Thomas Gottschall

Alignment-free, all-spliced fiber laser source for CARS microscopy based on four-wave-mixing

An environmentally-stable low-repetition rate fiber oscillator is developed to produce narrow-bandwidth pulses with several tens of picoseconds duration. Based on this oscillator an alignment-free all-fiber laser for multi-photon microscopy is realized using in-fiber frequency conversion based on four-wave-mixing. Both pump and Stokes pulses for coherent anti-Stokes Raman scattering (CARS) microscopy are readily available from one fiber end, intrinsically overlapped in space and time, which drastically simplifies the experimental handling for the user. The complete laser setup is mounted on a home-built laser scanning microscope with small footprint. High-quality multimodal microscope images of biological tissue are presented probing the CH-stretching resonance of lipids at an anti-Stokes Raman-shift of 2845 cm(-1) and second-harmonic generation of collagen. Due to its simplicity, compactness, maintenance-free operation, and ease-of-use the presented low-cost laser is an ideal source for bio-medical applications outside laser laboratories and in particular inside clinics.

Expanding Multimodal Microscopy by High Spectral Resolution Coherent Anti-Stokes Raman Scattering Imaging for Clinical Disease Diagnostics

Over the past years fast label-free nonlinear imaging modalities providing molecular contrast of endogenous disease markers with subcellular spatial resolution have been emerged. However, applications of these imaging modalities in clinical settings are still at the very beginning. This is because single nonlinear imaging modalities such as second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) have only limited value for diagnosing diseases due to the small number of endogenous markers. Coherent anti-Stokes Raman scattering (CARS) microscopy on the other hand can potentially be added to SHG and TPEF to visualize a much broader range of marker molecules. However, CARS requires a second synchronized laser source and the detection of a certain wavenumber range of the vibrational spectrum to differentiate multiple molecules, which results in increased experimental complexity and often inefficient excitation of SHG and TPEF signals. Here we report the application of a novel near-infrared (NIR) fiber laser of 1 MHz repetition rate, 65 ps pulse duration, and 1 cm(-1) spectral resolution to realize an efficient but experimentally simple SGH/TPEF/multiplex CARS multimodal imaging approach for a label-free characterization of composition of complex tissue samples. This is demonstrated for arterial tissue specimens demonstrating differentiation of elastic fibers, triglycerides, collagen, myelin, cellular cytoplasm, and lipid droplets by analyzing the CARS spectra within the C-H stretching region only. A novel image analysis approach for multispectral CARS data based on colocalization allows correlating spectrally distinct pixels to morphologic structures. Transfer of this highly precise but compact and simple to use imaging approach into clinical settings is expected in the near future.

Energetic sub-2-cycle laser with 216 W average power.

Few-cycle lasers are essential for many research areas such as attosecond physics that promise to address fundamental questions in science and technology. Therefore, further advancements are connected to significant progress in the underlying laser technology. Here, two-stage nonlinear compression of a 660 W femtosecond fiber laser system is utilized to achieve unprecedented average power levels of energetic ultrashort or even few-cycle laser pulses. In a first compression step, 408 W, 320 μJ, 30 fs pulses are achieved, which can be further compressed to 216 W, 170 μJ, 6.3 fs pulses in a second compression stage. To the best of our knowledge, this is the highest average power few-cycle laser system presented so far. It is expected to significantly advance the fields of high harmonic generation and attosecond science.

Fiber-based source for multiplex-CARS microscopy based on degenerate four-wave mixing

We present a fiber-based laser source for multiplex coherent anti-Stokes Raman scattering (CARS) microscopy. This source is very compact and potentially alignment-free. The corresponding pump and Stokes pulses for the CARS process are generated by degenerate four-wave mixing (FWM) in photonic-crystal fibers. In addition, an ytterbium-doped fiber laser emitting spectrally narrow 100 ps pulses at 1035 nm wavelength serves as pump for the FWM frequency conversion. The FWM process delivers narrow-band pulses at 648 nm and drives a continuum-like spectrum ranging from 700 to 820 nm. With the presented source vibrational resonances with energies between 1200 cm-1 and 3200 cm-1 can be accessed with a resolution of 10 cm-1. Additionally, the temporal characteristics of the FWM output have been investigated by a cross-correlation setup, revealing the suitability of the emitted pulses for CARS microscopy. This work marks a significant step towards a simple and powerful all-fiber, maintenance-free multiplex-CARS source for real-world applications outside a laboratory environment.

