{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:22:58Z","timestamp":1777936978701,"version":"3.51.4"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["21H01841"],"award-info":[{"award-number":["21H01841"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JPMXP1222UT1049"],"award-info":[{"award-number":["JPMXP1222UT1049"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ARIM Japan","award":["21H01841"],"award-info":[{"award-number":["21H01841"]}]},{"name":"ARIM Japan","award":["JPMXP1222UT1049"],"award-info":[{"award-number":["JPMXP1222UT1049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>A high-sensitivity silicon microring (Si MRR) optical biosensor for detecting the nucleocapsid protein of SARS-CoV-2 is proposed and demonstrated. In the proposed biosensor, the surface of a Si MRR waveguide is modified with antibodies, and the target protein is detected by measuring a resonant wavelength shift of the MRR caused by the selective adsorption of the protein to the surface of the waveguide. A Si MRR is fabricated on a silicon-on-insulator substrate using a CMOS-compatible fabrication process. The quality factor of the MRR is approximately 20,000. The resonant wavelength shift of the MRR and the detection limit for the environmental refractive index change are evaluated to be 89 nm\/refractive index unit (RIU) and 10\u22124 RIU, respectively. The sensing characteristics are examined using a polydimethylsiloxane flow channel after the surface of the Si MRR waveguide is modified with the IgG antibodies through the Si-tagged protein. First, the selective detection of the protein by the MRR sensor is experimentally demonstrated by the detection of bovine serum albumin and human serum albumin. Next, various concentrations of nucleocapsid protein solutions are measured by the MRR, in which the waveguide surface is modified with the IgG antibodies through the Si-tagged protein. Although the experimental results are very preliminary, they show that the proposed sensor has a potential nucleocapsid sensitivity in the order of 10 pg\/mL, which is comparable to the sensitivity of current antigen tests. The detection time is less than 10 min, which is much shorter than those of other antigen tests.<\/jats:p>","DOI":"10.3390\/s24103250","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T11:06:41Z","timestamp":1716203201000},"page":"3250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Silicon Microring Resonator Biosensor for Detection of Nucleocapsid Protein of SARS-CoV-2"],"prefix":"10.3390","volume":"24","author":[{"given":"Yusuke","family":"Uchida","sequence":"first","affiliation":[{"name":"Graduate School of Engineering, Yokohama National University, 79-5 Tokiwada, Hodogaya-ku, Yokohama 240-8501, Japan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9474-7399","authenticated-orcid":false,"given":"Taro","family":"Arakawa","sequence":"additional","affiliation":[{"name":"Graduate School of Engineering, Yokohama National University, 79-5 Tokiwada, Hodogaya-ku, Yokohama 240-8501, Japan"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4595-0929","authenticated-orcid":false,"given":"Akio","family":"Higo","sequence":"additional","affiliation":[{"name":"System Design Lab, School of Engineering, The University of Tokyo, 2-11-16, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan"}]},{"given":"Yuhei","family":"Ishizaka","sequence":"additional","affiliation":[{"name":"Department of Science and Engineering, Kanto Gakuin University, 1-50-1 Mutsuura-higashi, Kanazawa-ku, Yokohama 236-8501, Japan"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s42247-020-00150-w","article-title":"Smart materials-integrated sensor technologies for COVID-19 diagnosis","volume":"4","author":"Erdem","year":"2021","journal-title":"Emergent Mater."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7226","DOI":"10.1021\/acs.analchem.0c00784","article-title":"Rapid and Sensitive Detection of anti-SARS-CoV-2 IgG, Using Lanthanide-Doped Nanoparticles-Based Lateral Flow Immunoassay","volume":"92","author":"Chen","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"104363","DOI":"10.1016\/j.jcv.2020.104363","article-title":"Clinical characteristics of 225 patients with COVID-19 in a tertiary Hospital near Wuhan, China","volume":"127","author":"Li","year":"2020","journal-title":"J. Clin. Virol."},{"key":"ref_4","first-page":"141","article-title":"Characteristics of SARS- CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1146\/annurev-med-042921-020956","article-title":"COVID-19: Challenges of Viral Variants","volume":"74","author":"Jacobs","year":"2023","journal-title":"Annu. Rev. