In recent years, laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) has gained increasing importance for biological analysis, where ultratrace imaging at micrometer resolution is required. However, while undoubtedly a valuable research tool, the washout times and sensitivity of current technology have restricted its routine and clinical application. Long periods between sampling points are required to maintain adequate spatial resolution. Additionally, temporal signal dispersion reduces the signal-to-noise ratio, which is a particular concern when analyzing discrete samples, such as individual particles or cells. This paper describes a novel, two-volume laser ablation cell and integrated ICP torch designed to minimize aerosol dispersion for fast, efficient sample transport. The holistic design utilizes a short, continuous diameter fused silica conduit, which extends from the point of ablation, through the ICP torch, and into the base of the plasma. This arrangement removes the requirement for a dispersive component for argon addition, and helps to keep the sample on axis with the ICP cone orifice. Hence, deposition of sample on the cones is theoretically reduced with a resulting improvement in the absolute sensitivity (counts per unit mole). The system described here achieved washouts of 1.5, 3.2, and 4.9 ms for NIST 612 glass, at full width half, 10%, and 1% maximum, respectively, with an 8–14-fold improvement in absolute sensitivity, compared to a single volume ablation cell. To illustrate the benefits of this performance, the system was applied to a contemporary bioanalytical challenge, specifically the analysis of individual biological cells, demonstrating similar improvements in performance.

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 × 106 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.

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 108 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.

This paper describes a set of fast and selective high performance liquid chromatography (HPLC) methods coupled to electro-spray ionisation linear ion trap mass spectrometry (ESI–MS), sector-field inductively coupled plasma mass spectrometry (SF-ICP-MS) and UV detection for in vitro studies of the bifunctional adducts of oxaliplatin with mono-nucleotides, di-nucleotides and cellular DNA. The stationary phases and the optimised conditions used for each separation are discussed. Interaction of oxaliplatin with A and G mono-nucleotides resulted in the formation of five bifunctional platinum diaminocyclohexane (DACHPt) adducts. These were two isomers of the A-DACHPt-A and A-DACHPt-G adducts, and one G-DACHPt-G adduct, as confirmed by MS/MS spectra obtained by collision induced dissociation. These adducts were also characterised by UV absorption data and SF-ICP-MS elemental 195Pt and 31P signals. Further, interaction of oxaliplatin with AG and GG di-nucleotides resulted in the formation of three adducts: DACHPt-GG and two isomers of the DACHPt-AG adduct, as confirmed by ESI-MS and the complementary data obtained by UV and SF-ICP-MS. Finally, a very sensitive LC-ICP-MS method for the quantification of oxaliplatin GG intra-strand adducts (DACHPt-GG) was developed and used for monitoring the in vitro formation and repair of these adducts in human colorectal cancer cells. The method detection limit was 0.14 ppb Pt which was equivalent to 0.22 Pt adduct per 106 nucleotides based on a 10 μg DNA sample. This detection limit makes this method suitable for in vivo assessment of DACHPt-GG adducts in patients undergoing oxaliplatin chemotherapy.

Numerical simulations of gas flows through an open, non-contact cell for laser ablation are presented. The cell consists of dual, annular, concentric micro-jet gas arrays to entrain ablated material (the carrier flow) and exclude atmosphere (the curtain flow). This study shows that the design of the cell affords a very high degree of exclusion of atmospheric gases, using a relatively low curtain flow of 2.5 l min−1 (with a carrier flow of 1.2 l min−1He), and demonstrates the efficacy of the micro-jet arrays in providing an axially symmetric exclusion zone. Minimum particle transit times through the cell were calculated to be of the order of 50–100 ms.

