Infrared Free Electron Laser Research Articles

Application of Infrared Free-Electron Laser Irradiation of Protein Complexes Binding to Salen-Type Schiff Base Zn(II) Complexes Using Secondary Conformational Changes in the Proteins for the Treatment of Alzheimer’s Disease

Alzheimer’s disease causes the destruction of cranial nerve cells and is said to be caused by neuronal cell death due to the accumulation of amyloid-β protein. One method for the treatment of Alzheimer’s disease is to reduce the toxicity of the amyloid beta protein. Among the possibilities is to reduce toxicity by changing the secondary structure of the protein. In this study, the secondary structure of the protein was verified by binding a zinc complex to the protein and irradiating it with an infrared free-electron laser (IR-FEL). By binding Salen-Type zinc complexes to human serum albumin (HSA) and irradiating it with IR-FEL, structural changes were observed in the α-helix and β-sheet, the secondary structure of HSA. In addition to researching the possibility of binding zinc complexes to small proteins, docking simulations were examined. GOLD docking simulations showed that it is possible to bind zinc complexes to lysozyme (Lyz), a small protein. These results suggest that binding zinc complexes to amyloid-β and inducing a secondary conformational change through IR-FEL irradiation could be used for the treatment of Alzheimer’s disease by making the complexes lose their toxicity.

Design and Performance of Hefei Infrared Free-Electron Laser Facility

Design and Performance of Hefei Infrared Free-Electron Laser Facility

Disassembly of Amyloid Fibril with Infrared Free Electron Laser.

Amyloid fibril causes serious amyloidosis such as neurodegenerative diseases. The structure is composed of rigid β-sheet stacking conformation which makes it hard to disassemble the fibril state without denaturants. Infrared free electron laser (IR-FEL) is an intense picosecond pulsed laser that is oscillated through a linear accelerator, and the oscillation wavelengths are tunable from 3 μm to 100 μm. Many biological and organic compounds can be structurally altered by the mode-selective vibrational excitations due to the wavelength variability and the high-power oscillation energy (10-50 mJ/cm2). We have found that several different kinds of amyloid fibrils in amino acid sequences were commonly disassembled by the irradiation tuned to amide I (6.1-6.2 μm) where the abundance of β-sheet decreased while that of α-helix increased by the vibrational excitation of amide bonds. In this review, we would like to introduce the IR-FEL oscillation system briefly and describe combination studies of experiments and molecular dynamics simulations on disassembling amyloid fibrils of a short peptide (GNNQQNY) from yeast prion and 11-residue peptide (NFLNCYVSGFH) from β2-microglobulin as representative models. Finally, possible applications of IR-FEL for amyloid research can be proposed as a future outlook.

Field-resolved THz-pump laser-probe measurements with CEP-unstable THz light sources

Radiation sources with a stable carrier-envelope phase (CEP) are highly demanded tools for field-resolved studies of light-matter interaction, providing access both to the amplitude and phase information of dynamical processes. At the same time, many coherent light sources, including those with outstanding power and spectral characteristics lack CEP stability, and so far could not be used for this type of research. In this work, we present a method enabling linear and non-linear phase-resolved terahertz (THz) -pump laser-probe experiments with CEP-unstable THz sources. THz CEP information for each pulse is extracted using a specially designed electro-optical detection scheme. The method correlates the extracted CEP value for each pulse with the THz-induced response in the parallel pump-probe experiment to obtain an absolute phase-resolved response after proper sorting and averaging. As a proof-of-concept, we demonstrate experimentally field-resolved THz time-domain spectroscopy with sub-cycle temporal resolution using the pulsed radiation of a CEP-unstable infrared free-electron laser (IR-FEL) operating at 13 MHz repetition rate. In spite of the long history of IR-FELs and their unique operational characteristics, no successful realization of CEP-stable operation has been demonstrated yet. Being CEP-unstable, IR-FEL radiation has so far only been used in non-coherent measurements without phase resolution. The technique demonstrated here is robust, operates easily at high-repetition rates and for short THz pulses, and enables common sequential field-resolved time-domain experiments. The implementation of such a technique at IR-FEL user end-stations will facilitate a new class of linear and non-linear experiments for studying coherent light-driven phenomena with increased signal-to-noise ratio.

