Mass spectrometry imaging (MSI) of metals in mouse spinal cord by laser ablation ICP-MS

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed as a powerful MS imaging (MSI) tool for the direct investigation of element distributions in biological tissues. Here, this technique was adapted for the analysis of native mouse spinal cord cryosections of 3.1 mm × 1.7 mm by implementing a new conventional ablation system (NWR-213) and improving the spatial resolution from 120 μm to 65 μm in routine mode. Element images of the spinal cord are provided for the first time and the metalloarchitecture was established using a multimodal atlas approach. Furthermore, the spatial distribution of Rb was mapped for the first time in biological tissue. Metal concentrations were quantified using matrix-matched laboratory standards and normalization of the respective ion intensities to the average (13)C ion intensity of standards and samples as a surrogate of slice thickness. The "butterfly" shape of the central spinal grey matter was visualized in positive contrast by the distributions of Fe, Mn, Cu and Zn and in negative contrast by C and P. Mg, Na, K, S and Rb showed a more homogenous distribution. The concentrations averaged throughout grey matter and white matter were 8 and 4 μg g(-1) of Fe, 3 and 2 μg g(-1) of Cu, 8 and 5 μg g(-1) of Zn, 0.4 and 0.2 μg g(-1) of Mn. The carbon concentration in white matter exceeded that of grey matter by a factor of 1.44. Zn and Cu at 9 and 4 μg g(-1), respectively, were particularly enriched in the laminae I and II, in line with the high synaptic and cellular density there. Surprisingly Zn but not Cu was enriched in the central channel. Rb occurred at 0.3 μg g(-1) with a distribution pattern congruent to that of K. The coefficients of variation were 6%, 5%, 8% and 10% for Fe, Cu, Zn and Mn, respectively, throughout three different animals measured on different days. These MSI analyses of healthy wild type spinal cords demonstrate the suitability of the established techniques for investigating diseased or transgenic states in future imaging studies

Biomonitoring for arsenic, toxic and essential metals in single hair strands by laser ablation inductively coupled plasma mass spectrometry

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed as reliable analytical technique for the quantitation of metal distributions at micrometre resolution. In this work a novel microanalytical strategy for biomonitoring of arsenic, toxic and essential metals in single hair strands is proposed. Two different calibration strategies in LA-ICP-MS were developed using either certified hair standard reference material (IAEA 086) or prepared matrix-matched laboratory hair standards doped with analytes of interest at defined concentration. Powdered hair standards and human hair strands mounted on a sticky tape in the LA chamber were analyzed under the same experimental conditions by an optimized LA-ICP-MS technique. The use of hair powder standard allows calibration curves to be obtained by plotting the analyte ion (M+) intensity normalized to S-34(+) (the ratio M+/S-34(+)) as a function of the concentration determined by ICP-MS of acidic digests. The linear correlation coefficients (R) of calibration curves for analytes As, Ba, Cd, Ce, Co, Cr, Cu, Fe, Ga, Hg, Mg, Mo, Ni, Pb, Rb, Sr, Ti and U were typically between 0.985 and 0.999. The limit of detection (LOD) was 0.6 mu g g(-1) for As and ranged from 0.3 to 7.8 mu g g(-1) for the other analytes. Distinct elemental exposition time profiles were observed in hair samples from five volunteers. (C) 2011 Elsevier B.V. All rights reserved

Mass spectrometry analysis of metals, other elements and lipids in urine samples of Fabry disease patients

Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of alpha-galactosidase A leading to accumulation of globotriaosylceramide in tissues and biological fluids of affected patients. Mass spectrometry is a powerful tool to quantify components of interest in biological fluids. Our study had four objectives: (1) to devise an ICP-MS methodology for quantitative determination of metal and other element concentrations in urine specimens of Fabry patients; (2) to analyze urinary Gb(3)/creatinine and lyso-Gb(3)/creatinine in these patients; (3) to evaluate correlations between urinary lipid concentrations versus metals and other elements in Fabry patients and healthy controls; (4) to evaluate which metals and other elements discriminate groups of patients and controls according to gender and treatment. We found that the excretion of barium was elevated in Fabry females and calcium and strontium levels were lower in Fabry males compared to controls. Preliminary results for treated and untreated Fabry disease patients indicate that ERT seems to have little effect on urine elements analyzed. Statistically significant correlations were established between urinary lyso-Gb(3)/creatinine. Gb(3)/creatinine and levels of magnesium, copper, mercury, nickel, lead, barium and calcium, whereas no significant correlations were found for the other 15 elements examined. Our results indicate that further studies are warranted in larger cohorts of Fabry disease patients for the investigation of possible roles of metals and other elements. (C) 2011 Elsevier B.V. All rights reserved

Biomonitoring of essential and toxic metals in single hair using on-line solution-based calibration in laser ablation inductively coupled plasma mass spectrometry

