Functionalization Techniques Empowering Optical Fiber Biosensors in Label-Free Cancer Biomarker Detection.

Optical fibers are gaining increasing attention in biomedical applications due to their unique advantages, including flexibility, biocompatibility, immunity to electromagnetic interference, potential for miniaturization, and the ability to perform remote, real-time, and in situ sensing. Label-free optical fiber biosensors represent a promising alternative to conventional cancer diagnostics, offering comparable sensitivity and specificity while enabling real-time detection at ultra-low concentrations without the need for complex labeling procedures. However, the sensing performance of biosensors is fundamentally governed by surface modification. The choice of optimal functionalization strategy is dictated by the sensor type, target biomarker, and detection environment. This review paper presents a comprehensive and expanded overview of various surface functionalization methods specifically designed for cancer biomarker detection using optical fiber biosensors, including silanization, self-assembled monolayers, polymer-based coatings, and different dimensional nanomaterials (0D, 1D, and 2D). Furthermore, the emerging integration of computational methods and machine learning in optimizing functionalized optical sensing has been discussed. To the best of our knowledge, this is the first work that consolidates existing surface modification approaches into a single, cohesive resource, providing valuable insights for researchers developing next-generation fiber optic biosensors for cancer diagnostics. Moreover, the paper points out the current technical challenges and outlines the future perspectives of optical fiber-based biosensors.