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.
Highlights
Optical imaging techniques have long served as important tools for biomedical applications[1]
Different from prior realizations of synchronized pulse generation typically seeded by noise[20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35], here, the synchronization between the two-colour pulsed laser beams is based on coherent wavelength generation (CWG) with a passive self-stabilization scheme
The laser cavity consists of a short piece of ytterbium-doped fibre (Yb), a drop-in polarization controller (PC) and a fibre-based optically integrated module (OIM) that provides polarization-sensitive isolation, pump/signal multiplexing and signal extraction
Summary
Optical imaging techniques have long served as important tools for biomedical applications[1]. Recent developments in advanced fibre optics have created new opportunities for generating high-quality ultrafast laser pulses and have expanded their application potential[36,37,38,39], including (1) heavy doping of active fibres, enabling high output power per unit length up to hundreds of milliwatts from a centimetre-long active fibre[40,41]; (2) the design of double-cladding fibres (DCFs)[42,43], which allows efficient cladding pumping based on cost-effective multimode fibre-coupled pump laser diodes (MMFPLDs) and creates brightness orders of magnitude higher than the core pumping scheme[44]; (3) fibre chirped-pulse amplification (FCPA) technology[45], which further boosts the energy and the peak power of ultrashort laser pulses by eliminating the detrimental pulse distortion that mainly arises from fibre nonlinearities; and (4) the fabrication of multifunctional hybrid fibre components that reduce the overall complexity of ultrafast fibre lasers and enhance their robustness[46,47] By leveraging these advanced fibre optic technologies, we present a novel high-power, lownoise, self-synchronized two-colour pulsed fibre laser system utilizing coherent wavelength generation (CWG) through cross-phase modulation (XPM)[48]. We demonstrate high-quality CARS and SRS imaging, and other nonlinear imaging modalities without the need for balanced detection, which is otherwise required to cancel laser noise in SRS imaging[32,35], enabling high scan speeds while keeping the complexity of the detection setup low
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