A Caltech Library Service

Performance of electrochemical immunoassays for clinical diagnostics of SARS-CoV-2 based on selective nucleocapsid N protein detection: Boron-doped diamond, gold and glassy carbon evaluation

Białobrzeska, Wioleta and Ficek, Mateusz and Dec, Bartłomiej and Osella, Silvio and Trzaskowski, Bartosz and Jaramillo-Botero, Andres and Pierpaoli, Mattia and Rycewicz, Michał and Dashkevich, Yanina and Łęga, Tomasz and Malinowska, Natalia and Cebula, Zofia and Bigus, Daniel and Firganek, Daniel and Bięga, Ewelina and Dziąbowska, Karolina and Brodowski, Mateusz and Kowalski, Marcin and Panasiuk, Mirosława and Gromadzka, Beata and Żołędowska, Sabina and Nidzworski, Dawid and Pyrć, Krzysztof and Goddard, William A., III and Bogdanowicz, Robert (2022) Performance of electrochemical immunoassays for clinical diagnostics of SARS-CoV-2 based on selective nucleocapsid N protein detection: Boron-doped diamond, gold and glassy carbon evaluation. Biosensors and Bioelectronics, 209 . Art. No. 114222. ISSN 0956-5663. PMCID PMC8989705. doi:10.1016/j.bios.2022.114222.

[img] PDF - Accepted Version
See Usage Policy.

[img] MS Word (Supplementary data) - Supplemental Material
See Usage Policy.


Use this Persistent URL to link to this item:


The 21st century has already brought us a plethora of new threats related to viruses that emerge in humans after zoonotic transmission or drastically change their geographic distribution or prevalence. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first spotted at the end of 2019 to rapidly spread in southwest Asia and later cause a global pandemic, which paralyzes the world since then. We have designed novel immunosensors targeting conserved protein sequences of the N protein of SARS-CoV-2 based on lab-produced and purified anti-SARS-CoV-2 nucleocapsid antibodies that are densely grafted onto various surfaces (diamond/gold/glassy carbon). Titration of antibodies shows very strong reactions up to 1:72 900 dilution. Next, we showed the mechanism of interactions of our immunoassay with nucleocapsid N protein revealing molecular recognition by impedimetric measurements supported by hybrid modeling results with both density functional theory and molecular dynamics methods. Biosensors allowed for a fast (in less than 10 min) detection of SARS-CoV-2 virus with a limit of detection from 0.227 ng/ml through 0.334 ng/ml to 0.362 ng/ml for glassy carbon, boron-doped diamond, and gold surfaces, respectively. For all tested surfaces, we obtained a wide linear range of concentrations from 4.4 ng/ml to 4.4 pg/ml. Furthermore, our sensor leads to a highly specific response to SARS-CoV-2 clinical samples versus other upper respiratory tract viruses such as influenza, respiratory syncytial virus, or Epstein-Barr virus. All clinical samples were tested simultaneously on biosensors and real-time polymerase chain reactions.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Białobrzeska, Wioleta0000-0001-7662-1880
Ficek, Mateusz0000-0003-2334-9697
Dec, Bartłomiej0000-0001-5103-2000
Osella, Silvio0000-0001-8541-1914
Trzaskowski, Bartosz0000-0003-2385-1476
Jaramillo-Botero, Andres0000-0003-2844-0756
Pierpaoli, Mattia0000-0002-7508-1824
Rycewicz, Michał0000-0002-1186-6657
Malinowska, Natalia0000-0001-9146-9565
Cebula, Zofia0000-0002-4506-6498
Bigus, Daniel0000-0001-8477-3761
Firganek, Daniel0000-0002-8870-2714
Bięga, Ewelina0000-0002-2216-5493
Dziąbowska, Karolina0000-0002-0226-3635
Brodowski, Mateusz0000-0001-5439-4701
Panasiuk, Mirosława0000-0001-7470-7306
Gromadzka, Beata0000-0002-3525-2158
Żołędowska, Sabina0000-0001-6218-8342
Nidzworski, Dawid0000-0003-0533-0837
Pyrć, Krzysztof0000-0002-3867-7688
Goddard, William A., III0000-0003-0097-5716
Bogdanowicz, Robert0000-0002-7543-2620
Additional Information:© 2022 Elsevier. Received 22 October 2021, Revised 17 March 2022, Accepted 24 March 2022, Available online 8 April 2022. We thank SkyWayBiolab for providing upper respiratory tract inactivated viruses that served as negative controls in our experiments and for the technological input needed for antibody production. The authors gratefully acknowledge financial support from the National Science Centre (NCN) under Grant “Express Call – Research on COVID-19” No. 2020/01/0/ST7/00104. The DS funds of the Faculty of Electronics, Telecommunications and Informatics of the Gdańsk University of Technology are also acknowledged. Molecular Dynamics simulations have been performed in part at the Interdisciplinary Centre for Mathematical and Computational Modelling of the University of Warsaw (grants g86-1058 and g87-1079). Author contributions: W.B., R.B., B.G., D.N. and K.P. conceived and designed the work. T.Ł, Y.D., B.G. and M.P. produced the recombinant protein and polyclonal antibody. M.F., M. R., Z.C., E.B. and W.B. prepared electrodes. M.B., M.K., W.B., D.B., and K.D. modified electrodes. M.B., M.K., N.M., D.F. and W.B. optimized the assays and performed analysis. W.B.; B.G., M. Pi., and R.B. wrote the manuscript with corrections from all authors. Theoretical and computational validation models were conceived and prepared by B.D, W.A.G., A.J.B., B.T and S.O. R.B , D.N. and S.Ż. were responsible for project administration and funding acquisition. All the authors analyzed the data, discussed the results, and reviewed the manuscript. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Funding AgencyGrant Number
National Science Centre (Poland)2020/01/0/ST7/00104
Gdańsk University of TechnologyUNSPECIFIED
Other Numbering System:
Other Numbering System NameOther Numbering System ID
PubMed Central ID:PMC8989705
Record Number:CaltechAUTHORS:20220412-226237000
Persistent URL:
Official Citation:Wioleta Białobrzeska, Mateusz Ficek, Bartłomiej Dec, Silvio Osella, Bartosz Trzaskowski, Andres Jaramillo-Botero, Mattia Pierpaoli, Michał Rycewicz, Yanina Dashkevich, Tomasz Łęga, Natalia Malinowska, Zofia Cebula, Daniel Bigus, Daniel Firganek, Ewelina Bięga, Karolina Dziąbowska, Mateusz Brodowski, Marcin Kowalski, Mirosława Panasiuk, Beata Gromadzka, Sabina Żołędowska, Dawid Nidzworski, Krzysztof Pyrć, William A. Goddard, Robert Bogdanowicz, Performance of electrochemical immunoassays for clinical diagnostics of SARS-CoV-2 based on selective nucleocapsid N protein detection: Boron-doped diamond, gold and glassy carbon evaluation, Biosensors and Bioelectronics, Volume 209, 2022, 114222, ISSN 0956-5663,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:114269
Deposited By: George Porter
Deposited On:13 Apr 2022 14:14
Last Modified:26 Apr 2022 15:55

Repository Staff Only: item control page