This technical note describes the development of Laser Ablation of a Sample In Liquid (LASIL), a technique where the ablation occurs at a solid sample surface submerged in a liquid. LASIL can be performed in a 25 µl isolated, freestanding droplet that acts as a micro-laser cavity, to produce a suspended particulate that can be analysed either directly, or following in-droplet chemistry, by calibration against aqueous standards. The technique is robust and easy to implement being carried out in air, offline to the detection apparatus. The analytical characteristics of LASIL are its ease of quantification, containment of particles, the ease of generating suspended solids in solution from insoluble materials and the control over dissolution and dilution to generate measurable concentrations. NIST 611 (trace elements in glass) was employed as a test sample as it is a commonly used reference material in conventional Laser Ablation (LA) studies. Droplet LASIL allowed the quantification of trace elements in NIST 611 and also investigation of the particle sizes and shapes generated by the ablation process. Particle sizes were found to vary with laser fluence, with higher fluences producing a wider particle size distribution with greater variation in shape. The types of particles found were: jagged particles of 1–2 µm in diameter most probably created by micro-jet impingement, spherical nanometre sized particles from vapour condensation and melt ejection, and thin, string-like particles from particle agglomeration or liquid jet fragmentation. At lower fluences the particle morphology tended towards spherical shapes and formed agglomerates. At this small particle size (below 250 nm), Brownian motion ensures a very slow settling rate in the liquid medium yielding solutions that are stable for analysis over several days. Alternatively, as demonstrated here, post-ablation chemistry can be carried out in the droplet, e.g. acid dissolution, or clean up using micro-extraction techniques. The liquid droplet was analysed by inductively coupled plasma-mass spectrometry (ICP-MS) with calibration against aqueous standards. The ablation yield from the sample was normalised using the found versus known concentration of uranium in the sample and ratioing measured elemental concentrations to this factor. LASIL on a sample immersed in liquid facilitated the study of the effect of the solution composition on the LASIL process.

This paper describes methodologies, based on sector field inductively-coupled plasma mass spectrometry (SF-ICP-MS), and their application in the holistic study of the fate of Pt in human cell populations following treatment with cis- or oxaliplatin and combination treatments. Pt–DNA adduct formation data at several time points has been determined in the leukocytes from patients undergoing Pt-based chemotherapy demonstrating significant inter-patient variability and excellent reproducibility of the assay. The sensitivity of the technique enabled quantitation of as little as 0.2 Pt adducts per 106 nucleotides using 10 μg of patient DNA. Further, the first ever reported in vivo sub-cellular Pt fractionation data on a patient sample is presented indicating the feasibility of applying the methods presented here in a clinical environment. For in vitro studies, three cell models were used: A549 human lung adenocarcinoma epithelial cells were exposed to 50 μM cisplatin for 1 h; HCA7 human colorectal cancer cells were treated with either FOLFOX (200 μM 5-fluorouracil, 200 μM folinic acid and 50 μM oxaliplatin) or 50 μM oxaliplatin; and HT29 human colorectal cancer cells were treated with 50 μM oxaliplatin in combination with 20 μM methaneseleninic acid, CH3SeO2H (MSA). The cells were harvested and either the DNA extracted and/or a commercially available kit used to fractionate the treated cells into four sub-cellular compartments. Each of the sub-cellular fractions and extracted DNA were digested separately, evaporated to dryness and reconstituted in 2% nitric acid for analysis by SF-ICP-MS. The sub-cellular Pt distribution for cisplatin treated A549 cells was shown to be as follows: ∼70% localized in the cytosol, ∼17% in the membrane and membrane localized fraction, ∼9% in the nuclear fraction and ∼4% in the cytoskeletal fraction. Both FOLFOX and oxaliplatin treated HCA7 cells showed comparable sub-cellular Pt distributions, and Pt–DNA adduct formation was similar for the oxaliplatin and FOLFOX treatments with adduct yields of 5.6 and 5.5 adducts per 106 nucleotides respectively. It was found that the combination of oxaliplatin with 20 μM MSA did not change the distribution of Pt or significantly alter its accumulation in the cytosol of the HT29 cells. Mass balance experiments showed a >99% recovery of the total Pt in the sub-cellular fractions. These experiments are the first to provide such a detailed quantitation of Pt-drug partitioning and they show that the Pt broadly follows the total protein content of the individual compartments with the majority being scavenged in the cytosol compartment.Graphical abstractResearch highlights▶ Partitioning of Pt-based drugs in cells of patients undergoing Pt-based chemotherapy. ▶ New data on Pt -DNA adduct formation and persistence over extended treatment cycles. ▶ Variability in patient response and evidence of adduct repair. ▶ The effect of combination therapy, such as the FOLFOX regimen. ▶ Effect of Se supplementation, and cell partitioning of drug.

