Professor Philip Doble is the Director of the Elemental Bio-imaging Facility (EBF) within the School of Chemistry and Forensic Science at UTS. He has extensive expertise in the development and application of novel techniques to current analytical problems, with a particular interest in analysis of metals in biological systems and novel spectroscopic diagnostic techniques.
The Elemental Bio-imaging Facility contains a unique collection of state of the art analytical technologies including laser ablation-ICP-MS and chip-based liquid chromatography systems all housed in purpose built laboratories. The EBF fosters strong collaborations both nationally and internationally.
Philip and his group at the EBF have diverse skills in areas including analytical chemistry, instrumentation, neurosciences and forensic detection; and the group has a strong postgraduate research program. His contributions to research at UTS were recognised by the Vice Chancellor’s award for Research Excellence in 2013.
Can supervise: YES
Professor Philip Doble’s research centres on the development of advanced analytical technologies including techniques for spatial quantification of elements in biological materials. Recent work has applied these techniques to investigations in palaeontology, basic mechanistic biology, environmental exposure to toxic elements and understanding the complexities of neural function in health and disease. He has published more than 100 peer reviewed articles in these areas. Philip’s research bridges the gap between biologists, neuroscientists, medical specialists and their requirements for new analytical technologies and methods.
Clases, D, de Vega, RG, Funke, S, Lockwood, TE, Westerhausen, MT, Taudte, RV, Adlard, PA & Doble, PA 2020, 'Matching sensitivity to abundance: high resolution immuno-mass spectrometry imaging of lanthanide labels and endogenous elements in the murine brain', JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY, vol. 35, no. 4, pp. 728-735.View/Download from: Publisher's site
Pamphlett, R, Jew, SK, Doble, PA & Bishop, DP 2020, 'Elemental imaging shows mercury in cells of the human lateral and medial geniculate nuclei', PLoS ONE, vol. 15, no. 4.View/Download from: Publisher's site
© 2020 Pamphlett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective Interference with the transmission of sensory signals along visual and auditory pathways has been implicated in the pathogenesis of hallucinations. The relay centres for vision (the lateral geniculate nucleus) and hearing (the medial geniculate nucleus) appear to be susceptible to the uptake of circulating mercury. We therefore investigated the distribution of mercury in cells of both these geniculate nuclei. Materials and methods Paraffin-embedded tissue sections containing the lateral geniculate nucleus were obtained from 50 adults (age range 20–104 years) who at autopsy had a variety of clinicopathological conditions, including neurological and psychiatric disorders. The medial geniculate nucleus was present in seven sections. Sections were stained for mercury using autometallography. Laser ablation-inductively coupled plasma-mass spectrometry was used to confirm the presence of mercury. Results Ten people had mercury in cells of the lateral geniculate nucleus, and in the medial geniculate nucleus of three of these. Medical diagnoses in these individuals were: none (3), Parkinson disease (3), and one each of depression, bipolar disorder, multiple sclerosis, and mercury self-injection. Mercury was distributed in different groups of geniculate capillary endothelial cells, neurons, oligodendrocytes, and astrocytes. Mass spectrometry confirmed the presence of mercury. Conclusion Mercury is present in different combinations of cell types in the lateral and medial geniculate nuclei in a proportion of people from varied backgrounds. This raises the possibility that mercury-induced impairment of the function of the geniculate nuclei could play a part in the genesis of visual and auditory hallucinations....
Pamphlett, R, Satgunaseelan, L, Jew, SK, Doble, PA & Bishop, DP 2020, 'Elemental bioimaging shows mercury and other toxic metals in normal breast tissue and in breast cancers', PLOS ONE, vol. 15, no. 1.View/Download from: Publisher's site
Pyke, GH, Kalman, JRM, Bordin, DM, Blanes, L & Doble, PA 2020, 'Patterns of floral nectar standing crops allow plants to manipulate their pollinators', Scientific Reports, vol. 10, no. 1.View/Download from: Publisher's site
© 2020, The Author(s). 'Pollination syndromes' involving floral nectar have eluded satisfactory evolutionary explanation. For example, floral nectars for vertebrate-pollinated plants average low sugar concentrations, while such animals prefer high concentrations, perplexing pollination biologists and arousing recent controversy. Such relationships should result from evolutionary games, with plants and pollinators adopting Evolutionarily Stable Strategies, and nectar manipulating rather than attracting pollinators. Plant potential to manipulate pollinators depends on relationships between neighbouring flowers within plants, for all nectar attributes, but this has not been investigated. We measured nectar volume, concentration and sugar composition for open flowers on naturally-growing Blandfordia grandiflora plants, presenting classic bird-pollinated plant syndrome. To evaluate potential pollinator manipulation through nectar, we analysed relationships between neighbouring flowers for nectar volume, concentration, proportion sucrose, log(fructose/glucose), and sugar weight. To evaluate potential attraction of repeat-visits to flowers or plants through nectar, we compared attributes between successive days. Nearby flowers were positively correlated for all attributes, except log(fructose/glucose) as fructose≈glucose. Most relationships between nectar attributes for flowers and plants on successive days were non-significant. Nectar-feeding pollinators should therefore decide whether to visit another flower on a plant, based on all attributes of nectar just-obtained, enabling plants to manipulate pollinators through adjusting nectar. Plants are unlikely to attract repeat pollinator-visits through nectar production. Floral nectar evolution is conceptually straightforward but empirically challenging. A mutant plant deviating from the population in attributes of nectar-production per flower would manipulate, rather than attract, nectar-feeding pollinators, altering poll...
Rao, SS, Lago, L, Gonzalez de Vega, R, Bray, L, Hare, DJ, Clases, D, Doble, PA & Adlard, PA 2020, 'Characterising the spatial and temporal brain metal profile in a mouse model of tauopathy', METALLOMICS, vol. 12, no. 2, pp. 301-313.View/Download from: Publisher's site
Billings, JL, Gordon, SL, Rawling, T, Doble, PA, Bush, AI, Adlard, PA, Finkelstein, DI & Hare, DJ 2019, 'l-3,4-dihydroxyphenylalanine (l-DOPA) modulates brain iron, dopaminergic neurodegeneration and motor dysfunction in iron overload and mutant alpha-synuclein mouse models of Parkinson's disease.', Journal of neurochemistry, vol. 150, no. 1, pp. 88-106.View/Download from: Publisher's site
Treatment with the dopamine (DA) precursor l-3,4-dihydroxyphenylalanine (l-DOPA) provides symptomatic relief arising from DA denervation in Parkinson's disease. Mounting evidence that DA autooxidation to neurotoxic quinones is involved in Parkinson's disease pathogenesis has raised concern about potentiation of oxidative stress by l-DOPA. The rate of DA quinone formation increases in the presence of excess redox-active iron (Fe), which is a pathological hallmark of Parkinson's disease. Conversely, l-DOPA has pH-dependent Fe-chelating properties, and may act to 'redox silence' Fe and partially allay DA autoxidation. We examined the effects of l-DOPA in three murine models of parkinsonian neurodegeneration: early-life Fe overexposure in wild-type mice, transgenic human (h)A53T mutant α-synuclein (α-syn) over-expression, and a combined 'multi-hit' model of Fe-overload in hA53T mice. We found that l-DOPA was neuroprotective and prevented age-related Fe accumulation in the substantia nigra pars compacta (SNc), similar to the mild-affinity Fe chelator clioquinol. Chronic l-DOPA treatment showed no evidence of increased oxidative stress in wild-type midbrain and normalized motor performance, when excess Fe was present. Similarly, l-DOPA also did not exacerbate protein oxidation levels in hA53T mice, with or without excess nigral Fe, and showed evidence of neuroprotection. The effects of l-DOPA in Fe-fed hA53T mice were somewhat muted, suggesting that Fe-chelation alone is insufficient to attenuate neuron loss in an animal model also recapitulating altered DA metabolism. In summary, we found no evidence in any of our model systems that l-DOPA treatment accentuated neurodegeneration, suggesting DA replacement therapy does not contribute to oxidative stress in the Parkinson's disease brain.
Clases, D, Fingerhut, S, Jeibmann, A, Sperling, M, Doble, P & Karst, U 2019, 'LA-ICP-MS/MS improves limits of detection in elemental bioimaging of gadolinium deposition originating from MRI contrast agents in skin and brain tissues.', Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), vol. 51, pp. 212-218.View/Download from: Publisher's site
A novel analytical method to detect the retention of gadolinium from contrast agents for magnetic resonance imaging (MRI) in tissue samples of patients is presented. It is based on laser ablation - inductively coupled plasma - triple quadrupole - mass spectrometry (LA-ICP-MS/MS). Both Gd and P were monitored with a mass shift of +16, corresponding to mono-oxygenated species, as well as Zn, Ca, and Fe on-mass. This method resulted in a significantly reduced background and improved limits of detection not only for phosphorus, but also for gadolinium. These improvements were essential to perform elemental bioimaging with improved resolution of 5 μm x 5 μm, allowing the detection of small Gd deposits in fibrotic skin and brain tumour tissue with diameters of approximately 50 μm. Detailed analyses of these regions revealed that most Gd was accompanied with P and Ca, indicating co-precipitation.
Clases, D, Gonzalez De Vega, R, Adlard, PA & Doble, PA 2019, 'On-line reverse isotope dilution analysis for spatial quantification of elemental labels used in immunohistochemical assisted imaging mass spectrometry: Via LA-ICP-MS', Journal of Analytical Atomic Spectrometry, vol. 34, no. 2, pp. 407-412.View/Download from: Publisher's site
© 2019 The Royal Society of Chemistry. We present a novel on-line isotope dilution analysis (IDA) approach for the quantification of isotopically enriched metal labels used in immunohistochemical assisted imaging mass spectrometry. This technique advances recently reported on-line IDA for laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS) by performing on-line reverse IDA of isotopically enriched elements commonly used as labels for antibodies. This approach allows relative quantification of biomolecules and is superior to other methods that have long acquisition times such as three-dimensional LA-ICP-MS, or when higher sample throughput is required. As a proof of concept, anti-tyrosine hydroxylase was labelled with Yb isotopes and incubated on two parallel cryocut sections of a mouse brain. IDA dependent parameters were determined by ablation of matrix-matched standards. Quantification by IDA was compared against external calibration and was a more robust method, unaffected by sensitivity changes originating from plasma drifts or spontaneous plasma fluctuations.
Clases, D, Gonzalez de Vega, R, Bishop, D & Doble, P 2019, 'SEC-ICP-MS and on-line isotope dilution analysis for characterisation and quantification of immunochemical assays.', Analytical and bioanalytical chemistry, vol. 411, no. 16, pp. 3553-3560.View/Download from: Publisher's site
This study presents a novel size exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) method for the characterisation and quantification of immunoassays with lanthanide-labelled antibodies. SEC-ICP-MS in combination with a double isotope dilution approach enabled facile validation of the antibodies' integrity, the determination of the batch to batch labelling efficiency, monitoring of each labelling step, and quantification of the immunocomplexes after incubation with the target protein. The addition of oxygen into the dynamic reaction cell improved the detection of sulphur as a marker for the antibodies and target protein via mass-shifting (LOD = 3.7 ng/mL), whilst maintaining sufficient sensitivity for the analysis of the lanthanides. Ultra-high performance liquid chromatography (UHPLC) SEC ensured a rapid chromatographic method with separation times under 7 min of the labelled and unlabelled antibodies, the immunocomplexes, and the unconjugated polymer used to lanthanide-label the antibodies. SEC calibration estimated the molecular weights of all peaks and provided valuable insights in immunochemical reactions and the stoichiometry of the reactants and products. A novel on-line isotope dilution analysis (IDA) enabled absolute quantification of sulphur and lanthanide signals and the protein of interest. The chromatographic separation of immunocomplexes and labelled antibodies allowed the simultaneous determination of the antibody/metal stoichiometry and target protein concentration from a single mass flow chromatogram. An immunoglobulin protein was quantified after incubation with an 153Eu-labelled primary polyclonal antibody. The procedure was validated with direct labelling of the target protein with 156Gd for parallel, simultaneous quantification. The concentration determined via direct labelling of the protein deviated 1.9% from the immunochemical approach employing 153Eu-labelled polyclonal antibodies. Graphical abstract.
Eijkelkamp, BA, Morey, JR, Neville, SL, Tan, A, Pederick, VG, Cole, N, Singh, PP, Ong, C-LY, Gonzalez de Vega, R, Clases, D, Cunningham, BA, Hughes, CE, Comerford, I, Brazel, EB, Whittall, JJ, Plumptre, CD, McColl, SR, Paton, JC, McEwan, AG, Doble, PA & McDevitt, CA 2019, 'Dietary zinc and the control of Streptococcus pneumoniae infection.', PLoS pathogens, vol. 15, no. 8.View/Download from: Publisher's site
Human zinc deficiency increases susceptibility to bacterial infection. Although zinc supplementation therapies can reduce the impact of disease, the molecular basis for protection remains unclear. Streptococcus pneumoniae is a major cause of bacterial pneumonia, which is prevalent in regions of zinc deficiency. We report that dietary zinc levels dictate the outcome of S. pneumoniae infection in a murine model. Dietary zinc restriction impacts murine tissue zinc levels with distribution post-infection altered, and S. pneumoniae virulence and infection enhanced. Although the activation and infiltration of murine phagocytic cells was not affected by zinc restriction, their efficacy of bacterial control was compromised. S. pneumoniae was shown to be highly sensitive to zinc intoxication, with this process impaired in zinc restricted mice and isolated phagocytic cells. Collectively, these data show how dietary zinc deficiency increases sensitivity to S. pneumoniae infection while revealing a role for zinc as a component of host antimicrobial defences.
González de Vega, R, Clases, D, Fernández-Sánchez, ML, Eiró, N, González, LO, Vizoso, FJ, Doble, PA & Sanz-Medel, A 2019, 'MMP-11 as a biomarker for metastatic breast cancer by immunohistochemical-assisted imaging mass spectrometry.', Analytical and bioanalytical chemistry, vol. 411, no. 3, pp. 639-646.View/Download from: Publisher's site
MMP-11 is a member of the matrix metalloproteinase family (MMPs) which are overexpressed in cancer cells, stromal cells and the adjacent microenvironment. The MMP protein family encompasses zinc-dependent endopeptidases that degrade the extracellular matrix (ECM), facilitating the breakdown of the basal membrane and matrix connective tissues. This function is believed to be important in cancer development and metastasis. This paper investigated a gold nanoparticle-based immunohistochemical assay to visualise the distribution of MMP-11 in human breast cancer tissues from eight patients with and without metastases by employing laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The expression of MMP-11 was increased and more heterogeneous in metastatic specimens compared to non-metastatic tumour samples. These findings demonstrate that imaging breast tumours by LA-ICP-MS may be a useful tool to aid the prognosis and treatment of breast cancer. As an example, samples of two patients are presented who were diagnosed with matching characteristics and grades of breast cancer. Although both patients had a similar prognosis and treatment, only one developed metastases.
