microbiota collected from different anatomical GI sites. This proposal was conceived by three Tufts University researchers with complementary expertise. PI Dr. Sameer Sonkusale from the School of Engineering heads an interdisciplinary Nano Lab and specializes in micro- and nano-fabrication, and biomedical devices. Dr. Giovanni Widmer from the School of Veterinary Medicine has extensive experience with animal models, microbiota analysis and bioinformatics. Dr. Alice H Lichtenstein at the Jean Mayer USDA Human Nutrition Research Center for Aging brings to the project years of experience with diet-related human intervention trials.

项目摘要 本R21/R33提案是根据PAR-20-133提交的。该提案的重点是发展 一种被称为“微丸”的可摄取装置。微型药丸将被设计为自动采样肠道 从胃肠道（GI）中的预定解剖部位吸收内容物，这是一个目前 需要侵入性的方法微丸的开发得益于申请人的实验 与利用渗透泵进行取样的早期版本的药丸不同。确保GI的准确采样 腔内容物从特定的解剖部位，微型药丸将装有一个小型化的电机控制 pH和pO 2传感器。该概念利用了近端到远端的pH值上升和氧气下降 梯度，使得微丸将基于预编程的pH和O2阈值自主采样。 这种创新的控制机制对于这种应用是最佳的，因为它无需 X射线断层摄影或内置相机，可能需要跟踪药丸的位置，以进行空间选择性采样。 新的微型药丸将使用纽扣电池供电，还将支持无线磁激活 pH/pO 2水平可能因非典型胃肠道疾病而改变的个体。的架构 微丸被优化以能够对粘性肠内容物进行采样并减少泄漏和污染， 同时使收集的样品体积最大化并保持低比重以提高浮力 和胃肠道的蠕动 在R21阶段，将在模拟粘度的条件下构建微丸原型并进行体外测试 和离体猪肠中的胃肠道。优化设计将在生猪中进行测试。R21阶段是 组织在3个具体的目标：（1），设计，制造和验证体外机动微丸;（2）设计， 使用集成在微丸中的电子器件在体外和离体集成和测试pH/pO 2传感器;（3）测试 可在生猪体内摄取的微丸。R33阶段的目的是评估微生物制剂的有效性。 药丸（4）和进行2期随机对照交叉饮食试验在人类（5）。具体目标4 从预先确定的胃肠道区域取样成人管腔内容物的可行性将在 临床试验该试验不仅将评估微丸的功能，还将比较植物性药物的效果。 以及基于从不同解剖学GI部位收集的GI道微生物群的肉类饮食。 这项建议是由塔夫茨大学的三位研究人员提出的，他们具有互补的专业知识。PI医生 工程学院的Sameer Sonkusale领导着一个跨学科的纳米实验室，专门从事 微米和纳米制造以及生物医学设备。兽医学院的乔瓦尼·威德默博士 医学在动物模型、微生物群分析和生物信息学方面拥有丰富的经验。Alice H博士 美国农业部老龄化人类营养研究中心的Lichelton为该项目带来了多年的经验， 饮食相关的人类干预试验的经验。