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: 10693387
• 负责人: Steven Allan Soper
• 金额: $ 118.97万
• 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/10693387
• 关键词: Area; Automation; Biological; Biological Assay; Biology; Bioreactors; Biotechnology; Cells; Characteristics; Clinic; Clinical; Commercial Sectors; Communities; DNA; Data; Detection; Development; Devices; Diagnostic; Dimensions; Disease; Educational workshop; Electrophoresis; Engineering; Epigenetic Process; Funding; Genetic Transcription; Genome; Genomic DNA; Harvest; Infrastructure; Institution; Label; Leadership; 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; design; digital; exosome; extracellular vesicles; fabrication; 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; technology platform; 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：生物技术资源中心生物模块化多尺度系统（CBM2）精密医学 总体：开发新技术以实现精确医学 摘要/摘要 液体活检代表了对体外诊断（IVD）的激动人心的贡献 固定标记的性质，多种标记类型（循环生物细胞，无细胞分子[蛋白质， 微-RNA，无细胞DNA]和细胞外蔬菜[外泌体]）以及潜水员分子信息 携带。不幸的是，这些标记中的许多标记尚未在诊所主要使用，因为疾病 - 相关的液体活检标志物在混合人群中可能是少数人，因此难以找到和 分析。这部分是由于缺乏有效隔离的平台和分析有限的工具 液体活检分离株中包含的分离分子数量。例如，一个循环的肿瘤细胞 （CTC）载体〜6 pg的基因组DNA。下一个生成测序（NGS）需要约30 ng的输入核酸 材料。这是，必须使用高水平的扩增来分析单个CTC，这可能会产生偏见 基因组和/或掩盖重要分子特征的表示，例如表观遗传修饰。 生物技术资源中心的生物模块多尺度系统（CBM2）用于精确医学是 通过提供新的和创新的平台技术来处理液体活检，以发展其愿景 标记。平台技术将具有分离疾病相关的液体活检标记的能力 （来自活动性P41中心的输出），并使用无放大测定法分析其分子货物 足够的敏感性来处理单分子（该应用的新分子）。这将通过三个 紧密集中但高度互动的翻译研发工作：（1）固相酶促 纳米级反应堆和纳米电泳，用于检测和鉴定单分子； （2）无标签 使用在流体网络中中毒的双纳米飞行时间（TOF）传感器的检测策略以阅读 单分子的TOF，以高效鉴定； （3）混合尺度（NM→mm）和模块化流体 使用可靠策略组装的系统完成的特定于任务模块。模块化系统可以 对在放大的液体活检标记中固定的分子实体进行单分子处理 具有完整流程自动化的免费格式。将CBM2的平台技术交付给生物医学界 将通过中心运营的芯片生产管道实现。 CBM2由一个高度成就和多学科的团队组成，精通成功 大型多机构项目的结果。中心研究将由广泛的 基础设施是该中心当前运营阶段（2015 - 2020年）的结果。它的翻译 生物医学界的平台技术将通过引人入胜的培训/传播来准备 计划，以及积极的协作和服务项目组合。在中心的新平台上进行培训 技术将通过研讨会和CBM2成员的广泛研究和临床网络进行准备。 传播新发现将通过强大的网站，访问学者，会议准备 参与，及时出版物以及商业实体的参与。

项目成果

Enzymatic cleavage of uracil-containing single-stranded DNA linkers for the efficient release of affinity-selected circulating tumor cells.

• DOI: 10.1039/c4cc09765c
• 发表时间: 2015-02-21
• 期刊: Chemical communications (Cambridge, England)
• 作者: Nair SV;Witek MA;Jackson JM;Lindell MA;Hunsucker SA;Sapp T;Perry CE;Hupert ML;Bae-Jump V;Gehrig PA;Wysham WZ;Armistead PM;Voorhees P;Soper SA
• 通讯作者: Soper SA

Materials and microfluidics: enabling the efficient isolation and analysis of circulating tumour cells.

• DOI: 10.1039/c7cs00016b
• 发表时间: 2017-07-17
• 期刊: Chemical Society reviews
• 影响因子: 46.2
• 作者: Jackson JM;Witek MA;Kamande JW;Soper SA
• 通讯作者: Soper SA

Staphylococcus aureus extracellular vesicles (EVs): surface-binding antagonists of biofilm formation.

• DOI: 10.1039/c7mb00365j
• 发表时间: 2017-11-21
• 期刊: Molecular bioSystems
• 作者: Im H;Lee S;Soper SA;Mitchell RJ
• 通讯作者: Mitchell RJ

Electrokinetic transport properties of deoxynucleotide monophosphates (dNMPs) through thermoplastic nanochannels.

脱氧核苷酸单磷酸 (dNMP) 通过热塑性纳米通道的动电传输特性。

• DOI: 10.1016/j.aca.2018.04.047
• 发表时间: 2018
• 期刊: Analytica chimica acta
• 影响因子: 6.2
• 作者: O'Neil,Colleen;Amarasekara,CharuniA;Weerakoon-Ratnayake,KumudithaM;Gross,Bethany;Jia,Zheng;Singh,Varshni;Park,Sunggook;Soper,StevenA
• 通讯作者: Soper,StevenA

Methods for Isolating and Analyzing Physiological Hyaluronan: A Review.

• DOI: 10.1152/ajpcell.00019.2022
• 发表时间: 2022-02
• 期刊: American journal of physiology. Cell physiology
• 作者: Felipe Rivas;Dorothea Erxleben;I. Smith;Elaheh Rahbar;Paul J DeAngelis;M. Cowman;A. Hall