Lockwood, TE, Talebi, M, Minett, A, Mills, S, Doble, PA & Bishop, DP 2019, 'Micro solid-phase extraction for the analysis of per- and polyfluoroalkyl substances in environmental waters.', Journal of chromatography. A, vol. 1604.View/Download from: Publisher's site
Growing concern over the environmental and health impacts of per- and polyfluoroalkyl substances (PFASs) has led to the development of increasingly stringent regulatory guidelines. To meet these guidelines for the determination of PFASs in surface-water, solid-phase extraction (SPE) is commonly implemented for clean-up and pre-concentration of samples. In this paper a micro-SPE method for the clean-up and pre-concentration of PFASs from surface-water was developed. A micro-SPE packing phase was created to retain 13 long and short chain PFAS after examining combinations of four 3 µm particle size sorbents, with the optimal phase consisting of a 50:50 mixture of C18 and aminopropyl silica. Micro-SPE achieved similar results to conventional SPE methods while reducing sample preparation time to 5 min and using only 2 mL of sample. The method was validated using spiked recoveries (100 ng L-1) from PFAS contaminated surface-water samples with recoveries ranging from 86% to 111% and relative standard deviations below 18%. Concentrations of the PFASs in the samples ranged from below the limit of quantification to 898 ± 15 ng L-1. Automation of sample preparation, including the micro-SPE extraction, was also demonstrated. These results show the potential for automated micro-SPE to replace conventional SPE, with the decreases in sample preparation time, sample and solvent volumes crucial for incorporation into routine analyses in commercial laboratories.
Pamphlett, R, Kum Jew, S, Doble, PA & Bishop, DP 2019, 'Elemental Analysis of Aging Human Pituitary Glands Implicates Mercury as a Contributor to the Somatopause.', Frontiers in Endocrinology, vol. 10, no. JUN.View/Download from: Publisher's site
Background: Growth hormone levels often decline on aging, and this "somatopause" is associated with muscle and bone loss, visceral adiposity and impaired cardiovascular function. Mercury has been detected in human pituitary glands, so to see if mercury could play a part in the somatopause we measured the proportion of people at different ages who had mercury in their anterior pituitary cells. Materials and methods: Paraffin sections of pituitary glands taken at autopsy from 94 people between the ages of 2 and 99 years were stained for inorganic mercury using autometallography. Pituitary mercury content was classified as none, low (<30% of cells) or high (>30% of cells) in increasing two-decade age groups. Autometallography combined with immunohistochemistry determined which hormone-producing cells contained mercury. Laser ablation-inductively coupled plasma-mass spectrometry was used to confirm the presence of mercury. Results: The proportion of people with low-content pituitary mercury remained between 33 and 42% at all ages. The proportion of people with high-content mercury increased with increasing age, from 0% of people in the 2-20 year group to a peak of 50% of people in the 61-80 years group, followed by a fall to 35% of people in the 81-99 years group. Mercury, when present, was found always in somatotrophs, occasionally in corticotrophs, rarely in thyrotrophs and gonadotrophs, and never in lactotrophs. Laser ablation-inductively coupled plasma-mass spectrometry detected mercury in regions of pituitaries that stained with autometallography. Conclusions: The proportion of people with mercury in their anterior pituitary cells, mostly somatotrophs, increases with aging, suggesting that mercury toxicity could be one factor contributing to the decline in growth hormone levels found in advancing age.
Wenzel, RG, Major, D, Hesp, KF, Hall, E & Doble, P 2019, 'Cobalt accumulation in horses following repeated administration of cobalt chloride', AUSTRALIAN VETERINARY JOURNAL, vol. 97, no. 11, pp. 465-472.View/Download from: Publisher's site
Westerhausen, MT, Bishop, DP, Dowd, A, Wanagat, J, Cole, N & Doble, PA 2019, 'Super-Resolution Reconstruction for Two- and Three-Dimensional LA-ICP-MS Bioimaging', ANALYTICAL CHEMISTRY, vol. 91, no. 23, pp. 14879-14886.View/Download from: Publisher's site
Westerhausen, MT, Lockwood, TE, Gonzalez de Vega, R, Röhnelt, A, Bishop, DP, Cole, N, Doble, PA & Clases, D 2019, 'Low background mould-prepared gelatine standards for reproducible quantification in elemental bio-imaging.', The Analyst, vol. 144, no. 23, pp. 6881-6888.View/Download from: Publisher's site
Standard preparation for elemental bio-imaging by laser ablation-inductively coupled plasma-mass spectrometry is confounded by the chemical and physical differences between standard and sample matrices. These differences lead to variable ablation, aerosol generation and transportation characteristics and must be considered when designing matrix-matched standards for reliable calibration and quantification. The ability to precisely mimic sample matrices is hampered due to the complexity and heterogeneity of biological tissue and small variabilities in standard matrices and sample composition often negatively impact accuracy, precision and robustness. Furthermore, cumbersome preparation protocols may limit reproducibility and traceability. This work presents novel facile methods for the preparation of gelatine standards using both commercial and laboratory-made moulds. Surface roughness, thickness and robustness of the mould-prepared standards were compared against cryo-sectioned gelatine and homogenised brain tissue standards. The mould-prepared standards had excellent thickness accuracy and signal precision which allowed robust quantification, were easier to prepare and therefore easier to reproduce. We also compared gelatine standards prepared from a variety of animal sources and discuss their suitability to calibrate low level elemental concentrations. Finally, we present a simple method to remove background metals in gelatine using various chelating resins to increase the dynamic calibration range and to improve limits of analysis.
Benson, N, Dos Santos, RO, Griffiths, K, Cole, N, Doble, P, Roux, C & Blanes, L 2018, 'The development of a stabbing machine for forensic textile damage analysis (vol 273, pg 132, 2017)', FORENSIC SCIENCE INTERNATIONAL, vol. 285, pp. 161-161.View/Download from: Publisher's site
Bishop, DP, Cole, N, Zhang, T, Doble, PA & Hare, DJ 2018, 'A guide to integrating immunohistochemistry and chemical imaging.', Chemical Society reviews, vol. 47, no. 11, pp. 3770-3787.View/Download from: Publisher's site
Chemical imaging provides new insight into the fundamental atomic, molecular, and biochemical composition of tissue and how they are interrelated in normal physiology. Visualising and quantifying products of pathogenic reactions long before structural changes become apparent also adds a new dimension to understanding disease pathogenesis. While chemical imaging in isolation is somewhat limited by the nature of information it can provide (e.g. peptides, metals, lipids, or functional groups), integrating immunohistochemistry allows simultaneous, targeted imaging of biomolecules while also mapping tissue composition. Together, this approach can provide invaluable information on the inner workings of the cell and the molecular basis of diseases.
Bishop, DP, Grossgarten, M, Dietrich, D, Vennemann, A, Cole, N, Sperling, M, Wiemann, M, Doble, PA & Karst, U 2018, 'Correction: Quantitative imaging of translocated silver following nanoparticle exposure by laser ablation-inductively coupled plasma-mass spectrometry (Analytical Methods (2018) DOI: 10.1039/c7ay02294h)', Analytical Methods, vol. 10, no. 8.View/Download from: Publisher's site
© 2018 The Royal Society of Chemistry. The authors regret that the incorrect affiliation was shown initially for Nerida Cole. The corrected list of author affiliations for this paper is as shown above. The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.
Bishop, DP, Grossgarten, M, Dietrich, D, Vennemann, A, Cole, N, Sperling, M, Wiemann, M, Doble, PA & Karst, U 2018, 'Quantitative imaging of translocated silver following nanoparticle exposure by laser ablation-inductively coupled plasma-mass spectrometry', Analytical Methods, vol. 10, no. 8, pp. 836-840.View/Download from: Publisher's site
© 2018 The Royal Society of Chemistry. The likelihood of exposure to antimicrobial silver nanoparticles continues to grow with their increasing ubiquity in various medical and consumer products. While translocation of silver nanoparticles to major organs has been examined, the in situ location and concentration in the organs is not well characterised. Here we have used laser ablation-inductively coupled plasma-mass spectrometry to quantitatively image serial sections to construct a three-dimensional representation of the distribution of silver in rat spleen following respiratory tract exposure via intratracheal instillation of silver nanoparticles. Silver was distributed predominantly in the white pulp of the spleen at concentrations greater than 300 ng g-1. Imaging tissue sections via laser-ablation-inductively coupled plasma-mass spectrometry is an excellent tool for the visualisation and quantification of metals attributed to nanoparticles in organs allowing investigation of silver nanoparticle exposure in vivo.
Bishop, DP, Hare, DJ, Clases, D & Doble, PA 2018, 'Applications of liquid chromatography-inductively coupled plasma-mass spectrometry in the biosciences: A tutorial review and recent developments', TrAC - Trends in Analytical Chemistry, vol. 104.View/Download from: Publisher's site
© 2017. The biological function of minor and trace elements is ordinarily determined by their association with specific proteins, peptides and other biomolecules. Therefore, measuring the total elemental content of a biological sample provides limited information, particularly when a specific effect is due to an individual metal-protein complex. Speciation of metalloproteins, heteroatom-containing molecules or other compounds tagged with an exogenous metal can be used to overcome this limitation. A range of chromatographic separation techniques with on-line elemental detection using inductively coupled plasma-mass spectrometry (ICP-MS) have been applied to the biosciences, and each technique has intrinsic features that must be considered when designing speciation experiments. This tutorial review provides an overview of speciation in the biosciences, highlighting the unique abilities and limitations encountered. A selection of recent technical advances and new applications, the challenges of sample preparation and implementation of new technical developments are discussed, as well as the future directions of technology that is rapidly gaining a foothold in the contemporary biochemistry laboratory.
Doble, PA & Miklos, GLG 2018, 'Distributions of manganese in diverse human cancers provide insights into tumour radioresistance.', Metallomics : integrated biometal science, vol. 10, no. 9, pp. 1191-1210.View/Download from: Publisher's site
Many cancers are variably resistant to radiation treatment: some patients die within months, while others with the same tumour type and equivalent radiation protocol, survive for years. To determine why some tumours are radiosensitive, while others return after radiotherapy, requires new non-traditional approaches to oncology. Herein we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to test the hypothesis that Mn functions as a metabolic radioprotector and is an apex predictor of tumour radioresponsiveness. The genesis of this hypothesis lies in microbial and in vitro chemical systems. We measured the levels and spatial distributions of Mn in tissue sections of 7 specifically chosen tumour types with distinct clinically documented radioresponsiveness and patient outcomes, namely testis, lung, brain, skin, mesothelium, prostate and breast. Mn levels varied nearly 60-fold between individual tumours, from 0.02 μg g-1 to 1.15 μg g-1. The most radiosensitive cancer type, (testis), had the lowest Mn levels and the highest patient survival. Tumours at the radioresistant extreme (glioblastomas and melanomas) had the highest Mn levels and lowest patient survival. A direct association was found between total Mn contents and their variation, and clinically-inferred radioresponsiveness in each of these 7 tumour types, while no such association existed with Cu, Zn or Fe. The LA-ICP-MS data provided unique patient-specific 2D maps of the spatial metallomic heterogeneity of cancer cells and their stroma. These maps have fundamental and far reaching clinical implications. For the first time, Mn-based tumour data may allow for more precise radiodosages and improved treatment for the individual patient.
Ishikawa, AA, Bordin, DM, de Campos, EG, Blanes, L, Doble, P & De Martinis, BS 2018, 'A Gas Chromatography-Mass Spectrometry Method for Toxicological Analysis of MDA, MDEA and MDMA in Vitreous Humor Samples from Victims of Car Accidents.', Journal of analytical toxicology, vol. 42, no. 9, pp. 661-666.View/Download from: Publisher's site
Vitreous humor (VH) shows excellent potential as a matrix of choice for postmortem analytical toxicology due to the ease of sampling and low metabolic activity. This study demonstrates a simple and rapid analytical method to identify and quantify 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine and 3,4-methylenedioxy-ethylamphetamine in VH. Samples were collected with a simple eye puncture procedure, followed by liquid-liquid extraction and derivatization with heptafluorobutyric anhydride and analysis via gas chromatography-mass spectrometry. The accuracy of the method ranged 97-103%, intra-assay precision was between 4.54 and 9.14% relative standard deviation (RSD) and interassay precision ranged from 6.92 to 10.59% RSD. Limits of detection and quantification ranged from 1.0 to 2.5 ng/mL and 10 ng/mL, respectively. The validated method was successfully applied to detect methylenedioxyamphetamine derivatives in VH samples collected from victims of fatal car crashes.
Maixner, F, Turaev, D, Cazenave-Gassiot, A, Janko, M, Krause-Kyora, B, Hoopmann, MR, Kusebauch, U, Sartain, M, Guerriero, G, O´Sullivan, N, Teasdale, M, Cipollini, G, Paladin, A, Mattiangeli, V, Samadelli, M, Tecchiati, U, Putzer, A, Palazoglu, M, Meissen, J, Lösch, S, Rausch, P, Baines, JF, Kim, BJ, An, H, Gostner, P, Egarter-Vigl, E, Malfertheiner, P, Keller, A, Stark, RW, Wenk, M, Bishop, D, Bradley, DG, Fiehn, O, Engstrand, L, Moritz, RL, Doble, P, Franke, A, Nebel, A, Oeggl, K, Rattei, T, Grimm, R & Zink, A 2018, 'The Iceman´s last meal consisted of fat, wild meat and cereals', Current Biology, vol. 28, no. 14, pp. 2348-2355.View/Download from: Publisher's site
The history of humankind is marked by the constant adoption of new dietary habits affecting human physiology, metabolism, and even the development of nutrition-related disorders. Despite clear archaeological evidence for the shift from hunter-gatherer lifestyle to agriculture in Neolithic Europe , very little information exists on the daily dietary habits of our ancestors. By undertaking a complementary -omics approach combined with microscopy, we analyzed the stomach content of the Iceman, a 5,300-year-old European glacier mummy [2, 3]. He seems to have had a remarkably high proportion of fat in his diet, supplemented with fresh or dried wild meat, cereals, and traces of toxic bracken. Our multipronged approach provides unprecedented analytical depth, deciphering the nutritional habit, meal composition, and food-processing methods of this Copper Age individual.
Pamphlett, R, Bishop, DP, Kum Jew, S & Doble, PA 2018, 'Age-related accumulation of toxic metals in the human locus ceruleus.', PloS one, vol. 13, no. 9, pp. e0203627-e0203627.View/Download from: Publisher's site
Damage to the locus ceruleus has been implicated in the pathogenesis of a number of neurological conditions. Locus ceruleus neurons accumulate toxic metals such as mercury selectively, however, the presence of toxic metals in locus ceruleus neurons of people of different ages, and with a variety of disorders, is not known. To demonstrate at what age toxic metals are first detectable in the locus ceruleus, and to evaluate whether their presence is more common in certain clinicopathological conditions, we looked for these metals in 228 locus ceruleus samples. Samples were taken at coronial autopsies from individuals with a wide range of ages, pre-existing conditions and causes of death. Paraffin sections of pons containing the locus ceruleus were stained with silver nitrate autometallography, which indicates inorganic mercury, silver and bismuth within cells (termed autometallography-detected toxic metals, or AMG™). No locus ceruleus AMG neurons were seen in 38 individuals aged under 20 years. 47% of the 190 adults (ie, aged 20 years and over) had AMG locus ceruleus neurons. The proportion of adults with locus ceruleus AMG neurons increased during aging, except for a decreased proportion in the 90-plus years age group. No differences were found in the proportions of locus ceruleus AMG neurons between groups with different neurological, psychiatric, or other clinicopathological conditions, or among various causes of death. Elemental analysis with laser ablation-inductively coupled plasma-mass spectrometry was used to cross-validate the metals detected by AMG, by looking for silver, gold, bismuth, cadmium, chromium, iron, mercury, nickel, and lead in the locus ceruleus of ten individuals. This confirmed the presence of mercury in locus ceruleus samples containing AMG neurons, and showed cadmium, silver, lead, iron, and nickel in the locus ceruleus of some individuals. In conclusion, toxic metals stained by AMG (most likely inorganic mercury) appear in locus ceruleus ...
