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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

基本信息

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
项目类别：
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

项目摘要

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.