# An Optimized Graphene-Based Surface Plasmon Resonance Biosensor for Detecting SARS-CoV-2
## 1 Introduction  
Biosensors are analytical devices that integrate a biological recognition element with a physical transducer to convert a biological interaction into a measurable signal [1]. These devices are categorized based on their transduction mechanism, including electrochemical [2], optical [3], piezoelectric [3], and thermal [4] types. Optical biosensors, particularly those based on surface plasmon resonance (SPR), have gained significant attention for their ability to perform real-time, label-free detection with high sensitivity [5]. SPR biosensors operate by detecting shifts in the refractive index near the sensor surface, which arise from molecular interactions [6]. This capability makes SPR sensors highly effective for applications in pathogen detection [7], drug discovery [8], and biomolecular interaction [9] studies. The theory of SPR is based on the excitation of surface plasmons [10], or collective oscillations of free electrons, at the interface of a metal (often silver or gold) and a dielectric. When polarized light strikes the metal-dielectric interface at a specific angle, it transfers energy to the surface plasmons, resulting in a reduction in reflected light intensity at that angle. The resonance angle is sensitive to changes in the refractive index near the sensor surface [11], allowing SPR biosensors to monitor molecular binding events quantitatively and in real time. To enhance SPR sensor performance, multilayer architectures incorporating additional materials between the metal layer and the biological recognition layer are often employed. In these configurations, a metal layer, typically silver or gold, is deposited on a prism to initiate SPR. Additional layers, such as dielectrics like silicon nitride (Si\({}_{3}\)N\({}_{4}\)) [12] and two-dimensional (2D) materials like graphene [13], can be incorporated to improve optical characteristics and sensitivity. The metal layer facilitates plasmon excitation, the dielectric modifies the evanescent field to optimize analyte interaction, and the functionalized top layer provides specific binding sites for the target biomolecule. Two-dimensional materials, especially graphene, have shown great potential in biosensing applications. Graphene's atomic-scale thickness, high surface area, excellent conductivity, and tunable chemical properties make it an ideal candidate for enhancing SPR sensors [14]. Graphene can amplify the SPR signal through increased light-matter interaction at the metal-dielectric interface, which improves sensitivity and lowers the detection limit. Moreover, graphene's surface can be functionalized with various biomolecules, allowing for selective binding and detection of specific targets, including viral particles and proteins [15]. In this context, SARS-CoV-2, the causal agent of COVID-19 [16], is a highly transmissible virus characterized by distinct viral proteins and RNA, which serve as biomarkers for detection. Rapid and accurate SARS-CoV-2 detection is critical for managing outbreaks, requiring diagnostic tools that offer sensitivity, specificity, and rapid response. Traditional detection methods, such as RT-PCR [17], have limitations in terms of time and scalability, whereas biosensors, especially those based on SPR, present a promising alternative due to their capacity for real-time detection without extensive sample preparation [18]. In this study, we investigate a multilayer SPR biosensor incorporating graphene and silicon nitride to enable sensitive and specific detection of SARS-CoV-2 across varying concentrations (i.e., 150, 275, 400, and 525 mM [19]). The multilayer architecture is designed to optimize sensor performance by harnessing the unique properties of these materials. Graphene, with its high electron mobility and large surface area, enhances biosensor sensitivity, while silicon nitride contributes structural stability and optical transparency. This biosensor aims to facilitate rapid and accurate SARS-CoV-2 detection, presenting a potential tool for point-of-care diagnostics and epidemiological surveillance.