Light-driven biosensor for the rapid and selective detection of hypoxia-inducible factor-prolyl hydroxylase domain inhibitors in aqueous media and saliva

Abstract

Hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHI) are to increase the production of EPO and haemoglobin in patients with chronic kidney disease. HIF inhibitors such as Molidustat and Vadadustat are used as doping agents in racing sports. We present new sensitive and selective materials for the biosensing of Molidustat and Vadadustat in aqueous solution and saliva. Plasmonic nickel foam was synthesised using a reproducible chemical method that deposits forests of closely packed cauliflower-shaped gold nanostructures on the nickel surface. The plasmonic material showed a high enhancement factor of Raman signals (1.09 × 10⁷). Therefore, it was used as a sensor for the detection of HIF inhibitors by surface-enhanced Raman spectroscopy (SERS). A target-specific extractor chip for HIF-PHI was fabricated by functionalising the plasmonic nickel foam with prolyl hydroxylase domain-containing protein 2 (PHD2) molecules. The surface functionalisation was carried out by a green synthesis process that utilises deep UV LED light to convert the PHD2 molecule into a bio-thiol that attaches to the plasmonic nickel foam via Au–S bonds. Using the new SERS sensor and extractor chip, Molidustat and Vadadustat were quantified in aqueous solution down to 0.01 µg/L. The new materials were also utilised for the rapid screening of HIF-PHI in spiked saliva samples. The new materials and light-driven surface functionalisation process can be easily adopted to develop new screening methods for multiple biomolecules (e.g. drugs, proteins, disease biomarkers, environmental toxins) for many applications (e.g. therapeutic drug monitoring, doping control, clinical diagnostics environmental monitoring).

Graphical Abstract