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A rapid and cost-efficient tissue preparation protocol for laser ablation-inductively coupled plasma-mass spectrometry imaging (LA–ICP–MSI) has been developed within this study as an alternative to the current gold standard using fresh-frozen samples or other preparation techniques such as formalin fixation (FFix) and formalin-fixed paraffin-embedding (FFPE). Samples were vacuum dried at room temperature (RT) and stored in sealed vacuum containers for storage and shipping between collaborating parties. We compared our new protocol to established methods using prostate tissue sections investigating typical endogenous elements such as zinc, iron, and phosphorous with LA–ICP–MSI. The new protocol yielded comparable imaging results as fresh-frozen sections. FFPE sections were also tested due to the wide use and availability of FFPE tissue. However, the FFPE protocol and the FFix alone led to massive washout of the target elements on the sections tested in this work. Therefore, our new protocol presents an easy and rapid alternative for tissue preservation with comparable results to fresh-frozen sections for LA–ICP–MSI. It overcomes washout risks of commonly used tissue fixation techniques and does not require expensive and potentially unstable and time-critical shipping of frozen material on dry ice. Additionally, this protocol is likely applicable for several bioimaging approaches, as the dry condition may act comparable to other dehydrating fixatives, such as acetone or methanol, preventing degradation while avoiding washout effects.

Active anodes which are operating in highly stable protic media such as 1,1,1,3,3,3-hexafluoroisopropanol are rare. Nickel forms, within this unique solvent, a non-sacrificial active anode at constant current conditions, which is superior to the reported powerful molybdenum system. The reactivity for dehydrogenative coupling reactions of this novel active anode increases when the electrolyte is not stirred during electrolysis. Besides the aryl-aryl coupling, a dehydrogenative arylation reaction of benzylic nitriles was found while stirring the mixture providing quick access to synthetically useful building blocks.

Organometallic liquids provide good properties for ionization detectors. TriMethyl Bismuth (TMBi) has been proposed as a detector medium with charge and Cherenkov photon readout for Positron Emission Tomography. In this work, we present studies for the handling of TMBi at different electric fields and under different environmental conditions to find applicable configurations for the suppression of electrical breakdowns in TMBi at room temperature. A simple glass cell with two electrodes filled with TMBi was constructed and tested under different operation conditions. Working at the vapour pressure of TMBi at room temperature of about 40 mbar and electric fields of up to 20 kV/cm in presence of a small oxygen contamination we found the formation of a discharge channel in the liquid and a steady increase in the current. Further reduction of pressure by pumping caused the TMBi to boil and a spontaneous combustion. Eliminating the oxygen contamination led the TMBi under the same condition to only decompose. When operating the setup under an argon atmosphere of 1 bar we did not observe breakdowns of the electrical potential up to field strengths of 20 kV/cm. Still, in presence of a small oxygen contamination fluctuating currents in the nA range were observed, but no decomposition or combustion. We conclude from our experiments that TMBi at room temperature in a pure argon atmosphere of 1 bar remains stable against electrical breakdown at least up to electric field strengths of 20 kV/cm, presumably because the formation of gaseous TMBi was prevented., 14 page, 8 figures

Nocardia nova SH22a is an actinobacterium capable of degrading the polyisoprenes poly(cis-1,4-isoprene) and poly(trans-1,4-isoprene). Sequencing and annotating the genome of this strain led to the identification of a single gene coding for the key enzyme for the degradation of rubber: the latex clearing protein (Lcp). In this study, we showed that LcpSH22a-contrary to other already characterized rubber cleaving enzymes-is responsible for the initial cleavage of both polyisoprene isomers. For this purpose, lcpSH22a was heterologously expressed in an Escherichia coli strain and purified with a functional His6- or Strep-tag. Applying liquid chromatography electrospray ionization time-of-flight mass spectrometry (LC/ESI-ToF-MS) and a spectrophotometric pyridine hemochrome assay, heme b was identified as a cofactor. Furthermore, heme-associated iron was identified using total reflection X-ray fluorescence (TXRF) analysis and inhibition tests. The enzyme's temperature and pH optima at 30°C and 7, respectively, were determined using an oxygen consumption assay. Cleavage of poly(cis-1,4-isoprene) and poly(trans-1,4-isoprene) by the oxygenase was confirmed via detection of carbonyl functional groups containing cleavage products, using Schiff's reagent and electrospray ionization mass spectrometry (ESI-MS).

The bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 are essential for expression of hepcidin, a key iron regulatory hormone. In mice, hepatocyte-specific Alk2 deficiency leads to moderate iron overload with periportal liver iron accumulation, while hepatocyte-specific Alk3 deficiency leads to severe iron overload with centrilobular liver iron accumulation and a more marked reduction of basal hepcidin levels. The objective of this study was to investigate whether the two receptors have additive roles in hepcidin regulation. Iron overload in mice with hepatocyte-specific Alk2 and Alk3 (Alk2/3) deficiency was characterized and compared to hepatocyte-specific Alk3 deficient mice. Co-immunoprecipitation studies were performed to detect the formation of ALK2 and ALK3 homodimer and heterodimer complexes in vitro in the presence and absence of ligands. The iron overload phenotype of hepatocyte-specific Alk2/3-deficient mice was more severe than that of hepatocyte-specific Alk3-deficient mice. In vitro co-immunoprecipitation studies in Huh7 cells showed that ALK3 can homodimerize in absence of BMP2 or BMP6. In contrast, ALK2 did not homodimerize in either the presence or absence of BMP ligands. However, ALK2 did form heterodimers with ALK3 in the presence of BMP2 or BMP6. ALK3-ALK3 and ALK2-ALK3 receptor complexes induced hepcidin expression in Huh7 cells. Our data indicate that: (I) ALK2 and ALK3 have additive functions in vivo, as Alk2/3 deficiency leads to a greater degree of iron overload than Alk3 deficiency; (II) ALK3, but not ALK2, undergoes ligand-independent homodimerization; (III) the formation of ALK2-ALK3 heterodimers is ligand-dependent and (IV) both receptor complexes functionally induce hepcidin expression in vitro.

The latex clearing protein (Lcp) is the key enzyme of polyisoprene degradation in actinomycetes (Yikmis and Steinbuchel in Appl Environ Microbiol 78:4543–4551, https://doi.org/10.1128/AEM.00001-12 , 2012). In this study it was shown that Lcp from Gordonia polyisoprenivorans VH2 (Lcp1VH2) harbors a non-covalently bound heme b as cofactor, which was identified by pyridine hemochrome spectra and confirmed by LC/ESI-ToF-MS. It contains iron, most likely in the Fe3+ state. We focused on the characterization of the heme-cofactor, its accessibility with respect to the conformation of Lcp1VH2, and the identification of putative histidine residues involved in the coordination of heme. A change was detectable in UV/Vis-spectra of reduced Lcp1VH2 when imidazole was added, showing that Lcp1VH2 “as isolated” occurs in an open state, directly being accessible for external ligands. In addition, three highly conserved histidines (H195, H200 and H228), presumably acting as ligands coordinating the heme within the heme pocket, were replaced with alanines by site-directed mutagenesis. The effect of these changes on in vivo rubber-mineralization was investigated. The lcp- deletion mutant complemented with the H195A variant of lcp1VH2 was unable to mineralize poly(cis-1,4-isoprene). In vitro analyses of purified, recombinant Lcp1VH2H195A confirmed the loss of enzyme activity, which could be ascribed to the loss of heme. Hence, H195 is essential for the association of heme-b in the central region of Lcp1VH2.

Polycrystalline samples of Sr 0.95 Eu 0.05 Ba 8 [BN 2 ] 6 and Eu 0.937 Ba 8 [BN 2 ] 6 were synthesized via conventional solid-state reaction from the binary precursor compounds Sr 3 N 2 , EuN, Ba 3 N 2 and BN at 1000 °C. The structure of Eu 0.937 Ba 8 [BN 2 ] 6 was refined from single crystal X-ray diffractometer data: Eu 0.937 Ba 8 [BN 2 ] 6 type, Fd 3 ¯ m, a = 1594.54(9) pm, w R 2 = 0.0654, 380 F 2 values and 23 variables. The 8 a europium site shows an occupancy of only 93.7(9) % suggesting partial oxidation of europium to fulfil an electron-precise description, i. e. Eu II 0.81 Eu III 0.13 Ba 8 [BN 2 ] 6 . The mixed europium valence was confirmed by magnetic susceptibility measurements (reduced magnetic moment of 7.28 μ B per europium atom) and 151 Eu Mossbauer spectroscopy (Eu II : Eu III = 82: 18). The nitridoborate anions are coordinated by slightly distorted, mono-capped (europium) square prisms formed by the barium atoms. All metal cations are hexa-coordinated by nitrogen atoms. The EPR spectra of Eu x Sr 1-x Ba 8 [BN 2 ] 6 samples (0.001 ≤ x ≤ 0.01) suggest close to cubic local symmetry of the Eu 2+ dopant ions and reveal some highly unusual features: Magnetic hyperfine splitting is only observed with one of the Eu nuclear isotopes, and the coupling constant of 243.6 MHz is extremely large compared to values (90–100 MHz) typically observed in the literature for Eu 2+ doped crystalline materials.

