Ag Nanoparticles with Ultrathin Au Shell-Based Lateral Flow Immunoassay for Colorimetric and SERS Dual-Mode Detection of SARS-CoV-2 IgG

Abstract

Immunoglobulin detection is essential for diagnosing progression of SARS-CoV-2 infection, for which SARS-CoV-2 IgG is one of the most important indexes. In this paper, Ag nanoparticles with ultrathin Au shells (∼2 nm) embedded with 4-mercaptobenzoic acid (MBA) (Ag MBA @Au) were manufactured via a ligand-assisted epitaxial growth method and integrated into lateral flow immunoassay (LFIA) for colorimetric and SERS dual-mode detection of SARS-CoV-2 IgG. Ag MBA @Au possessed not only the surface chemistry advantages of Au but also the superior optical characteristics of Ag. Moreover, the nanogap between the Ag core and the Au shell also greatly enhanced the Raman signal. After being modified with anti-human antibodies, Ag MBA @Au recognized and combined with SARS-CoV-2 IgG, which was captured by the SARS-CoV-2 spike protein on the T line. Qualitative analysis was achieved by visually observing the color of the T line, and quantitative analysis was conducted by measuring the SERS signal with a sensitivity four orders of magnitude higher (detection limit: 0.22 pg/mL). The intra-assay and inter-assay variation coefficients were 7.7 and 10.3%, respectively, and other proteins at concentrations of 10 to 20 times higher than those of SARS-CoV-2 IgG could hardly produce distinguishable signals, confirming good reproducibility and specificity. Finally, this method was used to detect 107 clinical serum samples. The results agreed well with those obtained from enzyme-linked immunosorbent assay kits and were significantly better than those of the colloidal gold test strips. Therefore, this dual-mode LFIA has great potential in clinical practical applications and can be used to screen and trace the early immune response of SARS-CoV-2.

Recent Advances of Representative Optical Biosensors for Rapid and Sensitive Diagnostics of SARS-CoV-2

“…Recently, Liang et al reported a colorimetric and SERS dual-mode lateral flow immunoassay for the qualitative and quantitative detection of SARS-CoV-2 IgG, with a detection limit of 0.52 pg/mL in 15 min ( Figure 5 a). The excellent performance is related to the delicate structure of AgMBA@Au, prepared by a ligand-assisted epitaxial growth method [ 57 ]. Gao et al constructed a triple-mode biosensor to detect RNA in SARS-CoV-2 by using the colorimetric, SERS, and fluorescence properties of Au nanoparticles [ 58 ].…”

Colorimetric Systems for the Detection of Bacterial Contamination: Strategy and Applications

“…The fifth route is based on NP accumulation reactions [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. This strategy has been generally used in flat substrate-based systems, such as the lateral flow assay (LFA), µ-paper-based analytical device (µ-PAD), and paper-based dipstick system [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. These systems rely on the capillary action of fluids and colored NPs.…”

“…The concentrated NPs act as colorimetric labels or color generation factors. Colored NPs used for colorimetric detection include AuNPs, silver NPs (AgNPs), and colloidal carbon [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 ]. Red AuNPs are one of the widely used colorimetric labels because of their bright color, high stability, and high biocompatibility [ 80 ].…”

“…The fifth route is based on NP accumulation reactions [65][66][67][68][69][70][71][72][73][74][75][76][77][78][79]. This strategy has been generally used in flat substrate-based systems, such as the lateral flow assay (LFA), µ-paperbased analytical device (µ-PAD), and paper-based dipstick system [65][66][67][68][69][70][71][72][73][74][75][76][77][78][79].…”

Magnetic/fluorescent dual-modal lateral flow immunoassay based on multifunctional nanobeads for rapid and accurate SARS-CoV-2 nucleocapsid protein detection

“…However, high requirements for skilled operators and time-consuming steps limit their application for large-scale screening. Compared with these methods, lateral flow immunoassay (LFIA) owns its unique advantages of short reaction time, low-cost detection, portability, and user-friendliness which are suitable for screening, on-site, and rapidity to diagnose SARS-CoV-2 [ 20 , 21 ]. However, the traditional colloidal gold nanoparticles (AuNPs)-based LFIA has poor quantitative ability, high false negative rates and limited sensitive, due to the absence of readout system and the single signal of colorimetric [ [22] , [23] , [24] ].…”