Circulating markers found in accessible samples (blood, saliva, urine, etc.) represent an exciting biomarker class due to the minimally invasive nature of securing them. Potentially, these circulating markers can enable studies directed toward understanding the pathophysiology of a disease and translating those discoveries to the bedside for managing a host of human diseases by matching the molecular characteristics of the disease to proper treatment regimens (i.e., precision medicine). The attractive nature of circulating markers (i.e., liquid biopsy markers) is the plethora of marker types found in the sample such as biological cells, cell-free molecules (proteins and cell-free DNA) and extracellular vesicles (nanometer assemblies such as exosomes). Unfortunately, basic studies and clinical translation of these liquid biopsy markers has been challenging due to the lack of efficient platforms for their isolation that can also accommodate downstream molecular characterization of the circulating marker cargo. KIPM will generate the Biomedical Engineering Core that will provide to COBRE investigators transformative tools, including hardware and the associated assays, that can be programmed for the project at hand and provide to investigators high quality circulating markers to serve as inputs for a variety of molecular characterization assays (DNA/RNA Next Generation Sequencing, proteomics, immunoassays, mutation detection, liquid chromatography/mass spectrometry, and many others). The hardware tools are lab-on-a-chip or microfluidic platforms that have been optimized for the isolation of circulating markers and clinically validated in a variety of application areas. The microfluidic tools also have validated assays and an automated workflow that has been developed by members of the BME Core. These tools have noteworthy performance metrics compared to commercially available products directed for the isolation of circulating markers. The microfluidics are produced in a high scale production mode at low cost because they are made from plastics and formed into the appropriate structures using injection molding, an established production pipeline for producing CDs, DVDs and Blu-Ray discs. Using these tool sets, the BME Core will create a laboratory that can immediately service COBRE investigators on their precision medicine based projects. Due to the unique capabilities of the tools employed by the BME Core, the data sets generated by the KIPM investigators and the unique tools to acquire these data sets will improve their competitiveness in seeking federally-funded support of their projects. For COBRE projects that cannot be effectively serviced by the Core?s existing tools, the Core will work with the project PI to design new tools to accommodate their project that will also add new process capabilities to the BME Core. The BME Core has assay design capabilities and prototyping tools to support this activity.
