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: 8935774
• 负责人: Florin Selaru
• 金额: $ 35.72万
• 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/8935774
• 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; Health; 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; response; statistics; tool

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：我们设计了一种小型金属无线微型设备，称为微夹钳（β-夹钳）。β-夹钳的尺寸约为 1 毫米，具有手指状突起。初步数据表明，在体内动物模型中，β-夹具可以通过内窥镜插入胃肠道。可以将其均匀地附着在粘膜上，可以闭合并检索对生物信号（例如温度）做出反应的活检组织，并且可以对收集的生物材料进行细胞学和分子学分析（RNA和DNA）。我们的建议是，对生物组织进行有效的统计采样将显着提高疾病诊断能力，我们将在食道中进行动物研究，并将致力于将该技术应用于人类食道疾病，例如巴雷特食道。计划 1) 改进 �- 夹子的工程方面； 2) 改进 �- 夹子检索的内窥镜工具； 3) 表征 �- 夹子的灵敏度和特异性； 4) 改进使用回收的生物材料进行的分子生物学分析。 �-夹子，最后，5) 在 FDA 的指导下进行所有必需的动物研究，为人体 I 期临床试验做准备。这些研究的动机来自于通过生物组织获得的事实。活检是包括癌症在内的多种人类医疗状况的诊断基石。简而言之，当前的活检方案有两种主要类型：1. 对可视化并被感知为代表病理组织的病变进行活检；2. 对组织进行活检。随机地，由于在第一种情况下看不到病变，当前的活检钳及其变体是合适的工具。然而，在第二种情况下，许多人类状况需要随机活检（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，严重限制了可以进行的活检数量，进而限制了粘膜覆盖范围。我们将不再使用大型的系绳活检钳，而是使用微型无系绳工具，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这些部位进行细胞学检查。近年来，我们计划集中精力研究有关人类疾病（特别是癌症）的显着遗传和表观遗传信息，我们希望通过统计抽样来实现这些标记。使用 �- 夹具，再加上各种 RNA 和 DNA 标记（mRNA、microRNA、甲基化、突变等）的生物学分析，将彻底改变医学诊断。