Inductively Coupled Plasma Time-of-flight Mass Spectrometer Research Articles

Single cell-inductively coupled plasma-time of flight-mass spectrometry approach for ecotoxicological testing

Diatoms play a key role in assessing the ecotoxicology of metals and are already part of several national and international guidelines and regulations. Data on metal uptake and its correlation with a natural metal composition of the diatoms are mostly lacking on a cellular basis - mainly due to the lack of a suitable method on both the preparation and detection side. Therefore, within this work a fully automated approach based on the on-line coupling of a high performance liquid chromatograph (HPLC) and an inductively coupled plasma-time of flight-mass spectrometer (ICP-ToF-MS) was applied to analyze single cells of the alga Cyclotella meneghiniana multi-elementally in order to provide a deeper insight into the metal composition and its response to environmental stress. Multi-elemental analysis in single diatoms also enables assessment of combined toxicity of a set of metals. A set of four fingerprint elements, characteristically for diatoms (Mg, P, Si, Fe), were identified and hence the investigation of environmental stress onto the cells was enabled by performing incubation experiments with environmentally relevant toxic elements. It could be shown at moderate environmental stress caused by increasing the metal concentration in the medium (zinc) that the fingerprint element concentrations remained stable and thus the suitability of the selected elements for algae tracing was demonstrated. With regard to further ecotoxicological assessments, a multivariate approach was successfully applied allowing for cell classification upon different incubation concentration levels. This multivariate approach also facilitated an effective identification of three different diatom species (Cyclotella meneghiniana, Thalassiosira weissflogii and Thalassiosira pseudonana).

Coupling a Gas Chromatography Unit to an Inductively Coupled Plasma Mass Spectrometer

Although the eminent threat of a terrorist group detonating an improvised nuclear device (IND) in an urban environment is low, it is crucial that countries develop modern nuclear forensic capabilities to expedite response in a post-detonation scenario. In particular, new instruments need to be created to shorten dissolution time, expedite chemical separation, and improve forensic analysis of the nuclear melt glass that is created during the detonation of the device. To expedite this process, an instrument was designed to thermally couple a gas chromatograph (GC) to a time-of-flight inductively coupled plasma time-of-flight mass spectrometer (ICPTOFMS) In order to couple these two instruments, another instrument was designed to provide an isothermal atmosphere between the GC and TOFICPMS to expedite rapid gas separations processes. By using gas separations instead of the current wet chemistry processes, the required separation and analysis time of the melt glass significantly decreases. The new instrument would also provide a more detailed analysis of the elemental and isotopic composition of the melt glass. By completing these tasks simultaneously, this significantly decreases the required time to conduct these separations and improves the elemental and isotopic analysis.

Simultaneous mass quantification of nanoparticles of different composition in a mixture by microdroplet generator-ICPTOFMS.

This work investigated the potential of a high temporal resolution inductively coupled plasma time-of-flight mass spectrometer (ICPTOFMS) in combination with a microdroplet generator (MDG) for simultaneous mass quantification of different nanoparticles (NPs) in a mixture. For this purpose, a test system containing certified Au NPs, well characterized Ag NPs, and core-shell NPs composed of an Au core and an Ag shell was employed. Thanks to the full spectra coverage and rapid simultaneous detection of the TOFMS, the element composition of individual particles can be determined. The pure Ag NPs and the core-shell NPs could be differentiated despite the same mass of Ag they contain. Calibration with monodisperse droplets consisting of standard solutions allowed for the mass quantification of NPs without the use of NP certified materials. On the basis of this mass quantification, the sizes of NPs originating from the same aqueous suspension were simultaneously determined with an accuracy of 7-12%. The size-equivalent limits of detection estimated with the 3*σ criterion were 13 nm for Au and 16 nm for Ag. Estimation of the LODs using Poisson statistics resulted in 19 and 27 nm, respectively. In addition, the 30 μs temporal resolution of the ICPTOFMS allowed studying interactions of NPs with the ICP based on their transient MS signals. The results demonstrated a difference in vaporization behavior of the core-shell NPs and solutions and indicated that vaporization of the Ag shell takes place prior to the Au core.

