Anti-SARS-CoV-2 IgM/IgG antibodies detection using a patch sensor containing porous microneedles and a paper-based immunoassay

Abstract

Infectious diseases are among the leading causes of mortality worldwide. A new coronavirus named severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) was identified in Wuhan, China in 2019, and the World Health Organization (WHO) declared its outbreak, coronavirus disease 2019 (COVID-19), as a global pandemic in 2020. COVID-19 can spread quickly from person to person. One of the most challenging issues is to identify the infected individuals and prevent potential spread of SARS-CoV-2. Recently, anti-SARS-CoV-2 immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody tests using immunochromatographic methods have been used as a complement to current detection methods and have provided information of the approximate course of COVID-19 infection. However, blood sampling causes pain and poses risks of infection at the needle puncture site. In this study, a novel patch sensor integrating porous microneedles and an immunochromatographic assay (PMNIA) was developed for the rapid detection of anti-SARS-CoV-2 IgM/IgG in dermal interstitial fluid (ISF), which is a rich source of protein biomarkers, such as antibodies. Biodegradable porous microneedles (MNs) made of polylactic acid were fabricated to extract ISF from human skin by capillary effect. The extracted ISF was vertically transported and flowed into the affixed immunoassay biosensor, where specific antibodies could be detected colorimetrically on-site. Anti-SARS-CoV-2 IgM/IgG antibodies were simultaneously detected within 3 min in vitro. Moreover, the limit of detection of anti-SARS-CoV-2 IgM and IgG concentrations was as low as 3 and 7 ng/mL, respectively. The developed device integrating porous MNs and immunochromatographic biosensors is expected to enable minimally invasive, simple, and rapid anti-SARS-CoV-2 IgM/IgG antibody testing. Furthermore, the compact size of the MN and biosensor-integrated device is advantageous for its widespread use. The proposed device has great potential for rapid screening of various infectious diseases in addition to COVID-19 as an effective complementary method with other diagnostic tests.

Novel biotagging method using dissolvable microneedle arrays for individual identification of animals

“…After depilation, the cream was thoroughly wiped off with dried and wet wipes. MAPs were applied to the skin using a thin metal plate on the opposite side as a support to avoid direct physical damage to the rat body 21 . Regarding the evaluation of MAP dissolution, the time of MAP application was evaluated and determined by measuring the respective dissolved lengths of the MNs with changing application times.…”

Paper-based colorimetric sensors for point-of-care testing

“…Antibodies are highly specic proteins that can bind to target antigens with high affinity. [67][68][69] In paper-based colorimetric sensors, antibodies can be immobilized on the paper surface or conjugated with indicator particles, allowing the selective capture of target antigens. The presence of the target antigen leads to a visible color change, indicating the presence of the analyte.…”

“…Enzyme-based amplication techniques, such as enzyme-linked immunosorbent assay (ELISA), can be incorporated into paper-based sensors to enhance the sensitivity and enable the quantication of the analyte. 68,94 2.4.5.2. Nanoparticle-based amplication.…”

The SARS‐CoV‐2 specific IgG antibodies biophotonic sensor

“…In this study, we present a biophotonic sensor with a fiber‐optic biofunctionalized measurement head, dedicated to SARS‐CoV‐2 antibodies detection. The innovation of the presented sensing method mainly lies in: Design of a bioactive layer that selectively allows only specific SARS‐CoV‐2 antibody proteins to be attached in low concentrations [ 37 , 38 ]. In contrary to many other solutions which used plastic fiber optic [ 39 ], our sensor is made of the standard telecommunication optical fiber with a dedicated bioactive layer.…”

“…Design of a bioactive layer that selectively allows only specific SARS‐CoV‐2 antibody proteins to be attached in low concentrations [ 37 , 38 ].…”