ABSTRACT
Developing reliable, rapid, and quantitative point-of-care testing (POCT) technology of SARS-CoV-2-specific antibodies and understanding longitudinal vaccination response kinetics are highly required to restrain the ongoing coronavirus disease 2019 (COVID-19) pandemic. We demonstrate a novel portable, sensitive, and rapid chemiluminescent lab-on-fiber detection platform for detection of anti-SARS-CoV-2 antibodies: the chemiluminescent lab-on-fiber immunosensor (c-LOFI). Using SARS-CoV-2 Spike S1 RBD protein functionalized fiber bio-probe, the c-LOFI can detect anti-SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies with high sensitivity based on their respective horseradish peroxidase-labeled secondary antibodies. The limits of detection of anti-SARS-CoV-2 IgG and IgM antibodies were 0.6 and 0.3 ng/ml, respectively. The c-LOFI was successfully applied for direct detection of anti-SARS-CoV-2 antibodies in whole blood samples with simple dilution, which can serve as a finger prick test to rapidly detect antibodies. Furthermore, the longitudinal immune response (>12 months) kinetics following three-dose inactivated virus vaccines was evaluated based on anti-SARS-CoV-2 IgG detection results, which can provide important significance for understanding the immune mechanism against COVID-19 and identify individuals who may benefit from the vaccination and booster vaccination. The c-LOFI has great potential to become a sensitive, low-cost, rapid, high-frequency POCT tool for the detection of both SARS-CoV-2-specific antibodies and other biomarkers.
ABSTRACT
The COVID-19 pandemic brings unprecedented crisis for public health and economics in the world. Detecting specific antibodies to SARS-CoV-2 is a powerful supplement for the diagnosis of COVID-19 and is important for epidemiological studies and vaccine validations. Herein, a rapid and quantitative detection method of anti-SARS-CoV-2 IgG antibody was built based on the optofluidic point-of-care testing fluorescence biosensor. Without complicated steps needed, the portable system is suitable for on-site sensitive determination of anti-SARS-CoV-2 IgG antibody in serum. Under the optimal conditions, the whole detection procedure is about 25 min with a detection limit of 12.5 ng/mL that can well meet the diagnostic requirements. The method was not obviously affected by IgM and serum matrix and demonstrated to have good stability and reliability in real sample analysis. Compared to ELISA test results, the proposed method exhibits several advantages including wider measurement range and easier operation. The method provides a universal platform for rapid and quantitative analysis of other related biomarkers, which is of significance for the prevention and control of COVID-19 pandemic.
Subject(s)
Biosensing Techniques , COVID-19 , Antibodies, Viral , Humans , Immunoassay , Immunoglobulin G , Immunoglobulin M , Pandemics , Point-of-Care Testing , Reproducibility of Results , SARS-CoV-2 , Sensitivity and SpecificityABSTRACT
The ongoing global pandemic of SARS-CoV-2 has promoted to develop novel serological testing technologies since they can be effectively complementary to RT-PCR. Here, a new all-fiber Fresnel reflection microfluidic biosensor (FRMB) was constructed through combining all-fiber optical system, microfluidic chip, and multimode fiber bio-probe. The transmission of the incident light and the collection and transmission of Fresnel reflection light are achieved using a single-multi-mode fiber optic coupler (SMFC) without any other optical separation elements. This compact design greatly simplifies the whole system structure and improves light transmission efficiency, which makes it suitable for the label-free, sensitive, and easy-to-use point-of-care testing (POCT) of targets in nanoliter samples. Based on Fresnel reflection mechanism and immunoassay principle, both the SARS-CoV-2 IgM and IgG antibodies against the SARS-CoV-2 spike protein could be sensitively quantified in 7 min using the secondary antibodies-modified multimode fiber bio-probe. The FRMB performs in one-step, is accurate, label-free, and sensitive in situ/on-site detection of SARS-CoV-2 IgM or IgG in serum with simple dilution only. The limits of detection of SARS-CoV-2 IgM and SARS-CoV-2 IgG were 0.82 ng/mL and 0.45 ng/mL, respectively. Based on our proposed theory, the affinity constants of SARS-CoV-2 IgM or IgG antibody and their respective secondary antibodies were also determined. The FRMB can be readily extended as a universal platform for the label-free, rapid, and sensitive in situ/on-site measurement of other biomarkers and the investigation of biomolecular interaction.