Abstract

Screening Tests Using Micro- and Nanofluidics for Early Disease Detection at the Point-of-Care

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 that facilitates bench-to-bedside transition and point-of-care testing (PoCT) for large scale 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. In this presentation, we will talk about the evolution of our fabrication efforts of plastic-based microfluidic and nanofluidic devices as well as their surface modification to make devices biocompatible. Then, we will discuss two applications of these devices and the assays for selection of rare liquid biopsy targets from clinical samples to serve as screening tests: (1) Analysis of extracellular vesicles (EVs) for the early detection of ovarian cancer; and (2) detection of viral particles from saliva samples, in particular SARS-CoV-2.  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, which demands new strategies for early detection. The screening test we are developing consists of a microfluidic chip for EV 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 surface proteins were discovered for selection of ovarian cancer EV selection specifically for the early detection of disease. The infectious disease diagnostic accepts saliva samples and searches for viral particles using aptamers and counts the number of viral particles. For both disease examples, the selected particles were counted using a label-free approach; nano-Coulter Counter chip (nCC) consisting of in-plane nanopores. Both steps of the screening test described here were carried out using a microfluidic and nanofluidic chip. The chips were integrated to a control board for automating sample processing with results in <20 min.