A prototype of a new inductively coupled plasma time-of-flight mass spectrometer providing temporally resolved, multi-element detection of short signals generated by single particles and droplets

A prototype inductively coupled plasma time-of-flight mass spectrometer (ICPTOFMS) for time resolved measurements of transient signals in the microsecond regime is described in this work. Analytical figures of merit for the prototype are given for both liquid nebulization and single droplet introduction and are compared to a conventional quadrupole-based ICPMS using the same ICP source and vacuum interface. Quasi-simultaneous detection at a time resolution of 33 μs of the prototype ICPTOFMS allows multi-isotope monitoring of short signals (200–500 μs duration) generated from individual droplets and particles. The capabilities of the instrument for the analysis of single nanoparticles are studied using microdroplets consisting of a multi-element standard solution and containing 114 nm Au particles. The detection efficiencies for Ag and Au, calculated from the response of individual droplets and particles, are similar to those of the quadrupole-based instrument and amount to 1.3 × 10−6 ions per atom and 3.1 × 10−6 ions per atom, respectively. The sizes of the smallest detectable Ag, Au and U metallic nanoparticles are estimated to be 46 nm, 32 nm and 22 nm, respectively. Furthermore, time shifts of the signals of different elements within single droplets were observed. These new results demonstrate the advantage of the temporal resolution of the instrument for studying processes taking place in the plasma on the μs-time scale.

In torch laser ablation sampling for inductively coupled plasma time of flight mass spectrometry

In torch laser ablation (LA) sampling was implemented to an inductively coupled plasma time of flight mass spectrometer (ICP-TOFMS). The achieved signal to noise ratios (S/N) for minor elements were found to be two times higher than the S/N ratios calculated from continuous signals of conventional 10 Hz LA in an ablation cell. The elemental signal intensity ratios during single spot analysis were the same for in torch and in cell LA. This indicates that the same particle size distributions are formed by the laser impact and consequently sampled into the ICP. Fast Fourier Transformation (FFT) was used as an alternative data evaluation tool for the repetitive in torch LA signals. The ratios of the 10 Hz amplitudes in the FFT spectra of different elements and isotopes were identical to the ratios between peak maxima in the background corrected transient signals. Single shot in torch LA-ICP-MS exceeds the figures of merit of continuous LA in an ablation cell and provides 10 Hz LA analyses with single shot resolution.

Induction and Binding of Cd, Cu, and Zn to Metallothionein in Carp (Cyprinus carpio) Using HPLC-ICP-TOFMS

The binding of Cd, Cu, and Zn to metallothionein in carp was studied under control and acute Cd exposure scenarios. Carp were exposed to different Cd concentrations for 96 h. Total (Cu, Cd, Zn)-MT levels were determined by the cadmium thiomolybdate saturation assay. Total tissue and cytosolic Cd, Cu, and Zn concentrations were determined by ICP-MS. The cytosolic metal speciation was determined by high pressure liquid chromatography (size-exclusion [SE] in combination with anion exchange [AE]) directly coupled to an inductively coupled plasma time of flight mass spectrometer (ICP-TOFMS). This coupled technique allows the chromatographic separation and online determination of the metals associated to the protein fractions separated. Very strong differences in the tissue compartmentalization and cytosolic speciation of the metals were observed. For example, over 30% of cytosolic zinc was bound to MT in liver while this was only 2% in the kidneys although total cytosolic levels were considerably higher. Induction of metallothionein during cadmium exposure was also tissue specific, displaying different response patterns in gills, liver, and kidney. Cadmium accumulated much stronger in liver and kidney compared to the gills and the latter also showed much lower MT levels. The renal MT-induction was more sensitive to Cd exposure than the hepatic MT induction since a significant increase of Cd-MT and total MT levels occurred at lower tissue Cd concentrations in the kidney in comparison to the liver, except for the highest Cd exposure level where a drastic 10-fold increase in hepatic Cd-MT was observed. At this Cd exposure level also an apparent spill over of zinc to the high molecular weight fraction was observed in the kidneys.

