한빛사 논문
Yoon-Tae Kanga,1, Thomas Hadlocka,1, Shruti Jollyb, Sunitha Nagratha,c,*
aDepartment of Chemical Engineering and Biointerface Institute, University of Michigan, 2800 Plymouth Road, NCRC B10-A184, Ann Arbor, MI, 48109, USA
bRadiation of Oncology, University of Hospital, University of Michigan, 1500 E Medical Center Dr. Ann Arbor, MI, 48109, USA
cRoger Cancer Center, University of Michigan, 1500 E Medical Center Dr. Ann Arbor, 48109, USA
1Both authors contributed equally to this work.
*Corresponding author
Abstract
While significant advancements have been made in cancer therapeutics and treatments, early disease detection and diagnosis remains critical to ensuring favorable outcomes for patients. To that end, we propose a microfluidic based approach to the sensitive detection of an intriguing cancer biomarker, extracellular vesicles (EVs). Our extracellular vesicle on demand (EVOD) chip utilizes a catalyst-free click chemistry to rapidly and specifically isolate EVs of interest. This specific isolation is followed by subsequent dithiothreitol release of the isolated EVs for downstream functional analysis. This joint isolation and release provide a powerful tool for the screening and quantification of EVs of interest. By incorporating antibodies against cancer associated surface proteins into the click-chemistry, we were able to selectively recover cancer-associated exosomes, allowing for important insights into patient disease. This platform was also tested using non-small cell lung cancer (NSCLC) patient samples, where anti-epidermal growth factor receptor (EGFR) assisted platform were able to selectively isolate and release 76% more exosomes from NSCLC patients than from healthy donors. This matches the previously reported higher EGFR expression commonly found in NSCLC EVs. Through its rapid isolation kinetics and adaptability in marker targeting, the EVOD device provides a highly versatile liquid biopsy platform for clinicians to use in the fight against cancer.
Keywords : Extracellular vesicles; Microfluidics; Click chemistry; Vesicle release; Immunoaffinity isolation
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