Fiber-based 1150-nm femtosecond laser source for the minimally invasive harmonic generation microscopy

Abstract

Harmonic generation microscopy (HGM) has become one unique tool of optical virtual biopsy for the diagnosis of cancer and the in vivo cytometry of leukocytes. Without labeling, HGM can reveal the submicron features of tissues and cells in vivo. For deep imaging depth and minimal invasiveness, people commonly adopt 1100- to 1300-nm femtosecond laser sources. However, those lasers are typically based on bulky oscillators whose performances are sensitive to environmental conditions. We demonstrate a fiber-based 1150-nm femtosecond laser source, with 6.5-nJ pulse energy, 86-fs pulse width, and 11.25-MHz pulse repetition rate. It was obtained by a bismuth borate or magnesium-doped periodically poled lithium niobate (MgO:PPLN) mediated frequency doubling of the 2300-nm solitons, generated from an excitation of 1550-nm femtosecond pulses on a large mode area photonic crystal fiber. Combined with a home-built laser scanned microscope and a tailor-made frame grabber, we achieve a pulse-per-pixel HGM imaging in vivo at a 30-Hz frame rate. This integrated solution has the potential to be developed as a stable HGM system for routine clinical use.

Refractive index measurement using single fiber reflectance spectroscopy

“…As described by Zhang et al , n f can be determined from the measured reflected intensity spectra of two compounds with well‐known refractive indices, that is, water and air.…”

Multimodal imaging platform for optical virtual skin biopsy enabled by a fiber-based two-color ultrafast laser source

“…These sources typically include an ultrafast fiber laser emitting femtosecond pulses at a fixed wavelength and then rely on fiber-optic nonlinear techniques to derive ultrafast pulses in the wavelength range of 1150-1350 nm. For example, soliton self-frequency shift in combination with frequency doubling can generate 6.5-nJ, 86-fs pulses at 1150 nm [62] and 32-nJ, 99-fs pulses at 1200 nm [63]. Recently we demonstrated a new approach to generate wavelength widely tunable (>400 nm) and nearly transform-limited femtosecond pulses for NLOM [53,[64][65][66][67].…”

A review of the applications of Raman spectroscopy for breast cancer tissue diagnostic and their histopathological classification of epithelial to mesenchymal transition

“…Even though previous work on gene expression provides important understanding on metabolic changes during EMT in cancer, direct visualization of the relevant metabolites is lacking especially at the single‐cell level. In studies of EMT metabolic changes, important in developing cancer therapy strategies and drug resistance, it is crucial to develop alternative analytical techniques, RS being well‐positioned in this respect. Table S4 (supporting information) reviews key published literature focusing on RS of EMT in cancer, each demonstrating utility of the method.…”