Laser ablation-inductively coupled plasma-mass spectrometry analysis reveals differences in chemotherapeutic drug distribution in surgically resected pleural mesothelioma.

AIMS: Pleural mesothelioma (PM) is a highly aggressive thoracic tumour with poor prognosis. Although reduced tissue drug accumulation is one of the key features of platinum (Pt) resistance, little is known about Pt distribution in human PM. METHODS: We assessed Pt levels of blood samples and surgically resected specimens from 25 PM patients who had received neoadjuvant Pt-based chemotherapy (CHT). Pt levels and tissue distributions were measured by laser ablation-inductively coupled plasma-mass spectrometry and correlated with clinicopathological features. RESULTS: In surgically resected PM specimens, mean Pt levels of nontumourous (fibrotic) areas were significantly higher (vs tumourous regions, P = 0.0031). No major heterogeneity of Pt distribution was seen within the tumourous areas. Pt levels correlated neither with the microvessel area nor with apoptosis rate in the tumourous or nontumourous regions. A significant positive correlation was found between serum and both full tissue section and tumourous area mean Pt levels (r = 0.532, P = 0.006, 95% confidence interval [95% CI] 0.161-0.771 and r = 0.415, P = 0.039, 95% CI 0.011-0.702, respectively). Furthermore, a significant negative correlation was detected between serum Pt concentrations and elapsed time from the last cycle of CHT (r = -0.474, P = 0.017, 95% CI -0.738--0.084). Serum Pt levels correlated negatively with overall survival (OS) (P = 0.029). CONCLUSIONS: There are major differences in drug distribution between tumourous and nontumourous areas of PM specimens. Serum Pt levels significantly correlate with full section and tumourous area average Pt levels, elapsed time from the last CHT cycle, and OS. Further studies investigating clinicopathological factors that modulate tissue Pt concentration and distribution are warranted.

A Combined Deep Eutectic Solvent-Ionic Liquid Process for the Extraction and Separation of Platinum Group Metals (Pt, Pd, Rh).

Recovery of platinum group metals from spent materials is becoming increasingly relevant due to the high value of these metals and their progressive depletion. In recent years, there is an increased interest in developing alternative and more environmentally benign processes for the recovery of platinum group metals, in line with the increased focus on a sustainable future. To this end, ionic liquids are increasingly investigated as promising candidates that can replace state-of-the-art approaches. Specifically, phosphonium-based ionic liquids have been extensively investigated for the extraction and separation of platinum group metals. In this paper, we present the extraction capacity of several phosphonium-based ionic liquids for platinum group metals from model deep eutectic solvent-based acidic solutions. The most promising candidates, P66614Cl and P66614B2EHP, which exhibited the ability to extract Pt, Pd, and Rh quantitively from a mixed model solution, were additionally evaluated for their capacity to recover these metals from a spent car catalyst previously leached into a choline-based deep eutectic solvent. Specifically, P66614Cl afforded extraction of the three target precious metals from the leachate, while their partial separation from the interfering Al was also achieved since a significant amount (approx. 80%) remained in the leachate.

"Variances" and "in-variances" in hierarchical porosity and composition, across femoral tissues from cow, horse, ostrich, emu, pig, rabbit, and frog.

It is very well known that bone is a hierarchically organized material produced by bone cells residing in the fluid environments filling (larger) vascular pores and (smaller) lacunar pores. The extracellular space consists of hydroxyapatite crystals, collagen type I molecules, and water with non-collageneous organics. It is less known to which extent the associated quantities (mineral, organic, and water concentrations; vascular, lacunar, and extracellular porosities) vary across species, organs, and ages. We here investigate the aforementioned quantities across femoral shaft tissues from cow, horse, emu, frog, ostrich, pig, and rabbit; by means of light microscopy and dehydration-demineralization tests; thereby revealing interesting invariances: The extracellular volume fractions of organic matter turn out to be similar across all tested non-amphibian tissues; as do the extracellular volume fractions of hydroxyapatite across all tested mammals. Hence, the chemical composition of the femoral extracellular bone matrix is remarkably "invariant" across differently aged mammals; while the water content shows significant variations, as does the partitions of water between the different pore spaces. The latter exhibit strikingly varying morphologies as well. This finding adds to the ample "universal patterns" in the sense of evolutionary developmental biology; and it provides interesting design requirements for the development of novel biomimetic tissue engineering solutions.

