Photoelectrochemical IL‑6 Immunoassay Manufactured on Multifunctional Catecholate-Modified TiO2 Scaffolds

There is an increasing interest in using photoelectrochemistry for enhancing the signal-to-noise ratio and sensitivity of electrochemical biosensors. Nevertheless, it remains challenging to create photoelectrochemical biosensors founded on stable material systems that are also easily biofunctionalized for sensing applications. Herein, a photoelectrochemical immunosensor is reported, in which the concentration of the target protein directly correlates to a change in the measured photocurrent. The material system for the photoelectrode signal transducer involves using catecholate ligands to modify the properties of TiO₂ nanostructures in a three-pronged approach of morphology tuning, photoabsorption enhancement, and facilitating bioconjugation. The catecholate-modified TiO₂ photoelectrode is combined with a signal-off direct immunoassay to detect interleukin-6 (IL-6), a key biomarker for diagnosing and monitoring various diseases. Catecholate ligands are added during hydrothermal synthesis of TiO₂ to enable the growth of three-dimensional nanostructures to form highly porous photoelectrodes that provide a three-dimensional scaffold for immobilizing capture antibodies. Surface modification by catecholate ligands greatly enhances photocurrent generation of the TiO₂ photoelectrodes by improving photoabsorption in the visible range. Additionally, catecholate molecules facilitate bioconjugation and probe immobilization by forming a Schiff-base between their -COH group and the -NH₂ group of the capture antibodies. The highest photocurrent achieved herein is 8.89 μA cm^-2, which represents an enhancement by a factor of 87 from unmodified TiO₂. The fabricated immunosensor shows a limit-of-detection of 3.6 pg mL^-1 and a log-linear dynamic range of 2-2000 pg mL^-1 for IL-6 in human blood plasma.