Biotechnology Resource Center of Biomodular Multi scale Systems CBM2 for Precision Molecular Diagnostics

用于精密分子诊断的生物模块化多尺度系统 CBM2 生物技术资源中心

• 批准号: 8935077
• 负责人: Steven Allan Soper
• 金额: $ 127.44万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-16 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8935077
• 关键词: Address; Adopted; Affect; Area; Automation; Biological; Biological Assay; Biology; Biomedical Technology; Biotechnology; Blood; Blood Circulation; Body Fluids; Cells; Characteristics; Clinical; Clinical Paths; Clinical Research; Communicable Diseases; Communities; DNA; Data; Detection; Development; Diagnostic; Disease; Disease Management; Educational workshop; Engineering; Generations; Harvest; Home environment; In Vitro; Institution; Leadership; Length; Ligase; Liquid substance; Location; Malignant Neoplasms; Measures; Microfabrication; Microfluidics; Minority; Mission; Molecular; Molecular Profiling; Molecular Target; Names; Nature; North Carolina; Output; Phase; Plasma; Polymers; Population; Private Sector; Process; Property; Proteins; RNA; Reaction; Research; Research Infrastructure; Resources; Sampling; Secure; Services; Site; Solid; Stroke; System; Techniques; Technology; Training; Translating; Translational Research; Translations; Travel; Tube; Universities; Variant; Vesicle; Whole Blood; base; cell free DNA; clinical practice; clinically relevant; design; digital; experience; innovation; meetings; member; minimally invasive; multidisciplinary; nanofabrication; nanofluidic; nanometer; nanoscale; nanosensors; new technology; programs; public health relevance; research and development; sensor; single molecule; tool

 DESCRIPTION (provided by applicant): Circulating markers from blood represents an exciting in vitro diagnostic scenario because of the minimally invasive nature of securing these markers and the plethora of marker types found in blood, such as biological cells, cell-free molecules (proteins and cell-free DNA) and vesicles (nanometer assemblies such as exosomes). Unfortunately, many of these blood-borne markers have not been effectively utilized in clinical practice to manage challenging diseases such as cancer, infectious diseases and stroke to name a few. This deficiency has arisen primarily from the fact that disease-associated blood markers are a vast minority in a mixed population making them difficult to find and analyze due to the lack of efficient platforms for their isolation and systems that can determine the molecular structural variations they may harbor. To address this pressing need, a new Biotechnology Resource Center is proposed (CBM2), which consists of a highly accomplished and multidisciplinary team that will generate innovative systems for the selection of circulating markers from whole blood and process disease-specific molecular signatures. The envisioned system takes advantage of multiple length scales (mm-to-nm) to affect unique processing capabilities offered by the system. The system will process whole blood (=1 mL) and concentrate clinically relevant markers to nL volumes (>106 enrichment factor) and search for a variety of sequence variations from both DNA and RNA molecules using a solid-phase ligase detection reaction (spLDR) carried out on millions of polymer pillars fabricated in a single step using replication-based technologies. spLDR products are electrokinetically swept into nanometer flight tubes with their identification based on molecular-dependent electrophoretic mobilities; single-molecule processing will be carried out using nanometer flight tubes with detection performed non-optically. The system will provide the ability to select all clinically relevant markers (cells, cell-free DNA and exosomes) from a single blood draw and secure pertinent information from those markers in a fully automated fashion to allow transitioning the platform into clinical practice. The research will be facilitated by extensive infrastructure alreay in place and an aggressive Collaborative and Service Project Center portfolio. Novel technology dissemination and training to the biomedical community will be facilitated through compelling workshops offered by CBM2 and the members' extensive networks.

 描述（由申请人提供）：血液中的循环标记代表了一种令人兴奋的体外诊断方案，因为保护这些标记的微创性质以及血液中发现的大量标记类型，例如生物细胞、无细胞分子（蛋白质和无细胞 DNA）和囊泡（纳米组件，例如外泌体）。不幸的是，许多这些血源性标记物尚未在临床实践中有效地用于治疗癌症、传染病和中风等具有挑战性的疾病。这种缺陷主要是由于以下事实造成的：与疾病相关的血液标志物在混合人群中只占极少数，由于缺乏有效的分离平台和可以确定分子水平的系统，因此很难找到和分析它们。 它们可能存在结构变异。为了满足这一迫切需求，建议建立一个新的生物技术资源中心（CBM2），该中心由一支经验丰富的多学科团队组成，该团队将生成用于从全血中选择循环标记物并处理疾病特异性分子特征的创新系统。设想的系统利用多个长度尺度（毫米到纳米）来影响系统提供的独特处理能力。该系统将处理全血（= 1 mL）并将临床相关标记物浓缩至 nL 体积（> 106 富集因子），并使用固相连接酶检测反应 (spLDR) 搜索 DNA 和 RNA 分子的各种序列变异，该反应在使用基于复制的技术一步制造的数百万个聚合物柱上进行。 spLDR 产品通过电动方式扫入纳米飞行管，并根据分子依赖性电泳迁移率进行识别；单分子处理将使用纳米飞行管进行，并以非光学方式进行检测。该系统将能够从单次抽血中选择所有临床相关标记物（细胞、无细胞 DNA 和外泌体），并以完全自动化的方式从这些标记物中获取相关信息，从而将该平台转变为临床实践。现有的广泛基础设施和积极的协作和服务项目中心组合将促进这项研究。 CBM2 和成员广泛的网络提供的引人注目的研讨会将促进生物医学界的新技术传播和培训。