Application study of infrared free-electron lasers towards the development of amyloidosis therapy.

Amyloidosis is known to be caused by the deposition of amyloid fibrils into various biological tissues; effective treatments for the disease are little established today. An infrared free-electron laser (IR-FEL) is an accelerator-based picosecond-pulse laser having tunable infrared wavelengths. In the current study, the irradiation effect of an IR-FEL was tested on an 11-residue peptide (NFLNCYVSGFH) fibril from β2-microglobulin (β2M) with the aim of applying IR-FELs to amyloidosis therapy. Infrared microspectroscopy (IRM) and scanning electron microscopy showed that a fibril of β2M peptide was clearly dissociated by IR-FEL at 6.1 µm (amide I) accompanied by a decrease of the β-sheet and an increase of the α-helix. No dissociative process was recognized at 6.5 µm (amide II) as well as at 5.0 µm (non-specific wavelength). Equilibrium molecular dynamics simulations indicated that the α-helix can exist stably and the probability of forming interchain hydrogen bonds associated with the internal asparagine residue (N4) is notably reduced compared with other amino acids after the β-sheet is dissociated by amide I specific irradiation. This result implies that N4 plays a key role for recombination of hydrogen bonds in the dissociation of the β2M fibril. In addition, the β-sheet was disrupted at temperatures higher than 340 K while the α-helix did not appear even though the fibril was heated up to 363 K as revealed by IRM. The current study gives solid evidence for the laser-mediated conversion from β-sheet to α-helix in amyloid fibrils at the molecular level.

Degradation of Lignin by Infrared Free Electron Laser.

Lignin monomers have attracted attention as functional materials for various industrial uses. However, it is challenging to obtain these monomers by degrading polymerized lignin due to the rigid ether linkage between the aromatic rings. Here, we propose a novel approach based on molecular vibrational excitation using infrared free electron laser (IR-FEL) for the degradation of lignin. The IR-FEL is an accelerator-based pico-second pulse laser, and commercially available powdered lignin was irradiated by the IR-FEL under atmospheric conditions. Synchrotron-radiation infrared microspectroscopy analysis showed that the absorption intensities at 1050 cm−1, 1140 cm−1, and 3400 cm−1 were largely decreased alongside decolorization. Electrospray ionization mass chromatography analysis showed that coumaryl alcohol was more abundant and a mass peak corresponding to hydrated coniferyl alcohol was detected after irradiation at 2.9 μm (νO-H) compared to the original lignin. Interestingly, a mass peak corresponding to vanillic acid appeared after irradiation at 7.1 μm (νC=C and νC-C), which was supported by our two-dimensional nuclear magnetic resonance spectroscopy analysis. Therefore, it seems that partial depolymerization of lignin can be induced by IR-FEL irradiation in a wavelength-dependent manner.

Role of Water Molecules and Helix Structure Stabilization in the Laser-Induced Disruption of Amyloid Fibrils Observed by Nonequilibrium Molecular Dynamics Simulations.

