Abstract
Surface-plasmon-resonance (SPR) sensors provide label-free nucleic-acid diagnostics, yet they must detect the sub-nanometre refractive-index changes generated by short HIV-DNA hybridisation. Using a transfer-matrix framework, we design a multilayer architecture that couples a 50 nm silver mirror to the analyte through a 7 nm (10 nm) silicon-nitride spacer capped with a monolayer of WS(2). This impedance-matched stack (Sys(3)) concentrates the evanescent field at the recognition surface while chemically passivating the metal. Numerical screening calibrated with published optical constants predicts an angular sensitivity of 167° RIU(-1), a limit of detection of 2.99 × 10(-5) RIU and a quality factor of 56.9 RIU(-1), outperforming gold-based benchmarks and approaching values reported for more reactive ZnSe buffers. Reversing the dielectric sequence (Sys(4)) increases sensitivity to 201° RIU(-1) but lowers fabrication yield and storage stability, establishing Sys(3) as the most scalable option. Proof-of-concept measurements demonstrate sub-picomolar quantification of HIV DNA in phosphate-buffered saline without enzymatic amplification. The materials palette is compatible with complementary-metal-oxide-semiconductor processes, enabling streamlined integration of high-resolution SPR sensing into point-of-care viral-load platforms for resource-limited settings.