A novel, open, non-contact cell for laser ablation, capable of sampling: large planar samples, embedded planar samples, or samples of less than 2 mm mounted on a planar platform, without an outer containment enclosure, is described. This cell, when tested on NIST-613 CRM, exhibited rapid wash-out (<3.6 s for 99% signal reduction), low limits of detection and good signal precision in LA-ICP-MS. The cell uses a dual, annular, micro-jet gas flow array to exclude atmospheric gases and to entrain the ablated sample aerosol. The micro-jet array employed enabled a sampling height, between the sample surface and the lowest plane of the cell, of up to 200 µm. The micro-jet array has the facility to be electrically biased if the application demands it, e.g. extracting a charged plume in Matrix-Assisted Laser Desorption/Ionisation (MALDI) or Desorption Electrospray Ionisation (DESI) experiments. This particular implementation of the cell featured dual sample output channels, which could enable connection of the cell to more than one analyser. A micro jet-pump was coupled to the cell to extract the ablated aerosol from the low-volume inner ablation chamber, provide mixing of the aerosol with the injector flow of the ICP and to isolate the cell from downstream conditions in the injector flow. Potential applications of this cell include: analysis of silicon wafers, gel-plates/membranes, tissue samples, multiple sample analysis in high throughput facilities; and toxic fume removal and analysis in laser scribing, cutting and etching.

A fundamental requirement of ICP-MS-CLS is a post mass separation ion beam with an energy spread of less than ∼0.2 eV to enable efficient pumping of fluorescent lines with a narrow band (Δν ∼ 100 kHz) laser for the optical detection step. The role of a 3D quadrupole ion trap for ion beam cooling, as an accessory for a new generation of ICP-MS-CLS (inductively coupled plasma mass spectrometry, coincidence laser spectroscopy) (B. L. Sharp, P. S. Goodall, L. M. Ignjatović and H. Teng, J. Anal. At. Spectrom., 2007, 22, 1447) instrument, was investigated by means of numerical simulation. Whereas in-trap ion cooling is well established, it was found that extraction of cooled ions from the trap introduced additional broadening and a loss of transmission efficiency. Modelling was based on a beam of 20 eV mean energy with a spread of 3 eV which represents a worst case scenario for the ions derived from an ICP source. The efficiency of the cooling process (trapping + extraction), as well as the energy distributions of ions exiting the trap, were calculated and compared for several methods of extraction. Trapping efficiencies of ∼25% were obtained at buffer gas pressures up to 10 mTorr. The addition of virtual reflectrons to the trap resulted in an improvement in the energy distribution of the trapped ions by lowering the wings of the distribution, but did not significantly improve the efficiency. Zero field, rf field only, quadrupolar field and homogeneous field ion extraction were investigated to recover ions from the trap, and of these quadrupolar extraction was best. However, extraction efficiency and ion energy distribution were inversely related so that quadrupolar extraction at Uq = 10 V yielded an exit ion energy distribution of 0.5 eV half width, compared with a trapped width of 0.03 eV, but with only 10% transmission efficiency. Thus, it was demonstrated that a 3D trap can be used to cool energetic ions for post-trap mass or spectroscopic examination, but the low efficiency makes it unsuitable for use with ICP-MS-CLS.

Oligonucleotides containing a biotin functionality were successfully labelled with a streptavidin nanogold conjugate and subsequently separated and analysed by high performance liquid chromatography–inductively coupled plasma–mass spectrometry (HPLC-ICP-MS).