Nocardia nova SH22a is an actinobacterium capable of degrading the polyisoprenes poly(cis-1,4-isoprene) and poly(trans-1,4-isoprene). Sequencing and annotating the genome of this strain led to the identification of a single gene coding for the key enzyme for the degradation of rubber: the latex clearing protein (Lcp). In this study, we showed that Lcp

Since the 1980s, the broad application of gadolinium(Gd)-based contrast agents for magnetic resonance imaging (MRI) has led to significantly increased concentrations of Gd in the aqueous environment. Little is known about the stability of these highly polar xenobiotics under environmental conditions, in wastewater and in drinking water treatment. Therefore, the stability of frequently applied Gd-based MRI contrast agents towards UV radiation was investigated. The hyphenation of hydrophilic interaction liquid chromatography (HILIC) with inductively coupled plasma mass spectrometry (ICP-MS) and of HILIC with electrospray ionization mass spectrometry (ESI-MS) provided quantitative elemental information as well as structural information. The contrast agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A showed a high stability in irradiation experiments applying a wavelength range from 220 nm to 500 nm. Nevertheless, the degradation of Gd-BOPTA as well as the formation of Gd-containing transformation products was observed by means of HILIC-ICP-MS. Matrix-dependent irradiation experiments showed a degradation of Gd-BOPTA down to 3% of the initial amount in purified water after 300 min, whereas the degradation was slowed down in drinking water and surface water. Furthermore, it was observed that the sum of species continuously decreased with proceeding irradiation in all matrices. After irradiation in purified water for 300 min only 16% of the sum of species was left. This indicates a release of Gd(III) ions from the complex in course of irradiation. HILIC-ESI-MS measurements revealed that the transformation products mostly resulted from O-dealkylation and N-dealkylation reactions. In good correlation with retention times, the majority of transformation products were found to be more polar than Gd-BOPTA itself. Based on accurate masses, sum formulas were obtained and structures could be proposed.

A new and powerful active anode system that can be operated in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) has been discovered. In HFIP the molybdenum anode forms a compact, conductive, and electroactive layer of higher-valent molybdenum species. This system can replace powerful but stoichiometrically required MoV reagents for the dehydrogenative coupling of aryls. This electrolytic reaction is more sustainable and allows the conversion of a broad scope of activated arenes.

Summary Nutrient acquisition is entangled with growth and stress in sessile organisms. The bHLH transcription factor FIT is a key regulator of Arabidopsis iron (Fe) acquisition and post-translationally activated upon low Fe. We identified CBL-INTERACTING PROTEIN KINASE CIPK11 as a FIT interactor. Cytosolic Ca2+ concentration and CIPK11 expression are induced by Fe deficiency. cipk11 mutant plants display compromised root Fe mobilization and seed Fe content. Fe uptake is dependent on CBL1/CBL9. CIPK11 phosphorylates FIT at Ser272, and mutation of this target site modulates FIT nuclear accumulation, homo-dimerization, interaction with bHLH039, and transcriptional activity and affects the plant’s Fe-uptake ability. We propose that Ca2+-triggered CBL1/9-mediated activation of CIPK11 and subsequent phosphorylation of FIT shifts inactive into active FIT, allowing regulatory protein interactions in the nucleus. This biochemical link between Fe deficiency and the cellular Ca2+ decoding machinery represents an environment-sensing mechanism to adjust nutrient uptake.

Laser ablation-inductively coupled plasma-optical emission spectroscopy (LA-ICP-OES) is presented as a valuable tool for elemental bioimaging of alkali and earth alkali elements in plants. Whereas LA-ICP-OES is commonly used for micro analysis of solid samples, laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) has advanced to the gold standard for bioimaging. However, especially for easily excitable and ubiquitous elements such as alkali and earth alkali elements, LA-ICP-OES holds some advantages regarding simultaneous detection, costs, contamination, and user-friendliness. This is demonstrated by determining the calcium, sodium and potassium distribution in tobacco plant stem and leaf petiole tissues. A quantification of the calcium contents in a concentration range up to 1000 μg g−1 using matrix-matched standards is presented as well. The method is directly compared to a LA-ICP-MS approach by analyzing parallel slices of the same samples.

