Ultrasensitive Hemoglobin Photothermal Detection Using Stimulated Raman Frequency-Shift Feedback in a Whispering-Gallery-Mode Microbottle

Precise quantification of hemoglobin is critical for clinical diagnostics and biomedical analysis. We present an ultra-sensitive photothermal sensor enhanced by a frequency-shift feedback mechanism based on stimulated Raman scattering. A whispering-gallery-mode (WGM) hollow microbottle serves as a microfluidic channel while simultaneously exciting the Raman signal. The generated Raman signal is frequency-modulated outside the cavity and subsequently reinjected, where it coherently interferes with the intrinsic Raman mode. A photothermal response is induced within the cavity by a 405 nm laser, leading to a shift in the relaxation oscillation frequency of the intrinsic Raman mode. When this frequency approaches the modulation frequency, feedback-induced optical gain yields substantial signal amplification. The system enables rapid, label-free, and ultra-high sensitivity detection, achieving a limit of hemoglobin detection of 9.35×10⁻⁶ g/dL – nearly two orders of magnitude lower than that of wavelength-shift-based photothermal detection methods. It provides a compact and scalable platform for integrated biomedical sensing.