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Abstract In a viral pandemic, a few important tests are required for successful containment of the virus and reduction in severity of the infection. Among those tests, a test for the neutralizing ability of an antibody is crucial for assessment of population immunity gained through vaccination, and to test therapeutic value of antibodies made to counter the infections. Here, we report a sensitive technique to detect the relative neutralizing strength of various antibodies against the SARS-CoV-2 virus. We used bright, photostable, background-free, fluorescent upconversion nanoparticles conjugated with SARS-CoV-2 receptor binding domain as a phantom virion. A glass bottom plate coated with angiotensin-converting enzyme 2 (ACE-2) protein imitates the target cells. When no neutralizing IgG antibody was present in the sample, the particles would bind to the ACE-2 with high affinity. In contrast, a neutralizing antibody can prevent particle attachment to the ACE-2-coated substrate. A prototype system consisting of a custom-made confocal microscope was used to quantify particle attachment to the substrate. The sensitivity of this assay can reach 4.0 ng/ml and the dynamic range is from 1.0 ng/ml to 3.2  $$\upmu$$ μ g/ml. This is to be compared to 19 ng/ml sensitivity of commercially available kits. 

We present a robust fiber-based setup for Bessel-like beam extended depth-of-focus Fourier-domain optical coherence microscopy, where the Bessel-like beam is generated in a higher order mode fiber module. In this module a stable guided LP₀₂core mode is selectively excited by a long period grating written in the higher order mode fiber. Imaging performance of this system in terms of lateral resolution and depth of focus was analyzed using samples of suspended microbeads and compared to the case where illumination is provided by the fundamental LP₀₁mode of a single mode fiber. Illumination with the LP₀₂mode allowed for a lateral resolution down to 2.5 µm as compared to 4.5 µm achieved with the LP₀₁mode of the single mode fiber. A three-fold enhancement of the depth of focus compared to a Gaussian beam with equally tight focus is achieved with the LP₀₂mode. Analysis of the theoretical lateral point spread functions for the case of LP₀₁and LP₀₂illumination agrees well with the experimental data. As the design space of waveguides and long-period gratings allows for further optimization of the beam parameters of the generated Bessel-like beams in an all-fiber module, this approach offers a robust and yet flexible alternative to free-space optics approaches or the use of conical fiber tips.

 

Abstract Dr. Deborah Birx, the White House Coronavirus Task Force coordinator, told NBC News on “Meet the Press” that “[T]he U.S. needs a ‘breakthrough’ in coronavirus testing to help screen Americans and get a more accurate picture of the virus’ spread.” We have been involved with biopathogen detection since the 2001 anthrax attacks and were the first to detect anthrax in real-time. A variation on the laser spectroscopic techniques we developed for the rapid detection of anthrax can be applied to detect the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2 virus). In addition to detecting a single virus, this technique allows us to read its surface protein structure. In particular, we have been conducting research based on a variety of quantum optical approaches aimed at improving our ability to detect Corona Virus Disease-2019 (COVID-19) viral infection. Indeed, the detection of a small concentration of antibodies, after an infection has passed, is a challenging problem. Likewise, the early detection of disease, even before a detectible antibody population has been established, is very important. Our team is researching both aspects of this problem. The paper is written to stimulate the interest of both physical and biological scientists in this important problem. It is thus written as a combination of tutorial (review) and future work (preview). We join Prof. Federico Capasso and Editor Dennis Couwenberg in expressing our appreciation to all those working so heroically on all aspects of the COVID-19 problem. And we thank Drs. Capasso and Couwenberg for their invitation to write this paper.