Powdered samples have been pressed, utilising a standard KBr infrared (IR) press, to produce mechanically stable 13 mm discs. Three ‘absorbing’, organic based binders have been employed in this work, vanillic acid, pyrazinoic acid and nicotinic acid, chosen because of their high optical absorbance at the wavelength of the incident laser energy (213 nm). Poly(vinyl alcohol) (PVA) was employed as an example of a ‘non-absorbing’ binder and because its use has been described previously in the literature. Discs of various sample/binder compositions were prepared and their absorption properties characterised by diffuse reflectance spectroscopy. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to investigate the effect of different sample/binder compositions on signal sensitivity, whilst surface profilometry was performed on the resulting tracks to provide an estimate of the ablation depth achieved by the laser beam. It was found that discs prepared with vanillic acid had the highest optical absorbance at the wavelength of the laser system employed, resulting in a lower ablation depth and improved signal sensitivity, probably through the formation of smaller particles during the ablation process. Analysis of certified reference materials (CRMs) was performed using simple external calibration standards of similar and dissimilar CRMs. It was found that discs produced using a 40% vanillic acid binder, with a 60% sample composition gave superior quality analytical data when compared with the use of 40% PVA binder or no binder at all. These findings indicate the potential for fit-for-purpose quality analytical data to be obtained when employing external calibration standards, without internal standardisation and without exact matrix matching. These data also provide further evidence that standardisation of ablation conditions and mass flux to the plasma are prerequisites for robust calibration, particularly in the absence of a suitable internal standard element.

This paper reports a theoretical study of the feasibility of using laser-excited ionic fluorescence in time correlation with ion counting, termed coincidence laser spectroscopy (CLS), for improved specificity in the detection of ions in ICP-MS. The technique is here named ICP-MS-CLS. A number of factors are considered including: the preferred instrumental configuration, simulation of the performance of the optical detector and correlation step in reducing background, the spectroscopy of the selected of isotopes, 10Be+, 55Fe+, 63Ni+, 90Sr+, 99Tc+, 147Pm+, 238U+, 238Pu+ and 241Am+, which might be appropriate candidates for ICP-MS-CLS detection, the laser power required to attain saturation, the effects of ion energy and energy spread on pumping efficiency, the optical abundance sensitivity for adjacent isotopes of the same element, and the detection limits obtainable under a variety of scenarios. The ICP is established as an ideal ion source for elemental mass spectrometry, but as shown here, the ion energy spread produced is too large for optimum optical pumping because the ions are Doppler shifted to an extent that not all of them would be excited efficiently by a narrow-line laser source. This necessitates the inclusion of an ion cooler into the instrumental configuration so that ions maybe brought into resonance with the laser with 100% efficiency. The calculations show that for ions with simple spectra, such as 90Sr+ which can be repetitively pumped by the laser to produce a photon burst, ICP-MS-CLS can reduce the effect of very high backgrounds, 106 cps on mass and 1010 cps at adjacent mass, to low levels and improve detection limits by 2–3 orders of magnitude compared with the normal technique. Optical abundances of 10−5–10−9 are achievable which, combined with the mass abundance sensitivity of 10−5, yields overall abundance sensitivities of 10−10–10−14. This is of the same order as techniques such as accelerator mass spectrometry (AMS) or resonance ionisation mass spectrometry (RIMS). The technique is much less efficient for ions that undergo optical trapping and emit only one photon when pumped and/or exhibit hyperfine structure which distributes the oscillator strength over several hyperfine components. These factors significantly degrade performance and indicate a requirement for further refinement in terms of using two-colour excitation, or quenching of meta-stable levels, to enable the recycling of ions for further pumping.

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.

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.

Numerical simulations of gas flows through an open, non-contact cell for laser ablation are presented. The cell consists of dual, annular, concentric micro-jet gas arrays to entrain ablated material (the carrier flow) and exclude atmosphere (the curtain flow). This study shows that the design of the cell affords a very high degree of exclusion of atmospheric gases, using a relatively low curtain flow of 2.5 l min−1 (with a carrier flow of 1.2 l min−1He), and demonstrates the efficacy of the micro-jet arrays in providing an axially symmetric exclusion zone. Minimum particle transit times through the cell were calculated to be of the order of 50–100 ms.

