Few-cycle THz wave manipulation with a high degree of freedom via f-t modulation.

THz waves have been intensively applied in many fields, e.g., spectroscopy, imaging, and communications. However, owing to the rarity of available techniques for manipulating circularly polarized few-cycle THz waves on picosecond time scales, most of the current studies are conducted with linearly polarized THz waves. Here we demonstrate circularly polarized (CP) THz (dual) pulses generated by a polarization-twisting pulse/dual pulse (PTP/PTDP). The polarization-twisting optical dual pulses can be generated via a modified Michelson interferometer (MI) system, which provides the ability to control the frequency, helicity, and time interval of the dual pulses arbitrarily and individually. Such a novel, to the best of our knowledge, modulation technique shows huge potential for applications, not only in imaging and spectroscopy but also in next-generation communications.

Time-course quantitative mapping of caffeine within the epidermis, using high-contrast pump-probe stimulated Raman scattering microscopy.

BACKGROUND: An assessment of the drug penetration and distribution profiles within the skin is essential in dermatology and cosmetology. Recent advances in label-free imaging technologies have facilitated the direct detection of unlabeled compounds in tissues, with high resolution. However, it remains challenging to provide quantitative time-course distribution maps of drugs within the complex skin tissue. The present study aims at acquiring the real-time quantitative skin penetration profiles of topically applied caffeine, by means of a combination of pump-probe phase-modulated stimulated Raman scattering (PM-SRS) and confocal reflection microscopy. The recently developed PM-SRS microscopy is a unique imaging tool that can minimize strong background signals through a pulse-shaping technique, while providing high-contrast images of small molecules in tissues. MATERIALS AND METHODS: Reconstructed human skin epidermis models were used in order to analyze caffeine penetration in tissues. The penetration profiles of caffeine in an aqueous solution, an oil-in-water gel, and a water-in-oil gel were examined by combining PM-SRS and confocal reflection microscopy. RESULTS: The characteristic Raman signal of caffeine was directly detected in the skin model using PM-SRS. Integrating PM-SRS and confocal reflection microscopy allowed real-time concentration maps of caffeine to be obtained from formulation samples, within the skin model. Compared with the conventional Raman detection method, PM-SRS lowered the background tissue-oriented signals and supplied high-contrast images of caffeine. CONCLUSION: We successfully established real-time skin penetration profiles of caffeine from different formulations. PM-SRS microscopy proved to be a powerful, non-invasive, and real-time depth-profile imaging technique for use in quantitative studies of topically applied drugs.

Label-free skin penetration analysis using time-resolved, phase-modulated stimulated Raman scattering microscopy.

Skin penetration analysis of topically applied drugs or active compounds is essential in biomedical applications. Stimulated Raman scattering (SRS) microscopy is a promising label-free skin penetration analysis tool. However, conventional SRS microcopy suffers from limited signal contrast owing to strong background signals, which prevents its use in low-concentration drug imaging. Here, we present a skin penetration analysis method of topical agents using recently developed phase-modulated SRS (PM-SRS) microscopy. PM-SRS uses phase modulation and time-resolved signal detection to suppress both nonlinear background signals and Raman background signals from a tissue. A proof-of-concept experiment with a topically applied skin moisturizing agent (ectoine) in an in vitro skin tissue model revealed that PM-SRS with 1.7-ps probe delay yields a signal contrast 40 times higher than that of conventional amplitude-modulated SRS (AM-SRS). Skin penetration measurement of a topical therapeutic drug (loxoprofen sodium) showed that the mean drug concentration at the tissue surface layer after 240 min was 47.3 ± 4.8 mM. The proposed PM-SRS microscopy can be employed to monitor the spatial and temporal pharmacokinetics of small molecules in the millimolar concentration regime.

Femtosecond X-ray spectroscopy of haem proteins.

We discuss our recently reported femtosecond (fs) X-ray emission spectroscopy results on the ligand dissociation and recombination in nitrosylmyoglobin (MbNO) in the context of previous studies on ferrous haem proteins. We also present a preliminary account of femtosecond X-ray absorption studies on MbNO, pointing to the presence of more than one species formed upon photolysis.

Generation and manipulation of polarization-twisting dual pulses with a high degree of freedom.

A polarization-twisting dual-pulse (PTDP) system is demonstrated using a modified Michelson interferometer (MI), in which a pellicle beam splitter is inserted into each arm. By tuning the positions of the end mirrors and pellicle beam splitters in the MI, the polarization-twisting frequency, the helicity, and the interval between two pulses can be individually manipulated. This PTDP generation system has a high degree of freedom in terms of tuning and has applications in the study of helicity dynamics in quantum matter, particularly in the terahertz (THz) regime.

Femtosecond X-ray emission study of the spin cross-over dynamics in haem proteins.