Calcium-alginate aerogels augmented with zinc and silver can provide the next generation superabsorbent medical devices for advanced wound care with high cell and tissue tolerability and controlled compound release rates during wound healing. In this study, we addressed the fabrication and metal detection of alginate-based aerogels with these immunoactive cations. All three cations were incorporated into the alginate aerogel, albeit in different quantities, due to different magnitudes of leaching during solvent exchange step; an effect not reported previously. Silver addition led to an increase in aerogel zinc content without influencing calcium incorporation. All three metal ions were released into supernatants upon swelling aerogels in aqueous solutions, comparable to those measured for common wound dressings in human and animal injury models. The in vitro bioactivity studies showed that Zn-enriched swelling supernatants were able to suppress NO production in stimulated RAW 264.7 macrophages, indicating an effective anti-inflammatory activity.

Polystyrene sulfonate polymer brushes, grown on the interior of the microchannels in a microreactor, have been used for the anchoring of gallium as a Lewis acid catalyst. Initially, gallium-containing polymer brushes were grown on a flat silicon oxide surface and were characterized by FTIR, ellipsometry, and X-ray photoelectron spectroscopy (XPS). XPS revealed the presence of one gallium per 2–3 styrene sulfonate groups of the polymer brushes. The catalytic activity of the Lewis acid-functionalized brushes in a microreactor was demonstrated for the dehydration of oximes, using cinnamaldehyde oxime as a model substrate, and for the formation of oxazoles by ring closure of ortho-hydroxy oximes. The catalytic activity of the microreactor could be maintained by periodic reactivation by treatment with GaCl3.

The plant-specific calcium binding protein CAS (calcium sensor) has been localized in chloroplast thylakoid membranes of vascular plants and green algae. To elucidate the function of CAS in Chlamydomonas reinhardtii, we generated and analyzed eight independent CAS knockdown C. reinhardtii lines (cas-kd). Upon transfer to high-light (HL) growth conditions, cas-kd lines were unable to properly induce the expression of LHCSR3 protein that is crucial for nonphotochemical quenching. Prolonged exposure to HL revealed a severe light sensitivity of cas-kd lines and caused diminished activity and recovery of photosystem II (PSII). Remarkably, the induction of LHCSR3, the growth of cas-kd lines under HL, and the performance of PSII were fully rescued by increasing the calcium concentration in the growth media. Moreover, perturbing cellular Ca2+ homeostasis by application of the calmodulin antagonist W7 or the G-protein activator mastoparan impaired the induction of LHCSR3 expression in a concentration-dependent manner. Our findings demonstrate that CAS and Ca2+ are critically involved in the regulation of the HL response and particularly in the control of LHCSR3 expression.

The use of the effective antineoplastic agent cisplatin is limited by its serious side effects, such as oto- and nephrotoxicity. Ototoxicity is a problem of special importance in children, because deafness hampers their language and psychosocial development. Recently, organic cation transporters (OCTs) were identified in vitro as cellular uptake mechanisms for cisplatin. In the present study, we investigated in an in vivo model the role of OCTs in the development of cisplatin oto- and nephrotoxicity. The functional effects of cisplatin treatment on kidney (24 hours excretion of glucose, water, and protein) and hearing (auditory brainstem response) were studied in wild-type and OCT1/2 double-knockout (KO) mice. No sign of ototoxicity and only mild nephrotoxicity were observed after cisplatin treatment of knockout mice. Comedication of wild-type mice with cisplatin and the organic cation cimetidine protected from ototoxicity and partly from nephrotoxicity. For the first time we showed that OCT2 is expressed in hair cells of the cochlea. Furthermore, cisplatin-sensitive cell lines from pediatric tumors showed no expression of mRNA for OCTs, indicating the feasibility of therapeutic approaches aimed to reduce cisplatin toxicities by competing OCT2-mediated cisplatin uptake in renal proximal tubular and cochlear hair cells. These findings are very important to establish chemotherapeutical protocols aimed to maximize the antineoplastic effect of cisplatin while reducing the risk of toxicities.

