Tear-Based Electrochemical Sensor for Detecting Complement III Protein Using Indium-Doped Zinc Oxide Nanofibers With Superior Dielectric Properties

The development of biomarker-based diagnostic devices is undoub-tedly changing the healthcare sector and reshaping clinical trial designs for disease prediction and therapeutic guidance. Age-related macular degeneration (AMD) is a chronic eye disease for ageing adults, which severely affects their vision, and the damage is irreversible. The use of tears for noninvasive sampling to quickly diagnose ocular diseases has always been appealing. In this work, we aim to deliver a noninvasive complement component III (C3) biomarker-based electrochemical biosensor for early diagnosis of AMD using human tears. Here, indium zinc oxide (InZnO) nanofibers are used as a biotransducing element, where ZnO is an n-type semiconductor with a wide band gap of 3.35–3.37 eV, and the incorporation of a group III element, i.e., indium, is used to improve its free charge carrier concentration. The conduction mechanism in the InZnO nanofibers is investigated through a dielectric study, unveiling that conduction depends on both frequency and temperature. Furthermore, the electrochemical biosensor was constructed by immobilizing the monoclonal anti-C3 antibody on the InZnO nanofiber using a suitable linker. The biosensor was calibrated by spiking a wide range of C3 protein concentrations from 50 pg/mL to 5
$\mu$
g/mL in an artificial tears matrix and capturing the electrochemical response using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV) techniques. The developed InZnO-based electrochemical biosensor response was also validated by testing the C3 protein in human tears from three healthy adults.