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（由适用提供）：来自血液的循环标记代表了令人兴奋的体外诊断情况，因为确保这些标记物的微创性质以及在血液中发现的大量标记物类型，例如生物细胞，无细胞的无细胞分子，无细胞的分子（蛋白质和无细胞蛋白和无细胞的DNA）和蔬菜组装（例如nanomer组装）。不幸的是，在临床实践中尚未有效利用许多这些血源性标记来管理癌症，传染病和中风等挑战疾病。由于疾病相关的血液标记物在混合种群中是少数族裔，因此由于缺乏有效的隔离平台和可以确定分子的系统，因此很难找到和分析，因此这种缺乏症的主要原因是很难找到和分析。 它们可能携带的结构变化。为了满足这种紧迫的需求，提出了一个新的生物技术资源中心（CBM2），该中心由一个高度成就且多学科的团队组成，该团队将生成创新的系统，用于从全血和过程疾病特异性分子签名中选择循环标记。设想的系统利用多个长度尺度（MM到NM）影响系统提供的独特处理功能。该系统将处理全血（= 1 mL），并将临床上相关的标记集中到NL体积（> 106富集因子），并使用固相连接酶检测反应（SPLDR）在单个基于单层的基于复制的聚合物柱上进行的固体相结合反应（SPLDR）搜索DNA和RNA分子的各种序列变化（SPLDR）。 SPLDR产物以电子依赖的电泳迁移率进行了电子扫描成纳米飞行试管的识别。单分子处理将使用纳米飞行管进行，并进行了非可行性进行检测。该系统将提供从单个血液抽血和以完全自动化的方式从单个血液抽血和安全相关信息中选择所有临床相关标记（无细胞DNA和外泌体）的能力，以允许将平台转变为临床实践。这项研究将由广泛的基础设施以及积极的合作和服务项目中心投资组合准备。通过CBM2和成员广泛的网络提供的引人注目的讲习班，将准备新的技术传播和对生物医学界的培训。