19F labelled glycosaminoglycan probes for solution NMR and non-linear (CARS) microscopy

Studying polysaccharide-protein interactions under physiological conditions by conventional techniques is challenging. Ideally, macromolecules could be followed by both in vitro spectroscopy experiments as well as in tissues using microscopy, to enable a proper comparison of results over these different scales but, often, this is not feasible. The cell surface and extracellular matrix polysaccharides, glycosaminoglycans (GAGs) lack groups that can be detected selectively in the biological milieu. The introduction of 19F labels into GAG polysaccharides is explored and the interaction of a labelled GAG with the heparin-binding protein, antithrombin, employing 19F NMR spectroscopy is followed. Furthermore, the ability of 19F labelled GAGs to be imaged using CARS microscopy is demonstrated. 19F labelled GAGs enable both 19F NMR protein-GAG binding studies in solution at the molecular level and non-linear microscopy at a microscopic scale to be conducted on the same material, essentially free of background signals

Development of a rapid profiling method for the analysis of polar analytes in urine using HILIC-MS and ion mobility enabled HILIC-MS

Introduction As large scale metabolic phenotyping is increasingly employed in preclinical studies and in the investigation of human health and disease the current LC–MS/MS profiling methodologies adopted for large sample sets can result in lengthy analysis times, putting strain on available resources. As a result of these pressures rapid methods of untargeted analysis may have value where large numbers of samples require screening. Objectives To develop, characterise and evaluate a rapid UHP-HILIC-MS-based method for the analysis of polar metabolites in rat urine and then extend the capabilities of this approach by the addition of IMS to the system. Methods A rapid untargeted HILIC LC–MS/MS profiling method for the analysis of small polar molecules has been developed. The 3.3 min separation used a Waters BEH amide (1 mm ID) analytical column on a Waters Synapt G2-Si Q-Tof enabled with ion mobility spectrometry (IMS). The methodology, was applied to the metabolic profiling of a series of rodent urine samples from vehicle-treated control rats and animals administered tienilic acid. The same separation was subsequently linked to IMS and MS to evaluate the benefits that IMS might provide for metabolome characterisation. Results The rapid HILIC–MS method was successfully applied to rapid analysis of rat urine and found, based on the data generated from the data acquired for the pooled quality control samples analysed at regular intervals throughout the analysis, to be robust. Peak area and retention times for the compounds detected in these samples showed good reproducibility across the batch. When used to profile the urine samples obtained from vehicle-dosed control and those administered tienilic acid the HILIC-MS method detected 3007 mass/retention time features. Analysis of the same samples using HILIC–IMS–MS enabled the detection of 6711 features. Provisional metabolite identification for a number of compounds was performed using the high collision energy MS/MS information compared against the Metlin MS/MS database and, in addition, both calculated and measured CCS values from an experimentally derived CCS database. Conclusion A rapid metabolic profiling method for the analysis of polar metabolites has been developed. The method has the advantages of speed and both reducing sample and solvent consumption compared to conventional profiling methods. The addition of IMS added an additional dimension for feature detection and the identification of metabolites

Broadband THz absorption spectrometer based on excitonic nonlinear optical effects

A broadly tunable THz source is realized via difference frequency generation, in which an enhancement to χ (3) that is obtained via resonant excitation of III–V semiconductor quantum well excitons is utilized. The symmetry of the quantum wells (QWs) is broken by utilizing the built-in electric-field across a p–i–n junction to produce effective χ (2) processes, which are derived from the high χ (3) . This χ (2) media exhibits an onset of nonlinear processes at ~4 W cm −2 , thereby enabling area (and, hence, power) scaling of the THz emitter. Phase matching is realized laterally through normal incidence excitation. Using two collimated 130 mW continuous wave (CW) semiconductor lasers with ~1-mm beam diameters, we realize monochromatic THz emission that is tunable from 0.75 to 3 THz and demonstrate the possibility that this may span 0.2–6 THz with linewidths of ~20 GHz and efficiencies of ~1 × 10 –5 , thereby realizing ~800 nW of THz power. Then, transmission spectroscopy of atmospheric features is demonstrated, thereby opening the way for compact, low-cost, swept-wavelength THz spectroscopy

Nova Laser System at Ultra High Fluence Levels

The Nova experimental facility consists of a ten arm laser system and five experimental stations and was completed in December 1984. Two of these stations are used for inertial confinement fusion (ICF) experiments and the other three are dedicated to doing large aperture (30 to 74 cm) laser experiments. The laser system is deployed in a master oscillator-power amplifier architecture and uses Nd: phosphate glass for the active medium. The fundamental wavelength of the system is 1.05 microns. Frequency converters constructed from potassium dihydrogen phosphate (KDP) crystals are located at the end of each of the ten arms and are used to produce high power frequency doubled (0.53 microns) and tripled (0.35 microns) beams for either ICF or laser experiments. Thus, the Nova laser system can produce high power beams with wavelengths ranging from the infrared to the ultraviolet