Barry L. Sharp

Pneumatic nebulisers and spray chambers for inductively coupled plasma spectrometry. A review. Part 1. Nebulisers

This review provides a comprehensive description of the mechanism of operation and operating characteristics of pneumatic nebulisers and spray chambers used for analytical atomic spectrometry. The relevant literature has been reviewed and new data presented that elucidate the geometric and parametric factors that determine performance. Based on these findings suggestions for new designs are presented and a set of benchmark tests advocated that enable the objective comparison of different systems.

Characterisation and correction of instrumental bias in inductively coupled plasma quadrupole mass spectrometry for accurate measurement of lead isotope ratios

The accuracy and external precision of isotope ratio measurements can be limited by any of a number of instrumental bias factors which include mass bias, pulse pile-up, background effects and mass scale shift. Measured isotope ratios are generally biased from their true value by the interaction of several of these instrumental bias factors. Attainment of accurate isotope ratio measurement requires careful consideration of all possible causes of instrumental bias and adoption of methods for their elimination or correction. The various forms of instrumental bias observed in measurement of the Pb isotope ratios for NIST SRM 981 Natural Lead (Isotopic) were minimised to reveal 204 Pb: 206 Pb=0.0592±0.0002, 207 Pb: 206 Pb=0.9148±0.0007, 208 Pb: 206 Pb=2.1709±0.0015 ( n =5) compared with certified values of 0.059042±0.000037, 0.91464±0.00033 and 2.1681±0.0008, respectively. The thallium mass bias concentration procedure was employed in obtaining this data. All uncertainties given as 2 σ .

Design and characterisation of a microconcentric nebuliser interface for capillary electrophoresis-inductively coupled plasma mass spectrometry

An interface for capillary electrophoresis (CE) and inductively coupled plasma mass spectrometry (ICP-MS) is reported. The interface was constructed using a commercial microconcentric nebuliser and home-built cyclonic spray chamber. Isoforms of the heavy metal binding protein, metallothionein, were separated and the bound metals detected to characterise the interface. Nebuliser suction was identified as the principal factor controlling separation resolution in the CE-ICP-MS system. Two methods for counterbalancing the nebuliser suction were investigated: in the first method an optimised make-up flow was employed, and in the second a negative pressure was applied to the inlet vial. Negative pressure was the preferred method for counterbalancing the nebuliser suction because sensitivity was not compromised. Separation resolution, under negative pressure conditions, was improved compared with that achieved using on-capillary UV detection. Absolute metal detection limits for114Cd, 111Cd, 66Zn and 64Zn were 2.09, 3.42, 8.93 and 9.12 fg, respectively.

On-line additions of aqueous standards for calibration of laser ablation inductively coupled plasma mass spectrometry: theory and comparison of wet and dry plasma conditions

This paper describes the theory of on-line additions of aqueous standards for calibration of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Establishment of a calibration curve enabled investigation of: fractionation, matrix effects, mass flow ratios, and the relative merits of wet and dry plasma conditions for laser ablation sampling. It was found that a wet plasma was much more tolerant of increased sample loading without reducing plasma robustness, leading to less severe and more constant mutual matrix effects. These findings indicate that the on-line addition of water is the preferred mode of operation for quantification by LA-ICP-MS. The analytical performance of the method was validated by the analysis of three certified reference materials: National Institute of Standards and Technology (NIST) 612 Trace Elements in Glass, European Reference Material (ERM) 681 Trace Elements in Polyethylene and British Chemical Standards (BCS) No. 387 Nimonic 901 Alloy. Analysis of NIST 612 was performed under both wet and dry plasma conditions, and the correlation with certified elemental concentrations was much better when a wet plasma was employed. Analyses of ERM 681 and BCS No. 387 were performed under wet plasma conditions, due to that method’s proven advantages. The differences between the found and certified elemental concentrations varied between 1–10% for the majority of elements, for all three certified reference materials.

