Quasi-random interferometric optical fiber biosensor for label-free quantitative detection of CD44-expressing cancer cells

The use of whole cancer cells as a biomarker, as opposed to smaller analytes such as proteins, is essential for advancing diagnostic tools. In this work, a quasi-random interferometer-based optical fiber biosensor is proposed for the quantitative, label-free, and real-time detection of CD44-expressing cancer cells. The sensor is low-cost, easy to fabricate, and able to distinguish cancer cells from normal cells based on CD44 expression levels and local refractive index changes. A weak interferometric cavity at the fiber tip is responsible for the quasi-random reflection pattern, where refractive index changes induced by cell binding modulate the reflected signal in concentration-dependent manner. Quantitative analysis demonstrated a limit of detection of 48.8 cells/mL and a sensitivity of 1.1 dB/10x for the breast cancer HCC1806 cell line with high level of CD44 expression. The sensor successfully stratified cells from breast and colorectal cancers and demonstrated high specificity by clearly distinguishing cancerous cells from normal kidney epithelial cells. This work contributes to the development of biosensing platforms for whole-cell detection based on phenotypic markers, offering a simple and reproducible approach suitable for integration into microfluidic and future clinical diagnostic systems.