Ingestible Pill for spatially targeted sampling of gut microbiome

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”的可食用装置。这种微型药丸将被设计成自动采集肠道样本 来自胃肠道(GI)预定解剖部位的内容物，这一过程目前 需要侵入性的方法。微丸的研制得益于申请者的实验 较早版本的药丸使用渗透泵进行采样。确保对胃肠道的准确采样 来自特定解剖部位的管腔内容物，微型药丸将配备一个微型马达控制 通过pH和PO2传感器。这一概念利用了从近端到远端的pH值上升和氧气下降的优势 梯度，这样微丸将根据预先设定的pH和O2阈值自动采样。 这种创新的控制机制是该应用的最佳选择，因为它不需要 体层摄影术或内置摄像头，可能需要跟踪药丸的位置，以进行空间选择性采样。 新的微型药丸将由硬币电池供电，并将支持无线磁力激活 PH/pO2水平可能因非典型胃肠道状况而改变的个体。的体系结构 微丸经过优化，能够对粘性肠道内容物进行采样，减少泄漏和污染， 同时最大化采集的样品体积并保持较低的比重以提高浮力 以及通过胃肠道的运动。 在R21阶段，将建立微丸原型，并在模拟粘度的条件下进行体外测试 胃肠腔和猪肠道的体外实验。优化的设计将在生猪身上进行测试。R21阶段是 组织在3个具体目标：(1)，设计，制造和验证体外电动微丸；(2)设计， 利用集成在微丸中的电子器件，在体外和体外集成和测试pH/PO2传感器；(3)测试 活体猪体内可食微丸。R33阶段的目标是评估微创治疗的疗效 药片(4)，并在人类中进行两阶段随机对照交叉饮食试验(5)。在特定目标中4 从预先确定的胃肠道区域采样成人腔内容物的可行性将在 临床试验。这项试验不仅将评估微丸的功能，还将比较以植物为基础的 以及从不同的胃肠道解剖部位收集的肠道微生物区系上的以肉类为主的饮食。 这项提议是由塔夫茨大学的三名具有互补专业知识的研究人员构思的。少年派博士。 工程学院的Sameer Sonkusale领导着一个跨学科的纳米实验室，专门研究 微米和纳米制造以及生物医学设备。兽医学院乔瓦尼·威德默博士 医学在动物模型、微生物区系分析和生物信息学方面拥有丰富的经验。爱丽丝·H博士 让·梅耶尔美国农业部老龄化人类营养研究中心的利希滕斯坦为该项目带来了几年 与饮食相关的人类干预试验的经验。

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.