Portbury, SD, Hare, DJ, Bishop, DP, Finkelstein, DI, Doble, PA & Adlard, PA 2018, 'Trehalose elevates brain zinc levels following controlled cortical impact in a mouse model of traumatic brain injury', METALLOMICS, vol. 10, no. 6, pp. 846-853.View/Download from: Publisher's site
Wenzel, R, Major, D, Hesp, K & Doble, P 2018, 'Determination of vitamin B12 in equine urine by liquid chromatography - inductively coupled plasma - mass spectrometry.', Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), vol. 50, pp. 634-639.View/Download from: Publisher's site
Regulating authorities in the racing industry have restricted the administration of potentially performance enhancing cobalt salts to horses. There are severe penalties for trainers presenting horses with elevated urine cobalt concentrations, and compliance is ensured via analysis of total urinary cobalt at thresholds of 100 μg/L. When cobalt is present as part of the cobalamin molecule it is not considered performance enhancing. This paper demonstrates that a horse can excrete a significant proportion of a commercially available vitamin B12 injection in urine without metabolic modification. A liquid chromatography - inductively coupled plasma - mass spectrometry (LC-ICP-MS) method is presented for urinary cobalt speciation. Given the serious nature surrounding performance enhancing drug offences, we conclude that presumptive positives identified by urine total cobalt measurements require further analysis to differentiate inorganic cobalt from vitamin B12.
Benson, N, Dos Santos, RO, Griffiths, K, Cole, N, Doble, P, Roux, C & Blanes, L 2017, 'The development of a stabbing machine for forensic textile damage analysis.', Forensic Science International, vol. 273, pp. 132-139.View/Download from: Publisher's site
This article describes the development of a horizontal stabbing machine with an interchangeable knife holder to simulate stab events. The machine consists of a motorised arm with a pneumatic system designed to deliver 60 unique stabbing positions. The mechanics were robust and the positioning system highly reproducible with standard deviations of less than 1.0mm in the x-axis and 2.3mm in the y-axis for a given stab position. The force of the instrument may be varied by the operator to a maximum of approximately 221N. The suitability of the instrument for simulating stab events was evaluated by measuring the severance length and textile damage from stab delivered from four different knives and nine penetrating angles.
Bishop, DP, Blanes, L, Wilson, AB, Wilbanks, T, Killeen, K, Grimm, R, Wenzel, R, Major, D, Macka, M, Clarke, D, Schmid, R, Cole, N & Doble, PA 2017, 'Microfluidic high performance liquid chromatography-chip hyphenation to inductively coupled plasma-mass spectrometry', Journal of Chromatography A, vol. 149, pp. 64-69.View/Download from: Publisher's site
© 2017 Elsevier B.V.The Agilent Chip Cube Interface is a microfluidic chip-based technology originally designed for nanospray molecular mass spectrometry in which the sample enrichment, nano-column, tubing, connectors and spray tip were integrated into a single biocompatible chip. Here we describe the hyphenation of the Chip Cube Interface to ICP-MS via modification of the standard HPLC chip design and a new total consumption nebuliser suitable for flow rates as low as 300nLmin-1. The potential of the instrument to eliminate common nanoLC - ICP-MS shortcomings such as leaks, blockages and band-broadening was demonstrated via analysis of cyanocobalamin in equine plasma. The method was linear over three orders of magnitude with an r2 of 0.9999, the peak area repeatability was 1.9% (n=7), and the detection limit was 14ngmL-1. This novel configuration of the Chip Cube Interface coupled to ICP-MS is a suitable platform for the analysis of biomolecules associated with trace metals and speciation applications.
Finkelstein, DI, Billings, JL, Adlard, PA, Ayton, S, Sedjahtera, A, Masters, CL, Wilkins, S, Shackleford, DM, Charman, SA, Bal, W, Zawisza, IA, Kurowska, E, Gundlach, AL, Ma, S, Bush, AI, Hare, DJ, Doble, PA, Crawford, S, Gautier, EC, Parsons, J, Huggins, P, Barnham, KJ & Cherny, RA 2017, 'The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson's disease.', Acta Neuropathologica Communications, vol. 5, no. 1, pp. 53-53.View/Download from: Publisher's site
Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions. In vitro, PBT434 was far less potent than deferiprone or deferoxamine at lowering cellular iron levels, yet was found to inhibit iron-mediated redox activity and iron-mediated aggregation of α-synuclein, a protein that aggregates in the neuropathology. In vivo, PBT434 did not deplete tissue iron stores in normal rodents, yet prevented loss of substantia nigra pars compacta neurons (SNpc), lowered nigral α-synuclein accumulation, and rescued motor performance in mice exposed to the Parkinsonian toxins 6-OHDA and MPTP, and in a transgenic animal model (hA53T α-synuclein) of PD. These improvements were associated with reduced markers of oxidative damage, and increased levels of ferroportin (an iron exporter) and DJ-1. We conclude that compounds designed to target a pool of pathological iron that is not held in high-affinity complexes in the tissue can maintain the survival of SNpc neurons and could be disease-modifying in PD.
Hare, DJ, Kysenius, K, Paul, B, Knauer, B, Hutchinson, RW, O'Connor, C, Fryer, F, Hennessey, TP, Bush, AI, Crouch, PJ & Doble, PA 2017, 'Imaging Metals in Brain Tissue by Laser Ablation - Inductively Coupled Plasma - Mass Spectrometry (LA-ICP-MS).', Journal of Visualized Experiments, no. 119, pp. 1-8.View/Download from: Publisher's site
Metals are found ubiquitously throughout an organism, with their biological role dictated by both their chemical reactivity and abundance within a specific anatomical region. Within the brain, metals have a highly compartmentalized distribution, depending on the primary function they play within the central nervous system. Imaging the spatial distribution of metals has provided unique insight into the biochemical architecture of the brain, allowing direct correlation between neuroanatomical regions and their known function with regard to metal-dependent processes. In addition, several age-related neurological disorders feature disrupted metal homeostasis, which is often confined to small regions of the brain that are otherwise difficult to analyze. Here, we describe a comprehensive method for quantitatively imaging metals in the mouse brain, using laser ablation - inductively coupled plasma - mass spectrometry (LA-ICP-MS) and specially designed image processing software. Focusing on iron, copper and zinc, which are three of the most abundant and disease-relevant metals within the brain, we describe the essential steps in sample preparation, analysis, quantitative measurements and image processing to produce maps of metal distribution within the low micrometer resolution range. This technique, applicable to any cut tissue section, is capable of demonstrating the highly variable distribution of metals within an organ or system, and can be used to identify changes in metal homeostasis and absolute levels within fine anatomical structures.
Portbury, SD, Hare, DJ, Sgambelloni, CJ, Bishop, DP, Finkelstein, DI, Doble, PA & Adlard, PA 2017, 'Age modulates the injury-induced metallomic profile in the brain.', Metallomics, vol. 9, no. 4, pp. 402-410.View/Download from: Publisher's site
The biological transition metals iron (Fe), copper (Cu) and zinc (Zn) are thought to contribute to the neuronal pathologies that occur following traumatic brain injury (TBI), and indeed our previously published work in young (3 month-old) mice clearly demonstrates a significant spatiotemporal modulation of metals following TBI. Of note, however, is the literature observation that there is both an apparent detrimental effect of aging on TBI outcomes and an alteration in metals and their various transporters with normal advancing age. Therefore, to determine whether there was an interaction between aging, metals and TBI, we have utilised laser ablation-inductively coupled plasma-mass spectrometry to examine the spatial and temporal distribution of Fe, Zn and Cu following an acute controlled cortical impact brain injury in aged (24 months) rodents. The relative abundance of metals in corresponding regions within the ipsilateral and contralateral hemispheres as well as the hippocampus was assessed. Substantial region and time point specific alterations in Fe, Zn and Cu were identified immediately and up to 28 days post-TBI. The data from this follow-up study has also been compared to our previous data from young animals, and aged mice exhibit an appreciably enhanced and persistent elevation of all metals in every region surveyed, with individual metal disparities at various time points observed post-injury. This may potentially contribute to the acceleration in the onset of cognitive decline and neurological disease that has been observed in the aged population following head trauma.
Bishop, DP, Clases, D, Fryer, F, Williams, E, Wilkins, S, Hare, DJ, Cole, N, Karst, U & Doble, PA 2016, 'Elemental bio-imaging using laser ablation-triple quadrupole-ICP-MS', JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY, vol. 31, no. 1, pp. 197-202.View/Download from: Publisher's site
Callahan, DL, Hare, DJ, Bishop, DP, Doble, PA & Roessner, U 2016, 'Elemental imaging of leaves from the metal hyperaccumulating plant Noccaea caerulescens shows different spatial distribution of Ni, Zn and Cd', RSC ADVANCES, vol. 6, no. 3, pp. 2337-2344.View/Download from: Publisher's site
Hare, DJ, Fryer, F, Paul, B, Bishop, DP & Doble, PA 2016, 'Characterisation of matrix-based polyatomic interference formation in laser ablation-inductively coupled plasma-mass spectrometry using dried micro-droplet ablation and its relevance for bioimaging', ANALYTICAL METHODS, vol. 8, no. 41, pp. 7552-7556.View/Download from: Publisher's site
Hare, DJ, Raven, EP, Roberts, BR, Bogeski, M, Portbury, SD, McLean, CA, Masters, CL, Connor, JR, Bush, AI, Crouch, PJ & Doble, PA 2016, 'Laser ablation-inductively coupled plasma-mass spectrometry imaging of white and gray matter iron distribution in Alzheimer's disease frontal cortex', NEUROIMAGE, vol. 137, pp. 124-131.View/Download from: Publisher's site
Leite Moraes, ML, Torres da Silva, HD, Blanes, L, Doble, P & Maggi Tavares, MF 2016, 'Optimization of chemometric approaches for the extraction of isorhamnetin-3-O-rutinoside from Calendula officinalis L.', JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, vol. 125, pp. 408-414.View/Download from: Publisher's site
Paul, B, Hare, DJ, Bishop, DP, Paton, C, Van, TN, Cole, N, Niedwiecki, MM, Andreozzi, E, Vais, A, Billings, JL, Bray, L, Bush, AI, McColl, G, Roberts, BR, Adlard, PA, Finkelstein, DI, Hellstrom, J, Hergt, JM, Woodhead, JD & Doble, PA 2016, 'Visualising mouse neuroanatomy and function by metal distribution using laser ablation-inductively coupled plasma-mass spectrometry imaging (vol 6, pg 5383, 2015)', CHEMICAL SCIENCE, vol. 7, no. 10, pp. 6576-6576.View/Download from: Publisher's site
Ueland, M, Blanes, L, Taudte, RV, Stuart, BH, Cole, N, Willis, P, Roux, C & Doble, P 2016, 'Capillary-driven microfluidic paper-based analytical devices for lab on a chip screening of explosive residues in soil', JOURNAL OF CHROMATOGRAPHY A, vol. 1436, pp. 28-33.View/Download from: Publisher's site
Adlard, PA, Parncutt, J, Lal, V, James, S, Hare, D, Doble, P, Finkelstein, DI & Bush, AI 2015, 'Metal chaperones prevent zinc-mediated cognitive decline', NEUROBIOLOGY OF DISEASE, vol. 81, pp. 196-202.View/Download from: Publisher's site
Bishop, DP, Hare, DJ, de Grazia, A, Fryer, F & Doble, PA 2015, 'Speciation and quantification of organotin compounds in sediment and drinking water by isotope dilution liquid chromatography-inductively coupled plasma-mass spectrometry', ANALYTICAL METHODS, vol. 7, no. 12, pp. 5012-5018.View/Download from: Publisher's site
Bishop, DP, Hare, DJ, Fryer, F, Taudte, RV, Cardoso, BR, Cole, N & Doble, PA 2015, 'Determination of selenium in serum in the presence of gadolinium with ICP-QQQ-MS', ANALYST, vol. 140, no. 8, pp. 2842-2846.View/Download from: Publisher's site
Cho, HR, Lee, Y, Doble, P, Bishop, D, Hare, D, Kim, Y-J, Kim, KG, Jung, HS, Park, KS, Choi, SH & Moon, WK 2015, 'Magnetic resonance imaging of the pancreas in streptozotocin-induced diabetic rats: Gadofluorine P and Gd-DOTA', WORLD JOURNAL OF GASTROENTEROLOGY, vol. 21, no. 19, pp. 5831-5842.View/Download from: Publisher's site
Davies, KM, Hare, DJ, Bohic, S, James, SA, Billings, JL, Finkelstein, DI, Doble, PA & Double, KL 2015, 'Comparative Study of Metal Quantification in Neurological Tissue Using Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry Imaging and X-ray Fluorescence Microscopy', ANALYTICAL CHEMISTRY, vol. 87, no. 13, pp. 6639-6645.View/Download from: Publisher's site
Hare, DJ, Arora, M, Jenkins, NL, Finkelstein, DI, Doble, PA & Bush, AI 2015, 'Is early-life iron exposure critical in neurodegeneration?', NATURE REVIEWS NEUROLOGY, vol. 11, no. 9, pp. 536-544.View/Download from: Publisher's site
Hare, DJ, Doecke, JD, Faux, NG, Rembach, A, Volitakis, I, Fowler, CJ, Grimm, R, Doble, PA, Cherny, RA, Masters, CL, Bush, AI & Roberts, BR 2015, 'Decreased Plasma Iron in Alzheimer's Disease Is Due to Transferrin Desatu ration', ACS CHEMICAL NEUROSCIENCE, vol. 6, no. 3, pp. 398-402.View/Download from: Publisher's site
Kim, SY, Naskar, D, Kundu, SC, Bishop, DP, Doble, PA, Boddy, AV, Chan, H-K, Wall, IB & Chrzanowski, W 2015, 'Formulation of Biologically-Inspired Silk-Based Drug Carriers for Pulmonary Delivery Targeted for Lung Cancer', SCIENTIFIC REPORTS, vol. 5.View/Download from: Publisher's site
Lee, S, Kim, J-E, Hong, S-H, Lee, A-Y, Park, E-J, Seo, HW, Chae, C, Doble, P, Bishop, D & Cho, M-H 2015, 'High Inorganic Phosphate Intake Promotes Tumorigenesis at Early Stages in a Mouse Model of Lung Cancer', PLOS ONE, vol. 10, no. 8.View/Download from: Publisher's site
Paul, B, Hare, DJ, Bishop, DP, Paton, C, Nguyen, VT, Cole, N, Niedwiecki, MM, Andreozzi, E, Vais, A, Billings, JL, Bray, L, Bush, AI, McColl, G, Roberts, BR, Adlard, PA, Finkelstein, DI, Hellstrom, J, Hergt, JM, Woodhead, JD & Doble, PA 2015, 'Visualising mouse neuroanatomy and function by metal distribution using laser ablation-inductively coupled plasma-mass spectrometry imaging', Chemical Science, vol. 6, no. 10, pp. 5383-5393.View/Download from: Publisher's site
Paul, B, Hare, DJ, Bishop, DP, Paton, C, Van, TN, Cole, N, Niedzwiecki, MM, Andreozzi, E, Vais, A, Billings, JL, Bray, L, Bush, AI, McColl, G, Roberts, BR, Adlard, PA, Finkelstein, DI, Hellstrom, J, Hergt, JM, Woodhead, JD & Doble, PA 2015, 'Visualising mouse neuroanatomy and function by metal distribution using laser ablation-inductively coupled plasma-mass spectrometry imaging (vol 6, pg 5383, 2015)', CHEMICAL SCIENCE, vol. 6, no. 11, pp. 6677-6677.View/Download from: Publisher's site
Ryan, TM, Roberts, BR, McColl, G, Hare, DJ, Doble, PA, Li, Q-X, Lind, M, Roberts, AM, Mertens, HDT, Kirby, N, Pham, CLL, Hinds, MG, Adlard, PA, Barnham, KJ, Curtain, CC & Masters, CL 2015, 'Stabilization of Nontoxic A beta-Oligomers: Insights into the Mechanism of Action of Hydroxyquinolines in Alzheimer's Disease', JOURNAL OF NEUROSCIENCE, vol. 35, no. 7, pp. 2871-2884.View/Download from: Publisher's site
Taudte, RV, Roux, C, Bishop, D, Blanes, L, Doble, P & Beavis, A 2015, 'Development of a UHPLC method for the detection of organic gunshot residues using artificial neural networks', Analytical Methods, vol. 7, no. 18, pp. 7447-7454.View/Download from: Publisher's site
The introduction of lead and heavy-metal free ammunition to the market challenges the current protocol for gunshot residue (GSR) investigations, which focuses on the inorganic components. Future proofing GSR analysis requires the development and implementation of new methods for the collection and analysis of organic GSR (OGSR) into operational protocols. This paper describes the development and optimisation of an ultra high performance liquid chromatography method for the analysis of 32 compounds potentially present in OGSR. An artificial neural network was applied to predict the retention times of the target analytes for various gradients for rapid determination of optimum separation conditions. The final separation and analysis time for the 32 target analytes was 27 minutes with limits of detection ranging from 0.03 to 0.21 ng. The method was applied to the analysis of smokeless powder and samples collected from the hands of a shooter following the discharge of a firearm. The results demonstrate that the method has the potential for use in cases involving GSR.
