Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation

04 June 2021, Version 2


Serological tests are essential for the control and management of COVID-19 pandemic, not only for current and historical diagnostics but especially for surveillance, epidemiological, and acquired immunity studies. Clinical COVID-19 serology is routinely performed by enzymatic or chemiluminescence immunoassays (i.e., ELISA or CLIA), which provide good sensitivities at the expense of relatively long turnaround times and specialized laboratory settings. Rapid serological tests, based on lateral flow assays, have also been developed and widely commercialized, but they suffer from limited reliability due to relatively low sensitivity and specificity. We have developed and validated a direct serological biosensor assay employing proprietary technology based on Surface Plasmon Resonance (SPR). The biosensor offers a rapid -less than 15 min- identification and quantification of SARS-CoV-2 antibodies directly in clinical samples, without the need of any signal amplification. The portable plasmonic biosensor device employs a custom-designed multi-antigen sensor biochip, combining the two main viral antigens (RBD peptide and N protein), for simultaneous detection of human antibodies targeting both antigens. The SPR serology assay reaches detection limits in the low ng mL-1 range employing polyclonal antibodies as standard, which are well below the commonly detected antibody levels in COVID-19 patients. The assay has also been implemented employing the first WHO approved anti-SARS-CoV-2 immunoglobulin standard. We have carried out a clinical validation with COVID-19 positive and negative samples (n=120) that demonstrates the excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor device as an accurate, robust, and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the management of COVID-19 patients and for the evaluation of immunological status during vaccination, treatment or in front of emerging variants.


Surface Plasmon Resonance
Serological Test
Receptor-binding domain (RBD)
Nucleocapside protein
Clinical Diagnosis

Supplementary materials

Calvo-Lozano ChemRxiv Supp Information


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.