Development of a Disposable Chemiresistive Biochip for Tear-Based Retinopathy of Prematurity Diagnosis: Early...

Retinopathy of prematurity (ROP) is a dreadful eye condition and is considered as leading cause of blindness in children around the globe. Lack of timely and appropriate treatment for this ocular condition leads to abnormal development of retinal blood vessels and progression to the severe stage ROP, resulting in irreversible blindness. Based on our previous studies that identified matrix metalloproteinases (MMPs) to be potential tear biomarkers, herein we are demonstrating that the increased levels of MMP-9 in tears can help in ROP risk prediction. A biochip integrated with vanadium disulfide nanowires (VS₂NWs) and resistance measurement circuitry for quantitative analysis of MMPs was established. The biochip fabrication process was optimized using a hybrid central composite design (CCD)-support vector regression (SVR) method resulted in an enhanced signal amplification of the sensor output (ΔR/R). The 30 preterm tear samples (10 healthy, 10 mild ROP and 10 severe ROP) were collected across the neonatal care units, and the tear MMPs were analyzed by the VS₂NW-based biochip and commercial ELISA kits. The VS₂NW biochip showed a similar inclination for the expression of MMP-2 and MMP-9 as seen using the commercial ELISA kits and exhibited an AUC of 0.9778 on the external test set, with 100% sensitivity and 96.67% specificity. This study proved the reliability of the VS₂NW biochip platform to identify ROP tear biomarkers and screen high-risk ROP babies in a quick and non-invasive manner.