Adlard, PA, Sedjahtera, A, Gunawan, L, Bray, L, Hare, DJ, Lear, J, Doble, PA, Bush, A, Finkelstein, D & Cherny, R 2014, 'A novel approach to rapidly prevent age-related cognitive decline', Aging Cell, vol. 13, no. 2, pp. 351-359.View/Download from: Publisher's site
The loss of cognitive function is a pervasive and often debilitating feature of the aging process for which there are no effective therapeutics. We hypothesized that a novel metal chaperone (PBT2; Prana Biotechnology, Parkville, Victoria, Australia) would enhance cognition in aged rodents. We show here that PBT2 rapidly improves the performance of aged C57Bl/6 mice in the Morris water maze, concomitant with increases in dendritic spine density, hippocampal neuron number and markers of neurogenesis. There were also increased levels of specific glutamate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-d-aspartate), the glutamate transporter (VGLUT1) and glutamate itself. Markers of synaptic plasticity [calmodulin-dependent protein kinase II (CaMKII) and phosphorylated CaMKII, CREB, synaptophysin] were also increased following PBT2 treatment. We also demonstrate that PBT2 treatment results in a subregion-specific increase in hippocampal zinc, which is increasingly recognized as a potent neuromodulator. These data demonstrate that metal chaperones are a novel approach to the treatment of age-related cognitive decline.
cho, H, kim, D, Kim, D, Doble, PA, Bishop, D, Hare, DJ, Park, C, Moon, WK, Han, MH & Choi, SH 2014, 'Malignant Glioma: MR imaging by using 5-Aminolevulinic acid in an animal model', Radiology, vol. 272, no. 3, pp. 720-730.View/Download from: Publisher's site
Chou, J, Austin, C, Doble, P, Ben-Nissan, B & Milthorpe, B 2014, 'Trace elemental imaging of coralline hydroxyapatite by laser-ablation inductively coupled plasma-mass spectroscopy', JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, vol. 8, no. 7, pp. 515-520.View/Download from: Publisher's site
Hare, DJ, George, J, Bray, L, Volitakis, I, Vais, A, Ryan, T, Cherny, R, Bush, A, Masters, C, Adlard, P, Doble, PA & Finkelstein, D 2014, 'The effect of paraformaldehyde fixation and sucrose cryoprotection on metal concentration in murine neurological tissue', Journal of Analytical Atomic Spectrometry, vol. 29, pp. 565-570.View/Download from: Publisher's site
Aldehyde preservation of tissue and cryoprotection by sugars and polyols has traditionally been used in histology to preserve structural integrity of samples. The effect of paraformaldehyde (PFA) fixation and sucrose cryoprotection on murine brain metals was studied by examining the changes in total brain metal levels throughout a complete fixation/cryoprotection protocol. Blank-corrected metal levels in 4% PFA and two changes of 30% sucrose solutions following brain immersion were determined by ICP-MS. Fixed and cryoprotected tissue was lyophilised, digested in HNO3/H2O2 and analysed using the same ICP-MS protocol. The sum of metal loss or gain in each solution and total digest was used to determine the percentage of total brain metal present in fixed, cryoprotected tissue. Almost all K (99.78%) and Mg (78.01%) leached from brain tissue during fixation and cryoprotection, whilst Ca and Sr either retained or absorbed additional metal ions from the sucrose solution. Less water-soluble transition metals displayed smaller degrees of metal leaching, with Fe, Cu and Zn losing 26.6131.62% of their total metal content during preparation for cryosectioning. These results suggest that metal leaching is highly metal specific, and that preparatory steps for cryosectioning of brain tissue should be approached according to this specificity.
Hare, DJ, George, JL, Bray, L, Volitakis, I, Vais, A, Ryan, TM, Cherny, RA, Bush, AI, Masters, CL, Adlard, PA, Doble, PA & Finkelstein, DI 2014, 'The effect of paraformaldehyde fixation and sucrose cryoprotection on metal concentration in murine neurological tissue (vol 29, pg 565, 2014)', JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY, vol. 29, no. 9, pp. 1726-1726.
Hare, DJ, Lei, P, Ayton, S, Roberts, B, Grimm, R, George, J, Bishop, D, Beavis, AB, Donovan, S, McColl, G, Volitakis, I, Masters, C, Adlard, P, Cherny, R, Bush, A, Finkelstein, D & Doble, PA 2014, 'An iron-dopamine index predicts risk of parkinsonian neurodegeneration in the substantia nigra pars compacta', Chemical Science, vol. 5, pp. 2160-2169.View/Download from: Publisher's site
The co-localization of iron and dopamine raises the risk of a potentially toxic reaction. Disturbance of the balance in this unique chemical environment makes neurons in the substantia nigra pars compacta (SNc) particularly vulnerable to parkinsonian neurodegeneration in the aging brain. In Parkinson's disease, these neurons degenerate coincident with an elevation in brain iron levels, yet relatively little is known about specific regional iron distribution with respect to dopamine. To directly appraise the irondopamine redox couple, we applied immuno-assisted laser ablation-inductively coupled plasma-mass spectrometry imaging to co-localize iron with the dopamine-producing enzyme tyrosine hydroxylase at the coronal level of the substantia nigra. We found that in the healthy brain the SNc does not contain the greatest concentration of iron within the midbrain, while the dopamine-rich environment in this region reflects an increased oxidative load. The product of iron and dopamine was significantly greater in the SNc than the adjacent ventral tegmental area, which is less susceptible to neuron loss in Parkinson's disease. Accordingly, this `risk factor was elevated further following 6-hydroxydopamine (6-OHDA) lesioning. Considering mounting evidence that brain iron increases with age, this measurable irondopamine index provides direct experimental evidence of a relationship between these two redox-active chemicals in degenerating dopaminergic neurons.
Lloyd, AE, Russell, M, Blanes, L, Somerville, R, Doble, PA & Roux, CP 2014, 'The application of portable microchip electrophoresis for the screening and comparative analysis of synthetic cathinone seizures', Forensic Science International, vol. 242, pp. 16-23.View/Download from: Publisher's site
Variation in the chemical composition of illicit tablets and powders is common among samples within a given drug seizure. Using microchip electrophoresis (ME), multiple tablets can be screened in a cost-effective and timely manner. This method could be used in conjunction with reporting methods that focus solely on statistical sampling to infer homogeneity or otherwise of a larger subset of tablets. Some frequently observed synthetic cathinones, often present in illicit tablets seized in New Zealand, were chosen for analysis. An ME device (Agilent Bioanalyzer 2100) was used to electrophoretically separate synthetic cathinones. The background electrolyte was composed of a 50mM sodium tetraborate buffer with 50mM sodium dodecyl sulphate at pH 9.66. Analytes were derivatised prior to analysis for 3min at 90°C, employing fluorescein isothiocyanate isomer I (FITC). A characteristic fluorescent profile was obtained for each tablet, in terms of the number of constituents, relative peak height ratios and migration times. The repeatability of the developed method was assessed for a wide range of tablets and relative standard deviations of 0.4-5.2% and 1.6-5.5% were calculated for migration times and peak height ratios, respectively. The use of microchip tablet profiles in the forensic case comparison of illicit drug seizure samples in realistic scenarios is discussed.
McGowan, N, Fowler, A, Parkinson, K, Bishop, D, Ganio, K, Doble, PA, Booth, DJ & Hare, DJ 2014, 'Beyond the transect: An alternative microchemical imaging method for fine scale analysis of trace elements in fish otoliths during early life', The Science of the Total Environment, vol. 494-495, pp. 177-186.View/Download from: Publisher's site
Microchemical analysis of otolith (calcified `ear stones used for balance and orientation) of fishes is an important tool for studying their environmental history and management. However, the spatial resolution achieved is often too coarse to examine short-termevents occurring in early life. Current methods rely on single points or transects across the otolith surface, which may provide a limited viewof elemental distributions, a matter that has not previously been investigated. Imaging by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS) permits microchemical analyses of short-term events in early life with high (b10 ìm) resolution, twodimensional (2D) visualization of elemental distributions. To demonstrate the potential of this method, we mapped the concentrations of Sr and Ba, two key trace elements, in a small number of juvenile otoliths of neon damselfish (Pomacentrus coelestis) using an 8 ìm beam diameter (laser fluence of 13.8 ± 3.5 J cm.2). Quantification was performed using the established method by Longerich et al. (1996), which is applied to 2D imaging of a biological matrix here for the first time. Accuracy of N97% was achieved using a multi-point non matrix-matched calibration of National Institute of Standards and Technology (NIST) 610 and 612 (trace elements in glass) using Longerich's calculation method against the matrix-matched standard FEBS-1 (powdered red snapper [Lutjanus campechanus] otolith). The spatial resolution achieved in the otolith corresponded to a time period of 2 ± 1 days during the larval phase, and 4 ± 1 days during the post-settlement juvenile phase. This method has the potential to improve interpretations of early life-history events at scales corresponding to specific events. While the images showed gradients in Sr and Ba across the larval settlement zone more clearly.
Pesenti, A, Taudte, RV, McCord, B, Doble, PA, Blanes, L & Roux, CP 2014, 'Coupling Paper-Based Microfluidics and Lab on a Chip Technologies for Confirmatory Analysis of Trinitro Aromatic Explosives', Analytical Chemistry, vol. 86, pp. 4707-4714.View/Download from: Publisher's site
A new microfluidic paper-based analytical device (ìPAD) in conjunction with confirmation by a lab on chip analysis was developed for detection of three trinitro aromatic explosives. Potassium hydroxide was deposited on the ìPADs (0.5 ìL, 1.5 M), creating a color change reaction when explosives are present, with detection limits of approximately 7.5 ± 1.0 ng for TNB, 12.5 ± 2.0 ng for TNT and 15.0 ± 2.0 ng for tetryl. For confirmatory analysis, positive ìPADs were sampled using a 5 mm hole-punch, followed by extraction of explosives from the punched chad in 30 s using 20 ìL borate/SDS buffer. The extractions had efficiencies of 96.5 ± 1.7%. The extracted explosives were then analyzed with the Agilent 2100 Bioanalyzer lab on a chip device with minimum detectable amounts of 3.8 ± 0.1 ng for TNB, 7.0 ± 0.9 ng for TNT, and 4.7 ± 0.2 ng for tetryl. A simulated in-field scenario demonstrated the feasibility of coupling the ìPAD technique with the lab on a chip device to detect and identify 1 ìg of explosives distributed on a surface of 100 cm2.
Porto, SKSS, Nogueira, T, Blanes, L, Doble, P, Sabino, BD, do Lago, CL & Angnes, L 2014, 'Analysis of Ecstasy Tablets Using Capillary Electrophoresis with Capacitively Coupled Contactless Conductivity Detection', JOURNAL OF FORENSIC SCIENCES, vol. 59, no. 6, pp. 1622-1626.View/Download from: Publisher's site
Roberts, B, Lim, N, McAllum, E, Donnelly, P, Hare, DJ, Doble, PA, Turner, B, Price, K, Lim, SC, Paterson, B, Hickey, J, Rhoads, T, Williams, J, Kunninen, K, Hung, L, Liddell, J, Grubman, A, Monty, J, Llanos, R, Kamer, D, Mercer, J, Bush, A, Masters, C, Duce, J, Li, Q, Beckman, J, Barnham, K, White, A & Crouch, P 2014, 'Oral Treatment with Cu(II)(atsm) Increases Mutant SOD1 In Vivo but Protects Motor Neurons and Improves the Phenotype of a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis', The Journal of Neuroscience, vol. 34, no. 23, pp. 8021-8031.View/Download from: Publisher's site
Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent phenotype in transgenic rodents. We show that oral treatment with the therapeutic agent diacetyl-bis(4- methylthiosemicarbazonato)copperII [CuII(atsm)] increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but paradoxically improved locomotor function and survival of the mice. To determine why the mice with increased levels of mutant SOD1 had an improved phenotype, we analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with CuII(atsm) decreased the pool of Cu-deficient SOD1 and increased the pool of fully metallated (holo) SOD1. Tracking isotopically enriched 65CuII(atsm) confirmed the increase in holo-SOD1 involved transfer of Cu from CuII(atsm) to SOD1, suggesting the improved locomotor function and survival of the CuII(atsm)-treated SOD1G37R mice involved, at least in part, the ability of the compound to improve the Cu content of the mutant SOD1. This was supported by improved survival of SOD1G37Rmice that expressed thehumangene for theCuuptake protein CTR1. Improving the metal content of mutantSOD1in vivo with CuII(atsm) did not decrease levels of misfolded SOD1. These outcomes indicate the metal content of SOD1 may be a greater determinant of the toxicity of the protein in mutant SOD1-associated forms of ALS than the mutations themselves. Improving the metal content of SOD1 therefore represents a valid therapeutic strategy for treating ALS caused by SOD1.
