Nanoparticle modified paper-based analytical sensor for calcium determination in human nasal secretions and its association with olfactory dysfunction

Olfactory dysfunction has emerged as an important clinical issue, particularly following the global rise in post-viral anosmia. Recent research suggests an association between altered calcium homeostasis and poor olfactory signaling, but there is no validated method for assessing calcium levels in nasal secretions. Herein, a novel paper-based electrochemical sensor for the direct determination of free calcium ions in nasal secretions, providing potential diagnostic biomarker in olfactory dysfunction. The sensor integrates multi-walled carbon nanotubes, carbon dots synthesized from guava fruit, and the calcium-selective ionophore ETH 1001 to improve conductivity and selectivity. It exhibits a Nernstian response with a slope of 29.14 ± 0.3 mV/decade over a linear range from 10^-7 to 10^-1 M, and a detection limit of 7.5 × 10^-8 M. The sensor has good consistency, with less than 1 mV fluctuation in potential over 180 days, and strong selectivity against interfering nasal electrolytes. Applied to nasal samples from 166 participants, the sensor demonstrated significantly elevated calcium levels in patients with anosmia compared to healthy controls (7.30 ± 0.004 × 10⁻² M vs. 1.84 ± 0.01 × 10⁻² M, p < 0.05). Compared to existing technologies, the proposed sensor achieves superior sensitivity, broader linearity, and greater pH tolerance.