Abstract

Screening Tests using Micro- and Nanofluidics for Early Detection of Ovarian Cancer with Extracellular Vesicles Serving as the Input

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

We are developing screening tests consisting of novel hardware, biomarkers, and assays to service a number of diseases, including the early detection of cancer and viral infections. The commonality in these tests is that they consist of microfluidic devices made from plastics via injection molding. Thus, our tests can be mass produced at low-cost to facilitate bench-to-bedside transition and point-of-care testing (PoCT) for large scale population screening. The assays are based on the use of liquid biopsy markers as the input, which can be secured in a non- to minimally-invasive manner appropriate for screening. Recently we have focused on developing plastic nanofluidic devices, which provides unique opportunities for single-entity analyses – these devices can also be injection molded. In this presentation, we will discuss the evolution of our fabrication efforts of plastic-based microfluidic and nanofluidic devices as well as their surface modification to make devices appropriate for screening using extracellular vesicles (EVs) as the input. Then, we will discuss the application of the device and the associated assay for selection of rare liquid biopsy targets (EVs) from clinical samples to serve as screening tests. The specific application we will discuss is the analysis of EVs for the early detection of ovarian cancer. Ovarian cancer is the 5th most deadly cancer for women in the US and has a 46.2% 5-y survival rate. Unfortunately, ~85% of cases are diagnosed at a late stage of disease providing pore outcomes for these patients. Therefore, new strategies for early detection are required. The screening test we are developing consists of a microfluidic chip for EV affinity selection, which consists of a high density array of pillars surface-decorated with antibodies to efficiently select EVs followed by the label-free enumeration to determine elevated levels of EVs in the plasma of patients suspected of having ovarian cancer. Unique EV-associated surface proteins were discovered for selection of ovarian cancer EV specifically for the early detection of disease. The selected EVs were counted using a nano-Coulter Counter chip (nCC), which consisted of in-plane nanopores. Both steps of the screening test described here were carried out using a microfluidic and nanofluidic chips integrated to a control board for automating sample processing with results produced within 20 min.