In this work, the recently introduced low flow inductively coupled plasma optical emission spectrometry (ICP-OES) with a total argon consumption below 0.7 L/min is applied for the first time to the field of food analysis. One goal is the investigation of the performance of this low flow plasma compared to a conventional ICP-OES system when non-aqueous samples with a certain matrix are introduced into the system. For this purpose, arsenic is determined in three different kinds of fish samples. In addition several nutrients (K, Na, Mg, Ca) and trace metals (Co, Cu, Mn, Cd, Pb, Zn, Fe, and Ni) are determined in honey samples (acacia) after microwave digestion. The precision of the measurements is characterized by relative standard deviations (RSD) and compared to the corresponding precision values achieved using the conventional Fassel-type torch of the ICP. To prove the accuracy of the low flow ICP-OES method, the obtained data from honey samples are validated by a conventional ICP-OES. For the measurements concerning arsenic in fish, the low flow ICP-OES values are validated by conventional Fassel-type ICP-OES. Furthermore, a certified reference material was investigated with the low gas flow setup. Limits of detection (LOD), according to the 3σ criterion, were determined to be in the low microgram per liter range for all analytes. Recovery rates in the range of 96–106% were observed for the determined trace metal elements. It was proven that the low gas flow ICP-OES leads to results that are comparable with those obtained with the Fassel-type torch for the analysis of food samples.

In order to reveal the time-depending mercury species uptake by human astrocytes, a novel approach for total mercury analysis is presented, which uses an accelerated sample introduction system combined on-line with an inductively coupled plasma mass spectrometer equipped with a collision/reaction cell. Human astrocyte samples were incubated with inorganic mercury (HgCl2), methylmercury chloride (MeHgCl), and thimerosal. After 1-h incubation with Hg(2+), cellular concentrations of 3 μM were obtained, whereas for organic species, concentrations of 14-18 μM could be found. After 24 h, a cellular accumulation factor of 0.3 was observed for the cells incubated with Hg(2+), whereas the organic species both showed values of about 5. Due to the obtained steady-state signals, reliable results with relative standard deviations of well below 5 % and limits of detection in the concentration range of 1 ng L(-1) were obtained using external calibration and species-unspecific isotope dilution analysis approaches. The results were further validated using atomic fluorescence spectrometry.

Collagen binding integrins are of essential importance in the crosstalk between cells and the extracellular matrix. Integrin α2β1 is a major receptor for collagen I, the most abundant protein in bone. In this study we show for the first time that integrin α2 deficiency is linked to collagen type I expression in bone. Investigating the femurs of wild type and integrin α2β1 deficient mice, we found that loss of integrin α2 results in altered bone properties. Histomorphometric analysis of integrin α2 long bones displayed more trabecular network compared to wild type bones. During age related bone loss the integrin α2β1 deficient bones retain trabecular structure even at old age. These findings were supported by functional, biomechanical testing, wherein the bones of integrin α2β1 deficient mice do not undergo age-related alteration of biomechanical properties. These results might be explained by the increased presence of collagen in integrin α2β1 deficient bone. Collagen type I could be detected in higher quantities in the integrin α2β1 deficient bones, forming abnormal, amorphous fibrils. This was linked to higher expression levels of collagen type I and other bone formation related proteins as alkaline phosphatase of integrin α2β1 deficient osteoblasts. Osteoclasts of integrin α2β1 deficient mice did not show any differences. Consequently these results indicate that the absence of integrin α2β1 alleviates the effects of age related bone degradation through over-expression of collagen type I and demonstrate a molecular mechanism how collagen binding integrins might directly impact bone aging.

A simple and rapid method to determine gadolinium (Gd) concentrations in urine and blood plasma samples by means of total reflection X-ray fluorescence (TXRF) was developed. With a limit of detection (LOD) of 100 μg L(-1) in urine and 80 μg L(-1) in blood plasma and a limit of quantification (LOQ) of 330 μg L(-1) in urine and 270 μg L(-1) in blood plasma, it allows analyzing urine samples taken from magnetic resonance imaging (MRI) patients during a period of up to 20 hours after the administration of Gd-based MRI contrast agents by means of TXRF. By parallel determination of the urinary creatinine concentration, it was possible to monitor the excretion kinetics of Gd from the patient's body. The Gd concentration in blood plasma samples, taken immediately after an MRI examination, could be determined after rapid and easy sample preparation by centrifugation. All measurements were validated with inductively coupled plasma mass spectrometry (ICP-MS). TXRF is considered to be an attractive alternative for fast and simple Gd analysis in human body fluids during daily routine in clinical laboratories.