In haemoglobin the change from the low-spin (LS) hexacoordinated haem to the high spin (HS, S = 2) pentacoordinated domed deoxy-myoglobin (deoxyMb) form upon ligand detachment from the haem and the reverse process upon ligand binding are what ultimately drives the respiratory function. Here we probe them in the case of Myoglobin-NO (MbNO) using element- and spin-sensitive femtosecond Fe Kα and Kß X-ray emission spectroscopy at an X-ray free-electron laser (FEL). We find that the change from the LS (S = 1/2) MbNO to the HS haem occurs in ~800 fs, and that it proceeds via an intermediate (S = 1) spin state. We also show that upon NO recombination, the return to the planar MbNO ground state is an electronic relaxation from HS to LS taking place in ~30 ps. Thus, the entire ligand dissociation-recombination cycle in MbNO is a spin cross-over followed by a reverse spin cross-over process.

Polarization envelope helicity dependent photovoltage in GaAs/Al0.3Ga0.7As modulation-doped quantum well.

In this study, we demonstrate the switching of the direction of the photocurrent in an n-type GaAs/Al0.3Ga0.7As modulation-doped quantum well using a polarization pulse-shaping apparatus containing a 4f setup. The right- and left-polarization-twisting pulses with a polarization rotation frequency in the THz-regime are incident on a modulation-doped quantum well. The results show that the sign of the photovoltage is dependent on the direction of rotation of the polarization-twisting pulses, which can be explained by the circular photogalvanic effect combined with the production of a classical edge photocurrent from the acceleration of free electrons in the vicinity of the sample edge by the incident optical electric field. The wide range over which the polarization-rotation frequency may be tuned makes this method a powerful tool to investigate the response of an extensive variety of materials in the THz-regime.

Femtosecond time-resolved X-ray absorption spectroscopy of anatase TiO2 nanoparticles using XFEL.

The charge-carrier dynamics of anatase TiO2 nanoparticles in an aqueous solution were studied by femtosecond time-resolved X-ray absorption spectroscopy using an X-ray free electron laser in combination with a synchronized ultraviolet femtosecond laser (268 nm). Using an arrival time monitor for the X-ray pulses, we obtained a temporal resolution of 170 fs. The transient X-ray absorption spectra revealed an ultrafast Ti K-edge shift and a subsequent growth of a pre-edge structure. The edge shift occurred in ca. 100 fs and is ascribed to reduction of Ti by localization of generated conduction band electrons into shallow traps of self-trapped polarons or deep traps at penta-coordinate Ti sites. Growth of the pre-edge feature and reduction of the above-edge peak intensity occur with similar time constants of 300-400 fs, which we assign to the structural distortion dynamics near the surface.

41-fs, 35-nJ, Green Pulse Generation from a Yb-doped Fiber Laser System.

We report ultrafast green pulse generation from a Yb-doped fiber laser system with gain-narrowing compensation. The chirped-pulse amplification system outputs repetitive 3 MHz pulses with an energy of 35 nJ and a reconstructed pulse duration of 41 fs.

Direct label-free measurement of the distribution of small molecular weight compound inside thick biological tissue using coherent Raman microspectroscopy.

Distributions of small molecular weight (less than 300 Da) compounds inside biological tissue have been obscure because of the lack of appropriate methods to measure them. Although fluorescence techniques are widely used to characterise the localisation of large biomolecules, they cannot be easily applied to the cases with small molecule compounds. We used CARS spectroscopy to detect and identify a label-free small molecule compound. To facilitate detection in aqueous environment, we utilised time-resolved and phase-sensitive techniques to reduce non-resonant background generated from water. We applied this technique to detect small molecular weight compound, taurine, inside mouse cornea tissue immersed in taurine solution as an initial model experiment. We detected a Raman peak of taurine near wavenumber 1033 cm(-1) inside cornea and successfully characterised its depth profile in the tissue. Our CARS spectra measurement can be a promising method to measure and visualise the distribution of small bio-related compounds in biological background without using any labeling, paving the way for new cell biological analysis in various disciplines.

65-fs Yb-doped fiber laser system with gain-narrowing compensation.

We report a broadband Yb-doped fiber laser system with a gain-narrowing compensator comprised of multiple dielectric layers. Utilizing this filter, we obtained broadband pulses over a bandwidth of 1020-1080 nm directly from the amplifier. After the dispersion compensation, the chirped pulse amplification system delivered 65-fs pulses with energies of 100 nJ and a repetition rate of 3 MHz.

Femtosecond time-resolved X-ray absorption spectroscopy of liquid using a hard X-ray free electron laser in a dual-beam dispersive detection method.

We present femtosecond time-resolved X-ray absorption spectroscopy of aqueous solution using a hard x-ray free electron laser (SACLA) and a synchronized Ti:sapphire laser. The instrumental response time is 200 fs, and the repetition rate of measurement is 10 Hz. A cylindrical liquid beam 100 µm in diameter of aqueous ammonium iron(III) oxalate solution is photoexcited at 400 nm, and the transient X-ray absorption spectra are measured in the K-edge region of iron, 7.10 - 7.26 keV, using a dual X-ray beam dispersive detection method. Each of the dual beams has the pulse energy of 1.4 µJ, and pump-induced absorbance change on the order of 10(-3) is successfully detected. The photoexcited iron complex exhibits a red shifted iron K-edge with the appearance time constant of 260 fs. The X-ray absorption difference spectra, with and without the pump pulses, are independent of time delay after 1.5 ps up to 100 ps, indicating that the photoexcited species is long-lived.

