Abstract
Tumor cells release biomarkers, such as CD44, into circulation, offering a minimally invasive window into tumor biology. However, conventional analytical methods often lack the sensitivity and dynamic range needed to detect these markers reliably in complex biological samples. Here, we exploit graphene oxide-coated semi-distributed interferometry to fabricate an optical fiber biosensor for sensitive CD44 detection. To establish the proof-of-concept, we focus on CD44 because of its well-established role as a circulating biomarker in breast cancer. We functionalize the sensor surface with anti-CD44 antibodies, confirm successful biofunctionalization and antibody specificity through complementary surface characterization and immunological assays, and optimize the platform to achieve a wide dynamic range and a limit of detection of 175 aM. Validation using clinical serum samples from breast cancer patients demonstrated a higher signal for cancer patients than for the healthy group, while successful detection of soluble CD44 in urine further demonstrated the biosensor's compatibility with multiple biological matrices. These findings establish the graphene oxide-coated semi-distributed interferometric biosensor as a highly sensitive platform for CD44 detection in clinically relevant samples. The demonstrated performance, together with the adaptability of the underlying SDI sensing architecture, highlights its potential for future development toward the detection of other circulating biomarkers.