Toxic trace metals in size-segregated fine particulate matter: Mass concentration, respiratory deposition, and risk assessment.

To characterise the mass concentration, size-distribution, and respiratory deposition of selected trace metals (Cr, Mn, Fe, Ni, Cu, Zn, Ba, and Pb) in size-segregated PM2.5, a long-term monitoring campaign was undertaken at an urban background site in Como (Northern Italy). 96-h aerosol samples were collected weekly, from May 2015 to March 2016, using a 13-stage low pressure impactor and analysed via laser ablation-inductively coupled plasma-mass spectrometry. Significantly higher levels of trace metals were generally found during the heating season (two to more than four times) compared to the non-heating period at all size ranges, especially for concentrations in PM0.1-1. Distinct distribution profiles characterised the different elements, even though the corresponding heating and non-heating shapes always exhibited similar features, with negligible seasonal shifts in the average mass median aerodynamic diameters. Fe, Ba, and Cu had >70% of their mass in PM1-2.5, whereas Pb, Zn, and Ni showed higher contributions in the accumulation mode (>60%). Finally, broad size-distributions were found for Cr and Mn. The multiple-path particle dosimetry model estimated the overall deposition fractions in human airways varying between 27% (Pb) and 48% (Ba). The greatest deposition variability was always registered in the head region of the respiratory system, with the highest contributions for those metals predominantly accumulated in the PM2.5 coarse modes. In contrast, the deposition in the deepest respiratory tract maintained nearly constant proportions over time, becoming notably important for Pb, Ni, and Zn (∼13%) with respect to their total deposition. The comparison with national limits established for Pb and Ni suggested the absence of significant risks for the local population, as expected, with average concentrations two orders of magnitude lower than the corresponding annual limit and objective value. Similar findings were reported for all the other metals, for which the estimated hazard quotients were always well <1.

Multi-element analysis of size-segregated fine and ultrafine particulate via Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry.

In this study a novel and reliable Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) measurement protocol for the elemental characterization of size-segregated particulate was developed. Special efforts were made to improve and optimize sample pre-treatment steps and LA operating conditions to avoid some critical drawbacks encountered during analysis and to make the particulate samples suitable for an accurate and reproducible LA-ICP-MS analysis, regardless of the mass loading on each filter. For example, a new approach for dust-fixation on the sample-carrier was developed using a glycerol coverage, which allowed to overcome problematic sample losses during the ablation process. Under the optimum conditions, dust samples, blank filters and standards for calibration were analyzed by multiple rastering of defined spot areas. Quantitative analysis was accomplished with dried micro-droplets of aqueous standard solutions. Derived method detection limits varied between 0.001 and 0.1 ng m-3 and allowed even for the smallest particle fraction quantitative measurements. The accuracy of LA-ICP-MS results was verified by comparison with conventional ICP-MS analysis of selected PM samples after sample mineralization. The proposed LA treatment procedure benefits from a simple and fast sample preparation, thus overcoming the laborious pre-treatment steps required for wet chemical digestion. Moreover, the better sensitivity of the LA-ICP-MS approach provided more complete information about the mass concentration and size-distribution of the investigated elements, thus allowing to deeper investigate the composition of the most dangerous PM fractions in terms of health concern.

Photosynthetic poly-ß-hydroxybutyrate accumulation in unicellular cyanobacterium Synechocystis sp. PCC 6714.

Poly-ß-hydroxybutyrate (PHB) production from CO2 has the potential to reduce the production cost of this biodegradable polyesters, and also to make the material more sustainable compared to utilization of sugar feedstocks. In this study the unicellular cyanobacterium, Synechocystis sp. PCC 6714 has been identified as an unexplored potential organism for production of PHB. Synechocystis sp. PCC 6714 was studied under various cultivation conditions and nutritional limitations. Combined effects of nitrogen and phosphorus deficiency led to highest PHB accumulation under photoautotrophic conditions. Multivariate experimental design and quantitative bioprocess development methodologies were used to identify the key cultivation parameters for PHB accumulation. Biomass growth and PHB accumulation were studied under controlled defined conditions in a lab-scale photobioreactor. Specific growth rates were fourfold higher in photobioreactor experiments when cultivation conditions were controlled. After 14 days of cultivation in nitrogen and phosphorus, limited media intracellular PHB levels reached up to 16.4% from CO2. The highest volumetric production rate of PHB was 59 ± 6 mg L-1 day-1. Scanning electron microscopy of isolated PHB granules of Synechocystis sp. PCC 6714 cultivated under nitrogen and phosphorus limitations showed an average diameter of 0.7 µm. The results of this study might contribute towards a better understanding of photoautotrophic PHB production from cyanobacteria.