Water plays a crucial role in the formation and destruction of biomolecular structures. The mechanism for destroying biomolecular structures was thought to be an active breaking of hydrogen bonds by water molecules. However, using nonequilibrium molecular dynamics simulations, in which an amyloid-β amyloid fibril was destroyed via infrared free-electron laser (IR-FEL) irradiation, we discovered a new mechanism, in which water molecules disrupt protein aggregates. The intermolecular hydrogen bonds formed by C═O and N-H in the fibril are broken at each pulse of laser irradiation. These bonds spontaneously re-form after the irradiation in many cases. However, when a water molecule happens to enter the gap between C═O and N-H, it inhibits the re-formation of the hydrogen bonds. Such sites become defects in the regularly aligned hydrogen bonds, from which all hydrogen bonds in the intermolecular β-sheet are broken as the fraying spreads. This role of water molecules is entirely different from other known mechanisms. This new mechanism can explain the recent experiments showing that the amyloid fibrils are not destroyed by laser irradiation under dry conditions. Additionally, we found that helix structures form more after the amyloid disruption; this is because the resonance frequency is different in a helix structure. Our findings provide a theoretical basis for the application of IR-FEL to the future treatment of amyloidosis.

The IR-FEL facility at RRCAT: Commissioning experiments and first saturation of lasing at [formula omitted] wavelength

An Infrared Free Electron Laser (IR-FEL) has been designed and developed at RRCAT for potential use in the IR/THz spectroscopy of materials in low temperature and high magnetic field environment. The first commissioning experiments on the IR-FEL setup were performed in 2016, but the out-coupled power achieved in these experiments was two to three orders of magnitude lower than the saturated out-coupled power predicted by the FEL design simulations, mainly due to certain limitations in its injector system. The setup has recently undergone a major upgrade with the installation and commissioning of a new injector system, and lasing at a wavelength of 28μm has recently been observed in the setup. This is the first saturation of lasing of an FEL in India, with a measured Continuous Wave (CW) out-coupled IR power of 5 - 7.3 mW. This paper discusses the present status of the IR-FEL project at RRCAT, and the results from recent commissioning experiments leading to lasing in the setup.

A tunable autocorrelator for pulse measurements at IR FEL-oscillator facilities

Radiation characteristics of a Free-Electron Laser (FEL) such as pulse length, time structure, intensity, bandwidth, wavelength, power, frequency, etc., which were measured on a diagnostics table, are thoroughly discussed. In this respect, pulse length measurements of an Infrared FEL (IR-FEL) beam are evaluated through an intensity autocorrelator, designed and installed as a diagnostics tool at the “Helmholtz-Zentrum Dresden-Rossendorf (HZDR)-Radiation Source ELBE” of Germany. In addition, the autocorrelator was designed as a unique, cost-effective, and in-house setup. It operates within the wavelength range of 3–35 microns, using Cadmium-Telluride (CdTe) crystals in the Second Harmonic Generation (SHG) medium. The intensity autocorrelation curves were obtained for the FEL beam with the wavelength of 26.2 microns, indicating an FWHM pulse duration ranging between 3.29–8.03 ps with different optical cavity detuning values. Furthermore, the pulse duration of Ti: sapphire laser beam is measured between 1–3 ps through the designed autocorrelator at the ELBE light source. On the other hand, the setup may pave the way for pulse length measurements of the Turkish infrared FEL-oscillator facility (TARLA) as well, which is currently under the hardware installation phase. Finally, it is elaborated in section 3 that the unique autocorrelator design fully meets all requirements for pulse length measurements of an infrared FEL source.

Hefei Infrared Free-Electron Laser Facility

Hefei Infrared Free-Electron Laser Facility

Commissioning and validation of the injector and electron beam transport systems for the IR-FEL at RRCAT

The first observation of lasing in an infra-red free electron laser (IR-FEL) at the Raja Ramanna Centre for Advanced Technology has been reported recently with a measured power output, i.e. $${\sim }10^{5}$$ times higher than the expected spontaneous radiation power for the electron beam parameters used in the experiment. IR-FEL design simulations, however, estimate a power gain of $$10^{7}$$ which is three orders of magnitude higher than the experimentally achieved value. To understand this difference between the measured and the expected power output from the IR-FEL, the electron beam used in the experiments has been characterised and FEL simulations have been repeated after considering the measured electron beam parameters. A reasonably good agreement is obtained between the measured results and those predicted by FEL simulations. Experiments have also been performed to study the expected variation in electron beam properties over a macropulse, which should be minimum for an oscillator FEL like the IR-FEL. This paper reports the results from the experiments for characterisation of the electron beam in the IR-FEL set-up and the results from FEL simulations, considering these measured electron beam parameters.

