Label-free multiplexed detection of diabetic retinopathy biomarkers using fiber optic biosensors: Towards lab-in-the-tear

Abstract

Diabetic retinopathy is a common disease in diabetic patients accompanied by such complications as edema, formation of hard exudates, hemorrhages, and eventually vision loss. Detection of the disease at an early stage could increase the effectiveness of therapy and preserve the patient's vision. Measuring the levels of diabetic retinopathy-associated biomarkers using more reliable methods is an alternative and promising way of diagnosis. Optical fiber biosensors have gained rising popularity in providing affordable platforms due to their high-performance capabilities, miniature size, and label-free nature of detection. These properties made them a sensor of choice for developing biosensors for a multiplexed in situ detection of biomarkers in this study. Here, we report an optical fiber-based biosensor that is based on simply fabricated semi-distributed interferometry sensors. After fabrication, sensitive sensors were chosen for further functionalization with two antibodies against biomarkers relevant to diabetic retinopathy to produce biosensors. The detection of the biomarkers was evaluated in artificial tear fluid in static conditions and most importantly in dynamic conditions simulating natural tear flow. This method allowed label-free monitoring of the intensity change with the increasing concentrations of analytes specifically binding on the biosensor surface. Namely, it was possible to detect lipocalin 1 protein with a limit of detection of 5.98 ng/mL and vascular endothelial growth factor down to 26.6 fg/mL. The designed biosensors can become the basis for developing a new method for a clinical diagnosis of eye diseases at early stages of development.