Use of a solvent-free dry matrix coating for quantitative matrix-assisted laser desorption ionization imaging of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate in rat brain and quantitative analysis of the drug from laser microdissected tissue regions

A dry matrix application for matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was used to profile the distribution of 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylate, monohydrochloride (BDNC, SSR180711) in rat brain tissue sections. Matrix application involved applying layers of finely ground dry alpha-cyano-4-hydroxycinnamic acid (CHCA) to the surface of tissue sections thaw mounted onto MALDI targets. It was not possible to detect the drug when applying matrix in a standard aqueous-organic solvent solution. The drug was detected at higher concentrations in specific regions of the brain, particularly the white matter of the cerebellum. Pseudomultiple reaction monitoring imaging was used to validate that the observed distribution was the target compound. The semiquantitative data obtained from signal intensities in the imaging was confirmed by laser microdissection of specific regions of the brain directed by the imaging, followed by hydrophilic interaction chromatography in combination with a quantitative high-resolution mass spectrometry method. This study illustrates that a dry matrix coating is a valuable and complementary matrix application method for analysis of small polar drugs and metabolites that can be used for semiquantitative analysis.

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats.

Structure of fiber gratings directly written by infrared femtosecond laser

Structural modification m gratings inscribed point-by-point by a femtosecond laser is investigated using quantitative phase microscopy. The gratings present a central region with a depressed refractive index surrounded by an outer corona with increased index. © 2006 Optical Society of America.

3D Reconstruction of the complex dielectric function of glass during femtosecond laser micro-fabrication

We report on a new technique to reconstruct the 3D dielectric function change in transparent dielectric materials and the application of the technique for on-line monitoring of refractive index modification in BK7 glass during direct femtosecond laser microfabrication. The complex optical field scattered from the modified region is measured using two-beam, single-shot interferogram and the distribution of the modified refractive index is reconstructed by numerically solving the inverse scattering problem in Born approximation. The optical configuration suggested is further development of digital holographic microscopy (DHM). It takes advantage of high spatial resolution and almost the same optical paths for both interfering beams, and allows ultrafast time resolution.

Inscription and characterization of waveguides written into borosilicate glass by a high-repetition-rate femtosecond laser at 800 nm

A series of waveguides was inscribed in a borosilicate glass (BK7) by an 11 MHz repetition rate femtosecond laser operating with pulse energies from 16 to 30 nJ and focused at various depths within the bulk material. The index modification was measured using a quantitative phase microscopy technique that revealed central index changes ranging from 5×10-3 to 10-2, leading to waveguides that exhibited propagation losses of 0.2 dB/cm at a wavelength of 633 nm and 0.6 dB/cm at a wavelength of 1550 nm with efficient mode matching, less than 0.2 dB, to standard optical fibers. Analysis of the experimental data shows that, for a given inscription energy, the index modification has a strong dependence on inscription scanning velocity. At higher energies, the index modification increases with increasing inscription scanning velocity with other fabrication parameters constant.

3D reconstruction of the complex dielectric function of glass during femtosecond laser micro-fabrication

We report on a new technique to reconstruct the 3D dielectric function change in transparent dielectric materials and the application of the technique for on-line monitoring of refractive index modification in BK7 glass during direct femtosecond laser microfabrication. The complex optical field scattered from the modified region is measured using two-beam, single-shot interferogram and the distribution of the modified refractive index is reconstructed by numerically solving the inverse scattering problem in Born approximation. The optical configuration suggested is further development of digital holographic microscopy. It takes advantage of high spatial resolution and almost the same optical paths for both interfering beams, and allows ultrafast time resolution. © Springer Science+Business Media, LLC. 2011.

Highly efficient SHG at 561 nm using a QD laser and a PPLN waveguide

Compact CW lasers in the visible spectral region are of great importance for vast number of applications including biophotonics, photomedicine, spectroscopy and confocal microscopy. Currently, commercially available lasers of this spectral region are bulky, expensive and inconvenient in use. Also, there is a lack of diode lasers emitting in the visible spectral range, particularly in the yellow region, where a range of important fluorescent probes are optimally excited. An attractive way to realize a compact yellow laser source is second harmonic generation (SHG) in a periodically poled nonlinear crystal containing a waveguide which allows high-efficient frequency conversion even at moderate power level. In this respect, periodically poled lithium niobate (PPLN) waveguided crystal is one of the best candidates for efficient SHG. In recent years, the progress made with the fabrication of good quality waveguides in PPLN crystals in combination with availability of low-cost, good quality semiconductor diode lasers, offering the coverage of a broad spectral range between 1 µm and 1.3 µm, allows compact CW laser sources in the visible spectral region to be realized.

