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.

项目概要： 我们设计了小型金属无线微型设备，称为微夹钳（¿-夹钳）。 - 夹具的尺寸约为 1 毫米，并具有手指状突起。 -可提供夹具 初步数据显示，通过内窥镜插入胃肠道（GI）。 在体内动物模型中，¿ - 夹持器可输送，均匀铺展至粘膜，可闭合并 可以检索对生物线索（例如温度）做出反应的活检组织，并且可以检索生物线索 收集的材料可以进行细胞学和分子学（RNA 和 DNA）分析。 当前提案的总体假设是有效的统计抽样 生物组织将极大地提高疾病诊断能力。 食管，并将致力于将该技术应用于人类食管疾病，例如 我们计划 1) 完善 ¿ 的工程方面。 - 夹具；2）改进内窥镜 工具 ¿ -夹具检索；3) 表征 ¿ - 夹具；4) 精炼 使用 ¿ 检索到的生物材料进行分子生物学分析- 夹具和 最后，5) 在 FDA 指导下进行所有必需的动物研究，为 I 期临床做准备 人体试验。 这些研究的动机来自于这样一个事实：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。 目前的活检方案有两种主要类型： 1. 对可视化并感知的病变进行活检 代表病理组织；和 2. 随机活检组织，因为在第一种情况下没有可见病变。 目前的活检钳及其变体是一种合适的工具，但在第二种情况下却不是。 许多人类疾病需要随机活检（例如溃疡性结肠炎、巴雷特食管等）。 活检钳的尺寸相对较大，加上其连续操作，严重限制了活检钳的数量。 可以进行的活检，以及通过扩展，我们提出的是一个范例。 转变：我们将采用微型无系绳工具，而不是使用大型系绳活检钳 可以同时在数十、数百甚至数千个位置进行活检。 尽管初步数据表明我们可以对生物制品进行细胞学检查 取回组织后，我们计划专注于近年来带来的显着遗传标记。 我们的工作将使我们更接近人类疾病，特别是癌症的表观遗传信息。 我们设想用 ¿ 进行统计抽样。 - 夹子，结合各种 RNA 和 DNA 标记（mRNA、microRNA、甲基化、 突变等）将彻底改变医学诊断。