Aptamer-Driven Metal-Enhanced Fluorescence for Highly Sensitive Liver Cancer Biomarker Detection

Complete surgical removal remains the sole curative treatment for liver cancer, underscoring the critical impact of early detection on patient survival rates. Detecting liver cancer at an early stage is pivotal, as it enables timely intervention and improves outcomes. Monitoring the presence of cancer biomarkers in circulation serves as a potential method for early diagnosis. However, the concentration of these biomarkers is typically extremely low. Thus, highly sensitive biosensors capable of detecting these low concentrations are essential.<br/>Here, we utilized metal-enhanced fluorescence (MEF) phenomena for precise analysis of liver cancer biomarkers. This method integrates fluorescence-labeled aptamer molecules with arrays of plasmonic gold (Au) nanostructure. The strategy of the suggested method relies on the change of conformation of the aptamer structure caused by its interaction with biomarkers. This conformational change dynamically adjusts the distance between the fluorophores and the gold nanostructure, modulating the ON/OFF signal of the fluorescence label. To develop this platform, a well-defined Laser interference lithography (LIL) technique and deposition of gold were employed to achieve the desired metallic nanostructure. A strong electromagnetic field was generated by localized surface plasmon resonance (LSPR) phenomena upon interaction with the incident light and gold nanostructures. This electromagnetic field could intensify nearby fluorophores' fluorescence when the distance between the fluorophore and the gold nanostructure is in the range. The systemic performance was optimized by testing various shapes and sizes of the gold nanostructure as well as the lengths of the aptamers. Furthermore, the 5-(and-6)-carboxy-fluorescein (FAM) was also carefully selected as the fluorophore, as it could exhibit strong interaction with the absorbance of a gold nanostructure, ensuring optimal plasmonic coupling and signal enhancement. Given the high sensitivity of our MEF-based aptasensor, we believe our biosensing technology has the potential to significantly advance biomedical research and clinical diagnostics by promoting early detection and personalized treatment strategies for cancer patients.