Tuberculosis biomarker detection using the intrinsic photoluminescence of carbonated hydroxyapatite nanoparticles

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), classified as one of the main causes of death from infectious diseases in the world. Conventional diagnosis relies on sputum culture, an accurate but time-consuming method that requires specialized infrastructure, highlighting the urgent need for alternative diagnostic approaches. Here, we report the development of an optical nanosensor based on the intrinsic photoluminescence (PL) of carbonated hydroxyapatite nanoparticles (HA NPs) for the detection of the CFP10/ESAT6 protein complex, a typical TB biomarker. The intrinsic PL properties of chemically precipitated HA NPs were optimized by tailoring the density of defect-related emission centers through a combined strategy of carbonate incorporation and thermal treatment, eliminating the need for lanthanide ions doping, organic fluorophores, or secondary luminescent materials. Carbonated HA NPs were functionalized with citrate ions and specific antibodies, as confirmed through morphological, topological, and compositional analyses. Using the PL intensity of the functionalized HA NPs as the signal response, a quenching effect was observed upon interaction with the target molecule, demonstrating that the optical properties of this nanostructured system can be used for detecting molecules of interest. The optimized HA NPs-based biosensor exhibited analytical sensitivity of 0.15 ± 0.02%/(ng/mL), a working range from 300 to 500 ng/mL, and a limit of detection (LOD) of 132 ng/mL within 30 min. While the selectivity assessment was limited to a single negative control protein, these proof-of-concept results demonstrate the potential of intrinsically photoluminescent carbonated HA NPs as a simple, rapid, and label-free optical biosensing platform, without complex architectures, or signal-amplification steps.