Abstract
Accurate and noninvasive detection of cancer cells is critical for advancing early stage cancer diagnostics and monitoring tumor progression. While manual enumeration methods, such as hemocytometry, remain in use, they suffer from limited sensitivity and scalability. In this article, we report the first feasibility study demonstrating a graphene oxide (GO)-functionalized long-period fiber grating (LPG) sensor for the label-free detection of MCF-7 human breast cancer cell density via secreted cellular byproducts. The sensing mechanism is based on refractive index (RI) modulation in the culture medium, where the GO overlay serves as a functional interface to enhance light-matter interaction and mode coupling between the LPG device and the external medium. GO nanocoatings were deposited on the device surface via an in situ layer-by-layer (i-LbL) assembly method and characterized using scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman spectroscopy. Furthermore, by precisely controlling the thickness of the GO nanocoating, we experimentally investigated the impact of the GO thickness on the optical properties, revealing distinct thickness-dependent behavior. Resonance changes correlated clearly with metabolite accumulation, thus enabling indirect detection of cancer cell density. The GO-LPG sensor demonstrated detection of MCF-7 cell densities ranging from 0 to 1 × 10(5) cells/mL, achieving ultrahigh sensitivity with a limit of detection (LOD) as low as 270 cells/mL. This GO-functionalized fiber optic configuration offers significant potential as a real-time, label-free, and noninvasive bionanophotonic platform for cancer diagnostics and metabolic sensing in complex biological environments.