Rapid Optical Biosensing of SARS-CoV-2 Spike Proteins in Artificial Samples

Abstract

Tests for SARS-CoV-2 are crucial for the mass surveillance of the incidence of infection. The long waiting time for classic nucleic acid test results highlights the importance of developing alternative rapid biosensing methods. Herein, we propose a fiber-optic biolayer interferometry-based biosensor (FO-BLI) to detect SARS-CoV-2 spike proteins, extracellular domain (ECD), and receptor-binding domain (RBD) in artificial samples in 13 min. The FO-BLI biosensor utilized an antibody pair to capture and detect the spike proteins. The secondary antibody conjugated with horseradish peroxidase (HRP) reacted with the enzyme substrate for signal amplification. Two types of substrates, 3,3′-diaminobenzidine (DAB) and an advanced 3-Amino-9-ethylcarbazole (i.e., AMEC), were applied to evaluate their capabilities in enhancing signals and reaching high sensitivity. After careful comparison, the AMEC-based FO-BLI biosensor showed better assay performance, which detected ECD at a concentration of 32–720 pM and RBD of 12.5–400 pM in artificial saliva and serum, respectively. The limit of detection (LoD) for SARS-CoV-2 ECD and RBD was defined to be 36 pM and 12.5 pM, respectively. Morphology of the metal precipitates generated by the AMEC-HRP reaction in the fiber tips was observed using field emission scanning electron microscopy (SEM). Collectively, the developed FO-BLI biosensor has the potential to rapidly detect SARS-CoV-2 antigens and provide guidance for “sample-collect and result-out on-site” mode.

Dynamic Profiling and Prediction of Antibody Response to Booster Inactivated Vaccines by Microsample-driven Biosensor and Machine Learning

“…The multiplexed FO-BLI biosensor to detect NAbs towards WT and Omicron subvariants in 100-fold diluted sera was summarized in Table S1. Compared to its previous version [6], this biosensor used a more environmentally and user-friendly biomaterial 3-Amino-9-ethylcarbazole (namely, AMEC) as signal enhancer (adopted from our previous study [12]) and the high-salt SD buffer for sample dilution (adopted from another study [13])). Using functionalized fibers, multiple samples or one sample towards multiple subvariants were detected within 6.5-7.5 min (Fig.…”

Challenges and perspectives of multi-virus biosensing techniques: A review

“…Interferometric biosensors with bilayer configurations reflect light from different material interface interferences, and the interference pattern/light intensity changes due to viral target binding [ 10 , [37] , [38] , [39] ]. They are simple and robust for label-free detection [ 10 ].…”

“…The independent detection units miniaturize cross-infection, and multiplexed detection is achieved using a multichannel apparatus. Currently, commercialized multi-channel detection platforms such as the Fortebio [ 38 ] and multichannel electrochemical workstations are available. However, these platforms can only detect several targets simultaneously because of their limited scanning speed and channel amount/space [ 24 , 115 ].…”

A Framework for Biosensors Assisted by Multiphoton Effects and Machine Learning

“…In recent years, some of the investigations have been focused on the design of optical biosensors for the efficient and rapid detection of the SARS-CoV-2 virus. The recognition elements of optical biosensors can be divided into aptamers, molecular imprint polymers (MIPs), and antibodies [ 49 ]. Wenjuan and his colleagues created the first unique microfluidic biosensor using Fresnel reflection for the detection of SARS-CoV-2 without a label that is quick, simple, and sensitive [ 50 ].…”