Diagnosis of disease at an early, curable, and reversible stage allows more conservative treatment and better patient outcomes. Fluorescence biosensing is a widely used method to detect biomarkers, which are early indicators of disease. Importantly, biosensing requires a high level of sensitivity. Traditionally, these sensors use antibodies or enzymes as biorecognition molecules; however, these can lack the specificity required in a clinical setting, limiting their overall applicability. Aptamers are short, single stranded nucleotides that are receiving increasing attention over traditional recognition molecules. These exhibit many advantages, such as high specificity, making them promising for ultrasensitive biosensors. Metal enhanced fluorescence (MEF) utilizes plasmonic materials, which can increase the sensitivity of label-based fluorescent biosensors. The fluorescence enhancement achieved by placing metallic nanostructures in close proximity to fluorophores allows for detection of ultra-low biomarker concentrations. Plasmonic biosensors have been successfully implemented as diagnostic tools for a number of diseases, such as cancer, yet reproducible systems exhibiting high specificity and the ability to multiplex remain challenging. Similarly, while aptasensors have been extensively reported, few systems currently incorporate MEF, which could drastically improve biosensor sensitivity. Here, we review the latest advancements in the field of aptamer biosensing based on MEF that have been explored for the detection of a wide variety of biological molecules. While this emerging biosensing technology is still in its infant stage, we highlight the potential challenges and its clinical potential in early diagnosis of diseases.
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