Efficient heterodyne CARS measurement by combining spectral phase modulation with temporal delay technique.

We propose and demonstrate an improved heterodyne coherent anti-Stokes Raman scattering (CARS) measurement with a rapid phase modulation and temporal displacement of the background, to simplify signal extraction and effectively reduce a nonresonant background (NRB). This method is a modification of the single-beam CARS spectroscopy originally proposed by Oron et al. in which a narrowband phase modulation is used to enhance contrast between resonant signals and the NRB through heterodyne detection [Phys. Rev. Lett. 89, 273001 (2002)]. In our scheme, a large delay between the narrow- and broadband components enables us to reduce the NRB while maintaining signal enhancement by heterodyne detection. We develop a frequency-resolved Michelson interferometer in which the narrow- and broadband components are spatially separated and recombined with an arbitrary delay. We show that sharp Raman lines can be obtained from chloroform molecules by the observation of difference spectra and phase sensitive detection. The spectral resolution achieved, which is limited by that of the spectrometer we used, is < 8 cm(-1). This method can potentially be extended to make real-time measurements by further developing a spectrometer that directly accumulates difference spectra.

In vivo molecular labeling of halogenated volatile anesthetics via intrinsic molecular vibrations using nonlinear Raman spectroscopy.

Halogenated volatile anesthetics are frequently used for inhaled anesthesia in clinical practice. No appropriate biological method has been available for visualizing their localization in action. Therefore, despite their frequent use, the mechanism of action of these drugs has not been fully investigated. We measured coherent anti-Stokes Raman scattering (CARS) spectra of sevoflurane and isoflurane, two of the most representative volatile anesthetics, and determined the low-frequency vibrational modes without nonresonant background disturbance. Molecular dynamics calculations predict that these modes are associated with multiple halogen atoms. Because halogen atoms rarely appear in biological compounds, the entire spectral landscape of these modes is expected to be a good marker for investigating the spatial localization of these drugs within the intracellular environment. Using live squid giant axons, we could detect the unique CARS spectra of sevoflurane for the first time in a biological setting.

Interferometric polarization pulse shaper stabilized by an external laser diode for arbitrary vector field shaping.

We achieved reliable and stable generation of pulses with all possible polarization states by a Mach-Zehnder pulse shaper. This was realized by incorporating a stabilization mechanism using an external laser diode in the interferometric pulse shaper. This stabilization mechanism has overcome an inherent instability in the Mach-Zehnder interferometer, which caused serious distortion of shaped pulses. For a demonstration of polarization shaping, we generated and measured chiral pulses with a rotating major axis of polarizing orientations at arbitrary frequencies. We expect these chiral pulses enables us to study on new chirality-related light-matter interactions.

Nonlinear optical response of wave packets on quantized potential energy surfaces.

We calculated the dynamics of nuclear wave packets in coupled electron-vibration systems and their nonlinear optical responses. We found that the quantized nature of the vibrational modes is observed in pump-probe spectra particularly in weakly interacting electron-vibration systems such as cyanine dye molecules. Calculated results based on a harmonic potential model and molecular orbital calculations are compared with experimental results, and we also found that the material parameters regarding the geometrical structure of potential energy surfaces are directly determined by accurate measurement of time-resolved spectra.

Rapid motion capture of mode-specific quantum wave packets selectively generated by phase-controlled optical pulses.

Rapid motion capture of phase-controlled wave packets was realized using a sensitive wave-packet spectrometer, which was previously developed by the present authors. Two-dimensional Fourier-transformed spectrograms obtained by the wave-packet spectrometer provide us full information about the wave-packet motion on both excited- and ground-state potential surfaces. Vibrational wave packet associated with a twisting mode in a DTTCI molecule was observed to be dependent on the pulse chirp, and was generated in the excited state preferably with negatively chirped excitation. The result indicates that the excited-state wave packet can be driven along a favorable configuration coordinate by using phase-controlled femtosecond pulses. The present method is essential to adaptive coherent-control application.

Generation of a 10.6-THz ultrahigh-repetition-rate train by synthesizing phase-coherent Raman-sidebands.

A train of highly-stable, high-beam-quality ultrashort pulses is successfully produced by synthesizing phase-coherent rotational-Raman-sidebands in parahydrogen. The-intensity-waveform of this ultrashort-pulse-train is directly evaluated in time domain based on a sum-frequency-generation autocorrelation-technique. It is shown that a 10.6-THz ultrahigh-repetition-train of short pulses is formed with an effective-duration of 20 fs and a high peak-power of 2 MW.