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been established as a powerful and sensitive surface analytical technique for the determination of concentration and distribution of trace metals within biological systems at micrometer spatial resolution. LA-ICP-MS allows easy quantification procedures if suitable standard references materials (SRM) are available. In this work a new SRM-free approach of solution-based calibration method in LA-ICP-MS for element quantification in hair is described. A dual argon flow of the carrier gas and nebulizer gas is used. A dry aerosol produced by laser ablation (LA) of biological sample and a desolvated aerosol generated by pneumatic nebulization (PN) of standard solutions are carried by two different flows of argon as carrier or nebulizer gas, respectively and introduced separately in the injector tube of a special ICP torch, through two separated apertures. Both argon flows are mixed directly in the ICP torch. External calibration via defined standard solutions before analysis of single hair was employed as calibration strategy. A correction factor, calculated using hair with known analyte concentration (measured by ICP-MS), is applied to correct the different elemental sensitivities of ICP-MS and LA-ICP-MS. Calibration curves are obtained by plotting the ratio of analyte ion M(+)/(34)S(+) ion intensities measured using LA-ICP-MS in dependence of analyte concentration in calibration solutions. Matrix-matched on-line calibration in LA-ICP-MS is carried out by ablating of human hair strands (mounted on a sticky tape in the LA chamber) using a focused laser beam in parallel with conventional nebulization of calibration solutions. Calibrations curves of Li, Na, Mg, Al, K, V, Cr, Mn, Fe, Ni, Co, Cu, Zn, Sr, Mo, Ag, Cd, I, Hg, Pb, Tl, Bi and U are presented. The linear correlation coefficients (R) of calibration curves for analytes were typically between 0.97 and 0.999. The limits of detection (LODs) of Li, V, Mn, Ni, Co, Cu, Sr, Mo, Ag, Ba, Cd, I, Hg, Pb, Bi and U in a single hair strand were in the range of 0.001-0.90 μg g(-1), whereas those of Cr and Zn were 3.4 and 5.1 μg g(-1), respectively. The proposed quantification strategy using on-line solution-based calibration in LA-ICP-MS was applied for biomonitoring (the spatial resolved distribution analysis) of essential and toxic metals and iodine in human hair and mouse hair

Bioimaging of Metals and Biomolecules in Mouse Heart by Laser Ablation Inductively Coupled Plasma Mass Spectrometry and Secondary Ion Mass Spectrometry

Bioimaging mass spectrometric techniques allow direct mapping of metal and biomolecule distributions with high spatial resolution in biological tissue. In this study laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) was used for imaging of transition metals (Fe, Cu, Zn, Mn, and Ti), alkali and alkaline-earth metals (Na, K, Mg, and Ca, respectively), and selected nonmetals (such as C, P, and S) in native cryosections of mouse heart. The metal and nonmetal images clearly illustrated the shape and the anatomy of the samples. Zinc and copper were inhomogeneously distributed with average concentrations of 26 and 11 μg g(-1), respectively. Titanium and manganese were detected at concentrations reaching 1 and 2 μg g(-1), respectively. The highest regional metal concentration of 360 μg g(-1)was observed for iron in blood present in the lumen of the aorta. Secondary ion mass spectrometry (SIMS) as an elemental and biomolecular mass spectrometric technique was employed for imaging of Na, K, and selected biomolecules (e.g., phosphocholine, choline, cholesterol) in adjacent sections. Here, two different bioimaging techniques, LA-ICPMS and SIMS, were combined for the first time, yielding novel information on both elemental and biomolecular distributions

Scaling down the bioimaging of metals by laser microdissection inductively coupled plasma mass spectrometry (LMD-ICP-MS)

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been established as a powerful quantitative elemental imaging technique in routine mode for biological tissue with a spatial resolution of 12-160 mu m. Several applications necessitate an improved spatial resolution of LA-ICP-MS at the low micrometre scale and below. To achieve the improvement of spatial resolution of LA-ICP-MS we created a new experimental arrangement by coupling a laser microdissection system (LMD) used for laser ablation of tissue with a sensitive quadrupole-based inductively coupled plasma mass spectrometer for the subsequent analysis of ablated material. A flat laser ablation chamber made of glass was inserted into the LMD, fitted to the microscope slide with the specimen. The biological tissue fixed on the glass slide was ablated using the focused solid-state Nd:YAG laser of the LMD. The laser ablated material was transported by argon as carrier gas into the inductively coupled plasma of the mass spectrometer and analysed according to the mass-to-charge ratio. Using this novel LMD-ICP-MS arrangement, in initial experiments ion signals of 63Cu* and 65Cte were measured from a 30-p.m-thick cryosection impregnated with a droplet of a Cu solution. A spatial resolution of about 3 pm was obtained using the modified LMD system coupled to the ICP-MS. Laser-induced mass spectrometric measurements of metal distributions can be performed together with simultaneous inspection of the tissue section via the microscope of the LMD and be combined with other modalities of the LMD system. In future, a more powerful laser in the LMD apparatus will allow ablation down to the sub-micrometre scale to study the elemental distribution in small tissue sections. (C) 2010 Elsevier By. All rights reserved