Characterisation of a hydraulic high-pressure sample introduction assisted flow injection—inductively coupled plasma time-of-flight mass spectrometry system and its application to the analysis of biological samples

A flow injection (FI) method was developed using hydraulic high-pressure nebulization as a sample introduction system, coupled to inductively coupled plasma time-of-flight mass spectrometer (ICP-TOFMS) for rapid and simultaneous determination of 19 elements. The operating conditions of the system (analyte flow rate, heating and cooling temperatures of the desolvation module, carrier gas flow rate) for the simultaneous determination of 19 analytes were optimised. The optimum parameters of the sample introduction system were found to be 1.4mlmin−1 and 1.35lmin−1 for the analyte solution and nebulizer flow rates, respectively. A compromised condition for heating and cooling stage temperatures of 170 and −5°C was chosen. The detection limits were compared to those obtained by using ICP-TOFMS with alternative sample introduction techniques e.g. conventional nebulization, flow injection chemical hydride generation (FI-CHG) and the obtained results were comparable or better than those resulting from alternative sample introduction. Applying the optimised conditions the simultaneous determination of Ag, As, Ba, Cd, Co, Cu, Ga, In, Li, Mn, Mo, Pb, Sb, Se, Sn, Sr, Tl, V and Zn was carried out. Absolute detection limits (3σ) in the range of 2–750pg and precision between 0.5 and 9.6% from five replicate measurements of 10ngml−1 multielemental sample solutions were achieved by using a 200μl sample loop. The developed method was applied for the analysis of certified reference materials of biological origin (TORT-2 “Lobster Hepatopancrease”, BCR-422 “Cod Muscle” and IAEA MA-B-3/TM “Fish Homogenate”), and the results showed good agreement with the certified values.

Performance optimization of isotope ratio measurements in transient signals by FI-ICP-TOFMS

Isotopic ratios for Pb (NIST 981) and Rb (NIST 984) and their precisions measured in transient and steady state signals are presented and discussed in this work. The transient signals were generated using a flow injection system (FI) using four different loop volumes coupled to an Inductively Coupled Plasma Time-of-Flight Mass Spectrometer (ICP-TOFMS). Pneumatic nebulization (PN) with a Meinhard nebulizer or an ultrasonic nebulizer (USN) was used for sample introduction. The isotopic reference materials of Pb and Rb were dissolved and diluted to between 0.5 and 100 ng ml−1 in 4% HNO3 in Milli-Q water. Another set of mixtures was prepared with the same concentrations but fortified with 110 mg l−1 of Na. This set was introduced to produce a matrix load to the plasma in order to investigate possible effects on the isotope ratio with respect to precision and mass bias. No matrix effect on isotopic ratio and precision was observed. Analytical data for steady state signals are included for comparison to establish the best possible precision attainable on the present instrumentation given the above mentioned concentrations employing 30 s integration time and n > 5. Under those conditions, the best possible precision for isotopic ratios was 0.08% (as RSD) for 85Rb/87Rb, 0.04% for 207Pb/206Pb, 0.49% for 204Pb/206Pb and 0.07% for 208Pb/206Pb, respectively, using the analog detection mode. In transient mode the corresponding precisions were 0.2, 0.3, 1.0 and 0.3% RSD, respectively. It was found that calculation of ratio and precision performed on the whole peak profile for non-unity ratios resulted in deteriorated precision compared with calculations performed at peak apex on a minimum of five data points. As the peak intensity increases or decreases over the transient peak profile a slight change in the ratios close to the rims of the transient peak could be observed. The quality of the measurements improved for longer integration times (as long as the transient peak profile can be properly defined) and higher concentrations and with transient peak profiles that reached a steady state level. The data obtained for the two smallest loops was of poorer quality and especially for the 10 ng ml−1 solution since the analog signals obtained were rather low. For these transients results using the ion counting mode are also reported. The ion counting data obtained for concentrations ≥10 ng ml−1 and the two larger loops had, however, to be dead-time corrected. The use of USN resulted in improved precision thanks to a 10-fold increase in signal intensity.

Multi-element speciation of metalloproteins in fish tissue using size-exclusion chromatography coupled "on-line" with ICP-isotope dilution-time-of-flight-mass spectrometry.