Combining Dispersed Particle Extraction with Dried-Droplet Laser Ablation ICP-MS for Determining Platinum in Airborne Particulate Matter.

A combination of analyte pre-concentration using dispersed particle extraction (DPE) and dried-droplet laser ablation inductively coupled mass spectrometry (LA-ICP-MS) was developed with the aim to quantify Pt and Pd in urban particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5). The PM2.5 aerosol was collected on cellulose ester filters during a sampling period of three days, with sampling intervals of 4 h only. Each of the filters was chemically digested, and the resulting solution was pre-concentrated using DPE. Droplets taken from the pre-concentrated sample were deposited on polymeric disks and dried. These dry spots were then analyzed by means of LA-ICP-MS. This approach allowed ICP-MS analysis of solutions with high content of dissolved sorbent particles coming from the DPE procedure. Furthermore, spectral interferences arising from sample-inherent matrix elements as well as solvent-related interferences could be removed by the proposed approach. The method was validated by determining the Pt concentration in Bureau Communautaire de Référence certified reference material (BCR CRM) 723 road dust certified reference material and a good agreement with the certified value was obtained. The temporal variation of Pt during the three-day sampling period is discussed, with respect to automotive traffic. The daily average of Pt measured in the air corresponds to typical values observed in urban areas in Central Europe. Although the pre-concentration of palladium is feasible with dispersed particle extraction, the method detection limits achieved here did not allow to quantify this element in the CRM or in the PM2.5 samples. The source for these high method detection limits for palladium are blank values arising from the filter material as well as the digestion procedure of the PM2.5 samples. Instrumental sensitivity of the approach would, however, suggest that palladium quantification is possible, provided the abovementioned blank issues are controlled better.

Self-aliquoting micro-grooves in combination with laser ablation-ICP-mass spectrometry for the analysis of challenging liquids: quantification of lead in whole blood.

We present a technique for the fast screening of the lead concentration in whole blood samples using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). The whole blood sample is deposited on a polymeric surface and wiped across a set of micro-grooves previously engraved into the surface. The engraving of the micro-grooves was accomplished with the same laser system used for LA-ICP-MS analysis. In each groove, a part of the liquid blood is trapped, and thus, the sample is divided into sub-aliquots. These aliquots dry quasi instantly and are then investigated by means of LA-ICP-MS. For quantification, external calibration against aqueous standard solutions was relied on, with iron as an internal standard to account for varying volumes of the sample aliquots. The (208)Pb/(57)Fe nuclide ratio used for quantification was obtained via a data treatment protocol so far only used in the context of isotope ratio determination involving transient signals. The method presented here was shown to provide reliable results for Recipe ClinChek® Whole Blood Control levels I-III (nos. 8840-8842), with a repeatability of typically 3 % relative standard deviation (n = 6, for Pb at 442 µg L(-1)). Spiked and non-spiked real whole blood was analysed as well, and the results were compared with those obtained via dilution and sectorfield ICP-MS. A good agreement between both methods was observed. The detection limit (3 s) for lead in whole blood was established to be 10 µg L(-1) for the laser ablation method presented here. Graphical Abstract Micro-grooves are filled with whole blood, dried, and analyzed by laser ablation ICP-mass spectrometry. Notice that the laser moves in perpendicular direction with regard to the micro-grooves.

Extraction and pre-concentration of platinum and palladium from microwave-digested road dust via ion exchanging mesoporous silica microparticles prior to their quantification by quadrupole ICP-MS.

