Detection of antibodies against SARS-CoV-2 spike protein by gold nanospikes in an opto-microfluidic chip

Abstract

The ongoing global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to active research in its associated diagnostics and medical treatments. While quantitative reverse transcription polymerase chain reaction (qRT-PCR) is the most reliable method to detect viral genes of SARS-CoV-2, serological tests for specific antiviral antibodies are also important as they identify false negative qRT-PCR responses, track how effectively the patient’s immune system is fighting the infection, and are potentially helpful for plasma transfusion therapies. In this work, based on the principle of localized surface plasmon resonance (LSPR), we develop an opto-microfluidic sensing platform with gold nanospikes, fabricated by electrodeposition, to detect the presence and amount of antibodies specific to the SARS-CoV-2 spike protein in 1 L of human plasma diluted in 1mL of buffer solution, within 30min. The target antibody concentration can be correlated with the LSPR wavelength peak shift of gold nanospikes caused by the local refractive index change due to the antigen–antibody binding. This label-free microfluidic platform achieves a limit of detection of 0.08ng/mL ( 0.5pM), falling under the clinical relevant concentration range. We demonstrate that our opto-microfluidic platform offers a promising point-of-care testing tool to complement standard serological assays and make SARS-CoV-2 quantitative diagnostics easier, cheaper, and faster.

Wastewater-based epidemiology—surveillance and early detection of waterborne pathogens with a focus on SARS-CoV-2, Cryptosporidium and Giardia

“…that can generate physicochemical signals (optical, electrochemical, etc.) are increasingly being developed for pathogen detection (Ryan et al 2017 ; Cesewski and Johnson 2020 ), including Cryptosporidium (Luka et al 2019 ) and SARS-CoV-2 (Funari et al 2020 ; Mavrikou et al 2020 ; Qiu et al 2020 ; Seo et al 2020 ). Biosensors have the potential for rapid and real-time WBE and have been applied to wastewater (Yang et al 2017 ), but still present many technical challenges including sensitivity, specificity and detection limit (Ryan et al 2017 ; Cesewski and Johnson 2020 ; Mao et al 2020c ).…”

Electrochemical Immunosensor for the Early Detection of Rheumatoid Arthritis Biomarker: Anti-Cyclic Citrullinated Peptide Antibody in Human Serum Based on Avidin-Biotin System

“…The fabrication of electrochemical antibody detection biosensors, for the quantitative analysis and monitoring of disease biomarkers, is presently an emerging field of research activity. Recently, a few electrochemical biosensors for the sensitive detection of antibodies for SARS-CoV-2 spike protein [ 19 ], Zika virus specific antibodies [ 20 ], glutathione (GSH) monoclonal antibody [ 21 ], Human IgG [ 22 ] and anti-infiximab antibody [ 23 ] were reported. In spite of the substantial developments provided by the electrochemical biosensors, only a few bio-sensing devices are available for Anti-CCP-ab detection.…”

Trends in biosensing platforms for SARS-CoV-2 detection: A critical appraisal against standard detection tools

“…The assay presented a detection limit of 1.02 pM for the detection of SARS-CoV-2. More recently, Shen’s group detected antibodies against SARS-CoV-2 spike protein using Au nanospikes in opto-microfluidic sensing platform as shown in Figure 2 C [ 83 ]. The opto-microfluidic sensor was developed based on the principle of localized surface plasmon resonance (LSPR), and Au nanospikes were electrodeposited for the detection of antibodies against SARS-CoV-2 spike protein 1 μL of human plasma.…”

“…(A) Schematic representation of smartphone reader used for optical immunosensor in the detection of IgA, Reprinted with permission [ 78 ] (B) Preparation and operating-principle of (a) SARS-CoV-2 S protein coupled SiO 2 @Ag SERS tags and (b) simultaneous detection of anti- SARS-CoV-2 antibodies, Reprinted with permission [ 79 ] (C) Schematic representation of localized surface plasmon resonance based opto-microfluidic sensor to detect SARS-CoV-2 antibodies. Reprinted with permission [ 83 ]. …”

“… Biosensor Pathogen Detection target Limit of detection Linear range Ref. EC SARS-CoV-2 S or N protein 19 ng/mL and 8 ng/mL - [ 103 ] EC SARS-CoV-2 Antibodies - - [ 101 ] EC SARS-CoV-2 N-gene 6.9 copies/μL 585.4 to 5.854 × 10 7 copies/μL [ 99 ] Cell-based SARS-CoV-2 Antigen 1 fgmL 1- 10 fg and 1 μg mL 1- [ 105 ] Optofluidic SARS-CoV-2 Antibody 0.5 pM 1- [ 83 ] Nanoplasmonic SARS-CoV-2 Virus particles 370 vp/mL 0 to 10 7 vp/mL [ 80 ] SPR SARS-CoV-2 Antibody 1.02 pM 2-1000 pM [ 82 ] LSPR SARS-CoV-2 RNA 1 pM 1 nM to 1 μM [ 106 ] Lateral flow optical/chemiluminescence SARS-CoV-2 Serum IgA - - [ 78 ] SERS-LFIA SARS-CoV-2 Antibody 1.28×10 7 -fold dilution - [ 79 ] Lateral flow SARS-CoV-2 RNA 12 copies...…”