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Open AccessArticle

Electron-Beam-Lithographed Nanostructures as Reference Materials for Label-Free Scattered-Light Biosensing of Single Filoviruses

1
Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD 20993, USA
2
Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA
*
Author to whom correspondence should be addressed.
Sensors 2018, 18(6), 1670; https://doi.org/10.3390/s18061670
Received: 22 March 2018 / Revised: 14 May 2018 / Accepted: 20 May 2018 / Published: 23 May 2018
(This article belongs to the Special Issue Label-free Optical Nanobiosensors)
Optical biosensors based on scattered-light measurements are being developed for rapid and label-free detection of single virions captured from body fluids. Highly controlled, stable, and non-biohazardous reference materials producing virus-like signals are valuable tools to calibrate, evaluate, and refine the performance of these new optical biosensing methods. To date, spherical polymer nanoparticles have been the only non-biological reference materials employed with scattered-light biosensing techniques. However, pathogens like filoviruses, including the Ebola virus, are far from spherical and their shape strongly affects scattered-light signals. Using electron beam lithography, we fabricated nanostructures resembling individual filamentous virions attached to a biosensing substrate (silicon wafer overlaid with silicon oxide film) and characterized their dimensions with scanning electron and atomic force microscopes. To assess the relevance of these nanostructures, we compared their signals across the visible spectrum to signals recorded from Ebola virus-like particles which exhibit characteristic filamentous morphology. We demonstrate the highly stable nature of our nanostructures and use them to obtain new insights into the relationship between virion dimensions and scattered-light signal. View Full-Text
Keywords: optical biosensing; electron beam lithography; label-free; filovirus; reference materials; scattered light; interferometry optical biosensing; electron beam lithography; label-free; filovirus; reference materials; scattered light; interferometry
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Agrawal, A.; Majdi, J.; Clouse, K.A.; Stantchev, T. Electron-Beam-Lithographed Nanostructures as Reference Materials for Label-Free Scattered-Light Biosensing of Single Filoviruses. Sensors 2018, 18, 1670.

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