Investigation by DFT Methods of the Damage of Human Serum Albumin Including Amino Acid Derivative Schiff Base Zn(II) Complexes by IR-FEL Irradiation

An infrared free electron laser (IR-FEL) can decompose aggregated proteins by excitation of vibrational bands. In this study, we prepared hybrid materials of protein (human serum albumin; HSA) including several new Schiff base Zn(II) complexes incorporating amino acid (alanine and valine) or dipeptide (gly-gly) derivative moieties, which were synthesized and characterized with UV-vis, circular dichroism (CD), and IR spectra. Density functional theory (DFT) and time dependent DFT (TD-DFT) calculations were also performed to investigate vibrational modes of the Zn(II) complexes. An IR-FEL was used to irradiate HSA as well as hybrid materials of HSA-Zn(II) complexes at wavelengths corresponding to imine C=N, amide I, and amide II bands. Analysis of secondary structures suggested that including a Zn(II) complex into HSA led to the structural change of HSA, resulting in a more fragile structure than the original HSA. The result was one of the characteristic features of vibrational excitation of IR-FEL in contrast to electronic excitation by UV or visible light.

First Lasing in an Infrared Free Electron Laser at RRCAT, Indore

An Infrared Free Electron Laser (IR-FEL) designed to operate in the 12.5–50 μm wavelength band is presently in an advanced stage of commissioning at the Raja Ramanna Centre for Advanced Technology (RRCAT), Indore. Here we report results from first experiments on the IR-FEL after installation of its optical cavity, which has resulted in a power output that is ~105 times the expected spontaneous emission power for the beam parameters used in the experiment. The estimated out-coupled peak micro-pulse power during these experiments is ~2 kW. This is the first observed signature of lasing in the IR-FEL, and the first reported lasing in a FEL in India. This communication discusses the development of the IR-FEL, the recent experimental results, and the ongoing efforts to further increase the IR power to the design peak out-coupled power of 2 MW.

SNOM Imaging of a Crypt‐Like Feature in Adenocarcinoma Associated with Barrett's Oesophagus

The development of more accurate and sensitive diagnostic techniques is a key factor in efforts to improve cancer survival rates. The technique of infrared aperture fibre scanning near‐field optical microscopy (IR‐SNOM), together with radiation from the infrared free‐electron laser (IR‐FEL) on ALICE at Daresbury Laboratory (UK), has been used to obtain IR images of a crypt‐like feature and the surrounding tissue; the tissue was taken from a patient with oesophageal adenocarcinoma and with a history of Barrett's oesophagus. We have shown that the DNA signal is enhanced relative to other contributions in the region of the crypt, and the glycoprotein signal shows a less pronounced increase in the region of the crypt. The Amide II signal is found to be anti‐correlated with the DNA and glycoprotein profiles. The absorbance of the Amide II signal is found to differ for three different types of cancer tissue. High‐resolution IR images of the crypt reveal additional structure that would not be resolved in diffraction‐limited techniques.

Electron injector for Iranian Infrared Free Electron Laser

The quality of the electron beam for applications like free electron lasers (FELs) has a direct impact on the quality of the laser radiation. The electron injector considered for Iranian Infrared Free Electron Laser (IRIFEL) includes a thermionic RF electron gun plus a bunch compressor as the electron preinjector and a 50 MeV constant gradient traveling wave linac as the main accelerator of the electron injector. In the present work, a thermionic RF gun is designed and matched with an optimized linac to produce a high quality mono-energetic electron beam. The results show that the preinjector is capable of delivering an electron bunch with 1 ps bunch length and 3 mm-mrad emittance to the linac entrance which is desirable for IRIFEL operation. The results also show that by geometrical manipulation and optimization of the linac structure, the pattern of the RF fields in the linac will be more symmetric, which is important in order to produce high stable mono-energetic bunches.

