High-contrast, fast chemical imaging by coherent Raman scattering using a self-synchronized two-colour fibre laser

Abstract

Coherent Raman scattering (CRS) microscopy is widely recognized as a powerful tool for tackling biomedical problems based on its chemically specific label-free contrast, high spatial and spectral resolution, and high sensitivity. However, the clinical translation of CRS imaging technologies has long been hindered by traditional solid-state lasers with environmentally sensitive operations and large footprints. Ultrafast fibre lasers can potentially overcome these shortcomings but have not yet been fully exploited for CRS imaging, as previous implementations have suffered from high intensity noise, a narrow tuning range and low power, resulting in low image qualities and slow imaging speeds. Here, we present a novel high-power self-synchronized two-colour pulsed fibre laser that achieves excellent performance in terms of intensity stability (improved by 50 dB), timing jitter (24.3 fs), average power fluctuation (<0.5%), modulation depth (>20 dB) and pulse width variation (<1.8%) over an extended wavenumber range (2700–3550 cm⁻¹). The versatility of the laser source enables, for the first time, high-contrast, fast CRS imaging without complicated noise reduction via balanced detection schemes. These capabilities are demonstrated in this work by imaging a wide range of species such as living human cells and mouse arterial tissues and performing multimodal nonlinear imaging of mouse tail, kidney and brain tissue sections by utilizing second-harmonic generation and two-photon excited fluorescence, which provides multiple optical contrast mechanisms simultaneously and maximizes the gathered information content for biological visualization and medical diagnosis. This work also establishes a general scenario for remodelling existing lasers into synchronized two-colour lasers and thus promotes a wider popularization and application of CRS imaging technologies.

Raman-scattering microscopy: Fiber laser reduces the bulk

An extremely stable fiber laser makes the high-resolution imaging technique of coherent Raman scattering (CRS) microscopy more practical for use in hospitals. CRS employs two pulsed laser beams to probe human tissues, providing structural and chemical information without the need for chemical labelling. However, current CRS systems require bulky laser systems that are impractical for clinical use. Now, Thomas Huser at Bielefeld University in Germany, with coworkers in Hong Kong (Kenneth K. Y. Wong) and the USA (Xiaoming Wei), have demonstrated CRS imaging using a compact pulsed fiber laser that provides excellent stability over a wide frequency range. Their system produced fast, high contrast images of living human cells and mouse tissues including the kidney and brain. Moreover, the fiber-based laser beam could easily be connected to other optical imaging systems such as endoscopes, to acquire images inside the body.