Xeno Nucleic Acid Nanosensors for Enhanced Stability Against Ion-Induced Perturbations

The omnipresence of salts in biofluids creates a pervasive challenge in designing sensors suitable for in vivo applications. Fluctuations in ion concentrations have been shown to affect the sensitivity and selectivity of optical sensors based on single-walled carbon nanotubes wrapped with single-stranded DNA (ssDNA–SWCNTs). We herein observe fluorescence wavelength shifting for ssDNA–SWCNT-based optical sensors in the presence of divalent cations at concentrations above 3.5 mM. In contrast, no shifting was observed for concentrations up to 350 mM for sensors bioengineered with increased rigidity using xeno nucleic acids (XNAs). Transient fluorescence measurements reveal distinct optical transitions for ssDNA- and XNA-based wrappings during ion-induced conformation changes, with XNA-based sensors showing increased permanence in conformational and signal stability. This demonstration introduces synthetic biology as a complementary means for enhancing nanotube optoelectronic behavior, unlocking previously unexplored possibilities for developing nanobioengineered sensors with augmented capabilities.