Low emittance lattice for the storage ring of the Turkish Light Source Facility TURKAY**Supported by Turkish Republic Ministry of Development (DPT2006K120470)

The TAC (Turkish Accelerator Center) project aims to build an accelerator center in Turkey. The first stage of the project is to construct an Infra-Red Free Electron Laser (IR-FEL) facility. The second stage is to build a synchrotron radiation facility named TURKAY, which is a third generation synchrotron radiation light source that aims to achieve a high brilliance photon beam from a low emittance electron beam at 3 GeV. The electron beam parameters are highly dependent on the magnetic lattice of the storage ring. In this paper a low emittance storage ring for TURKAY is proposed and the beam dynamic properties of the magnetic lattice are investigated.

DISTRIBUTED MICROCONTROLLER BASED CONTROL SCHEME FOR REMOTE CONTROL OF FEL POWER SUPPLY

Infrared Free Electron Laser (IRFEL) which is under development at RRCAT Indore. The IRFEL machine consists of 90keV thermionic gun as electron source, beam transport line, 25MeV Linear Accelerator (LINAC) and an undulator magnet. There are various magnets on beam transport line. These magnets are energized by power supplies. These power supplies have local as well as remote control and located at equipment hall. The control room and equipment hall are at approximate distance of 300 m. When in operation Free Electron Laser generates X-ray radiations which are harmful for human body. Hence, when FEL is operational no personnel can enter FEL hall. Therefore, power supply kept in this hall needs a remote operation. In this paper, a distributed control system hardware and parameter display for Controlling and monitoring of power supply is designed based on network management protocol i.e. Modbus protocol makes the system flexible for Humans

Numerical method for full calculation of the electromagnetic field in a rectangular waveguide within overmoded configuration, using the fast Fourier transform

This paper describes a method of calculation of the transverse distributions of electric E( x, y ) and magnetic H( x, y ) fields, in a rectangular waveguide within overmoded configuration – i.e., when a large number eigenmodes are present. It uses the fast Fourier transform, instead of the conventional decomposition in a series of TEM pq modes. Although not using the eigenmode decomposition, this method still exhibits the amplitude of the whole set of eigenmodes TEM pq . As an example, a single mode propagation is shown to facilitate understanding of the method. Another example is shown, using a 2D Gaussian profile as input, which contains a large number of eigenmodes (overmoded configuration). As a result, a series of 2D profiles are displayed along the longitudinal axis z of the waveguide, to show the transverse amplitude distribution of the fields E( x, y, z ) and H( x, y, z ) when a Gaussian profile is used at waveguide entrance. This non-standard configuration may be observed, for example, in infrared Free-Electron Lasers. This method is used here to calculate the ohmic losses which are integrated along the waveguide propagation, and which are deduced from the transverse distribution of magnetic field.

Beam transport and bunch compression at TARLA

The Turkish Accelerator and Radiation Laboratory in Ankara (TARLA) will operate two InfraRed Free Electron Lasers (IR-FEL) covering the range of 3–250μm. The facility will consist of an injector fed by a thermionic triode gun with two-stage RF bunch compression, two superconducting accelerating ELBE modules operating at continuous wave (CW) mode and two independent optical resonator systems with different undulator period lengths. The electron beam will also be used to generate Bremsstrahlung radiation. In this study, we present the electron beam transport including beam matching to the undulators and the shaping of the longitudinal phase space using magnetic dispersive sections.

Near-field optical microscopy with an infra-red free electron laser applied to cancer diagnosis

We show that the combination of a scanning near field optical microscope and an infra-red free electron laser yields chemical images with sub-cellular spatial resolution that have the potential to provide a diagnostic for oesophageal adenocarcinoma.