We report on the use of mesoporous silica microparticles (µPs) functionalized with quarternary amino groups for the isolation of platinum and palladium tetrachloro complexes from aqueous road dust digests. The µPs have a size ranging from 450 to 850 nm and are suspended directly in the aqueous digests, upon which the anionic Pt and Pd complexes are retained on the cationic surface. Subsequently, the µPs are separated by centrifugation. Elements that cause spectral interferences in ICP-MS determination of Pt and Pd can be quantitatively removed by adding fresh 0.240 mol L-1 HCl to the µPs and by repeating the centrifugation step. The analyte-loaded µPs are then dissolved in 0.1 mL of 2 mol L-1 HF, diluted to 2 mL, and the solutions thus obtained are analyzed by quadrupole ICP-MS. This method avoids analyte elution from the sorbent. This "dispersed particle extraction" approach yielded a run-to-run relative standard deviation ≤ 5 % for Pt and ≤ 4 % for Pd (at 0.1 ng mL-1, n = 4 road dust digests). Method detection limits (expressed as concentrations in the dust samples) are 2 and 1 ng g-1 for Pt and Pd, respectively. The method was validated by analysis of a reference material (BCR CRM 723) and applied to the analysis of road dust samples collected in downtown Vienna. Pt and Pd concentrations in samples collected in summer and in winter were compared, with concentrations ranging from 205 to 1445 ng g-1 for Pt and from 201 to 1230 ng g-1 for Pd. Graphical AbstractMesoporous silica microparticles (µPs) functionalized with quarternary amino groups were used for isolating platinum and palladium from aqueous road dust digests. The µPs were suspended directly in the aqueous digests, and the analyte-loaded µPs were analyzed using "dispersed particle extraction".

Recent advances in quantitative LA-ICP-MS analysis: challenges and solutions in the life sciences and environmental chemistry.

Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) is a widely accepted method for direct sampling of solid materials for trace elemental analysis. The number of reported applications is high and the application range is broad; besides geochemistry, LA-ICP-MS is mostly used in environmental chemistry and the life sciences. This review focuses on the application of LA-ICP-MS for quantification of trace elements in environmental, biological, and medical samples. The fundamental problems of LA-ICP-MS, such as sample-dependent ablation behavior and elemental fractionation, can be even more pronounced in environmental and life science applications as a result of the large variety of sample types and conditions. Besides variations in composition, the range of available sample states is highly diverse, including powders (e.g., soil samples, fly ash), hard tissues (e.g., bones, teeth), soft tissues (e.g., plants, tissue thin-cuts), or liquid samples (e.g., whole blood). Within this article, quantification approaches that have been proposed in the past are critically discussed and compared regarding the results obtained in the applications described. Although a large variety of sample types is discussed within this article, the quantification approaches used are similar for many analytical questions and have only been adapted to the specific questions. Nevertheless, none of them has proven to be a universally applicable method.

Radial line-scans as representative sampling strategy in dried-droplet laser ablation of liquid samples deposited on pre-cut filter paper disks.

Nebulising liquid samples and using the aerosol thus obtained for further analysis is the standard method in many current analytical techniques, also with inductively coupled plasma (ICP)-based devices. With such a set-up, quantification via external calibration is usually straightforward for samples with aqueous or close-to-aqueous matrix composition. However, there is a variety of more complex samples. Such samples can be found in medical, biological, technological and industrial contexts and can range from body fluids, like blood or urine, to fuel additives or fermentation broths. Specialized nebulizer systems or careful digestion and dilution are required to tackle such demanding sample matrices. One alternative approach is to convert the liquid into a dried solid and to use laser ablation for sample introduction. Up to now, this approach required the application of internal standards or matrix-adjusted calibration due to matrix effects. In this contribution, we show a way to circumvent these matrix effects while using simple external calibration for quantification. The principle of representative sampling that we propose uses radial line-scans across the dried residue. This compensates for centro-symmetric inhomogeneities typically observed in dried spots. The effectiveness of the proposed sampling strategy is exemplified via the determination of phosphorus in biochemical fermentation media. However, the universal viability of the presented measurement protocol is postulated. Detection limits using laser ablation-ICP-optical emission spectrometry were in the order of 40 µg mL- 1 with a reproducibility of 10 % relative standard deviation (n = 4, concentration = 10 times the quantification limit). The reported sensitivity is fit-for-purpose in the biochemical context described here, but could be improved using ICP-mass spectrometry, if future analytical tasks would require it. Trueness of the proposed method was investigated by cross-validation with conventional liquid measurements, and by analyzing IAEA-153 reference material (Trace Elements in Milk Powder); a good agreement with the certified value for phosphorus was obtained.