Abstract

Precision Medicine Using Liquid Biopsies: A New Paradigm for Managing Cancer Diseases

Steve Soper, Foundation Distinguished Professor; Director, Center of BioModular Multi-scale System for Precision Medicine, Adjunct Professor, Ulsan National Institute of Science & Technology, The University of Kansas

Precision medicine seeks to match patients to appropriate therapies that optimize clinical outcome from molecular signatures of their disease. These molecular signatures can be secured from circulating markers found in blood (i.e., liquid biopsies). The marker types include circulating tumor cells (CTCs), cell-free DNA (cfDNA), and extracellular vesicles (EVs). Unfortunately, many disease-associated blood markers are a vast minority in a mixed population making them difficult to analyze due to deficiencies in current technologies used for their isolation. To address this deficiency, we are generating innovative microfluidic tools for selecting circulating markers from whole blood and determining the presence/absence of disease-specific molecular signatures secured from the liquid biopsy markers to guide therapy for a patient. The microfluidics can process whole blood (=1 mL) and search for CTCs, cfDNA, or EVs and make them available for downstream molecular processing. The microfluidics are made in plastics via injection molding, making them particularly attractive for clinical implementation, which demands low-cost disposables. In this keynote address, I will discuss our microfluidic platform for cfDNA and EV isolation. The chip consists of 1.4 million pillars that provides a high surface area for generating high loads of the target material. The chip is made from a plastic via injection molding. For the EV isolation, the pillars contain surface-immobilized antibodies directed against antigens from cancer cells that are epithelial based (EpCAM) and those with a mesenchymal phenotype (fibroblast activation protein alpha, FAPa). I will talk extensively about our EV isolation chip, and its use in several clinical examples and securing molecular information from the affinity-selected exosomes, for example mRNA expression profiling using droplet digital PCR.