Widely-tunable synchronisation-free picosecond laser source for multimodal CARS, SHG, and two-photon microscopy

Abstract

We demonstrate a continuous wave (CW) seeded synchronization-free optical parametric amplifier (OPA) pumped by a picosecond, 1 µm laser and show its performance when used as a simple yet powerful source for label-free coherent anti-Stokes Raman scattering (CARS), concurrent second harmonic generation (SHG), and two-photon fluorescence microscopy in an epi-detection geometry. The average power level of above 175 mW, spectral resolution of 8 cm −1 , and 2 ps pulse duration are well optimized for CARS microscopy in bio-science and bio-medical imaging systems. Our OPA is a much simpler setup than either the “gold-standard” laser and optical parametric oscillator (OPO) combination traditionally used for CARS imaging, or the more recently developed OPA systems pumped with femtosecond pulses [1]. Rapid and accurate tuning between resonances was achieved by changing the poled channels and temperature of the periodically-poled lithium niobate (PPLN) OPA crystal together with the OPA seed wavelength. The Pump-Stokes frequency detuning range fully covered the C-H stretching band used for the imaging of lipids. By enabling three multiphoton techniques using a compact, synchronization free laser source, our work paves the way for the translation of label-free multi-photon microscopy imaging from biomedical research to an imaging based diagnostic tool for use in the healthcare arena.

Towards quantum-enhanced Raman spectroscopy for bioimaging applications

“…Frequency-doubled picosecond pulses will then pump two travelingwave optical parametric amplifiers (OPAs), one of them generating the Raman pump for the SRS. This way, the system will be made synchronization-free and simpler than typical Raman setups [15]. The other OPA, seeded by the fundamental pulses, will produce amplitude-squeezed light at 1064 nm, further used as the Raman probe.…”

Two-Photon Absorption: An Open Door to the NIR-II Biological Window?

“…Yang et al demonstrated 2P NIR-II imaging by using a multicolour ultrafast OPO source (Yang et al, 2013), where brain tissues of a tdTomato-expressing mouse were imaged with 2PE at 1070 nm (Section 3.2, Table 3). Xu et al have developed a periodically poled lithium niobate OPA system operating at 2-ps pulse duration (Xu et al, 2021). In their work, imaging at a depth of 40 μm was achieved in both label-free coherent anti-Stokes Raman scattering (CARS) and 2PE based imaging of mitochondrial flavin adenine dinucleotide autofluorescence in tissue samples.…”