Electron Perturbation for Chiral DNA Point Mutation

Advances in molecular nanotechnology have enabled the design of systems that exploit nanoscale interactions for enhanced biosensing and diagnostics. Here, we present a plasmonic nematic film (PNF) that leverages nanoscale plasmonic hotspots to amplify electron perturbations induced 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 Δλ_dip. These shifts exhibit a strong correlation with target DNA concentration (<i>R</i>² > 0.99), enabling precise, quantitative detection of mutation-induced asymmetry. The underlying mechanism is modeled by the asymmetric chiral signal <i>I</i>_asy = ∫Ψ_PNF*(Ω)Ψ_PNF d<i>V</i>, where Ψ_PNF is the wave function of the PNF and Ω represents its chiroptical response. Simulations and electric field analysis further validate that mutation-driven perturbations at the PNF-DNA interface enhance local field intensity at λ_dip, while no significant changes occur at nonresonant wavelengths. Through this mechanism, the PNF platform achieves over 240% enhancement in chiroptical signal compared to wild-type DNA and enables mutation detection down to 1534 pg. These findings highlight the system's potential for high-specificity diagnostics of clinically relevant mutations, including those associated with hereditary hearing impairment, and may inform the development of future chiral biosensing platforms.