TY - JOUR
T1 - Ultrasensitive lateral-flow assays via plasmonically active antibody-conjugated fluorescent nanoparticles
AU - Gupta, Rohit
AU - Gupta, Prashant
AU - Wang, Sean
AU - Melnykov, Artem
AU - Jiang, Qisheng
AU - Seth, Anushree
AU - Wang, Zheyu
AU - Morrissey, Jeremiah J.
AU - George, Ige
AU - Gandra, Sumanth
AU - Sinha, Pratik
AU - Storch, Gregory A.
AU - Parikh, Bijal A.
AU - Genin, Guy M.
AU - Singamaneni, Srikanth
N1 - Funding Information:
The serum or plasma samples collected before COVID-19 breakout were collected under the study approved by the Human Research Protection Office at Washington University in St. Louis under HRPO 201102546. The clinical samples used in the study were acquired from the repository of saliva, serum, plasma and NP swab samples from individuals confirmed or suspected with COVID-19 disease, located at Washington University School of Medicine in St Louis, and from the Barnes Jewish Clinical Microbiology Laboratory; acquisition of samples was supported by: the Barnes-Jewish Hospital Foundation; the Siteman Cancer Center grant P30 CA091842 from the National Cancer Institute of the National Institutes of Health (NIH); and the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the NIH. This repository was developed and is maintained by Jane O’Halloran, MD, PhD; Charles Goss, PhD; and Phillip Mudd, MD, PhD. Control NP swab samples from asymptomatic healthy volunteers were obtained with prior written consent. For evaluation of cross reactivity with seasonal coronaviruses, samples were obtained from adults at Barnes-Jewish Hospital who were tested positive with either of the four seasonal coronaviruses or respiratory diseases via clinically warranted NP samples tests. Washington University School of Medicine Human Research Protection Office approved the study. All clinical data pre-existed at the time of data collection. A prior waiver of consent was obtained for the clinical information and data on COVID-19 PCR results.
Funding Information:
We acknowledge support from the National Science Foundation (CBET-2027145, CBET-2029105 and CMMI 1548571) and the National Cancer Institute-Innovative Molecular Analysis Technologies (R21CA236652 and R21CA236652-S1). Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). We also thank Nano Research Facility (NRF) and Institute of Materials Science and Engineering (IMSE) at Washington University for providing access to electron microscopy facilities. Part of schematic illustrations depicted in Figs. , , , and were created in BioRender.com. We thank H. Baldi for his help with BioRender images. We thank M. S. Diamond, A. Ellebedy, D. H. Fremont and S. P. J. Whelan of the Washington University School of Medicine and J. Luan of the Washington University McKelvey School of Engineering for helpful discussions. We thank G. J. Weil and P. U. Fischer, Washington University School of Medicine, for kindly providing pre-COVID-19 samples. The samples used in this study were obtained from the Washington University School of Medicine’s COVID-19 biorepository, which is supported by the Barnes-Jewish Hospital Foundation; the Siteman Cancer Center grant P30 CA091842 from the National Cancer Institute of the NIH; and the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from NCATS of the NIH. This repository was developed and is maintained by J. O’Halloran, C. Goss and P. Mudd. The content is solely the responsibility of the authors and does not necessarily represent the view of the NIH.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023
Y1 - 2023
N2 - Lateral-flow assays (LFAs) are rapid and inexpensive, yet they are nearly 1,000-fold less sensitive than laboratory-based tests. Here we show that plasmonically active antibody-conjugated fluorescent gold nanorods can make conventional LFAs ultrasensitive. With sample-to-answer times within 20 min, plasmonically enhanced LFAs read out via a standard benchtop fluorescence scanner attained about 30-fold improvements in dynamic range and in detection limits over 4-h-long gold-standard enzyme-linked immunosorbent assays, and achieved 95% clinical sensitivity and 100% specificity for antibodies in plasma and for antigens in nasopharyngeal swabs from individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Comparable improvements in the assay’s performance can also be achieved via an inexpensive portable scanner, as we show for the detection of interleukin-6 in human serum samples and of the nucleocapsid protein of SARS-CoV-2 in nasopharyngeal samples. Plasmonically enhanced LFAs outperform standard laboratory tests in sensitivity, speed, dynamic range, ease of use and cost, and may provide advantages in point-of-care diagnostics.
AB - Lateral-flow assays (LFAs) are rapid and inexpensive, yet they are nearly 1,000-fold less sensitive than laboratory-based tests. Here we show that plasmonically active antibody-conjugated fluorescent gold nanorods can make conventional LFAs ultrasensitive. With sample-to-answer times within 20 min, plasmonically enhanced LFAs read out via a standard benchtop fluorescence scanner attained about 30-fold improvements in dynamic range and in detection limits over 4-h-long gold-standard enzyme-linked immunosorbent assays, and achieved 95% clinical sensitivity and 100% specificity for antibodies in plasma and for antigens in nasopharyngeal swabs from individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Comparable improvements in the assay’s performance can also be achieved via an inexpensive portable scanner, as we show for the detection of interleukin-6 in human serum samples and of the nucleocapsid protein of SARS-CoV-2 in nasopharyngeal samples. Plasmonically enhanced LFAs outperform standard laboratory tests in sensitivity, speed, dynamic range, ease of use and cost, and may provide advantages in point-of-care diagnostics.
UR - http://www.scopus.com/inward/record.url?scp=85147284943&partnerID=8YFLogxK
U2 - 10.1038/s41551-022-01001-1
DO - 10.1038/s41551-022-01001-1
M3 - Article
C2 - 36732621
AN - SCOPUS:85147284943
SN - 2157-846X
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
ER -