Instrument response functions, mass bias and matrix effects in isotope ratio measurements and semi-quantitative analysis by single and multi-collector ICP-MS

This paper proposes a new approach to the estimation and correction of mass bias based on modelling the underlying instrument response function. Conventional definitions of mass bias are shown to be flawed and it is proposed that this quantity be recognised as merely the consequence of the instrument response function whose constants have a more fundamental importance. More accurate prediction of the bias in isotope ratio determinations is necessary and possible because of the improved precision afforded by multi-collector ICP-MS instrumentation. Isotope ratio measurements of Cd and Sn were used to study the variation of the mass bias with time, absolute mass and mass difference. No statistically significant variations were seen over a 20 min period, after which the data deviated significantly from the original measurement. After inclusion of the uncertainties in the natural abundances used to calculate the mass bias, no significant variation with increasing average isotope mass was observed. The reproducibility of the pattern of the points about the mean value suggested spectral interference and/or inaccurate values for the true isotope ratios. This was illustrative of the danger of using locally determined parameters to predict the mass bias. The variation of bias with mass difference showed a linear relationship, the implications of this for modelling are discussed. The common mass bias correction models are shown to be directly derivable from assumptions about the nature of the instrument response function. When the true instrument response function was investigated using a multi-element solution, a second order polynomial was found to provide the best fit to the data. The mass bias correction expression derived from such a model was used to calculate corrected Cd isotope ratios that were closer to the natural values than those obtained from the commonly used correction expressions. Increasing the concentration of a matrix element (bismuth or calcium) was found to significantly affect the value of Cd and Mg isotope ratios measured by multi-collector ICP-MS. The direction and magnitude of the effect was dependent on the position on the multi-collector array in which the isotopes were collected, with the heavier isotopes suffering higher levels of suppression. Measurements using an instrument with different multi-collector hardware did not show the same behaviour. A method of semi-quantitative analysis was developed that used the bias of 16 isotope ratios across the mass range to define the parameters in a quadratic instrument response function. This function was then applied to calculate the concentration of 24 analyte elements based on knowledge of ionisation efficiencies and the concentration of a single internal standard. This approach gave errors in the calculated concentrations that were comparable to the results obtained by using 6 internal standards, and did not require separate measurement of a standard solution to predetermine the instrument response.

Determination of iodine and molybdenum in milk by quadrupole ICP-MS

A reliable method for the determination of iodine and molybdenum in milk samples, using alkaline digestion with tetramethylammonium hydroxide and hydrogen peroxide, followed by quadrupole ICP-MS analysis, has been developed and tested using certified reference materials. The use of He+O2 (1.0 ml min(-1) and 0.6 ml min(-1)) in the collision-reaction cell of the mass spectrometer to remove (129)Xe+-- initially to enable the determination of low levels of 129I--also resulted in the quantitative conversion of Mo(+) to MoO2+ which enabled the molybdenum in the milk to be determined at similar mass to the iodine with the use of Sb as a common internal standard. In order to separate and pre-concentrate iodine at sub microg l(-1) concentrations, a novel method was developed using a cation-exchange column loaded with Pd2+ and Ca2+ ions to selectively retain iodide followed by elution with a small volume of ammonium thiosulfate. This method showed excellent results for aqueous iodide solutions, although the complex milk digest matrix made the method unsuitable for such samples. An investigation of the iodine species formed during oxidation and extraction of milk sample digests was carried out with a view to controlling the iodine chemistry.

