Real-Time and Highly Sensitive Detection of Matrix Metalloproteinase 9 (MMP-9) in Tears Using Aptamer Functionalized Electrolyte-Gated IGZO Thin-Film Transistors

Dry eye disease (DED) is a common disorder characterized by unstable tear film homeostasis. Its symptoms range from foreign body sensations to pain and fluctuations in visual function. Current diagnostics include physical examination and ocular surface imaging. Matrix metalloproteinase-9 (MMP-9) in tears correlates with clinical signs of DED; however, because of the limited sample volume, quantitative and real-time detection of MMP-9 is a significant need, complicated by the biochemical complexity of tears. We developed an ultrasensitive, real-time MMP-9 sensor based on electrolyte-gated indium-gallium-zinc oxide thin-film transistors (IGZO-EGTFTs), capable of analyzing submicroliter sample volumes. The sensor surface was functionalized at the nanoscale to improve the binding capability of the aptamer, achieving a limit of detection of 1 fg/mL. The sensor demonstrated excellent reproducibility over a dynamic detection range spanning 8 orders of magnitude up to 100 ng/mL (10^-7 g/mL), which was consistent with the clinical range of DED patients. Additionally, the sensing performance remained stable for up to 4 weeks, highlighting its potential for future commercial applications. The MMP-9 concentration in human tear samples could be determined by the developed sensor in real time with high sensitivity, which provides promising diagnostic tools for early detection, progression assessment, and timely treatment of DED.