A compact microscope setup for multimodal nonlinear imaging in clinics and its application to disease diagnostics

The past years have seen increasing interest in nonlinear optical microscopic imaging approaches for the investigation of diseases due to the methods unique capabilities of deep tissue penetration, 3D sectioning and molecular contrast. Its application in clinical routine diagnostics, however, is hampered by large and costly equipment requiring trained staff and regular maintenance, hence it has not yet matured to a reliable tool for application in clinics. In this contribution implementing a novel compact fiber laser system into a tailored designed laser scanning microscope results in a small footprint easy to use multimodal imaging platform enabling simultaneously highly efficient generation and acquisition of second harmonic generation (SHG), two-photon excited fluorescence (TPEF) as well as coherent anti-Stokes Raman scattering (CARS) signals with optimized CARS contrast for lipid imaging for label-free investigation of tissue samples. The instrument combining a laser source and a microscope features a unique combination of the highest NIR transmission and a fourfold enlarged field of view suited for investigating large tissue specimens. Despite its small size and turnkey operation rendering daily alignment dispensable the system provides the highest flexibility, an imaging speed of 1 megapixel per second and diffraction limited spatial resolution. This is illustrated by imaging samples of squamous cell carcinoma of the head and neck (HNSCC) and an animal model of atherosclerosis allowing for a complete characterization of the tissue composition and morphology, i.e. the tissues morphochemistry. Highly valuable information for clinical diagnostics, e.g. monitoring the disease progression at the cellular level with molecular specificity, can be retrieved. Future combination with microscopic probes for in vivo imaging or even implementation in endoscopes will allow for in vivo grading of HNSCC and characterization of plaque deposits towards the detection of high risk plaques.

Fiber-based optical parametric oscillator for high resolution coherent anti-Stokes Raman scattering (CARS) microscopy

Imaging based on coherent anti-Stokes Raman scattering (CARS) relies on the interaction of high peak-power, synchronized picosecond pulses with narrow bandwidths and a well-defined frequency difference. Recently a new type of fiber-based CARS laser source based on four-wave-mixing (FWM) has been developed. In order to enhance its spectral resolution and efficiency, a FWM based fiber optical parametric oscillator (FOPO) is proposed in this work. The source delivers 180 mW with 5.6 kW peak power for the CARS pump and 130 mW with 2.9 kW peak power for the Stokes signal. CARS resonances around 2850 and 2930 cm(-1) can be resolved with a resolution of 1 cm(-1) enabling high-contrast, spectrally resolved CARS imaging of biological tissue.

Degenerate optical parametric amplifier delivering sub 30 fs pulses with 2GW peak power

Degenerated optical parametric amplification (OPA) is a well known technique to achieve broadband amplification necessary to generate ultrashort pulses. Here we present a parametric amplifier pumped by the frequency doubled output of a state-of-the-art fiber chirped pulse amplification system (FCPA) delivering mJ pulse energy at 30 kHz repetition rate and 650 fs pulse duration. The parametric amplifier and the FCPA system are both seeded by the same Yb:KGW oscillator. Additional spectral broadening of the OPA seed provides enough bandwidth for the generation of ultrashort pulses. After amplification in two 1mm BBO crystals a pulse energy of 90 microJ is yielded at 30 kHz. Subsequent compression with a sequence of chirped mirrors shortens the pulses to 29 fs while the pulse energy is as high as 81 microJ resulting in 2GW of peak power.

A 325-W-Average-Power Fiber CPA System Delivering Sub-400 fs Pulses

A high-average-power Yb-doped fiber chirped-pulse amplification system is presented. Compressed average power of 325 W at 40 MHz repetition rate corresponding to 8.2 muJ pulse energy is extracted. Compression in a highly efficient dielectric-grating-based compressor yields pulses as short as 375 fs, resulting in 22 MW of peak power.

Four-wave-mixing-based optical parametric oscillator delivering energetic, tunable, chirped femtosecond pulses for non-linear biomedical applications.

A novel concept for an optical parametric oscillator based on four-wave mixing (FOPO) in an optical fiber is presented. This setup has the ability of generating highly chirped signal and idler pulses with compressed pulse durations below 600 fs and pulse energies of up to 250 nJ. At a fixed pump wavelength of 1040 nm, the emerging signal and idler wavelengths can be easily tuned between 867 to 918 nm and 1200 to 1300 nm, respectively, only by altering the cavity length. With compressed peak powers >100 kW and a repetition rate of only 785 kHz, this source provides tunable intense ultra-short pulses at moderate average powers. This setup constitutes a stable, simple and in many ways superior alternative to bulk state-of-the-art OPO light converters for demanding biomedical applications and non-linear microspectroscopy.

Long-term stabilization of high power optical parametric chirped-pulse amplifiers

The long-term stability of optical parametric chirped-pulse amplifiers is hindered by thermal path length drifts affecting the temporal pump-to-signal overlap. A kilowatt-pumped burst amplifier is presented delivering broadband 1.4 mJ pulses with a spectral bandwidth supporting sub-7 fs pulse duration. Active temporal overlap control can be achieved by feedback of optical timing signals from cross-correlation or spectral measurements. Using a balanced optical cross-correlator, we achieve a pump-to-signal synchronization with a residual jitter of only (46 ± 2) fs rms. Additionally, we propose passive pump-to-signal stabilization with an intrinsic jitter of (7.0 ± 0.5) fs rms using white-light continuum generation.