A Portable D-Shaped POF-SPR Sensor Integrated with NanoMIPs for High-Affinity Detection of the SARS-CoV-2 RBD Protein

The rapid and accurate detection of SARS-CoV-2 biomarkers remains a critical requirement for effective outbreak control and decentralized diagnostics. Although RT-PCR is the current gold standard, its reliance on centralized laboratories and long processing times limits its applicability in point-of-care settings. In this context, optical biosensing platforms based on surface plasmon resonance (SPR) offer attractive features, including label-free, real-time, and quantitative detection. This study explores the use of synthetic receptors for the highly sensitive detection of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Specifically, soft molecularly imprinted polymer nanoparticles (nanoMIPs) were employed as synthetic receptors and integrated into a high-sensitivity, portable plasmonic platform based on a D-shaped plastic optical fiber (POF) SPR sensor. The nanoMIPs were selectively imprinted against the RBD, characterized by Dynamic Light Scattering (DLS), Isothermal Titration Calorimetry (ITC), and Scanning Electron Microscopy (SEM) to confirm nanoMIPs size, binding properties, and surface morphology. Next, the nanoMIPs were immobilized onto a gold-coated sensing surface, enabling enhanced specificity, affinity, and signal amplification compared to conventional biological recognition elements. The resulting RBD-SPR-nanoMIPs sensor demonstrated promising analytical performance, exhibiting high selectivity against potentially interfering proteins and an anticipated sensitivity suitable for RBD detection at femtomolar concentrations. The inherent stability of nanoMIPs suggests the potential for reusable SPR sensing platforms, paving the way for next-generation synthetic receptor-based plasmonic biosensors.