This paper reports a theoretical study of the feasibility of using laser-excited ionic fluorescence in time correlation with ion counting, termed coincidence laser spectroscopy (CLS), for improved specificity in the detection of ions in ICP-MS. The technique is here named ICP-MS-CLS. A number of factors are considered including: the preferred instrumental configuration, simulation of the performance of the optical detector and correlation step in reducing background, the spectroscopy of the selected of isotopes, 10Be+, 55Fe+, 63Ni+, 90Sr+, 99Tc+, 147Pm+, 238U+, 238Pu+ and 241Am+, which might be appropriate candidates for ICP-MS-CLS detection, the laser power required to attain saturation, the effects of ion energy and energy spread on pumping efficiency, the optical abundance sensitivity for adjacent isotopes of the same element, and the detection limits obtainable under a variety of scenarios. The ICP is established as an ideal ion source for elemental mass spectrometry, but as shown here, the ion energy spread produced is too large for optimum optical pumping because the ions are Doppler shifted to an extent that not all of them would be excited efficiently by a narrow-line laser source. This necessitates the inclusion of an ion cooler into the instrumental configuration so that ions maybe brought into resonance with the laser with 100% efficiency. The calculations show that for ions with simple spectra, such as 90Sr+ which can be repetitively pumped by the laser to produce a photon burst, ICP-MS-CLS can reduce the effect of very high backgrounds, 106 cps on mass and 1010 cps at adjacent mass, to low levels and improve detection limits by 2–3 orders of magnitude compared with the normal technique. Optical abundances of 10−5–10−9 are achievable which, combined with the mass abundance sensitivity of 10−5, yields overall abundance sensitivities of 10−10–10−14. This is of the same order as techniques such as accelerator mass spectrometry (AMS) or resonance ionisation mass spectrometry (RIMS). The technique is much less efficient for ions that undergo optical trapping and emit only one photon when pumped and/or exhibit hyperfine structure which distributes the oscillator strength over several hyperfine components. These factors significantly degrade performance and indicate a requirement for further refinement in terms of using two-colour excitation, or quenching of meta-stable levels, to enable the recycling of ions for further pumping.

A fundamental requirement of ICP-MS-CLS is a post mass separation ion beam with an energy spread of less than ∼0.2 eV to enable efficient pumping of fluorescent lines with a narrow band (Δν ∼ 100 kHz) laser for the optical detection step. The role of a 3D quadrupole ion trap for ion beam cooling, as an accessory for a new generation of ICP-MS-CLS (inductively coupled plasma mass spectrometry, coincidence laser spectroscopy) (B. L. Sharp, P. S. Goodall, L. M. Ignjatović and H. Teng, J. Anal. At. Spectrom., 2007, 22, 1447) instrument, was investigated by means of numerical simulation. Whereas in-trap ion cooling is well established, it was found that extraction of cooled ions from the trap introduced additional broadening and a loss of transmission efficiency. Modelling was based on a beam of 20 eV mean energy with a spread of 3 eV which represents a worst case scenario for the ions derived from an ICP source. The efficiency of the cooling process (trapping + extraction), as well as the energy distributions of ions exiting the trap, were calculated and compared for several methods of extraction. Trapping efficiencies of ∼25% were obtained at buffer gas pressures up to 10 mTorr. The addition of virtual reflectrons to the trap resulted in an improvement in the energy distribution of the trapped ions by lowering the wings of the distribution, but did not significantly improve the efficiency. Zero field, rf field only, quadrupolar field and homogeneous field ion extraction were investigated to recover ions from the trap, and of these quadrupolar extraction was best. However, extraction efficiency and ion energy distribution were inversely related so that quadrupolar extraction at Uq = 10 V yielded an exit ion energy distribution of 0.5 eV half width, compared with a trapped width of 0.03 eV, but with only 10% transmission efficiency. Thus, it was demonstrated that a 3D trap can be used to cool energetic ions for post-trap mass or spectroscopic examination, but the low efficiency makes it unsuitable for use with ICP-MS-CLS.

A novel, open, non-contact cell for laser ablation, capable of sampling: large planar samples, embedded planar samples, or samples of less than 2 mm mounted on a planar platform, without an outer containment enclosure, is described. This cell, when tested on NIST-613 CRM, exhibited rapid wash-out (<3.6 s for 99% signal reduction), low limits of detection and good signal precision in LA-ICP-MS. The cell uses a dual, annular, micro-jet gas flow array to exclude atmospheric gases and to entrain the ablated sample aerosol. The micro-jet array employed enabled a sampling height, between the sample surface and the lowest plane of the cell, of up to 200 µm. The micro-jet array has the facility to be electrically biased if the application demands it, e.g. extracting a charged plume in Matrix-Assisted Laser Desorption/Ionisation (MALDI) or Desorption Electrospray Ionisation (DESI) experiments. This particular implementation of the cell featured dual sample output channels, which could enable connection of the cell to more than one analyser. A micro jet-pump was coupled to the cell to extract the ablated aerosol from the low-volume inner ablation chamber, provide mixing of the aerosol with the injector flow of the ICP and to isolate the cell from downstream conditions in the injector flow. Potential applications of this cell include: analysis of silicon wafers, gel-plates/membranes, tissue samples, multiple sample analysis in high throughput facilities; and toxic fume removal and analysis in laser scribing, cutting and etching.

