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      A Multiplex “Disposable Photonics” Biosensor Platform and Its Application to Antibody Profiling in Upper Respiratory Disease

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          Abstract

          Photonic technologies promise to deliver quantitative, multiplex, and inexpensive medical diagnostic platforms by leveraging the highly scalable processes developed for the fabrication of semiconductor microchips. However, in practice, the affordability of these platforms is limited by complex and expensive sample handling and optical alignment. We previously reported the development of a disposable photonic assay that incorporates inexpensive plastic micropillar microfluidic cards for sample delivery. That system as developed was limited to singleplex assays due to its optical configuration. To enable multiplexing, we report a new approach addressing multiplex light I/O, in which the outputs of individual grating couplers on a photonic chip are mapped to fibers in a fiber bundle. As demonstrated in the context of detecting antibody responses to influenza and SARS-CoV-2 antigens in human serum and saliva, this enables multiplexing in an inexpensive, disposable, and compact format.

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          Most cited references26

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          Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations

          Antibodies elicited by infection accumulate somatic mutations in germinal centers that can increase affinity for cognate antigens. We analyzed 6 independent groups of clonally related severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) Spike receptor-binding domain (RBD)-specific antibodies from 5 individuals shortly after infection and later in convalescence to determine the impact of maturation over months. In addition to increased affinity and neutralization potency, antibody evolution changed the mutational pathways for the acquisition of viral resistance and restricted neutralization escape options. For some antibodies, maturation imposed a requirement for multiple substitutions to enable escape. For certain antibodies, affinity maturation enabled the neutralization of circulating SARS-CoV-2 variants of concern and heterologous sarbecoviruses. Antibody-antigen structures revealed that these properties resulted from substitutions that allowed additional variability at the interface with the RBD. These findings suggest that increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying SARS-CoV-2 populations, and perhaps against other pandemic threat coronaviruses. SARS-CoV-2 RBD-binding antibodies accumulate mutations over months of convalescence, but how maturation affects antibody properties is unclear. Muecksch et al. analyze 6 groups of clonally related neutralizing antibodies from convalescent donors and reveal that antibody maturation increases affinity, potency, and breadth, and restricts viral escape options. They also identify the structural basis for these improved antibody properties during maturation.
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            Universal relations for coupling of optical power between microresonators and dielectric waveguides

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              ELISA in the multiplex era: Potentials and pitfalls

              Multiplex immunoassays confer several advantages over widely adopted singleplex immunoassays including increased efficiency at a reduced expense, greater output per sample volume ratios and higher throughput predicating more resolute, detailed diagnostics and facilitating personalised medicine. Nonetheless, to date, relatively few protein multiplex immunoassays have been validated for in vitro diagnostics in clinical/point‐of‐care settings. This review article will outline the challenges, which must be ameliorated prior to the widespread integration of multiplex immunoassays in clinical settings: (i) biomarker validation; (ii) standardisation of immunoassay design and quality control (calibration and quantification); (iii) availability, stability, specificity and cross‐reactivity of reagents; (iv) assay automation and the use of validated algorithms for transformation of raw data into diagnostic results. A compendium of multiplex immunoassays applicable to in vitro diagnostics and a summary of the diagnostic products currently available commercially are included, along with an analysis of the relative states of development for each format (namely planar slide based, suspension and planar/microtitre plate based) with respect to the aforementioned issues.
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                Author and article information

                Journal
                ACS Sens
                ACS Sens
                se
                ascefj
                ACS Sensors
                American Chemical Society
                2379-3694
                29 March 2024
                26 April 2024
                : 9
                : 4
                : 1799-1808
                Affiliations
                []Department of Dermatology, University of Rochester , Rochester, New York 14627, United States
                []Department of Biochemistry and Biophysics, University of Rochester , Rochester, New York 14627, United States
                [§ ]Department of Chemistry, University of Rochester , Rochester, New York 14627, United States
                []Department of Nanoscale Science & Engineering, University at Albany , Albany, New York 12203, United States
                []University of California at Santa Barbara , Santa Barbara, California 93106, United States
                [# ]QuidelOrtho, Inc. , Rochester, New York 14626, United States
                []The Institute of Optics, University of Rochester , Rochester, New York 14627, United States
                []ZDing Tech, LLC , Pittsford, New York 14534, United States
                Author notes
                Author information
                https://orcid.org/0000-0003-4345-3627
                https://orcid.org/0000-0003-0701-2728
                https://orcid.org/0000-0001-9168-8047
                Article
                10.1021/acssensors.3c02225
                11059096
                38549498
                95c232bc-c069-4b07-956c-5f365c9bc12e
                © 2024 The Authors. Published by American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 22 October 2023
                : 18 March 2024
                : 08 February 2024
                Funding
                Funded by: National Institute of Standards and Technology, doi 10.13039/100000161;
                Award ID: 70NANB22H015
                Categories
                Article
                Custom metadata
                se3c02225
                se3c02225

                ring resonator,coupling,fiber bundle,antibody assay,passive microfluidics,sars-cov-2

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