Taudte, RV, Beavis, AB, Blanes, L, Cole, NA, Doble, PA & Roux, CP 2014, 'Detection of Gunshot Residues Using Mass Spectrometry', BioMed Research International, vol. 965403, pp. 1-16.View/Download from: Publisher's site
In recent years, forensic scientists have become increasingly interested in the detection and interpretation of organic gunshot residues (OGSR) due to the increasing use of lead- and heavy metal-free ammunition. This has also been prompted by the identification of gunshot residue- (GSR-) like particles in environmental and occupational samples. Various techniques have been investigated for their ability to detect OGSR.Mass spectrometry (MS) coupled to a chromatographic system is a powerful tool due to its high selectivity and sensitivity. Further,modernMS instruments can detect and identify a number of explosives and additives whichmay require different ionization techniques. Finally,MS has been applied to the analysis of bothOGSR and inorganic gunshot residue (IGSR), although the gold standard for analysis is scanning electron microscopy with energy dispersive X-ray microscopy (SEM-EDX). This review presents an overview of the technical attributes of currently available MS and ionization techniques and their reported applications to GSR analysis.
Austin, CE, Smith, TM, Bradman, A, Hinde, K, Joannes-Boyau, R, Bishop, DP, Hare, DJ, Doble, PA, Eskenazi, B & Arora, M 2013, 'Barium distributions in teeth reveal early-life dietary transitions in primates', Nature, vol. 498, pp. 216-219.View/Download from: Publisher's site
Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations1, 2. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth3. Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization4. Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mothers milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation.
Finkelstein, DI, George, JL, Adlard, PA, Masters, CL, Hare, DJ, Doble, PA, Gautier, E, Parsons, J, Kok, G, Huggins, P, Barnham, KJ, Bush, AI & Cherny, RA 2013, 'PBT434, a novel 8-hydroxyquinazolinone, preserves nigro-striatal circuitry, improves motor performance and inhibits alpha synuclein accumulation in animal models of Parkinson's disease by modulation of iron homeostasis', MOVEMENT DISORDERS, vol. 28, pp. S369-S369.
Hare, DJ, Adlard, PA, Doble, PA & Finkelstein, DI 2013, 'Metallobiology of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine neurotoxicity', Metallomics, vol. 5, no. 2, pp. 91-109.View/Download from: Publisher's site
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent toxin used to selectively destroy dopaminergic neurons in the substantia nigra and induce parkinsonism. MPTP is metabolised to the 1-methyl-4-phenylpyridinium ion (MPP(+)) in glia, after which it enters the neuron via the dopamine transporter and results in elevated levels of oxidative stress. The mechanism through which MPP(+) causes cell death is thought to involve redox-active metals, particularly iron (Fe). This review will examine how cellular metal metabolism is altered following MPTP insult, and how this relates to metal dyshomeostasis in idiopathic Parkinson's disease. This includes both cell damage arising from increased metal concentration, and how metal-binding proteins respond to MPTP-induced neurotoxicity. Implications for using MPTP as a model for human Parkinson's disease will be discussed in terms of cell metallobiology.
Hare, DJ, Grubman, A, Ryan, T, Lothian, A, Liddell, J, Grimm, R, Matsuda, T, Doble, PA, Cherny, R, Bush, A, White, A, Masters, C & Roberts, BR 2013, 'Profiling the iron, copper and zinc content in primary neuron and astrocyte cultures by rapid online quantitative size exclusion chromatography-inductively coupled plasma-mass spectrometry', Metallomics, vol. 5, no. 12, pp. 1656-1662.View/Download from: Publisher's site
Metals often determine the chemical reactivity of the proteins to which they are bound. Each cell in the body tightly maintains a unique metalloproteomic profile, mostly dependent on function. This paper describes an analytical online flow injection quan
Hare, DJ, Lear, J, Bishop, DP, Beavis, AB & Doble, PA 2013, 'Protocol for production of matrix-matched brain tissue standards for imaging by laser ablation-inductively coupled plasma-mass spectrometry', Analytical Methods, vol. 5, no. 8, pp. 1915-1921.View/Download from: Publisher's site
Calibration with matrix-matched standards remains the most practical means for producing quantitative images of trace metal distribution in tissue sections by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). A general guide for producing matrix-matched standards for assay of trace metals in brain tissue is presented. Cortical tissue was taken from pooled sheep brains and spiked with varying approximate concentrations of standard solutions of Co, Cu, Fe, Mg, Mn, Sr, Se and Zn. The tissue was homogenised and the total analyte amount accurately determined by solution nebulisation ICP-MS. The analytical ?gures of merit for LA-ICP-MS imaging were determined from these tissue standards cryosectioned at 30 mm. Repeated 8-point calibration curves were reproducibly linear, with correlation coe?cients ranging from 0.9874 (Mg) to 0.9991 (Sr). Limits of analysis were suitable for quantifying most analytes in a sample mouse brain, with the exception of Co and Se
Lloyd, AE, Russell, M, Blanes, L, Doble, PA & Roux, CP 2013, 'Lab-on-a-chip screening of methamphetamine and pseudoephedrine in samples from clandestine laboratories', Forensic Science International, vol. 228, no. 1-3, pp. 8-14.View/Download from: Publisher's site
The clandestine manufacture of methamphetamine in New Zealand predominantly involves the reduction of pseudoephedrine, extracted from pharmaceutical preparations, using hydrogen iodide. This method of illicit manufacture leaves a variety of materials at the scene that are a rich source of information. Efficient processing and preliminary identification of extraction and reaction mixtures, precursors and products is essential to minimise exposure to potential hazardous materials and to provide investigative and intelligence information. In this study, we employed a portable lab-on-a-chip instrument for the rapid and cost effective screening of methamphetamine, pseudoephedrine and ephedrine in a variety of sample types found in typical clandestine laboratory scenarios
Nuchtavorn, N, Smejkal, P, Breadmore, MC, Guijt, RM, Doble, PA, Bek, F, Foret, F, Suntornsuk, L & Macka, M 2013, 'Exploring chip-capillary electrophoresis-laser-induced fluorescence field-deployable platform flexibility: Separations of fluorescent dyes by chip-based non-aqueous capillary electrophoresis', Journal of Chromatography A, vol. 1286, no. 1, pp. 216-221.View/Download from: Publisher's site
Microfluidic chip electrophoresis (chip-CE) is a separation method that is compatible with portable and on-site analysis, however, only few commercial chip-CE systems with laser-induced fluorescence (LIF) and light emitting diode (LED) fluorescence detection are available. They are established for several application tailored methods limited to specific biopolymers (DNA, RNA and proteins), and correspondingly the range of their applications has been limited. In this work we address the lack of commercially available research-type flexible chip-CE platforms by exploring the limits of using an application-tailored system equipped with chips and methods designed for DNA separations as a generic chip-CE platform this is a very significant issue that has not been widely studied. In the investigated Agilent Bioanalyzer chip-CE system, the fixed components are the Agilent chips and the detection (LIF at 635 nm and LEDIF at 470 nm), while the chemistry (electrolyte) and the programming of all the high voltages are flexible. Using standard DNA chips, we show that a generic CE function of the system is easily possible and we demonstrate an extension of the applicability to non-aqueous CE (NACE). We studied the chip compatibility with organic solvents (i.e. MeOH, ACN, DMF and DMSO) and demonstrated the chip compatibility with DMSO as a non-volatile and non-hazardous solvent with satisfactory stability of migration times over 50 h. The generic CE capability is illustrated with separations of fluorescent basic blue dyes methylene blue (MB), toluidine blue (TB), nile blue (NB) and brilliant cresyl blue (BC).
Sanchez-Bayo, FP, Hyne, R, Kibria, G & Doble, PA 2013, 'Calibration and field application of Chemcatcher passive samplers for detecting amitrole residues in agricultural drain waters', Bulletin Of Environmental Contamination And Toxicology, vol. 90, no. 6, pp. 635-639.View/Download from: Publisher's site
A passive sampler device suitable for monitoring of residues of the hydrophilic ionic herbicide amitrole in irrigation waterways was developed. Uptake of amitrole on styrenedivinylbenzene-reverse phase sulfonated Empore disks was linear and proportional to its water concentration over the range of 110 µg/L with a sampling rate of 23.1 mL/day under laboratory flow-through conditions. Performance of the sampler was evaluated by deployment in an agricultural irrigation drain for 10 days. The amount of amitrole adsorbed by the passive samplers compared well with the cumulative mean water concentrations calculated from daily spot samplings of the drain water.
Taudte, RV, Beavis, AB, Wilson-Wilde, L, Roux, CP, Doble, PA & Blanes, L 2013, 'A portable explosive detector based on fluorescence quenching of pyrene deposited on coloured wax-printed µpADs', Lab on a Chip - Miniaturisation for Chemistry,Physics, Biology, materials science and bioengineering, vol. 13, no. 21, pp. 4164-4172.View/Download from: Publisher's site
A new technique for the detection of explosives has been developed based on fluorescence quenching of pyrene on paper-based analytical devices (µPADs). Wax barriers were generated (150 °C, 5 min) using ten different colours. Magenta was found as the most suitable wax colour for the generation of the hydrophobic barriers with a nominal width of 120 µm resulting in fully functioning hydrophobic barriers. One microliter of 0.5 mg mL-1 pyrene dissolved in an 80:20 methanolwater solution was deposited on the hydrophobic circle (5 mm diameter) to produce the active microchip device. Under ultra-violet (UV) illumination, ten different organic explosives were detected using the µPAD, with limits of detection ranging from 100600 ppm. A prototype of a portable battery operated instrument using a 3 W power UV light-emitting-diode (LED) (365 nm) and a photodiode sensor was also built and evaluated for the successful automatic detection of explosives and potential application for field-based screening.
Veasey, SC, Lear, J, Zhu, Y, Grinspan, JB, Hare, DJ, Wang, S, Bunch, D, Doble, PA & Robinson, SR 2013, 'Long-Term Intermittent Hypoxia Elevates Cobalt Levels in the Brain and Injures White Matter in Adult Mice', Sleep, vol. 36, no. 10, pp. 1471-1481.View/Download from: Publisher's site
Study Objectives: Exposure to the variable oxygenation patterns in obstructive sleep apnea (OSA) causes oxidative stress within the brain. We hypothesized that this stress is associated with increased levels of redox-active metals and white matter injury. Design: Participants were randomly allocated to a control or experimental group (single independent variable). Setting: University animal house. Participants: Adult male C57BL/6J mice. Interventions: To model OSA, mice were exposed to long-term intermittent hypoxia (LTIH) for 10 hours/day for 8 weeks or sham intermittent hypoxia (SIH).
Blanes, L, Tomazelli Coltro, WK, Saito, RM, Van Gramberg, AA, do Lago, CL & Doble, PA 2012, 'High-voltage power supplies to capillary and microchip electrophoresis', Electrophoresis, vol. 33, no. 6, pp. 893-898.View/Download from: Publisher's site
Over the past years, the development of capillary electrophoresis (CE) and microchip electrophoresis (ME) systems has grown due to instrumental simplicity and wide application. In both CE andME, the application of a high voltage (HV) is a crucial step in the electrokinetic (EK) injection and separation processes. Particularly on ME devices, EK injection is often performed with three different modes: gated, pinched, and unpinched. In all these cases, different potential values may be applied to one or multiple channels to control the injection of small sample volumes as well as the separation process. For this reason, the construction of reliable HV power supplies (HVPS) is required. This review covers the advances of the development of commercial and laboratory-built HVPS for CE and ME. Moreover, it intends to be a guide for new developers of electrophoresis instrumentation.
Hare, DJ, Austin, CE & Doble, PA 2012, 'Quantification strategies for elemental imaging of biological samples using laser ablation-inductively coupled plasma-mass spectrometry', The Analyst, vol. 137, pp. 1527-1537.View/Download from: Publisher's site
This review provides analysts with critical insights of current approaches for quantification by laser ablation-inductively coupled plasma-mass spectrometry in the field of elemental imaging. This encompasses both calibration strategies that have been used with success in imaging biological samples, as well as those with potential to improve analytical accuracy and precision if applied to imaging. Methods reviewed include the use of CRMs, laboratory prepared matrix matched standards, internal standardisation, online standard addition and a variety of novel approaches that makes elemental imaging accessible to a wider base of analysts. The importance of quantification and factors affecting its use in imaging will also be considered.
Hare, DJ, Lee, JK, Beavis, AB, Van Gramberg, AA, George, J, Adlard, PA, Finkelstein, DI & Doble, PA 2012, 'Three-dimensional atlas of iron, copper, and zinc in the mouse cerebrum and brainstem', Analytical Chemistry, vol. 84, no. 9, pp. 3990-3997.View/Download from: Publisher's site
Atlases depicting molecular and functional features of the brain are becoming an integral part of modern neuroscience. In this study we used laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS) to quantitatively measure iron (Fe), copper (Cu), and zinc (Zn) levels in a serially sectioned C57BL/6 mouse brain (cerebrum and brainstem). Forty-six sections were analyzed in a single experiment of approximately 158 h in duration. We constructed a 46-plate reference atlas by aligning quantified images of metal distribution with corresponding coronal sections from the Allen Mouse Brain Reference Atlas. The 46 plates were also used to construct three-dimensional models of Fe, Cu, and Zn distribution. This atlas represents the first reconstruction of quantitative trace metal distribution through the brain by LA-ICPMS and will facilitate the study of trace metals in the brain and help to elucidate their role in neurobiology.
Lear, J, Hare, DJ, Adlard, P, Finkelstein, D & Doble, PA 2012, 'Improving acquisition times of elemental bio-imaging for quadrupole-based LA-ICP-MS', Journal of Analytical Atomic Spectrometry, vol. 27, no. 1, pp. 159-164.View/Download from: Publisher's site
Elemental bio-imaging experiments by quadrupole-based LA-ICP-MS normally employ scan speeds where the distance traversed in one second is equal to or less than the diameter of the laser beam. Consequently, data for a higher-resolution (pixel size = 15 µm2) image of a 5 mm2 tissue section can take upwards of 30 h to acquire. Appropriate laser scan speeds may be calculated by consideration of the relationship between laser scan speed, laser spot diameter and the total scan cycle of the quadrupole mass analyser. This paper presents a simple method to calculate the laser scan speeds capable of reducing the acquisition time by up to a factor of 5 whilst maintaining dimensional integrity of the image.
Lear, J, Hare, DJ, Fryer, F, Adlard, PA, Finkelstein, DI & Doble, PA 2012, 'High-resolution elemental bioimaging of Ca, Mn, Fe, Co, Cu, and Zn employing LA-ICP-MS and hydrogen reaction gas', Analytical Chemistry, vol. 84, no. 15, pp. 6707-6714.View/Download from: Publisher's site
Imaging of trace metal distribution in tissue sections by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is typically performed using spatial resolutions of 30 µm2 and above. Higher resolution imaging is desirable for many biological applications in order to approach the dimensions of a single cell. The limiting factor for increasing resolution is sensitivity, where signal-to-noise ratios are poor due to inherent background spectral interferences and reduced sample volume with decreasing laser beam diameter. Several prominent spectral interferences are present for a number of biologically relevant isotopes, including the 40Ar16O+ spectral interference on 56Fe+. We examined if H2 as a reaction gas could improve the analytical performance of imaging experiments for a range of masses with spectral interferences. At low (<1 mL min1) H2 flow rates, greater spectral interference due to H+ adducts was observed for 55Mn, 57Fe, and 59Co. At higher flow rates of up to 3 mL H2 per minute, the spectral interferences were reduced leading to improvement in limits of analysis for masses with O- and N-based polyatomic interferences. Enhanced sensitivity with the reaction cell allowed construction of high resolution (6 µm2) imaging of 56Fe in the mouse brain that approached the dimensions of single cells.