This technical note describes the development of Laser Ablation of a Sample In Liquid (LASIL), a technique where the ablation occurs at a solid sample surface submerged in a liquid. LASIL can be performed in a 25 µl isolated, freestanding droplet that acts as a micro-laser cavity, to produce a suspended particulate that can be analysed either directly, or following in-droplet chemistry, by calibration against aqueous standards. The technique is robust and easy to implement being carried out in air, offline to the detection apparatus. The analytical characteristics of LASIL are its ease of quantification, containment of particles, the ease of generating suspended solids in solution from insoluble materials and the control over dissolution and dilution to generate measurable concentrations. NIST 611 (trace elements in glass) was employed as a test sample as it is a commonly used reference material in conventional Laser Ablation (LA) studies. Droplet LASIL allowed the quantification of trace elements in NIST 611 and also investigation of the particle sizes and shapes generated by the ablation process. Particle sizes were found to vary with laser fluence, with higher fluences producing a wider particle size distribution with greater variation in shape. The types of particles found were: jagged particles of 1–2 µm in diameter most probably created by micro-jet impingement, spherical nanometre sized particles from vapour condensation and melt ejection, and thin, string-like particles from particle agglomeration or liquid jet fragmentation. At lower fluences the particle morphology tended towards spherical shapes and formed agglomerates. At this small particle size (below 250 nm), Brownian motion ensures a very slow settling rate in the liquid medium yielding solutions that are stable for analysis over several days. Alternatively, as demonstrated here, post-ablation chemistry can be carried out in the droplet, e.g. acid dissolution, or clean up using micro-extraction techniques. The liquid droplet was analysed by inductively coupled plasma-mass spectrometry (ICP-MS) with calibration against aqueous standards. The ablation yield from the sample was normalised using the found versus known concentration of uranium in the sample and ratioing measured elemental concentrations to this factor. LASIL on a sample immersed in liquid facilitated the study of the effect of the solution composition on the LASIL process.

Oligonucleotides containing a biotin functionality were successfully labelled with a streptavidin nanogold conjugate and subsequently separated and analysed by high performance liquid chromatography–inductively coupled plasma–mass spectrometry (HPLC-ICP-MS).

Powdered samples have been pressed, utilising a standard KBr infrared (IR) press, to produce mechanically stable 13 mm discs. Three ‘absorbing’, organic based binders have been employed in this work, vanillic acid, pyrazinoic acid and nicotinic acid, chosen because of their high optical absorbance at the wavelength of the incident laser energy (213 nm). Poly(vinyl alcohol) (PVA) was employed as an example of a ‘non-absorbing’ binder and because its use has been described previously in the literature. Discs of various sample/binder compositions were prepared and their absorption properties characterised by diffuse reflectance spectroscopy. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to investigate the effect of different sample/binder compositions on signal sensitivity, whilst surface profilometry was performed on the resulting tracks to provide an estimate of the ablation depth achieved by the laser beam. It was found that discs prepared with vanillic acid had the highest optical absorbance at the wavelength of the laser system employed, resulting in a lower ablation depth and improved signal sensitivity, probably through the formation of smaller particles during the ablation process. Analysis of certified reference materials (CRMs) was performed using simple external calibration standards of similar and dissimilar CRMs. It was found that discs produced using a 40% vanillic acid binder, with a 60% sample composition gave superior quality analytical data when compared with the use of 40% PVA binder or no binder at all. These findings indicate the potential for fit-for-purpose quality analytical data to be obtained when employing external calibration standards, without internal standardisation and without exact matrix matching. These data also provide further evidence that standardisation of ablation conditions and mass flux to the plasma are prerequisites for robust calibration, particularly in the absence of a suitable internal standard element.