Abstract
The plaque assay has long served as the "gold standard" to measure virus infectivity and test antiviral drugs, but the assay is labor-intensive, lacks sensitivity, uses excessive reagents, and is hard to automate. Recent modification of the assay to exploit flow-enhanced virus spread with quantitative imaging has increased its sensitivity. Here we performed flow-enhanced infection assays in microscale channels, employing passive fluid pumping to inoculate cell monolayers with virus and drive infection spread. Our test of an antiviral drug (5-fluorouracil) against vesicular stomatitis virus infections of BHK cell monolayers yielded a two-fold improvement in sensitivity, relative to the standard assay based on plaque counting. The reduction in scale, simplified fluid handling, image-based quantification, and higher assay sensitivity will enable infection measurements for high-throughput drug screening, sero-conversion testing, and patient-specific diagnosis of viral infections.
References
Jan 31, 1991·Biochemical and Biophysical Research Communications·J Yin
Jan 1, 1973·Journal of Virology·B R WareM E Reichmann
Jul 16, 2002·Annual Review of Biomedical Engineering·David J BeebeGlenn M Walker
Oct 2, 2003·Nature Biotechnology·George M Whitesides
Oct 2, 2003·Nature Biotechnology·Jong Wook Hong, Stephen R Quake
Apr 22, 2004·Lab on a Chip·Glenn M Walker, David J Beebe
Dec 24, 2004·Lab on a Chip·Anna TourovskaiaAlbert Folch
Apr 19, 2005·Biotechnology and Bioengineering·Vy LamJohn Yin
Jun 1, 2005·The Journal of Family Planning and Reproductive Health Care·UNKNOWN Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness Unit
Mar 3, 2006·Lab on a Chip·Lily KimJoel Voldman
Jul 28, 2006·Nature·Jamil El-AliKlavs F Jensen
Nov 10, 2006·Journal of Virological Methods·Ying Zhu, John Yin
Dec 14, 2006·The Journal of Infectious Diseases·Martin PetricCathy A Petti
Mar 3, 2007·Lab on a Chip·Hongmei YuDavid J Beebe
Jun 1, 2007·Lab on a Chip·Hongmei YuDavid J Beebe
Dec 21, 2007·Lab on a Chip·Halong N VuMartin L Yarmush
Dec 17, 2008·Virology·Ying ZhuJohn Yin
Citations
Jun 16, 2010·Analytical and Bioanalytical Chemistry·Iuliana OitaDebby Mangelings
Dec 23, 2009·Integrative Biology : Quantitative Biosciences From Nano to Macro·Samartha G AnekalJohn Yin
Jun 5, 2013·Biomicrofluidics·Elisa CimettaNicola Elvassore
Jan 1, 2012·Biomicrofluidics·Na XuZhi-Ling Zhang
Apr 22, 2015·Annual Review of Virology·Vyas RamananSangeeta N Bhatia
Oct 1, 2010·Microfluidics and Nanofluidics·Amy L McPherson, Glenn M Walker
Jan 10, 2012·Virology·Andrea Timm, John Yin
Feb 28, 2013·Biophysical Journal·Camilla LuniNicola Elvassore
Jan 27, 2015·Annual Review of Pathology·Kambez H BenamDonald E Ingber
Sep 29, 2012·Journal of the American Chemical Society·Darija MuharemagicMaxim V Berezovski
Aug 19, 2017·Lab on a Chip·Philip C GachAnup K Singh
Jun 10, 2016·Journal of Virology·Fulya AkpinarJohn Yin
Jan 10, 2013·Lab on a Chip·Yun ShuZhi-Ling Zhang
Sep 16, 2011·Lab on a Chip·Siyuan XingTingrui Pan
Nov 15, 2018·Micromachines·Jeong A KimGyu Man Kim
Jul 24, 2020·Biomicrofluidics·Qasem Ramadan, Mohammed Zourob
Mar 7, 2021·Pathogens·Buket Baddal, Pasquale Marrazzo
Jun 15, 2021·Frontiers in Cellular and Infection Microbiology·Benjamin O MurrayJennifer L Rohn