Molnar, A, Lewis, JH, Doble, PA, Hansen, G, Prolov, T & Fu, S 2012, 'A Rapid And Sensitive Method For The Identification Of Delta-9-Tetrahydrocannabinol In Oral Fluid By Liquid Chromatography-Tandem Mass Spectrometry', Forensic Science International, vol. 215, no. 1-3, pp. 92-96.View/Download from: Publisher's site
A fast and sensitive method was developed for detecting delta-9-tetrahydrocannabinol (THC) in oral fluid by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method is suitable for samples of small volume and low concentration. For method de
Morelato, M, Beavis, AB, Ogle, A, Doble, PA, Kirkbride, KP & Roux, CP 2012, 'Screening of gunshot residues using desorption electrospray ionisation-mass spectrometry (DESI-MS)', Forensic Science International, vol. 217, no. 1-3, pp. 101-106.View/Download from: Publisher's site
Several studies have indicated that there are potential environmental sources of particles resembling inorganic primer found in gunshot residues (GSR); as a consequence examiners are reluctant to unambiguously assign the origin of inorganic particles. If organic gunshot residues (OGSR) were found in combination with inorganic particles, the possibility of environmental sources could be potentially eliminated, thereby significantly enhancing the strength of the evidence. Methods have been previously described whereby GSR specimens can be analysed for the presence of OGSR or inorganic GRS (IGSR). However, no methods have been reported that allow the analysis of both OGSR and IGSR on the same specimen. Described in this article is a direct method using desorption electrospray ionisation-mass spectrometry (DESI-MS) for the detection of methyl centralite (MC), ethyl centralite (EC) and diphenylamine (DPA) on adhesive tape GSR stubs typically used for scanning electron microscopy-energy-dispersive X-ray (SEM-EDX) analysis. The optimisation of numerous parameters was conducted using an experimental design. The results indicate that direct analysis of these organic components of GSR is possible although some limitations were also identified. This initial investigation has also indicated that subjecting stubs to DESI analysis does not interfere with subsequent SEM-EDX analysis of primer residues; therefore the technique described herein allows a comprehensive examination of GSR that would be highly probative in the event that both OGSR and IGSR are detected in the same specimen.
Arora, M, Hare, DJ, Austin, CE, Smith, DB & Doble, PA 2011, 'Spatial Distribution Of Manganese In Enamel And Coronal Dentine Of Human Primary Teeth', Science Of The Total Environment, vol. 409, no. 7, pp. 1315-1319.View/Download from: Publisher's site
Emerging evidence indicates that excessive exposure to manganese (Mn) during the prenatal period and early childhood may result in neurodevelopmental deficits. However, accurate exposure biomarkers are not well established, limiting our understanding of exposureresponse relationships over these susceptible periods of development. Naturally shed deciduous teeth are potentially a useful biomarker of environmental exposure to Mn. However, the uptake and distribution of Mn in human teeth has not been studied in detail. Mn distribution was measured at high resolution (~20 ìm) in eight human primary teeth using laser ablationinductively coupled plasma-mass spectrometry. A bio-imaging methodology was applied to construct detailed elemental maps of three incisors, and bone meal (NIST SRM 1486) was used to validate the analyses. The distribution of Mn in enamel and coronal dentine showed a distinct and reproducible pattern. In enamel, the 55Mn:43Ca ratio was highest at the outer edge of enamel (range=0.57 to 4.74) for approximately 2040 ìm butwas substantially lower in deeper layers (range=0.005 to 0.013). The highest levels ofMnwere observed in dentine immediately adjacent the pulpal margin (55Mn:43Ca range=2.27 to 6.95). Importantly, a clearly demarcated high Mn zone was observed in dentine at the incisal end of the teeth. Using confocal laser scanning microscopy to visualize the neonatal line, this region was identified as being in the prenatally formed dentine. The high-resolution map of the spatial distribution of Mn in human primary teeth highlighted specific reproducible patterns of Mn distribution in enamel and coronal dentine.
Austin, CE, Fryer, FI, Lear, J, Bishop, DP, Hare, DJ, Rawling, T, Kirkup, L, McDonagh, AM & Doble, PA 2011, 'Factors Affecting Internal Standard Selection For Quantitative Elemental Bio-Imaging Of Soft Tissues By LA-ICP-MS', Journal of Analytical Atomic Spectrometry, vol. 26, no. 7, pp. 1494-1501.View/Download from: Publisher's site
Element response variations under different laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) operating conditions were investigated to identify important factors for selecting an internal standard (IS) for quantitative elemental bi
Hare, DJ, Austin, CE, Doble, PA & Arora, M 2011, 'Elemental Bio-imaging Of Trace Elements In Teeth Using Laser Ablation-inductively Coupled Plasma-mass Spectrometry', Journal of Dentistry, vol. 39, no. 5, pp. 397-403.View/Download from: Publisher's site
Objectives: In this study we present the application of a novel laboratory method that employs laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to construct two-dimensional maps of trace elements in teeth. Methods: Teeth were secti
Lloyd, AE, Blanes, L, Beavis, AB, Roux, CP & Doble, PA 2011, 'A Rapid Method For The In-Field Analysis Of Amphetamines Employing The Agilent Bioanalyzer', Analytical Methods, vol. 3, no. 7, pp. 1535-1539.View/Download from: Publisher's site
This paper reports the first analysis of small molecules on the Agilent bio-analyser. The Bioanalyzer is a commercial lab-on-a-chip instrument designed for the analysis of DNA and proteins. We demonstrate that the instrument is suitable for analyses beyo
Tolmachev, SY, Ketterer, E, Hare, DJ, Doble, PA & James, AC 2011, 'The US Transuranium and Uranium Registries: forty years' experience and new directions in the analysis of actinides in human tissues', Radiochimica Acta, vol. 1, pp. 173-181.View/Download from: Publisher's site
The US Transuranium and Uranium Registries (USTUR) studies the distribution, biokinetics and tissue dosimetry of actinide elements through radiochemical analysis of autopsy tissues voluntarily donated by occupationally exposed persons. The paper provides an overview of the analytical methods for plutonium (Pu), americium (Am) and uranium (U) isotopic determination in human tissues currently applied at USTUR. The results of inter-comparing 239+240Pu, 241Am and 234,235,238U determinations by sector ?eld inductively coupled mass spectrometry (SF-ICP-MS), a-spectrometry (AS) and kinetic phosphorescence analysis (KPA) are discussed. SFICP-MS is a major advance over AS and KPA in enabling the measurement of the 240Pu/ 239Pu atom ratio, the short-lived ß-emitter 241Pu, and long-lived 236U. For the ?rst time, 241Am and 241Pu were measured in human tissues using SF-ICP-MS. The paper also presents a new avenue of USTUR research in the application of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to elemental bio-imaging (EBI) of the actinides in human tissues.
Austin, CE, Hare, DJ, Rawling, T, McDonagh, AM & Doble, PA 2010, 'Quantification method for elemental bio-imaging by LA-ICP-MS using metal spiked PMMA films', Journal of Analytical Atomic Spectrometry, vol. 25, no. 5, pp. 722-725.View/Download from: Publisher's site
A method for quantitative analysis of biological soft tissues by laser ablation-inductively coupled plasma-mass spectrometry has been developed. Polymer film standards were produced by spin coating spiked solutions of poly methyl methacrylate onto quartz substrates. Calibration curves throughout the range of 0--400"llg g-l yielded correlation coefficients better than 0.999 for 66Zn and 63CU. Spiked, homogenised soft tissue standards were quantified by LA-ICP-MS against the thin film standards. The results agreed with values calculated from solution nebulisation rCP-MS. A procedure for internal standardisation by employing ruthenium or yttrium in the underlying thin film was also assessed.
Epple, R, Blanes, L, Beavis, AB, Roux, CP & Doble, PA 2010, 'Analysis of amphetamine-type substances by capillary zone electrophoresis using capacitively coupled contactless conductivity detection', Electrophoresis, vol. 31, no. S1, pp. 2608-2613.View/Download from: Publisher's site
CE with capacitively coupled contactless conductivity detection (C4D) was employed for the separation and detection of seven amphetamine analogues as well as amphetamine, dextroamphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine. The separation electrolyte was 30 mM hydroxypropyl-~-cyclodextrin (HPPCD) in a 75 mM acetic acid+25 mM sodium acetate buffer adjusted to pH 4.55. Conductivity detection was compared with UV detection using this same electrolyte. Average detection limits for C4D and UV were 1.3 and 1.0 ppm, respectively. The effects of HPPCO -concentration and BGE composition on the selectivity of the separation were also investigated. An illicit, street-grade sample of 3,4-methylenedioxymethamphetamine (Ecstasy) and a prescription dextroamphetamine tablet were also analysed.
Hare, DJ, George, JL, Grimm, R, Wilkins, SW, Adlard, P, Cherny, R, Bush, A, Finkelstein, D & Doble, PA 2010, 'Three-Dimensional Elemental Bio-Imaging Of Fe, Zn, Cu, Mn And P In A 6-Hydroxydopamine Lesioned Mouse Brain', Metallomics, vol. 2, no. 11, pp. 745-753.View/Download from: Publisher's site
Three dimensional maps of iron (Fe), zinc (Zn), copper (Cu), manganese (Mn) and phosphorous (P) in a 6-hydroxydopamine (6-OHDA) lesioned mouse brain were constructed employing a novel quantitative laser ablation-inductively coupled plasma-mass spectromet
Hare, DJ, Tolmachev, S, James, A, Bishop, DP, Austin, CE, Fryer, FI & Doble, PA 2010, 'Elemental bio-imaging of thorium, uranium, and plutonium in tissues from occupationally exposed former nuclear workers', Analytical Chemistry, vol. 82, no. 8, pp. 3176-3182.View/Download from: Publisher's site
Internal exposure from naturally occurring radionuclides (including the inhaled long-lived actinides 232Th and 238U) is a component of the ubiquitous background radiation dose (National Council on Radiation Protection and Measurements. Ionizing radiation exposure of the population of the United States; NCRP Report No. 160; NCRP: Bethesda, MD, 2009). It is of interest to compare the concentration distribution of these natural ?-emitters in the lungs and respiratory lymph nodes with those resulting from occupational exposure, including exposure to anthropogenic plutonium and depleted and enriched uranium. This study examines the application of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS) to quantifying and visualizing the mass distribution of uranium and thorium isotopes from both occupational and natural background exposure in human respiratory tissues and, for the first time, extends this application to the direct imaging of plutonium isotopes. Sections of lymphatic and lung tissues taken from deceased former nuclear workers with a known history of occupational exposure to specific actinide elements (uranium, plutonium, or americium) were analyzed by LA-ICPMS.
Austin, CE, Hare, DJ, Rozelle, A, Robinson, W, Grimm, R & Doble, PA 2009, 'Elemental bio-imaging of calcium phosphate crystal deposits in knee samples from arthritic patients', Metallomics, vol. 1, no. 2, pp. 142-147.View/Download from: Publisher's site
Laser ablation inductively coupled plasma mass spectrometry (LA ICP-MS) was employed to image deposits of calcium phosphate based crystals in knee cartilage and synovial fluid from arthritic patients. A reaction/collision cell containing hydrogen minimised plasma interferences on calcium and also improved the image quality without significant sensitivity reduction. Areas of high calcium and phosphorus intensities consistent with crystal deposits were observed for both the cartilage and synovial fluid samples. These areas were also characterised by high magnesium and strontium intensities. Distribution patterns of other elements such as copper and sulfur did not correlate with the crystal deposits. Filtered and non-filtered solutions of calcium phosphate crystals grown in synthetic synovial fluid were also imaged as further evidence of crystal deposits. The crystal deposits were detected in the unfiltered Solution, and were absent from the filtered solutions.
Trace elements play a key role in a wide range of biological processes. A full understanding of those processes requires a knowledge not only of the genomics and proteomics of the organism, but also the distribution and concentration of trace elements. A new application of inductively coupled plasma mass spectrometry (ICP-MS) provides the capability to directly visualize trace elements in soft tissue, offering the promise of improved diagnosis and monitoring of disease. © 2009 The Biochemical Society.
Hare, DJ, Haarburger, D, Austin, CE, Fryer, FI, Grimm, R, Reedy, BJ, Scolyer, RA, Thompson, JF & Doble, PA 2009, 'Elemental bio-imaging of melanoma in lymph node biopsies', The Analyst, vol. 134, no. 3, pp. 450-453.View/Download from: Publisher's site
The spatial distribution of trace elements in human lymph nodes partially infiltrated by melanoma cells was determined by elemental bio-imaging. Imaging of 31P within the nodal capsule and normal lymph node tissue showed a clear demarcation of the tumour boundary, with a significant decrease in relative 31P concentration within the tumour. The location of the tumour boundary was confirmed by haematoxylin and eosin staining of serial sections and observation by light microscopy. Further enhancement of the tumour boundary was achieved by imaging the 31P/34S ratio. 31P/66Zn ratio images showed a decreasing ratio beyond the tumour boundary that extended into peritumour normal lymph node tissue.
Hare, DJ, Reedy, BJ, Grimm, R, Wilkins, S, Volitakis, I, George, JL, Cherny, R, Bush, A, Finkelstein, D & Doble, PA 2009, 'Quantitative elemental bio-imaging of Mn, Fe, Cu and Zn in 6-hydroxydopamine induced Parkinsonism mouse models', metallomics, vol. 1, no. 1, pp. 53-58.View/Download from: Publisher's site
This study demonstrates the application of quantitative elemental bio-imaging for the determination of the distribution Cu, Mn, Fe and Zn in Parkinsonism mouse model brains. Elevated concentrations of these metals within the substantia nigra (SN) are suspected to play a role on the development of Parkinsons disease. Elemental bio-imaging employs laser ablation inductively coupled mass spectrometry (LA-ICP-MS) to construct images of trace element distribution. Quantitative data was produced by ablating the standard tissue sections and recording the mean signal intensity calibrated against multi level matrix matched tissue standards. The concentrations of Fe within the substantia nigra of the lesioned animals increased significantly when compared against control animals. Furthermore, the data was compared against solution nebulisation ICP-MS in which the whole substantia nigra was excised. The trends were the same for both methods; however the elemental bio-imaging method returned significantly higher concentrations. This was caused by dilution from inclusion of surrounding tissue of the SN during the excision procedure.
Rawling, T, Austin, CE, Hare, DJ, Doble, PA, Zareie, HM & McDonagh, AM 2009, 'Thin films of Ruthenium Phthalocyanine complexes', Nano Research, vol. 2, pp. 678-687.View/Download from: Publisher's site
Four new ruthenium phthalocyanine complexes bearing axial ligands with thioacetate groups that facilitate thin film formation on gold surfaces are presented. Scanning tunnelling microscopy (STM) images and surface coverage data obtained by solution inductively coupled plasma mass spectrometry (ICP-MS) experiments show that peripheral and axial ligand substituents on the complexes have a significant effect on their surface coverage. A laser ablation ICP-MS technique that provides information about thin films across macro-sized areas is described here for the first time. Using the technique, the maximum surface coverage of a ruthenium phthalocyanine complex was found to occur within one minute of gold substrate immersion in the complexcontaining solution.
