Abstract

Abstract We have developed a novel microfluidic technology that makes use of Alternating Current Electrokinetics (ACE) to isolate macromolecules such as high-molecular-weight DNA and protein complexes as well as nanoparticles, including cell-derived exosomes. As one of the first applications of this novel technology, we have developed procedures and assays for the isolation and quantification of cell-free DNA (cfDNA) in plasma. We show that this methodology allows for the rapid, robust, and highly quantitative assay of cfDNA in undiluted plasma. Analytical studies indicate that these ACE assays are sensitive, have a very broad dynamic range, and allow for highly effective calibration strategies, thereby enabling comparison of results over time and between laboratories. Importantly, we show correspondence between the results of ACE assays and those that employ traditional technologies such as PCR. We have applied this technology to the quantification of cfDNA in plasma from cancer patients, with an initial focus on stage III and IV non-small cell lung cancer (NSCLC). With a goal of enabling less invasive, more frequent, and lower-cost treatment response monitoring in cancer patients, we have conducted clinical studies showing that the results generated from ACE assays provide informative and useful findings related to disease progression and therapeutic alternatives. We are conducting laboratory and clinical studies oriented toward the development of this technology for in vitro diagnostic use. Citation Format: Robert Kovelman, Juan Pablo Hinestrosa, Delia Ye, Patrick Desmond, Michelle Nguyen, Robert Turner, David Searson, Suren Uswatta, James Madsen, David Bodkin, Lyudmila Bazhenova, Afshin Bahador, Rajaram Krishnan. Diagnostic application of novel ACE technology: Treatment response monitoring via quantification of cell-free DNA (cfDNA) in plasma from late-stage cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3666.

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