Paper biosensors for detecting elevated IL-6 levels in blood and respiratory samples from COVID-19 patients

Cristina Adrover-Jaume; Alejandra Alba-Patiño; Antonio Clemente; Giulia Santopolo; Andreu Vaquer; Steven M Russell; Enrique Barón; María Del Mar González Del Campo; Joana M Ferrer; María Berman-Riu; Mercedes García-Gasalla; María Aranda; Marcio Borges; Roberto de la Rica

doi:10.1016/j.snb.2020.129333

Paper biosensors for detecting elevated IL-6 levels in blood and respiratory samples from COVID-19 patients

Sens Actuators B Chem. 2021 Mar 1:330:129333. doi: 10.1016/j.snb.2020.129333. Epub 2020 Dec 14.

Authors

Cristina Adrover-Jaume^{1

2}, Alejandra Alba-Patiño^{1

2}, Antonio Clemente¹, Giulia Santopolo^{1

2}, Andreu Vaquer¹, Steven M Russell¹, Enrique Barón¹, María Del Mar González Del Campo¹, Joana M Ferrer^{3

4}, María Berman-Riu³, Mercedes García-Gasalla⁵, María Aranda^{1

6}, Marcio Borges^{1

6}, Roberto de la Rica^{1

2}

Affiliations

¹ Multidisciplinary Sepsis Group, Health Research Institute of the Balearic Islands (IdISBa), Son Espases University Hospital, 07120, Palma de Mallorca, Spain.
² University of the Balearic Islands, Chemistry Department, Cra. de Valldemossa km 7.5, 07122, Palma de Mallorca, Spain.
³ Immune Response in Human Pathology Group, Health Research Institute of the Balearic Islands (IdISBa), Spain.
⁴ Immunology Department, Son Espases University Hospital, Spain Son Espases University Hospital, 07120, Palma de Mallorca, Spain.
⁵ Infectious Diseases-HIV Group, Health Research Institute of the Balearic Islands (IdISBa), Son Espases University Hospital, 07120, Palma de Mallorca, Spain.
⁶ Multidisciplinary Sepsis Unit, ICU, Son Llàtzer University Hospital, 07198, Palma de Mallorca, Spain.

Abstract

Decentralizing COVID-19 care reduces contagions and affords a better use of hospital resources. We introduce biosensors aimed at detecting severe cases of COVID-19 in decentralized healthcare settings. They consist of a paper immunosensor interfaced with a smartphone. The immunosensors have been designed to generate intense colorimetric signals when the sample contains ultralow concentrations of IL-6, which has been proposed as a prognosis biomarker of COVID-19. This is achieved by combining a paper-based signal amplification mechanism with polymer-filled reservoirs for dispensing antibody-decorated nanoparticles and a bespoken app for color quantification. With this design we achieved a low limit of detection (LOD) of 10^-3 pg mL^-1 and semi-quantitative measurements in a wide dynamic range between 10^-3 and 10² pg mL^-1 in PBS. The assay time is under 10 min. The low LOD allowed us to dilute blood samples and detect IL-6 with an LOD of 1.3 pg mL^-1 and a dynamic range up to 10² pg mL^-1. Following this protocol, we were able to stratify COVID-19 patients according to different blood levels of IL-6. We also report on the detection of IL-6 in respiratory samples (bronchial aspirate, BAS) from COVID-19 patients. The test could be easily adapted to detect other cytokines such as TNF-α and IL-8 by changing the antibodies decorating the nanoparticles accordingly. The ability of detecting cytokines in blood and respiratory samples paves the way for monitoring local inflammation in the lungs as well as systemic inflammation levels in the body.

Keywords: Biosensor; COVID-19; IL-6; Paper-based; SARS-CoV-2; Smartphone.