Webb, RR, Doble, PA & Dawson, M 2009, 'Optimisation of HPLC gradient separations using artificial neural networks (ANNs): Application to benzodiazepines in post-mortem samples', Journal Of Chromatography B-Analytical Technologi..., vol. 877, no. 7, pp. 615-620.View/Download from: Publisher's site
Artificial neural networks (ANNs) were used in conjunction with an experimental design to optimise a gradient HPLC separation of nine benzodiazepines. Using the best performing ANN, the optimum conditions predicted were 25 mM formate buffer (pH 2.8), 10% MeOH, acetonitrile (ACN) gradient 0-15 min, 6.5-48.5%. The error associated with the prediction of retention times and peak widths under these conditions was less than 5% for six of the nine analytes. The optimised method, with limits of detection (LODs) in the range of 0.0057-0.023 mu g/mL and recoveries between 58% and 92%, was successfully applied to authentic post-mortem samples. This method represents a more flexible and convenient means for optimising gradient elution separations using ANNs than has been previously reported.
Beavis, AB, Dawson, M, Doble, PA, Scolyer, RA, Bourne, R, Li, L, Murali, R, Stretch, JR, Lean, CL, Uren, RF & Thompson, JF 2008, 'Confirmation of sentinel lymph node identity by analysis of fine-needle biopsy samples using inductively coupled plasma-mass spectrometry', Annals Of Surgical Oncology, vol. 15, no. 3, pp. 934-940.View/Download from: Publisher's site
Background: The sentinel lymph node (SLN) biopsy technique is a reliable means of determining the tumor-harboring status of regional lymph nodes in melanoma patients. When technetium 99 m-labeled antimony trisulfide colloid ((99) Tc-m-Sb2S3) particles ar
huttunen, J, Doble, PA, Dawson, M, Roux, CP & Robertson, J 2008, 'Physical evidence in drug intelligence, Part 2: discrimination of packaging tapes by colour', Australian Journal of Forensic Sciences, vol. 40, no. 1, pp. 73-83.View/Download from: Publisher's site
The authors have considered routine exploitation of physical evidence from seized shipments of illicit drugs for intelligence purposes. Part 1 of this series addressed the identification of polymer type within the adhesive pf packaging tapes and raised important issues with regard to how data should be collated in a databse as a basis for reliable drug intelligence. this article expands onthis topic by addressingt eh sue of colour for achieving the same aim. By using a relatively simple instrumental technique to analyse opaque 'brown' packaging tapes, it was found that colour was an effective way to discriminate between different adhesive tape samples. However, unitial results showed that the analysis of colour in packaging tapes was more complex than assigning seminsubjective names to particular hues (e.g. light brown, greenm brown etc). Instead, samples in the population often differed only slightly from one another and hence proved difficult to categorise. Thus, a database or analyst must avoid using such 'discrete' labels and instead make use of 'continuous' numerical data. Here, CIELab chromaticity coordinates were used to define representative colour spaces for each tape sample and these were then compared to determine whether two such volumes intersected. This process would decide whether or not the sampes could be discriminated. While several sets of data were compared, further work needs to be carried out into the consistency of colour within single rolls of tape or batches of tape.
Karim, RZ, Scolyer, RA, Li, W, McKinnon, J, Li, L, Uren, RF, Lam, S, Beavis, AB, Dawson, M, Doble, PA, Hoon, DS & Thompson, JF 2008, 'False negative sentinel lymph node biopsies in melanoma may result from deficiencies in nuclear medicine, surgery, or pathology', Annals of Surgery, vol. 247, no. 6, pp. 1003-1010.View/Download from: Publisher's site
OBJECTIVE: To investigate a cohort of melanoma patients with false negative (FN) sentinel node (SN) biopsies (SNBs) to identify the reasons for the FN result. SUMMARY OF BACKGROUND DATA: SNB is a highly efficient staging method in melanoma patients. However, with long-term follow-up FN SNB results of up to 25% have been reported. METHODS: Seventy-four SNs from 33 patients found to have had an FN SNB were analyzed by reviewing the lymphoscintigraphy, surgical data, and histopathology, and by assessing nodal tissue using multimarker real-time quantitative reverse transcription (qRT) polymerase chain reaction, and antimony concentration measurements (as a marker of "true" SN status) using inductively coupled plasma mass spectroscopy. RESULTS: Nine SNs (12%) from 9 patients (27%) had evidence of melanoma on histopathologic review. Twelve SNs (16%) from 10 patients (30%) were qRT(+). Four of these 12 SNs were positive on histopathology review and 8 were negative. Four patients (12%) were upstaged by qRT. Sixteen patients had their SNB histology, lymphoscintigraphy, and surgical data reviewed. Identifiable causes of the FN SNBs were not found after review of all modalities in 4 patients. SNs from all 4 patients had antimony levels indicative of an SN. Of the SNs evaluable by qRT, 1 was qRT(+) and 7 SNs from 2 patients were qRT(-). CONCLUSIONS: An FN SN can occur because of deficiencies in nuclear medicine, surgery, or pathology. qRT can detect "occult" metastatic melanoma in SNs that have been identified as negative by histopathology. Â© 2008 Lippincott Williams & Wilkins, Inc.
Kelly, TL, Doble, PA & Dawson, M 2007, 'A Fast CE Method For The Achiral Separation Of Methadone And Its Major Metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyr-rolidine And 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline', Electrophoresis, vol. 28, no. 19, pp. 3566-3569.View/Download from: Publisher's site
The utilization of dynamic doubly coated capillaries for a fast separation of methadone and its two major metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-l-pyrroline (EMDP) was investigated. The coa
Tran, T, Hyne, RV & Doble, PA 2007, 'Calibration of a passive sampling device for time-integrated sampling of hydrophilic herbicides in aquatic environments.', Environmental Toxicology and Chemistry, vol. 26, no. 3, pp. 435-443.View/Download from: Publisher's site
two types of solid-phase materials, a styrenedivinylbenzene copolumer sorbent (embedded in a SDB-XC Empore disk) and a styrenedivinylbenzene copolymer sorbent modified with sulfonic acid functional groups (embeddedin a SCB-RPS Empore disk) were compared as a receiving phase in a passive sampling device for monitoring polar pesticied. The SDB-XC Empore disk was selected for further evaluation, pverlayed with either a polysulfone or a polyethersulfone diffusion membrane. The target herbicides included five nonionized herbicides (simazine, atrazine, diuron, clomazone and metolachlor) and four phenoxy acid herbicideds (diacamba, 92,4-dichlorophenoxy) acetic acid [2,4-D], (4-chloro-2-methylphenoxy)acetic acid [MCPA} and triclopyr) with log octanol/water partitian coefficient (log Kow) values of less than three in water. Uptake of these herbicides generally was higher into a device constructed of a SDB-XC Empore disk as a receiving phase covered with a polyethersulfone membrane compared to a similar device covered with a polysufone membrane.Using the device with a SDB-XC Empore disk covred with a polyethersulfone membrane,linear uptake of simazine, atrazine, diuron, clomazone and metoachlor was observed foruo tp 21 d, and daily sampling rates of the herbiccides from water in a laboratory flow-through system were setermined. Theuptake rate of each nonionized herbicide by the Empore disk-based passive sampler was linearly proportional to irs concentration in the water, and the sampling rate was independent of the water concentrations over the 21-d period. Uptake of the phenoxy acid herbicides (2,4-D, MCPA and triclopyr) obeyed first-order kinetics and rapidly reached equilibrium in the pasasive sampler after approximately 12d of exposure. The Empore disn-based passive sampler displayed isotropic kinetics, with a release half-life for triclopyr of approximately 6 d.
Tran, T, Hyne, RV & Doble, PA 2007, 'Determination of commonly used polar herbicides in agricultural drainage waters in Australia by HPLC', Chemosphere, vol. 67, no. 5, pp. 944-953.View/Download from: Publisher's site
The present study describes the application of different extraction techniques for the preconcentration of ten commonly found acidic and non-acidic polar herbicides (2,4-D, atrazine, bensulfuron-methyl, clomazone, dicamba, diuron, MCPA, metolachlor, sima
Tran, T, Hyne, RV, Pablo, F, Day, WR & Doble, PA 2007, 'Optimisation of the separation of herbicides by linear gradient high performance liquid chromatography utilising artificial neural networks', Talanta, vol. 71, no. 3, pp. 1268-1275.View/Download from: Publisher's site
An artificial neural network (ANN) was employed to model the chromatographic response surface for the linear gradient separation of 10 herbicides that are commonly detected in storm run-off water in agricultural catchments. The herbicides (dicamba, simaz
Webb, RR, Doble, PA & Dawson, M 2007, 'A Rapid Cze Method For The Analysis Of Benzodiazepines In Spiked Beverages', Electrophoresis, vol. 28, no. 19, pp. 3553-3565.View/Download from: Publisher's site
A rapid CZE method was developed for the simultaneous determination of nine benzodiazepines in spiked beverages (nitrazepam oxazepam, alprazolam, flunitrazepam, temazepam, diazepam, 7-aminoflunitrazepam, 7-aminonitrazepam and 7-aminoclonazepam). The meth
Burger, FJ, Dawson, M, Roux, CP, Maynard, PJ, Doble, PA & Kirkbride, KP 2005, 'Forensic analysis of condom and personal lubricants by capillary electrophoresis', Talanta, vol. 67, no. 2, pp. 368-376.View/Download from: Publisher's site
Condoms may offer sexual assailants a simple and relatively effective means by which they may remove and dispose of the biological evidence of their contact with the victim. Without this valuable probative evidence, the investigator may need to turn to s
Esseiva, P, Anglada, F, Dujourdy, L, Taroni, F, Margot, P, Du Pasquier, E, Dawson, M, Roux, CP & Doble, PA 2005, 'Chemical profiling and classification of illicit heroin by principal component analysis, calculation of inter sample correlation and artificial neural networks', Talanta, vol. 67, no. 2, pp. 360-367.View/Download from: Publisher's site
Artificial neural networks (ANNs) were utilised to validate illicit drug classification in the profiling method used at Institut de Police Scientifique of the University of Lausanne (IPS). This method established links between samples using a combination
Kelly, TL, Doble, PA & Dawson, M 2005, 'Chiral analysis of methadone and its major metabolites (EDDP and EMDP) by liquid chromatography-mass spectrometry', Journal Of Chromatography B-Analytical Technologies In The Biomedical And Life Sciences, vol. 814, no. 2, pp. 315-323.View/Download from: Publisher's site
Racemic methadone (MET) is administered to heroin users undergoing methadone maintenance therapy (MMT) in Australia. The enantiomers of methadone possess different pharmacological effects, and the enantioselective metabolism of methadone to its two major
Paull, B, Roux, C, Dawson, M & Doble, P 2004, 'Rapid screening of selected organic explosives by high performance liquid chromatography using reversed-phase monolithic columns', JOURNAL OF FORENSIC SCIENCES, vol. 49, no. 6, pp. 1181-1186.
Paull, B, Roux, CP, Dawson, M & Doble, PA 2004, 'Rapid screening of selected organic explosives by high performance liquid chromatography using reversed-phase monolithic columns', Journal of Forensic Science, vol. 49, no. 6, pp. 1-6.
Scolyer, RA, Thompson, JF, Li, L, Beavis, AB, Dawson, M, Doble, PA, Soper, R, Uren, RF, Stretch, JR, Sharma, R & McCarthy, SW 2004, 'Antimony concentrations in nodal tissue can confirm sentinel node identity', Modern Pathology, vol. 17, pp. 1191-1197.View/Download from: Publisher's site
Scolyer, RA, Thompson, JF, Li, LXL, Beavis, A, Dawson, M, Doble, P, Ka, VSK, McKinnon, JG, Soper, R, Uren, RF, Shaw, HM, Stretch, JR & McCarthy, SW 2004, 'Failure to remove true sentinel nodes can cause failure of the sentinel node biopsy technique: Evidence from antimony concentrations in false-negative sentinel nodes from melanoma patients', ANNALS OF SURGICAL ONCOLOGY, vol. 11, no. 3, pp. 174S-178S.View/Download from: Publisher's site
Burger, FJ, Doble, PA & Roux, CP 2003, 'Forensic Analysis Of Condom And Personal Lubricants Found In Sexual Assault Cases By Capillary Electrophoresis', Forensic Science International, vol. 136, pp. 247-247.
Casamento, SG, Kwok, BK, Roux, CP, Dawson, M & Doble, PA 2003, 'Optimization of the separation of organic explosives by capillary electrophoresis with artificial neural networks', Journal Of Forensic Sciences, vol. 48, no. 5, pp. 1075-1083.
Dawson, M, Doble, PA, Beavis, AB, Li, L, Soper, R, Scolyer, RA, Uren, RF & Thompson, JF 2003, 'Antimony by ICP-MS as a marker for sentinel lymph nodes in melanoma patients', The Analyst, vol. 128, no. 3, pp. 1-6.View/Download from: Publisher's site
A sensitive, accurate and specific method for the analysis of antimony by ICP-MS is presented as a marker of the sentinel lymph node in melanoma patients.
Doble, PA, Sandercock, PM, Du Pasquier, E, Petocz, P, Roux, CP & Dawson, M 2003, 'Classification of premium and regular gasoline by gas chromatography/mass spectrometry, principal component analysis and artificial neural networks', Forensic Science International, vol. 132, no. 1, pp. 26-39.View/Download from: Publisher's site
Detection and correct classification of gasoline is important for both arson and fuel spill investigation. Principal component analysis (PCA) was used to classify premium and regular gasolines from gas chromatographymass spectrometry (GCMS) spectral data obtained from gasoline sold in Canada over one calendar year. Depending upon the dataset used for training and tests, around 8093% of the samples were correctly classified as either premium or regular gasoline using the Mahalanobis distances calculated from the principal components scores. Only 4862% of the samples were correctly classified when the premium and regular gasoline samples were divided further into their winter/summer sub-groups. Artificial neural networks (ANNs) were trained to recognise premium and regular gasolines from the same GCMS data. The best-performing ANN correctly identified all samples as either a premium or regular grade. Approximately 97% of the premium and regular samples were correctly classified according to their winter or summer sub-group.
Kelly, T, Doble, P & Dawson, M 2003, 'Chiral separation of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) by capillary electrophoresis using cyclodextrin derivatives', Electrophoresis, vol. 24, no. 12-13, pp. 2106-2110.View/Download from: Publisher's site
A stereoselective method was developed for the simultaneous determination of methadone and its two major metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) by capillary electrophoresis. Five β-cyclodextrin (βCD) background electrolyte (BGE) additives were evaluated for resolution efficiency. The conditions for baseline resolution of each of the three enantiomer pairs was determined to be 1 mM heptakis-(2,6-di-O-methyl -β-cyclodextrin (DMβCD) in 100 mM phosphate at pH 2.6. This method represents the first successful method for the resolution of the six enantiomers associated with the metabolism of methadone. The utilisation of doubly coated capillaries in conjunction with βCD derivatives for a faster separation of the methadone-related enantiomers is also reported. The coated capillaries were prepared using a polycation of poly(diallyl-dimethylammonium chloride) (PDDAC) and a polyanion of dextran sulfate. Baseline resolution of the methadone enantiomers was achieved with a BGE of 8 mM (2-hydroxy propyl-β-cyclodextrin (HPβCD) in 100 mM phosphate at pH 2.6. The migration times for the stereoselective methadone separation were approximately 4 min, which represented a reduction by a factor of approximately three, compared to that attained using analogous conditions with the uncoated capillary.
