Tear-based MMP-9 detection: A rapid antigen test for ocular inflammatory disorders using vanadium disulfide nanowires assisted chemi-resistive biosensor

A sensitive, non-invasive, and biomarker detection in tear fluids for inflammation in potentially blinding eye diseases could be of great significance as a rapid diagnostic tool for quick clinical decisions. In this work, we propose a tear-based MMP-9 antigen testing platform using hydrothermally synthesized vanadium disulfide nanowires. Also, various factors contributing to baseline drifts of the chemiresistive sensor including nanowire coverage on the interdigitated microelectrode of the sensor, sensor response duration, and effect of MMP-9 protein in different matrix solutions were identified. The drifts on the sensor baseline due to nanowire coverage on the sensor were corrected using substrate thermal treatment providing a more uniform distribution of nanowires on the electrode which brought the baseline drift to 18% (coefficient of variations, CV = 18%). This biosensor exhibited sub-femto level limits of detection (LODs) of 0.1344 fg/mL (0.4933 fmoL/l) and 0.2746 fg/ mL (1.008 fmoL/l) in 10 mM phosphate buffer saline (PBS) and artificial tear solution, respectively. For a practical tear MMP-9 detection, the proposed biosensor response was validated with multiplex ELISA using tear samples from five healthy controls which showed excellent precision. This label-free and non-invasive platform can serve as an efficient diagnostic tool for the early detection and monitoring of various ocular inflammatory diseases.

Automated summary

A tear-based MMP-9 antigen testing platform using vanadium disulfide nanowires was proposed as a sensitive and non-invasive diagnostic tool for ocular inflammatory diseases. Various factors contributing to baseline drifts of the chemiresistive sensor were identified and corrected using thermal treatment, resulting in a more uniform distribution of nanowires. The biosensor showed sub-femto level limits of detection in phosphate buffer saline and artificial tear solution and demonstrated excellent precision in detecting tear MMP-9 using multiplex ELISA.