Tissue biopsying with wireless microgrippers within gastrointestinal tract

使用无线微夹钳在胃肠道内进行组织活检

• 批准号: 8614350
• 负责人: Florin Selaru
• 金额: $ 36.45万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-26 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8614350
• 关键词: Animal Model; Animals; Area; Autoimmune Process; Award; Barrett Esophagus; Biological Markers; Biological Models; Biopsy; Body cavities; Cancer Detection; Cardiovascular Diseases; Catheters; Clinical Trials; Communicable Diseases; Coupled; Cues; DNA; DNA Markers; Data; Databases; Detection; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Endoscopes; Endoscopy; Engineering; Ensure; Epidemiologic Studies; Epidemiology; Epigenetic Process; Esophageal Diseases; Esophageal mucous membrane; Esophagus; Fingers; Forcep; Gastrointestinal tract structure; Genetic; Human; Inflammatory; Learning; Lesion; Location; Malignant Neoplasms; Malignant neoplasm of lung; Manuscripts; Medical; Medicine; Messenger RNA; Metals; Methodology; Methylation; MicroRNAs; Miniaturization; Molecular Biology; Motivation; Mucous Membrane; Mutation; Operative Surgical Procedures; Organ; Organism; Paper; Pathologic; Patients; Phase; Phase I Clinical Trials; Physicians; Polymers; Population Study; Preparation; Production; Protocols documentation; PubMed; RNA; RNA marker; Relative (related person); Retrieval; Review Literature; Safety; Sampling; Science; Sensitivity and Specificity; Site; Smoking; Specimen; Surface; Surgeon; Techniques; Technology; Temperature; Testing; Thyroid Gland; Time; Tissue Sample; Tissues; Ulcerative Colitis; Variant; Wireless Technology; Work; abstracting; base; body cavity; court; disease diagnosis; falls; gastrointestinal; human disease; improved; in vivo; indexing; interest; mathematical methods; miniaturize; minimally invasive; molecular marker; novel; prevent; programs; public health relevance; response; statistics; tool

Project Summary: We have devised small, metallic, wireless microdevices, called microgrippers (¿-grippers). The ¿- grippers are approximately 1 mm in size and have finger-like projections. The ¿-grippers can be delivered within the gastrointestinal (GI) tract via a catheter inserted through the endoscope. Preliminary data shows that, in animal models in vivo, ¿-grippers can be delivered, spread uniformly to the mucosa, can be closed and biopsy tissue in response to biologic cues (such as temperature), can be retrieved, and that the biologic material collected can be analyzed cytologically and molecularly (RNA and DNA). The overarching hypothesis of the current proposal is that efficient statistical sampling of biologic tissue will dramatically improve disease diagnostic ability. We will perform animal studies in the esophagus and will gear towards application of this technology for human esophageal disorders, such as Barrett's esophagus. We plan to 1) refine engineering aspects of the ¿-grippers; 2) refine endoscopic tools for ¿-gripper retrieval; 3) characterize the sensitivity and specificity of ¿-grippers; 4) refine molecular biology analyses to be implemented using biologic material retrieved by the ¿-grippers and finally, 5) perform all required animal studies under FDA guidance in preparation for a Phase I Clinical Trial in humans. The motivation for these studies comes from the fact that biologic tissue, obtained via biopsy, represents the diagnostic cornerstone for a variety of human medical conditions, including cancer. In brief, current biopsying protocols are of 2 major types: 1. Biopsying of a lesion that is visualized and perceived to represent pathologic tissue; and 2. Biopsying tissue randomly, since no lesion is visible. In the first case, the current biopsy forceps, and its variations, is an appropriate tool. In the second case, however, it is not. A plethora of human conditions require random biopsies (such as Ulcerative Colitis, Barrett's esophagus, etc). The relative large size of the biopsy forceps, coupled with its serial maneuvering severely limit the number of biopsies that can be performed, and by extension, the mucosal coverage. What we propose is a paradigm shift: instead of using large, tethered biopsy forcepses, we will implement miniature, tether-free tools that can perform biopsying at tens to hundreds to thousands of locations simultaneously. Although preliminary data demonstrates that we can perform cytologic examinations on the biologic tissue retrieved, we plan on concentrating on molecular markers. Recent years brought phenomenal genetic and epigenetic information regarding human disease, in particular cancers. Our work will bring us closer to implementing these markers to human disease. We envision that the statistical sampling performed with the ¿- grippers, coupled with biologic analyses of various RNA and DNA markers (mRNA, microRNA, methylation, mutations, etc) will revolutionize diagnostics in medicine.

项目摘要： 我们已经设计了小的，金属的无线微电视，称为微流（`` - grippers）。 - 握手的尺寸约为1毫米，具有手指状的投影。 �-可以交付 在胃肠道（GI）的内部通过内窥镜插入的导管。初步数据显示 在体内动物模型中，可以递送麦科，均匀地传播到粘膜，可以关闭，并且 可以检索对生物学提示（例如温度）的活检组织，并可以检索生物学 可以通过细胞学和分子（RNA和DNA）对收集的材料进行分析。 当前建议的总体假设是有效的统计抽样 生物组织将显着提高疾病诊断能力。我们将在 食道，并将努力将这项技术用于人类食管疾病，例如 巴雷特的食道。我们计划1）完善``网络的工程方面''； 2）精炼内窥镜 用于检索的工具； 3）表征 - 促进者的灵敏度和特异性； 4）精炼 分子生物学分析将使用``麦格海克和 最后，5）根据FDA指导进行所有必需的动物研究，以准备I期临床 在人类中审判。 这些研究的动机来自以下事实：通过活检获得的生物组织 代表了包括癌症在内的各种人类医疗状况的诊断基石。简而言 当前的活检方案是2种主要类型：1。可视化和感知到的病变的活检 代表病理组织；和2。随机进行活检组织，因为看不到病变。在第一种情况下， 当前的活检镊子及其变化是一种合适的工具。但是，在第二种情况下，事实并非如此。一个 大量人类条件需要随机活检（例如溃疡性结肠炎，巴雷特的食管等）。 相对大尺寸的活检镊子，以及其连续机动的相对大小，严重限制了数量 可以进行粘膜覆盖的活检。我们建议的是范式 Shift：我们将实施微型，无绑扎的工具，而不是使用大型的束缚活检镊子 这可以简单地进行数十至数百至数千个位置的活检。 尽管初步数据表明我们可以对生物学进行细胞学检查 检索的组织，我们计划集中精力分子标记。近年来带来了惊人的遗传 以及有关人类疾病的表观遗传信息，特别是癌症。我们的工作将使我们更接近 将这些标记实施到人类疾病。我们设想使用„ - 握力，再加上各种RNA和DNA标记的生物学分析（mRNA，microRNA，甲基化， 突变等）将彻底改变医学的诊断。