The interaction of Mercurochrome, a medical preparation based on the mercury organic compound merbromin, with free thiols in low molecular weight peptides and in proteins has been investigated by means of liquid chromatography (LC) and electrospray mass spectrometry (ESI-MS). Beta-lactoglobulin A (beta-LGA) from bovine milk (18.4 kDa) has been used as the model protein. It was found that, in contrast to assumptions in literature, the commercial product itself is a heterogeneous mixture of moderate chemical stability, which may contain precipitated Hg salts depending on storage time and conditions. Further variability results from different degrees of bromination of the fluorescein backbone of the compound. The formation of mercury compound-protein adducts was detected. The peptide sequence T13 containing a free thiol residue was identified as the binding site for mercury species after tryptic digestion of beta-lactoglobulin A. While fresh Mercurochrome tends to the formation of a Hg(II)-beta-LGA adducts due to excess Hg(2+) in solution, investigations after precipitation of Hg salts yield Hg(merbromin)(beta-LGA) as the major product.

A thorough investigation of strategies to overcome the effect of mercury losses during TXRF analysis was carried out. The vaporisation of mercury on sampling targets, associated with too low concentrations determined, depends on the nature of the respective Hg species and the dwell time of the analytes on the target. To prevent vaporisation, oxidation with ammonium persulfate and complexation with ethylenediamine tetraacetate (EDTA) and dimercaptosuccinic acid (DMSA) were investigated. Whereas both approaches were effective in reducing the Hg losses by vaporisation, the complexation approaches turned out to be particularly efficient. Both EDTA and DMSA retain the different mercury species quantitatively over several hours. Based on this approach, a method for mercury determination by TXRF in liquid samples was developed, successfully validated by inductively coupled plasma optical emission spectrometry and applied to the analysis of a mercury-containing vaccine sample.

Total reflection X-ray fluorescence (TXRF) analysis is a powerful technique for simultaneous multi-element analysis. Benefits include limits of detection in the microgram per litre range, limited sample preparation for liquid samples and low operating costs. However, the determination of elements such as silver and palladium suffers from interferences, e.g. if an X-ray tube with a molybdenum anode is used, which normally offers the lowest detection limits for most of the elements of the periodic table. Argon emits its X-ray fluorescence radiation in the same energy range as these metals and therefore hinders their detection and subsequent quantification. Since argon is abundant in the atmosphere with approx. 0.93% and is easily activated by X-rays in a TXRF instrument, this interference is always present under routine measurement conditions. We have developed a new method for the analysis of silver and palladium by TXRF. A commercially available TXRF system was modified for being operated under a nitrogen purged atmosphere by surrounding it with an airtight and water-cooled box, which still allows accessing the main hardware components, changing the sample discs or performing long term measurements without temperature drift effects. An easy removal of the box is possible for a rapid change between the nitrogen purged and the common mode under ambient atmosphere. After flushing the system with nitrogen, the signal of argon decreased significantly, allowing the determination of silver and palladium with limits of detection for silver and palladium of 6.6 μg L−1 and 16.6 μg L−1 respectively.

Inductively coupled plasma mass spectrometry with quadrupole mass analyzers (ICP-QMS) is one of the most powerful analytical techniques due to its superb limits of detection and the fast, quasi simultaneous quantification of different elements in one single run. However, sample consumption is typically too large for use in biological studies and spectral as well as non-spectral interferences are often hard to compensate for. Hence, a flow injection (FIA) approach for quantification of manganese (Mn) in biologically relevant cell nutrient solutions was developed, extending the sample throughput and versatility of a common system. The investigated cell nutrient solutions are, for example, used in in vitro models of the blood-brain and the blood-liquor barrier and represent a complex matrix, while Mn is of interest due to its potential neurotoxic effects, but shows several challenges in ICP-QMS analysis. Therefore, the aim of the study was not only to devise a system as simple as possible, but also to have a tool allowing the measurement of several hundreds of samples within a short period of time. Furthermore, statistical data treatment was used to evaluate the need for matrix matching and internal standardization for the four different solutions. The calculated lowest detection limits (LODs) were in the low μg L(-1) range due to successful use of a collision/reaction cell, while only 11 μL of sample volume was needed per injection by means of a segment sample loop filling. The analysis of a certified reference material further confirmed the suitability of this approach in biological studies.

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