Development and application of novel fibre-based laser sources for coherent Raman based bio-imaging

Abstract

Early and accurate detection of cancerous tissue is key to increasing patient survival rates. Spontaneous Raman spectroscopy could potentially provide a useful imaging tool for that purpose, as it is a vibrational finger-printing technique with a highly chemically specific signal. It is, however, characterised by a very low signal-to-noise ratio which makes it unsuitable for rapid microscopic imaging as required in biomedical applications. This can be overcome by using nonlinear techniques based on Raman scattering such as Coherent AntiStokes Raman Scattering (CARS) and Stimulated Raman Scattering (SRS), making them increasingly applicable to medical diagnostic imaging.

Coherent Raman Scattering (CRS) techniques require synchronized, multi-wavelength laser sources. Such sources can be provided by fibre-based supercontinuum (SC) generation, which allows multiple vibration frequencies to be addressed and thus helps increase chemical specificity. However, commercially available fibre-based broadband sources currently have quite low Power Spectral Density (PSD) levels. In this work, coherent SC generation from fibres has been investigated in order to overcome this problem. The investigation has been conducted across wide parameter space for two fibre types: a Central Glass and Ceramic Research Institute (CGCRI) manufactured fibre (exhibiting both normal and anomalous dispersion), and a NKT-1050-NEG1 fibre (All Normal Dispersion [ANDi] profile). The SC output from the fibres was then compared with results from a NKT femtoWHITE CARS fibre. It was found that for the CGCRI fibre an optimal length of 17 mm gave a tailored spectral profile spread over 200 nm. The NKT ANDi fibre on the other hand resulted in 200 nm broadening after propagation along 85 mm of fibre. The spectra from both fibres had higher PSD in the required spectral ranges than the femtoWHITE CARS fibre.

Using NKT ANDI output, a hyperspectral CARS imaging system has been developed, and successfully used for imaging of animal tissue also enabling other concurrent modalities, such as SHG or TPEF. The acquisition time for these images was comparable or better than sources 7 currently used by the bioimaging community, at the same time providing significant technological improvements, stepping closer toward ultimate goal of the use of fibre-based sources in clinical environment.

To investigate potential low-cost multi extension to that setup, enabling efficient fs multiphoton TPEF imaging over a broadband range, the Supercontinuum has been compressed using a prism-based system, using the intensity of the Second Harmonic Generation (SHG) generated with BaTiO2 crystal as a metric of compression of the SC pulse. The registered signal intensity has been compared with the benchmark of a Ti:Sapph 100 fs laser oscillator.

In total, therefore, a robust fibre-based broadband laser source has been designed, optimised, characterized and applied for hyperspectral, multimodal imaging

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Identifiers

ORCID for Jonathan HV Price: orcid.org/0000-0003-0256-9172

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