Kelly, TL, Doble, PA & Dawson, M 2003, 'Chiral separation of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrol (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) by capillary electrophoresis using cyclodextrin derivatives', Electrophoresis, vol. 24, no. 12-13, pp. 2106-2110.View/Download from: Publisher's site
A stereoselective method was developed for the simultaneous determination of methadone and its two major metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) by capillary electrophoresis. Five -cyclodextrin (CD) background electrolyte (BGE) additives were evaluated for resolution efficiency. The conditions for baseline resolution of each of the three enantiomer pairs was determined to be 1 mM heptakis-(2,6-di-O-methyl)--cyclodextrin (DMCD) in 100 mM phosphate at pH 2.6. This method represents the first successful method for the resolution of the six enantiomers associated with the metabolism of methadone. The utilisation of doubly coated capillaries in conjunction with CD derivatives for a faster separation of the methadone-related enantiomers is also reported. The coated capillaries were prepared using a polycation of poly(diallyldimethylammonium chloride) (PDDAC) and a polyanion of dextran sulfate. Baseline resolution of the methadone enantiomers was achieved with a BGE of 8 mM (2-hydroxy)propyl--cyclodextrin (HPCD) in 100 mM phosphate at pH 2.6. The migration times for the stereoselective methadone separation were approximately 4 min, which represented a reduction by a factor of approximately three, compared to that attained using analogous conditions with the uncoated capillary.
Macka, M, Johns, C, Doble, PA & Haddad, PR 2001, 'Indirect Photometric Detection In Ce Using Buffered Electrolytes - Part Ii, Practical Rules', Lc Gc North America, vol. 19, no. 2, pp. 178-0.
Macka, M, Johns, C, Doble, PA, Haddad, PR & Altria, KD 2001, 'Indirect Photometric Detection In Ce Using Buffered Electrolytes - Part 1 Principles (vol 19, Pg 38, 2001)', LC GC North America, vol. 19, no. 2, pp. 188-188.
Macka, M, Johns, C, Doble, PA, Haddad, PR & Altria, KD 2001, 'Indirect Photometric Detection In Ce Using Buffered Electrolytes - Part I, Principles', Lc Gc North America, vol. 19, no. 1, pp. 38-0.
Vachirapatama, N, Doble, PA, Yu, Z, Macka, M & Haddad, PR 2001, 'Separation Of Niobium(v) And Tantalum(v) As Ternary Complexes With Citrate And Metallochromic Ligands By Capillary Electrophoresis', Analytica Chimica Acta, vol. 434, no. 2, pp. 301-307.View/Download from: Publisher's site
A method was developed for the determination of Nb(V) and Ta(V) as anionic ternary complexes of a metallochromic ligand and citrate as the auxiliary ligand by capillary electrophoresis. Three metallochromic ligands were evaluated, namely 4-(2-pyridylazo)
Boyce, M, Breadmore, M, Macka, M, Doble, PA & Haddad, PR 2000, 'Indirect Spectrophotometric Detection Of Inorganic Anions In Ion-exchange Capillary Electrochromatography', Electrophoresis, vol. 21, no. 15, pp. 3073-3080.View/Download from: 3.0.CO;2-H">Publisher's site
The application of indirect spectrophotometric detection was investigated for a capillary electrochromatographic system in which an anion-exchange stationary phase tin the form of aminated latex particles) was coated onto the wall of a fused-silica capil
Doble, PA, Macka, M & Haddad, PR 2000, 'Design Of Background Electrolytes For Indirect Detection Of Anions By Capillary Electrophoresis', Trac-trends In Analytical Chemistry, vol. 19, no. 1, pp. 10-17.View/Download from: Publisher's site
In capillary electrophoresis of inorganic and other low molecular weight anions using indirect photometric detection, the correct design of the background electrolyte can considerably reduce the time needed for method development and can increase the qua
Oreilly, D, Doble, PA, Tanaka, K & Haddad, PR 2000, 'Retention Behaviour Of Strong Acid Anions In Ion-exclusion Chromatography On Sulfonate And Carboxylate Stationary Phases', Journal Of Chromatography A, vol. 884, no. 1-2, pp. 61-74.
Some factors influencing the retention of strong-acid anions on ion-exclusion columns were investigated using columns with sulfonate and carboxylate functional groups. The nature of the functional group on the resin, the eluent pH and the eluent ionic st
Vachirapatama, N, Doble, PA & Haddad, PR 2000, 'On-line Preconcentration Of Niobium(v) And Tantalum(v) As 4-(2-pyridylazo) Resorcinol-citrate Ternary Complexes In Geological Samples By Ion Interaction High-performance Liquid Chromatography', Journal Of Chromatography A, vol. 885, no. 1-2, pp. 369-375.View/Download from: Publisher's site
4-(2-Pyridylazo) resorcinol (PAR) and citrate were used as pre-column complexing agents for the determination of Nb(V) and Ta(V) as ternary complexes in geological samples. Aliquots of 2 mi of the standard and sample solutions containing the Nb(V) and Ta
Vachirapatama, N, Doble, PA & Haddad, PR 2000, 'Separation And Determination Of Niobium(v) And Tantalum(v) As 2-(5-bromo-2-pyridylazo)-5-[n-propyl-n-(3-sulfopropyl)amino] Phenol Citrate Ternary Complexes In Geological Samples Using Ion Interaction High-performance Liquid Chromatography', Analytica Chimica Acta, vol. 409, no. 1-2, pp. 35-43.View/Download from: Publisher's site
A method for the simultaneous separation and determination of Nb(V) and Ta(V) as ternary complexes formed with 2-(5-bromo-2-pyridylazo)-5-[N-propyl-N-(3-sulfoproyl)amino]phenol (PAPS) and citrate was developed using ion interaction reversed-phase high-pe
Indirect photometric detection (absorbance and fluorescence) of anions by capillary electrophoresis is reviewed. Factors which influence the displacement process of analyte ions in background electrolytes containing one or more co-ions are discussed and
Doble, PA & Haddad, PR 1999, 'Use Of Electrolytes Containing Multiple Co-anions In The Analysis Of Anions By Capillary Electrophoresis Using Indirect Absorbance Detection', Analytical Chemistry, vol. 71, no. 1, pp. 15-22.View/Download from: Publisher's site
Background electrolytes (BGEs) containing more than one W-absorbing probe co-anion were investigated as possible means to control peak symmetries and improve the sensitivity of indirect detection in the separation of a mixture of inorganic and organic an
Haddad, PR, Doble, PA & Macka, M 1999, 'Developments In Sample Preparation And Separation Techniques For The Determination Of Inorganic Ions By Ion Chromatography And Capillary Electrophoresis', Journal Of Chromatography A, vol. 856, no. 1-2, pp. 145-177.View/Download from: Publisher's site
A review is presented of sample preparation and separation techniques for the determination of inorganic ions by ion chromatography (IC) and capillary electrophoresis (CE). Emphasis has been placed on those sample treatment methods which are specific to
Vachirapatama, N, Doble, PA, Yu, Z & Haddad, PR 1999, 'Determination Of Niobium(v) And Tantalum(v) As 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (br-padap)-citrate Ternary Complexes In Geological Materials Using Ion-interaction Reversed-phase High-performance Liquid Chromatography', Chromatographia, vol. 50, no. 9-10, pp. 601-606.View/Download from: Publisher's site
A method for the simultaneous separation and determination of Nb(V) and Ta(V) as ternary complexes with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (Br-PA-DAP) and citrate using ion-interaction reversed-phase high performance liquid chromatography on a
Doble, PA, Macka, M & Haddad, PR 1998, 'Factors Influencing The Choice Of Buffer In Background Electrolytes For Indirect Detection Of Fast Anions By Capillary Electrophoresis', Electrophoresis, vol. 19, no. 12, pp. 2257-2261.View/Download from: Publisher's site
The suitability of relatively slow (low absolute value of mobility) coanionic buffers in background electrolytes (BGEs) for indirect photometric detection of anions by capillary electrophoresis was investigated. As a model system, 2-(cyclohexylamino)etha
Doble, PA, Macka, M & Haddad, PR 1998, 'Use Of Dyes As Indirect Detection Probes For The High-sensitivity Determination Of Anions By Capillary Electrophoresis', Journal Of Chromatography A, vol. 804, no. 1-2, pp. 327-336.View/Download from: Publisher's site
High sensitivity for indirect detection was achieved by utilising highly absorbing species as the displaced co-ion (or probe). Two highly absorbing dyes, bromocresol green and indigo-tetrasulfonate, were investigated as potential probes in the determinat
Doble, PA, Andersson, P & Haddad, PR 1997, 'Determination And Prediction Of Transfer Ratios For Anions In Capillary Zone Electrophoresis With Indirect Uv Detection', Journal Of Chromatography A, vol. 770, no. 1-2, pp. 291-300.View/Download from: Publisher's site
Transfer ratios (i.e. the number of moles of the UV-absorbing probe anion displaced by one mole of analyte anion) were determined for the separation of inorganic and organic anions by capillary zone electrophoresis using indirect UV absorbance detection.
Doble, PA, Macka, M, Andersson, P & Haddad, PR 1997, 'Buffered Chromate Electrolytes For Separation And Indirect Absorbance Detection Of Inorganic Anions In Capillary Electrophoresis', Analytical Communications, vol. 34, no. 11, pp. 351-353.View/Download from: Publisher's site
Chromate is the most commonly used carrier electrolyte for the determination of low molecular weight and inorganic anions by capillary electrophoresis. However, chromate electrolytes are usually prepared in the sodium form and consequently have poor buff
© Springer Science+Business Media LLC 2017. Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) has been an invaluable tool for accurate and precise measurement of metals in geological and environmental samples. However, like many advanced analytical techniques its versatility has seen its translation into several other disciplines, including neuroimaging. In this chapter, we discuss the principles of LA-ICP-MS technology and how it is applied to mesoscale imaging of metals in neurological tissue; evaluate the various approaches available for image construction and analysis; discuss the challenges and opportunities for quantitative metal imaging; and present a selection of applications demonstrating the power of this analytical technique as a tool for assessing both spatial distribution and absolute levels of essential metals in the brain.
Blanes, L, Tomazelli Coltro, WK, Saito, RM, do Lago, CL, Roux, CP & Doble, PA 2013, 'Practical considerations for the design and implementation of High Voltage Power Supplies for Capillary and Microchip Capillary Electrophoresis' in Carlos, DGA, Karin, YCT & Emanuel, C (eds), Capillary Electrophoresis and Microchip Capillary Electrophoresis: Principles, Applications, and Lim, Wiley, Chichester, pp. 67-76.View/Download from: Publisher's site
Capillary electrophoresis (CE) and microchip capillary electrophoresis (MCE) are powerful analytical techniques used to analyze chemical and biological samples. For both techniques sample injection and separation are two crucial steps that depend on a reliable high-voltage power supply (HVPS) to ensure reproducible separations. Therefore, the source of high voltage (HV) is considered to be the heart for these instruments. Separation of the analytes occurs due to the influence of an applied potential difference between electrodes placed at the ends of the capillary or channel. As a consequence, the components present in the plug of injection are driven toward the detector. This book chapter is a comprehensive source of information of HVPS for CE and MCE. This chapter covers topics as such as fundamentals of HV, electroosmotic flow control, construction of bipolar HVPS from unipolar HVPS, commercially available HVPS and DC/DC converters, alternative sources of HV, HVPS controllers for MCE, and strategies to measure HV. The chapter also includes practical and safety considerations that can be helpful for development of new CE and MCE instrumentation
Van Gramberg, AA, Beavis, AB, Blanes, L & Doble, PA 2010, 'Optimisation Of The Separation Of Amino Acids By Capillary Electrophoresis Using Artificial Neural Networks' in Hanrahan, G & Gomez, FA (eds), Chemometric Methods in Capillary Electrophoresis, John Wiley & Sons, Inc, United States, pp. 169-180.
Many factors can affect the separation performance of a capillary electrophoresis (CE) electrolyte, such as the buffer, surfactant and organic modifier concentrations, pH, capillary temperature, and applied voltage (1). The efficient manipulation of these factors is critical to optimize the resolution of a given analysis in the shortest time frame. During the method development process, an analyst will usually attempt a separation based on a previously reported method that is similar or the same as the requirements of the analysis at hand. If the separation is inadequate, a univariate approach (2) is often employed to attempt to improve the separation. This involves altering one parameter at a time in a systematic way, and viewing the results by plotting the effect of the parameter on the migration time of the analytes. In this way, suitable electrolyte compositions may be found that separates all of the analytes. If suitable conditions are not found, a second electrolyte parameter is chosen and altered in a similar manner. This univariate procedure is then repeated until a suitable condition is found. This method of optimization is time-consuming, and it is unknown if the optimum is truly the global optimum.
Blanes, L, Dos Santos, RO, Diplock, M, Benson, N, Doble, P & Roux, C 2017, 'DEVELOPMENT OF AN ELECTRONIC EXPLOSIVE DETECTOR USING MICROFLUIDIC PAPER-BASED ANALYTICAL DEVICES', FORENSIC SCIENCE INTERNATIONAL, 21st Triennial Meeting of the International-Association-of-Forensic-Sciences (IAFS), ELSEVIER IRELAND LTD, Toronto, CANADA, pp. 199-200.
Blanes, L, Taudte, RV, Roux, C & Doble, P 2014, 'Using paper-based microfluidics and lab on a chip techonologies for the rapid analysis of trinitro aromatic explosives', 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014, 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, pp. 1581-1582.
© 14CBMS. We report a new microfluidic paper-based analytical device (μPAD) containing potassium hydroxide to create a color change reaction when in contact with trinitro aromatic explosives, followed by extraction and lab on a chip analysis. The procedure allowed the detection and identification of 1 μg of the target explosives distributed on a 100 cm < sup > 2 < /sup > surface.
Roberts, BR, Lim, NKH, McAllum, EJ, Donnelly, PS, Hare, DJ, Doble, PA, Turner, BJ, Price, KA, Lim, SC, Paterson, BM, Hickey, JL, Rhoads, TW, Williams, JR, Kanninen, KM, Hung, LW, Liddell, JR, Grubman, A, Monty, JF, Llanos, RM, Kramer, DR, Mercer, JFB, Bush, AI, Masters, CL, Duce, JA, Li, QX, Beckman, JS, Barnham, KJ, White, AR & Crouch, PJ 2014, 'Improved locomotor function and survival of mice with increased levels of mutant superoxide dismutase 1', JOURNAL OF NEUROCHEMISTRY, 12th Biennial Meeting of the Asian-Pacific-Society-for-Neurochemistry, WILEY-BLACKWELL, Kaohsiung, TAIWAN, pp. 44-44.
Molnar, A, Fu, S, Doble, PA & Lewis, JH 2010, 'A sensitive method to detect and quantify delta-9 tetrahydrocannabinol in oral fluid by liquid chromatography - tandem mass spectrometry', TIAFT Bulletin, Annual Meeting of the International-Association-of-Forensic-Toxicologists (TIAFT), GI Printing & Graphics, Bonn, Germany, pp. 45-47.
Delta9 -tetrahydrocannabinol (THC) is the major psychoactive constituent of cannabis. It causes a decrease in motor function and concentration making it hazardous for an individual to drive whilst under the inftuence of this drug. Roadside testing procedures for cannabis are therefore necessary since it is the most widely used illicit drug in Australia and around the world and is commonly implicated in drug-driving offences.