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

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.