Biotechnology Resource Center of BioModular Multi-scale Systems (CBM2) for Precision Medicine

精准医学生物模块化多尺度系统（CBM2）生物技术资源中心

• 批准号: 10172699
• 负责人: Steven Allan Soper
• 金额: $ 113.85万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 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 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10172699
• 关键词: Area; Automation; Biological; Biological Assay; Biology; Bioreactors; Biotechnology; Cells; Characteristics; Clinic; Clinical; Commercial Sectors; Communities; DNA; Data; Detection; Development; Devices; Diagnostic; Disease; Educational workshop; Electrophoresis; Engineering; Epigenetic Process; Funding; Genome; Genomic DNA; Harvest; Infrastructure; Label; Leadership; Liquid substance; Masks; Measures; MicroRNAs; Microfabrication; Microfluidics; Minority; Mission; Modification; Molecular; Molecular Analysis; Molecular Profiling; Molecular Target; Nanotubes; Nature; Neoplasm Circulating Cells; Nucleic Acids; Outcome; Output; Participant; Patient-Focused Outcomes; Peptide Mapping; Phase; Physicians; Play; Population; Preparation; Private Sector; Process; Production; Property; Proteins; Publications; RNA; Research; Research Personnel; Resources; Sampling; Secure; Services; Site; Solid; System; Techniques; Technology; Time; Training; Translating; Translational Research; Translations; Vision; cell free DNA; clinical diagnostics; design; digital; exosome; extracellular vesicles; improved; in-vitro diagnostics; innovation; innovative technologies; liquid biopsy; meetings; member; minimally invasive; multidisciplinary; nano; nanofabrication; nanofluidic; nanometer; nanopore; nanoscale; new technology; operation; precision medicine; prognostic; program dissemination; research and development; sensor; single molecule; tool; visiting scholar; web site

TITLE: Biotechnology Resource Center of BioModular Multi-scale Systems (CBM2) for Precision Medicine Overall: Developing New Technologies for Enabling Precision Medicine Abstract/Summary Liquid biopsies represent an exciting contribution to in vitro diagnostics (IVDs) because of the minimally invasive nature of securing markers, the plethora of marker types (circulating biological cells, cell-free molecules [proteins, micro-RNA, cell-free DNA], and extracellular vesicles [exosomes]), and the diverse molecular information they carry. Unfortunately, many of these markers have not been fully utilized in the clinic primarily because disease- associated liquid biopsy markers can be a vast minority in a mixed population making them difficult to find and analyze. This is partly due to a lack of platforms for their efficient isolation and tools to analyze the limited numbers of diseased molecules contained in a liquid biopsy isolate. For example, a single circulating tumor cell (CTC) carriers ~6 pg of genomic DNA. Next Generate Sequencing (NGS) requires ~30 ng of input nucleic acid material. Thus, high levels of amplification must be used to analyze a single CTC, which can create biased representation of the genome and/or mask important molecular features, such as epigenetic modifications. The Biotechnology Resource Center of BioModular Multi-scale Systems (CBM2) for Precision Medicine is seeking to evolve its vision with the delivery of new and innovative platform technologies to process liquid biopsy markers. The platform technologies will possess the ability to isolate disease-associated liquid biopsy markers (outputs from the active P41 Center) and analyze their molecular cargo using amplification-free assays with sufficient sensitivity to process single molecules (new to this application). This will be realized through three tightly focused, yet highly interactive Translational Research and Development efforts: (1) Solid-phase enzymatic nanoscale reactors and nano-electrophoresis for detection and identification of single-molecules; (2) label-free detection strategies using dual-nanopore time-of-flight (TOF) sensor poised within a fluidic network to read the TOF of single molecules for highly efficient identification; and (3) mixed-scale (nm → mm) and modular fluidic systems comprised of task-specific modules assembled using robust strategies. The modular system can perform single-molecule processing of a molecular entity secured from a liquid biopsy marker in an amplification- free format with full process automation. Delivery of CBM2's platform technologies to the biomedical community will be realized through a production pipeline of chips operated by the Center. CBM2 consists of a highly accomplished and multidisciplinary team that is well versed in producing successful outcomes from large multi-institutional projects. The Center research will be facilitated by the extensive infrastructure in place as a result of the Center's current phase of operation (2015 – 2020). Translation of its platform technologies into the biomedical community will be facilitated by an engaging training/dissemination program, and an aggressive Collaborative and Service Project portfolio. Training on the Center's new platform technologies will be facilitated through workshops and CBM2 members' extensive research and clinical networks. Dissemination of new discoveries will be facilitated through a robust website, visiting scholars, meeting participation, and timely publications as well as the involvement of commercial entities.

标题：精准医学生物模块化多尺度系统（CBM2）生物技术资源中心 总体而言：开发新技术以实现精准医疗 摘要/总结 由于微创性，液体活检对体外诊断 (IVD) 做出了令人兴奋的贡献 保护标记的性质、过多的标记类型（循环生物细胞、无细胞分子[蛋白质、 微小RNA、无细胞DNA]和细胞外囊泡[外泌体]），以及它们的多种分子信息 不幸的是，许多这些标记物尚未在临床中得到充分利用，主要是因为疾病- 相关的液体活检标记物在混合人群中可能只占极少数，因此很难找到和使用 这部分是由于缺乏有效隔离的平台和有限的分析工具。 液体活检分离物中含有的患病分子的数量，例如单个循环肿瘤细胞。 (CTC) 载体约 6 pg 基因组 DNA。下一步生成测序 (NGS) 需要约 30 ng 的输入核酸。 因此，必须使用高水平的扩增来分析单个 CTC，这可能会产生偏差。 基因组的表示和/或掩盖重要的分子特征，例如表观遗传修饰。 用于精准医学的生物模块化多尺度系统（CBM2）生物技术资源中心是 寻求通过提供新的创新平台技术来处理液体活检来发展其愿景 该平台技术将具备分离与疾病相关的液体活检标记物的能力。 （来自活跃 P41 中心的输出）并使用无扩增测定法分析其分子货物 足够的灵敏度来处理单分子（对于该应用来说是新的）这将通过三个来实现。 高度集中且高度互动的转化研究和开发工作：(1) 固相酶促 (2)无标签 使用位于流体网络中的双纳米孔飞行时间（TOF）传感器来读取的检测策略 用于高效识别的单分子 TOF；以及 (3) 混合尺度（nm → mm）和模块化流体 由使用稳健策略组装的特定任务模块组成的系统可以。 在扩增中对从液体活检标记物中获得的分子实体进行单分子处理 向生物医学界交付 CBM2 平台技术的自由格式。 将通过该中心运营的芯片生产线来实现。 CBM2 由一支卓有成就的多学科团队组成，他们精通于生产成功的产品 大型多机构项目的成果将得到广泛的促进。 中心当前运行阶段（2015 年至 2020 年）的基础设施建设情况。 有吸引力的培训/传播将促进平台技术进入生物医学界 计划，以及在中心新平台上进行的积极的协作和服务项目组合。 将通过研讨会和 CBM2 成员广泛的研究和临床网络来促进技术的发展。 将通过强大的网站、访问学者、会议等方式促进新发现的传播 参与、及时发布以及商业实体的参与。