Circulating markers secured from blood represents an exciting in vitro diagnostic scenario because of the minimally invasive nature of securing the 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 be effectively utilized from a clinical perspective 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 from 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, which can be used to guide clinical decisions for personalized medicine. 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 their molecular content to secure clinical information for the effective management of a variety of diseases. The envisioned system takes advantage of multiple length scales (mm ? nm) to affect unique processing capabilities. The systems will process whole blood (>1 mL) and concentrate clinically relevant markers to nL volumes (>106 enrichment factors) 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 the relevant clinical 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 already in place and an aggressive Collaborative and Service Project portfolio. Novel technology dissemination and training of the biomedical community will be facilitated through compelling workshops offered to the biomedical community and extensive networks.
|Effective start/end date||9/16/15 → 5/31/20|
- NIH National Institute of Biomedical Imaging and Bioengineering