Design and Numerical Analysis of a Graphene-Coated SPR Biosensor for Rapid Detection of the Novel Coronavirus

Abstract

In this paper, a highly sensitive graphene-based multiple-layer (BK₇/Au/PtSe₂/Graphene) coated surface plasmon resonance (SPR) biosensor is proposed for the rapid detection of the novel Coronavirus (COVID-19). The proposed sensor was modeled on the basis of the total internal reflection (TIR) technique for real-time detection of ligand-analyte immobilization in the sensing region. The refractive index (RI) of the sensing region is changed due to the interaction of different concentrations of the ligand-analyte, thus impacting surface plasmon polaritons (SPPs) excitation of the multi-layer sensor interface. The performance of the proposed sensor was numerically investigated by using the transfer matrix method (TMM) and the finite-difference time-domain (FDTD) method. The proposed SPR biosensor provides fast and accurate early-stage diagnosis of the COVID-19 virus, which is crucial in limiting the spread of the pandemic. In addition, the performance of the proposed sensor was investigated numerically with different ligand-analytes: (i) the monoclonal antibodies (mAbs) as ligand and the COVID-19 virus spike receptor-binding domain (RBD) as analyte, (ii) the virus spike RBD as ligand and the virus anti-spike protein (IgM, IgG) as analyte and (iii) the specific probe as ligand and the COVID-19 virus single-standard ribonucleic acid (RNA) as analyte. After the investigation, the sensitivity of the proposed sensor was found to provide 183.33°/refractive index unit (RIU) in SPR angle (θ_SPR) and 833.33THz/RIU in SPR frequency (SPRF) for detection of the COVID-19 virus spike RBD; the sensitivity obtained 153.85°/RIU in SPR angle and 726.50THz/RIU in SPRF for detection of the anti-spike protein, and finally, the sensitivity obtained 140.35°/RIU in SPR angle and 500THz/RIU in SPRF for detection of viral RNA. It was observed that whole virus spike RBD detection sensitivity is higher than that of the other two detection processes. Highly sensitive two-dimensional (2D) materials were used to achieve significant enhancement in the Goos-Hänchen (GH) shift detection sensitivity and plasmonic properties of the conventional SPR sensor. The proposed sensor successfully senses the COVID-19 virus and offers additional (1 + 0.55) × L times sensitivity owing to the added graphene layers. Besides, the performance of the proposed sensor was analyzed based on detection accuracy (DA), the figure of merit (FOM), signal-noise ratio (SNR), and quality factor (QF). Based on its performance analysis, it is expected that the proposed sensor may reduce lengthy procedures, false positive results, and clinical costs, compared to traditional sensors. The performance of the proposed sensor model was checked using the TMM algorithm and validated by the FDTD technique.

Keywords: COVID-19; SARS-CoV-2; biosensor; coronavirus; molecular detection; rapid detection; sensor; spike receptor-binding domain; surface plasmon resonance.

Figure 1

Schematic diagram of diagnosis biomarkers: (a) SARS-CoV-2 virus spike protein RBD, (b) IgG or IgM antibodies, and (c) or RNA-oligonucleotides are collected from nasopharyngeal swabs or human blood.

Figure 2

Schematic diagram of the five-layered (Bk₇/Au/PtSe₂/Graphene/PBS) SPR biosensor for diagnosis of SARS-CoV-2 cultured virus; three operating modes are represented to detect the SARS-CoV-2 virus: (a) rapid recognition of whole virus spike RBD with immobilized human mAbs (mAbs as ligand and spike RBD as analyte), (b) rapid recognition of mAbs with immobilized virus spike RBD (spike RBD as ligand and mAbs as analyte), and (c) or recognition of the virus RNA sequence with immobilized probe sequence onto the graphene implicated sensor surface.

Figure 3

Schematic diagram of the possible multi-layer film fabrication process of the proposed SPR sensor for detection of the SARS-Cov-2 virus;—in step 1, the sensor Bk₇/Au/PtSe₂/graphene layers are deposited sequentially, the synthesis technique of PtSe₂ and graphene film are also depicted. In step 2, the ligands;—(a) mAbs, (b) spike RBD, and (c) probe oligo are immobilized with the graphene layer through PBSE.

Figure 4

FDTD simulation schematic for the proposed SPR sensor.

Figure 5

Schematic diagram of: (a) SPR and (b) SPRF curve characteristics of Bk₇/Au(50 nm)/PtSe₂(2 nm)/Graphene(1.7 nm)/PBS (RI = 1.3348) layered model with variation in incident light wavelength $\left({\lambda }_{light}\right)$.

Figure 6

Schematic diagram of (a) SPR and (b) SPRF curve characteristics of the Bk₇/Au(50 nm)/PtSe₂(2 nm)/Graphene (1.7 nm) sensor with other conventional sensors with PBS analyte (RI = 1.3348).

Figure 7

Schematic diagram of (a) SPR and (b) SPRF curve characteristics of Bk₇/Au(50 nm)/PtSe₂(2 nm)/Graphene (0.34 nm × L) coated sensor reflectance and transmittance spectra with the thickness of the graphene layers (L = 0, 1, …, 5) before adsorption of the analyte.

Figure 8

The Schematic of: (a) SPR, and (b) SPR sensorgram absorption curve.

Figure 9

The schematic of (a) the angle of incidence, and (b) the electric field intensity as a function of normal distance from the interface for (i) three-layer, (ii) four-layer, and (iii) five-layer SPR sensor configuration.

Figure 10

Schematic diagram of: (a) SPR and (b) SPRF characteristics of Bk₇/Au(50 nm)/PtSe₂(2 nm)/Graphene(1.7 nm) substrates with immobilized IgG (H014 or S309) as ligand and different concentration levels of SARS-CoV-2 spike RBDs (concentration of 1.953125 nM to 62.5 nM) as the analyte.

Figure 11

Schematic diagram of (a) SPR and (b) SPRF characteristics of Bk₇/Au(50 nm)/PtSe₂(2 nm)/Graphene(1.7 nm) substrates with immobilized SARS-CoV-2 spike RBDs as the ligand and different concentration levels of IgG-H014 (concentration of 1.74 nM to 27.8 nM) as the analyte.

Figure 12

Schematic diagram of (a) SPR and (b) SPRF curve characteristics of Bk₇/Au(50 nm)/PtSe₂(2 nm)/Graphene (0.34 nm × L) substrates without probe (sh-Oligo), with sh-Oligo and different concentrated levels of oligonucleotide (wt or mr type) binding for recognition of SARS-Cov-2 virus RNA. ${\theta }_{SPR}$ angle and SPRF shift right due to binding with oligonucleotides.