Mengzhu Zhang 1 2 3, Jiafeng Shan 2 3, Zhijuan FuYang 1 2 3, Deng Pan 2 3 3, Xuqiang Wu 1 2 3, Benli Yu 1 2 3, Zhiqiang Wang 1 2 3
Sensitive detection of low-abundance biomarkers is crucial for clinical diagnostics and personalized medicine, yet conventional techniques often suffer from limited sensitivity and specificity under high background interference. To overcome this limitation, we developed an ultra-sensitive radio-frequency (RF) biosensor based on a mode-locked fiber laser integrated with a functionalized tilted fiber Bragg grating (TFBG). The TFBG, fabricated by femtosecond laser writing with cylindrical lens beam shaping and functionalized via silanization and protein-A immobilization, simultaneously enables mode-locking through power-dependent loss and serves as an in-cavity sensing element for real-time biomolecular detection. When protein-A on the TFBG binds to target anti-CK17, the local refractive index changes, altering the cavity’s optical path and shifting the laser’s repetition rate. Using precise RF measurement, the system quantifies anti-CK17 concentrations across eight orders of magnitude with a detection limit of 10-12 g/mL and a sensitivity of 40.95 Hz/decade, while maintaining high specificity. These results demonstrate that integrating mode-locked laser technology with optical biosensing provides a robust and versatile platform for high-performance biomarker detection, with significant potential for real-time biomedical diagnostics and rapid, ultra-sensitive disease marker analysis.