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
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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 该R21/R33提案是根据Par-20-133提交的。该提议着重于 一种被称为“微柱”的可观设备。微孔钻将被设计为自主采样肠 来自胃肠道（GI）区域中预定的解剖位点的内容，该过程当前 需要侵入性方法。微票的开发受益于申请人的实验 用较早的药丸版本，利用渗透泵进行采样。确保准确的GI采样 来自特定解剖部位的腔内含量，微电池将配备微型电动机控制 通过pH和PO2传感器。该概念利用近端到距离上升的pH和氧气下降 梯度，使微电池将根据预先编程的pH和O2阈值自主采样。 这种创新的控制机制对于此应用程序是最佳的，因为它消除了需求 可能需要进行层析成像或内置摄像头来跟踪药丸的位置以进行空间选择性采样。 新的微电池将通过硬币电池电池电源运行，还将支持无线磁性激活 在由于非典型胃肠道条件下可能会改变pH/PO2水平的个体中。架构 优化微柱以实现粘性肠含量并减少泄漏和污染， 同时最大化收集的样品体积并保持低特异性重量以提高浮力 和通过胃肠道的运动。 在R21相期间，将在模拟粘度的条件下在体外建造和测试MicroPill原型 猪肠中的胃肠道和离体的。优化的设计将在活猪中进行测试。 R21阶段是 以3个特定目的组织：（1），以设计，制造和验证在体外机动的微型票房； （2）设计， 使用集成在微电池中的电子设备在体外和离体中进行集成和测试pH/PO2传感器； （3）测试 活体内活猪中的无泡泡。 R33阶段的目的是评估微观的效率 药丸（4）并在人类中进行了2期随机对照跨饮食试验（5）。在特定目标4中 在预定的胃肠道区域中对人类成年人的腔内含量进行采样的可行性将在A中测试 临床试验。该试验不仅会评估微柱的功能，而且还将比较基于植物的效果 以及从不同解剖学gi部位收集的胃肠道菌群的基于肉类的饮食。 这项建议是由三名具有完整专业知识的塔夫茨大学研究人员构想的。 PI Dr. 工程学院的Sameer Sonkusale负责跨学科的Nano Lab，专门研究 微型和纳米制作以及生物医学设备。兽医学院的Giovanni Widmer博士 医学在动物模型，微生物群分析和生物信息学方面具有丰富的经验。爱丽丝·H博士 Jean Mayer USDA人类衰老中心的Lichtenstein为项目带来了 具有与饮食相关的人干预试验的经验。