73 nm wavelength tuning from a frequency-doubled quantum-dot laser in PPKTP waveguides

A compact all-room-temperature CW 73-nm tunable laser source in the visible spectral region (574nm-647nm) has been demonstrated by frequency-doubling of a broadly-tunable InAs/GaAs quantum dot external-cavity diode laser in periodically-poled potassium titanyl phosphate waveguides with a maximum output power in excess of 12mW and a maximum conversion efficiency exceeding 10%. Three waveguides with different cross-sectional areas (4×4μm2, 3×5μm2 and 2x6μm2) were investigated. Introduction - Development of compact broadly tunable laser sources in the visible spectral region is currently very attractive area of research with applications ranging from photomedicine and biophotonics to confocal fluorescence microscopy and laser projection displays. In this respect, semiconductor lasers with their small size, high efficiency, reliability and low cost are very promising for realization of such sources by frequency­doubling of the infrared light in nonlinear crystal waveguides. Furthermore, the wide tunability offered by quantum-dot (QD) external-cavity diode lasers (ECDL), due to the temperature insensibility and broad gain bandwidth [1,2], is very promising for the development of tunable visible laser sources [3,4]. In this work we show a compact green-to-red tunable all­room-temperature CW laser source using a frequency-doubled InAs/GaAs QD-ECDL in periodically-poled potassium titanyl phosphate (PPKTP) crystal waveguides. This laser source generates frequency-doubled light over the 574nm-647nm wavelength range utilizing the significant difference in the effective refractive indices of high-order and low-order modes in multimode waveguides [3]. Experimental results - Experimental setup used in this work was similar to that described in [3] and consisted of a QD gain chip in the quasi­Littrow configuration and a PPKTP waveguide. Coarse wavelength tuning of the QD-ECDL between 1140 nm and 1300 nm at 20°C was possible for pump current of 1.5 A. The laser output was coupled into the PPKTP waveguide using an AR-coated 40x aspheric lens (NA ~ 0.55). The PPKTP frequency-doubling crystal (not AR coated) used in our work was 18 mm in length and was periodically poled for SHG (with the poling period of ~ 11.574 11m). The crystal contained 3 different waveguides with cross-sectional areas of ~ 4x4 11m2, 3x5 11m2 and 2x6 11m2. Both the pump laser and the PPKTP crystal were operating at room temperature. The waveguides with cross-sectional areas of 4x411m2, 3x511m2 and 2x611m2 demonstrated the tunability in the wavelength ranges of 577nm - 647nm, 576nm -643nm and 574nm - 641nm, respectively, with a maximum output power of 12.04mW at 606 nm Conclusion - We demonstrated a compact all-room-temperature broadly­tunable laser source operating in the visible spectral region between 574nm and 647nm. This laser source is based on second harmonic generation in PPKTP waveguides with different cross-sectional areas using an InAs/GaAs QD-ECDL References [I] E.U. Rafailov, M.A. Cataluna, and W. Sibbett, Nat. Phot. 1,395 (2007). [2] K.A. Fedorova, M.A. Cataluna, I. Krestnikov, D. Livshits, and E.U. Rafailov, Opt. Express 18(18), 19438-19443 (2010). [3] K.A. Fedorova, G.S. Sokolovskii, P.R. Battle, D.A. Livshits, and E.U. Rafailov, Laser Phys. Lett. 9, 790-795 (2012). [4] K.A. Fedorova,G.S. Sokolovskii, D.T. Nikitichev, P.R. Battle, I.L. Krestnikov, D.A. Livshits, and E.U. Rafailov, Opt. Lett. 38(15), 2835-2837 (2013) © 2014 IEEE.

Analysis of femtosecond laser surface patterning on bulk single-crystalline diamond

Preliminary work is reported on 2-D and 3-D microstructures written directly with a Yb:YAG 1026 nm femtosecond (fs) laser on bulk chemical vapour deposition (CVD) single-crystalline diamond. Smooth graphitic lines and other structures were written on the surface of a CVD diamond sample with a thickness of 0.7mm under low laser fluences. This capability opens up the opportunity for making electronic devices and micro-electromechanical structures on diamond substrates. The fabrication process was optimised through testing a range of laser energies at a 100 kHz repetition rate with sub-500fs pulses. These graphitic lines and structures have been characterised using optical microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy and atomic force microscopy. Using these analysis techniques, the formation of sp2 and sp3 bonds is explored and the ratio between sp2 and sp3 bonds after fs laser patterning is quantified. We present the early findings from this study and characterise the relationship between the graphitic line formation and the different fs laser exposure conditions. © 2012 Taylor & Francis.