Recent progress in molecular nanotechnology has made it possible to engineer systems that utilize nanoscale interactions to improve biosensing and diagnostic precision. In this study, we introduce a plasmonic nematic film (PNF) that harnesses plasmonic hotspots at the nanoscale to intensify electron disturbances triggered by DNA mutations. Sequence-specific mismatches, particularly point mutations, significantly alter the local electromagnetic environment, leading to distinct and quantifiable spectral shifts in circular dichroism (CD), denoted as Δλdip. These shifts exhibit a strong correlation with target DNA concentration (R2 > 0.99), enabling precise, quantitative detection of mutation-induced asymmetry. The underlying mechanism is modeled by the asymmetric chiral signal Iasy = ∫ΨPNF*(Ω)ΨPNF dV, where ΨPNF is the wave function of the PNF and Ω represents its chiroptical response. Simulations and electric field analyses confirm that DNA mutation-induced perturbations at the PNF-DNA interface significantly boost local field intensity at the resonance wavelength (λ_dip), with minimal impact observed at nonresonant wavelengths. This effect drives more than a 240% increase in the chiroptical signal compared to wild-type DNA, enabling the detection of mutations at concentrations as low as 1534 pg. These results underscore the platform's potential for highly specific detection of clinically important mutations, including those linked to hereditary hearing loss, and provide a foundation for the development of next-generation chiral biosensing technologies.
