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

点击翻译按钮获取中文摘要

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.