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Huang, L., Ding, L., Zhou, J., Chen, S., Chen, F., Zhao, C., Xu, J., Hu, W., Ji, J., and Xu, H. (2021). One-step rapid quantification of SARS-CoV-2 virus particles via low-cost nanoplasmonic sensors in generic microplate reader and point-of-care device. Biosens. Bioelectron., 171.","DOI":"10.1016\/j.bios.2020.112685"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ong, V., Soleimani, A., Amirghasemi, F., Nejad, S.K., Abdelmonem, M., Razaviyayn, M., Hosseinzadeh, P., Comai, L., and Mousavi, M.P.S. (2023). Impedimetric Sensing: An Emerging Tool for Combating the COVID-19 Pandemic. Biosensors, 13.","DOI":"10.3390\/bios13020204"},{"key":"ref_8","first-page":"76","article-title":"A Brief Overview of Nanozyme-Based Colorimetric and Fluorometric Sensors for Early Diagnosis of COVID-19","volume":"1","year":"2023","journal-title":"Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100171","DOI":"10.1016\/j.sintl.2022.100171","article-title":"Sustainable materials and COVID-19 detection biosensor: A brief review","volume":"3","author":"Yasria","year":"2022","journal-title":"Sens. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1039\/D0MA00702A","article-title":"Nano- and biosensors for the detection of SARS-CoV-2: Challenges and opportunities","volume":"1","author":"Iravani","year":"2020","journal-title":"Mater. Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s41403-020-00128-4","article-title":"Optical Fiber Sensors for Rapid Screening of COVID-19","volume":"5","author":"Nag","year":"2022","journal-title":"Trans. Indian Natl. Acad. Eng."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1002\/cbic.202000744","article-title":"Optical Biosensors for Virus Detection: Prospects for SARS-CoV-2\/COVID-19","volume":"22","author":"Maddali","year":"2021","journal-title":"ChemBioChem"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"011002","DOI":"10.1088\/2515-7647\/abd4ee","article-title":"Nanophotonic biosensors for point-of-care COVID-19 diagnostics and coronavirus surveillance","volume":"3","author":"Soler","year":"2021","journal-title":"J. Phys. Photonics"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vogelbacher, F., Kothe, T., Muellner, P., EMelnik, E., Sagmeister, M., Kraft, J., and Hainberger, R. (2022). Waveguide Mach-Zehnder biosensor with laser diode pumped integrated single-mode silicon nitride organic hybrid solid-state laser. Biosens. Bioelectron., 197.","DOI":"10.1016\/j.bios.2021.113816"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"127655","DOI":"10.1016\/j.cej.2020.127655","article-title":"Sustainable and fast saliva-based COVID-19 virus diagnosis kit using a novel GO-decorated Au\/FBG sensor","volume":"420","author":"Samavati","year":"2021","journal-title":"Chem. Eng. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1021\/acssensors.0c01180","article-title":"How Nanophotonic Label-Free Biosensors Can Contribute to Rapid and Massive Diagnostics of Respiratory Virus Infections: COVID-19 Case","volume":"5","author":"Soler","year":"2020","journal-title":"ACS Sens."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1039\/D1LC00369K","article-title":"Disposable photonics for cost-effective clinical bioassays: Application to COVID-19 antibody testing","volume":"21","author":"Cognetti","year":"2021","journal-title":"Lab Chip"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"De Ara\u00fajo, M.M., and da Silva, J.P. (2023). The Design of a Glycerol Concentration Sensor Based on an LRSPP Hybrid Photonic Biosensor. Sensors, 23.","DOI":"10.3390\/s23042010"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.bios.2011.10.056","article-title":"Label-free virus detection using silicon photonic microring resonators","volume":"31","author":"McClellana","year":"2012","journal-title":"Biosens. Bioelectron."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Occhicone, A., Sinibaldi, A., Chiappetta, D., Di Matteo, P., Pileri, T., Danz, N., Sonntag, F., Munzert, P., Allegretti, M., and De Pascale, V. (2023). Detection of anti-SARS CoV-2 antibodies in human serum by means of Bloch surface waves on 1D photonic crystal biochips. Biosens. Bioelectron. X, 15.","DOI":"10.1016\/j.biosx.2023.100413"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Steglich, P., H\u00fclsemann, M., Dietzel, B., and Mai, A. (2019). Optical Biosensors Based on Silicon-on-Insulator Ring Resonators: A Review. Molecules, 24.","DOI":"10.20944\/preprints201901.0012.v1"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Matsuura, S., Yamasaku, N., Nishijima, Y., Okazaki, S., and Arakawa, T. (2020). Characteristics of Highly-Sensitive Hydrogen Gas 2 Sensor Based on Pt-WO3\/Si Microring Resonator. Sensors, 20.","DOI":"10.3390\/s20010096"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4644","DOI":"10.1016\/j.optcom.2008.06.006","article-title":"Integrated photonic glucose biosensor using a vertically coupled microring resonator in polymers","volume":"281","author":"Kim","year":"2008","journal-title":"Opt. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6800609","DOI":"10.1109\/JPHOT.2016.2630308","article-title":"A Metal-Assisted Silicon Slot Waveguide for Highly Sensitive Gas Detection","volume":"9","author":"Ishizaka","year":"2017","journal-title":"IEEE Photonics J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.jiac.2021.03.021","article-title":"Efficacy and validity of automated quantitative chemiluminescent enzyme immunoassay for SARS-CoV-2 antigen test from saliva specimen in the diagnosis of COVID-19","volume":"27","author":"Asai","year":"2021","journal-title":"J. Infect. Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.snb.2012.08.078","article-title":"Label-free aptamer sensor based on silicon microring resonators","volume":"176","author":"Park","year":"2013","journal-title":"Sens. Actuators B"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1049\/iet-opt.2018.5082","article-title":"Silicon photonic biosensors","volume":"13","author":"Ciminelli","year":"2019","journal-title":"IET Optoelectron."},{"key":"ref_28","unstructured":"Ali, L., Khan, M., Yousuf, A.H.B., Masud, H., and Chaudhry, M.H. (2023, September 26). IEEE Nanotechnology Symposium (ANTS) 2018. Available online: https:\/\/ieeexplore.ieee.org\/xpl\/conhome\/8648891\/proceeding."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1364\/OL.424858","article-title":"High contrast cleavage detection","volume":"46","author":"Dubrovsky","year":"2021","journal-title":"Opt. Lett."},{"key":"ref_30","unstructured":"Uchida, Y., Higo, A., Arakawa, T., and Ishizaka, Y. (2023, September 26). 28th Microoptics Conference, Miyazaki, Japan, 24\u201327 September 2023, F-3. Available online: https:\/\/moc2023.com\/."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ab.2008.11.001","article-title":"Oriented immobilization of antibodies on a silicon wafer using Si-tagged protein A","volume":"385","author":"Ikeda","year":"2009","journal-title":"Anal. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.optcom.2015.11.068","article-title":"Detection of antibody-antigen reaction by silicon nitride slot-ring biosensors using protein G","volume":"365","author":"Taniguchia","year":"2016","journal-title":"Opt. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.colsurfb.2011.04.020","article-title":"Why does the silica-binding protein \u201cSi-tag\u201d bind strongly to silica surfaces? Implications of conformational adaptation of the intrinsically disordered polypeptide to solid surfaces","volume":"86","author":"Ikeda","year":"2011","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Caroselli, R., Castell\u00f3, J.G., Escorihuela, J., Ba\u00f1uls, M.J., Maquieira, \u00c1., and Garc\u00eda-Rup\u00e9rez, J. (2018). Experimental Study of the Oriented Immobilization of Antibodies on Photonic Sensing Structures by Using Protein A as an Intermediate Layer. Sensors, 18.","DOI":"10.3390\/s18041012"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6232","DOI":"10.1039\/C4AY00614C","article-title":"Automated enzyme-linked immunosorbent assay using beads in a single tip (BIST) technology coupled with a novel anchor protein for oriented antibody immobilization","volume":"6","author":"Ikeda","year":"2014","journal-title":"Anal. Methods"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Erickson, H.P. (2009). Size and Shape of Protein Molecules at the Nanometer Level Determined by Sedimentation, Gel Filtration, and Electron Microscopy. Biol. Proced. Online, 11.","DOI":"10.1007\/s12575-009-9008-x"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1063\/1.555624","article-title":"Refractive index of silicon and germanium and its wavelength and temperature derivatives","volume":"9","author":"Li","year":"1980","journal-title":"J. Phys. Chem. Ref. Data"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1364\/JOSA.55.001205","article-title":"Interspecimen comparison of the refractive index of fused silica","volume":"55","author":"Malitson","year":"1965","journal-title":"J. Opt. Soc. Am."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1016\/j.bpj.2011.03.004","article-title":"On the Distribution of Protein Refractive Index Increments","volume":"100","author":"Zhao","year":"2011","journal-title":"Biophys. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"38003","DOI":"10.1209\/0295-5075\/117\/38003","article-title":"Resolving controversy of unusually high refractive index of a tubulin","volume":"117","author":"Cifra","year":"2017","journal-title":"Europhys. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1364\/BOE.7.001672","article-title":"Using optical trap to measure the refractive index of a single animal virus in culture fluid with high precision","volume":"7","author":"Pang","year":"2016","journal-title":"Biomed. Opt. Express"},{"key":"ref_42","unstructured":"(2024, March 01). Available online: https:\/\/www.mizuho-m.co.jp\/en\/product\/files\/QC_SARS-CoV-2_PI_V1.pdf."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/24\/10\/3250\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:45:19Z","timestamp":1760107519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/24\/10\/3250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,20]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["s24103250"],"URL":"https:\/\/doi.org\/10.3390\/s24103250","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,20]]}}}