@article{00aca3868c0c4927b265adc66bcdd709,
title = "Ultrasensitive Ebola Virus Antigen Sensing via 3D Nanoantenna Arrays",
abstract = "Sensitive detection of pathogens is crucial for early disease diagnosis and quarantine, which is of tremendous need in controlling severe and fatal illness epidemics such as of Ebola virus (EBOV) disease. Serology assays can detect EBOV-specific antigens and antibodies cost-effectively without sophisticated equipment; however, they are less sensitive than reverse transcriptase polymerase chain reaction (RT-PCR) tests. Herein, a 3D plasmonic nanoantenna assay sensor is developed as an on-chip immunoassay platform for ultrasensitive detection of Ebola virus (EBOV) antigens. The EBOV sensor exhibits substantial fluorescence intensity enhancement in immunoassays compared to flat gold substrate. The nanoantenna-based biosensor successfully detects EBOV soluble glycoprotein (sGP) in human plasma down to 220 fg mL−1, a significant 240 000-fold sensitivity improvement compared to the 53 ng mL−1 EBOV antigen detection limit of the existing rapid EBOV immunoassay. In a mock clinical trial, the sensor detects sGP-spiked human plasma samples at two times the limit of detection with 95.8% sensitivity. The results combined highlight the nanosensor's extraordinary capability of detecting EBOV antigen at ultralow concentration compared to existing immunoassay methods. It is a promising next-generation bioassay platform for early-stage disease diagnosis and pathogen detection for both public health and national security applications.",
keywords = "Ebola virus glycoprotein, biosensors, fluorescence enhancement, nanoantennas, optical resonance",
author = "Faheng Zang and Zhijuan Su and Liangcheng Zhou and Krishnamurthy Konduru and Gerardo Kaplan and Chou, {Stephen Y.}",
note = "Funding Information: S.Y.C. originated the idea of use of the nanoantenna array structures for immunoassay fluorescence and detection sensitivity enhancement and designed and directed the research. S.Y.C. and G.K. made initial experimental planning. F.Z. and Z.S. designed and performed the experiments of immunoassay and optical characterization. F.Z, L.Z, G.C., and S.Y.C. designed immunoassay protocol. K.K. and G.K. developed and purified the Ebola virus antigens and antibodies. F.Z., Z.S., and S.Y.C. designed and fabricated the nanoantenna array samples. F.Z., Z.S., G.K, and S.Y.C. contributed to data analysis and manuscript writing. The work was supported by a grant from the Bill and Melinda Gates Foundation (OPP1117592) to S.Y.C. and G.K., the Defense Threat Reduction Agency (HDTRA1-16-C-0025) to S.Y.C. and G.K., and National Science Foundation Scalable Nanomanufacturing Program (CMMI-1635443) to S.Y.C. The work was also supported by intramural funding from the Food and Drug Administration to G.K. The authors acknowledge the use of Princeton{\textquoteright}s Imaging and Analysis Center, which is partially supported by the Princeton Center for Complex Materials, a National Science Foundation (NSF)-MRSEC program (DMR-1420541). Our contributions are an informal communication and represent our own best judgment. These comments do not bind or obligate FDA. Note: Figure 3 was reset on July 23, 2019, after initial publication online as the labels for parts (c) and (d) were missing initially. Publisher Copyright: {\textcopyright} 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2019",
month = jul,
day = "26",
doi = "10.1002/adma.201902331",
language = "English (US)",
volume = "31",
journal = "Advanced Materials",
issn = "0935-9648",
publisher = "Wiley-VCH Verlag",
number = "30",
}