Occurrence and reduction of noise in inductively coupled plasma mass spectrometry for enhanced precision in isotope ratio measurement

The limitations imposed upon measurement precision by instrumental noise sources present within the inductively coupled plasma mass spectrometer used have been established using noise spectral analysis. Based upon the spectral information gained, a methodology for the sequential measurement of isotopes has been developed to minimize the deleterious influence of non-random instrumental noise. Efficient use of the noise reduction techniques available within the peak-jumping mode have been found to remove the majority of the instrumental noise associated with sample introduction and excitation, facilitating a measurement precision of approximately 0.05% relative standard deviation, with respect to the 107Ag: 109Ag isotope ratio. The precision of isotope ratios has been found to be limited by inaccuracies associated with the operation of the quadrupole mass analyser and the statistical error arising from the random arrival of ions at the detector.

Single Cell Tracking of Gadolinium Labeled CD4+ T Cells by Laser Ablation Inductively Coupled Plasma Mass Spectrometry

Cellular therapy is emerging as a promising alternative to conventional immunosuppression in the fields of hematopoietic stem cell (HSC) transplantation, autoimmune disease, and solid organ transplantation. Determining the persistence of cell-based therapies in vivo is crucial to understanding their regulatory function and requires the combination of an extremely sensitive detection technique and a stable, long-lifetime cell labeling agent. This paper reports the first application of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to perform single cell detection of T cell populations relevant to cellular immunotherapy. Purified human CD4(+) T cells were labeled with commercially available Gd-based magnetic resonance imaging (MRI) contrast agents, Omniscan and Dotarem, which enabled passive loading of up to 10(8) Gd atoms per cell. In mixed preparations of labeled and unlabeled cells, LA-ICP-MS was capable of enumerating labeled cells at close to the predicted ratio. More importantly, LA-ICP-MS single cell analysis demonstrated that the cells retained a sufficient label to remain detectable for up to 10 days post-labeling both in vitro and in vivo in an immunodeficient mouse model.

Recent developments in the design of rapid response cells for laser ablation-inductively coupled plasma-mass spectrometry and their impact on bioimaging applications

This review covers developments in the design of Laser Ablation (LA) cells, the associated transport tubing assembly, and their coupling to Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) instrumentation. Recent ablation cell designs have reduced the pulse response duration for a single laser shot to <10 ms, using the criterion of the full peak width at 1% of the height of the maximum signal intensity. The evolution towards these low dispersion systems has been profoundly influenced by our understanding of processes driving the initial dispersion, of the design aspects of the cell and tubing that influence transport-induced dispersion and transport efficiency, and of limitations imposed by the temporal resolution of ICP-MS instruments, all of which are discussed. Rapid response LA-ICP-MS systems greatly benefit throughput and sensitivity, which are key parameters in 2D and 3D imaging at high lateral resolution. The analysis and imaging of biological material has come to the forefront as a key application of LA-ICP-MS. The impact of the technical developments in LA-ICP-MS systems on emerging applications, including multiplexed metal-tagged antibody detection (for immunohistochemistry), nanoparticle and compound hypo- and hyperaccumulation, and (intra-) cellular/histological studies, is also discussed.

Quantitative Analysis of Gold Nanoparticles in Single Cells by Laser Ablation Inductively Coupled Plasma-Mass Spectrometry

Single cell analysis has become an important field of research in recent years reflecting the heterogeneity of cellular responses in biological systems. Here, we demonstrate a new method, based on laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS), which can quantify in situ gold nanoparticles (Au NPs) in single cells. Dried residues of picoliter droplets ejected by a commercial inkjet printer were used to simulate matrix-matched calibration standards. The gold mass in single cells exposed to 100 nM NIST Au NPs (Reference material 8012, 30 nm) for 4 h showed a log-normal distribution, ranging from 1.7 to 72 fg Au per cell, which approximately corresponds to 9 to 370 Au NPs per cell. The average result from 70 single cells (15 ± 13 fg Au per cell) was in good agreement with the result from an aqua regia digest solution of 1.2 × 10(6) cells (18 ± 1 fg Au per cell). The limit of quantification was 1.7 fg Au. This paper demonstrates the great potential of LA-ICPMS for single cell analysis and the beneficial study of biological responses to metal drugs or NPs at the single cell level.