An on-line isotope dilution (ID) method in combination with the coupling of size-exclusion high-performance liquid chromatography (SE-HPLC) to an axial inductively coupled plasma time-of-flight mass spectrometer (ICP-TOFMS) was applied to the quantitative speciation of Cu, Zn and Cd in carp and eel cytosols. Quantitative information on the distribution of essential and toxic metals between the different molecular weight fractions in kidney cytosols of control and Cd exposed carp was obtained with species-unspecific spiking by post-column addition of the enriched isotopes 65Cu, 67Zn and 106Cd. The isotope ratios 63Cu/65Cu, 64Zn/67Zn and 114Cd/106Cd, were monitored by ICP-TOFMS in transient signal mode. The determination of the total cytosolic element concentration was performed by flow injection conventional nebulization ICP-TOFMS. Speciation differences were encountered between control and Cd-stressed carp, indicating that quantitative speciation studies might be useful for ecotoxicological and biomonitoring purposes. Application of this methodology to quantitation of metals associated with metallothioneins (MT) in European eel, sampled at three different sites in Flanders, Belgium was also addressed. A significant increase of the amount of Cd, Cu and Zn bound to hepatic MT was observed with the increase of the total metal and MT concentrations of hepatic eel tissue.

Development of a tungsten filament electrothermal vaporizer for inductively coupled plasma time-of-flight mass spectrometry and its possibilities for the analysis of human whole blood and serum

A methodology was developed using a tungsten filament electrothermal vaporizer (WETV) as a sample introduction system, coupled to an inductively coupled plasma time-of-flight mass spectrometer (ICP-TOFMS), for rapid and simultaneous determination of Cr, Cu, Li and Pb in human whole blood and serum samples. The design of the vaporizer is based on a W-filament from Osram, which is positioned in a low volume (7.3 mL) quartz cell that is especially suited for the evaporation of minute amounts of samples and is coupled to the plasma torch via an 8 cm (3 mm id) glass tube. The tungsten coil was connected to the secondary side of a conventional ac power supply, the primary side of which was interfaced with a newly designed LabView™-based controllable four-channel switch box. Each channel was attached to a separate variable 0–220 V transformer, allowing indirect adjustment of the voltage on the secondary side of the power supply between 0 and 13.8 V. The voltage/current heating programs (drying, pyrolysis, vaporization and filament cleaning) for sample evaporation as well as the ICP-TOFMS operational parameters (carrier gas flow rate, modulation pulse width) for the simultaneous determination of 17 isotopes were optimized using sequential and “Modified Simplex” algorithm-based optimization techniques. The compromise operation parameters of the WETV system for multielemental determinations were found to be different for aqueous standard solutions, human whole blood and serum samples. An argon carrier gas flow rate of 1.16 L min−1 provided optimum results for the detection of transient signals. By using 10 µL sample volumes of aqueous multielemental standard solutions absolute detection limits (3σ) in the range of 0.007–0.1 pg for Ba, Cd, Co, Cr, Cu, Ga, In, Mn, Ni and Sr, 0.11–0.19 pg for Ag, As, Bi, Li, Pb and Pd and 11 pg for Fe, and a precision of 2–6% for 10 replicates of 5 ng mL−1 (20 ng mL−1 of Fe) multielemental sample solutions were achieved. The method accuracy was verified by the analysis of Reference Materials SRM 909 (Human Serum) from NIST and 404108 (Human Whole Blood) from Nycomed Pharma regarding their Cr, Cu, Li and Pb concentrations. Except the addition of a phosphate-based matrix modifier, followed by appropriate dilution, no additional sample pretreatment was necessary. Internal standardization using multielemental solutions was used for calibration. Good agreement with the certified values was observed and the filament had a lifetime of more than 350 firings.

Species-specific isotope-ratio measurements of volatile tin and antimony compounds using capillary GC-ICP-time-of-flight MS.

The analytical performance of an axial inductively-coupled-plasma time-of-flight mass spectrometer (ICP-TOFMS) as a detector for fast transient chromatographic signals resulting from the coupling to capillary gas chromatography (CGC) was investigated. A cryotrapping GC-ICP-TOFMS method for the determination of volatile metal(loid) compounds (VOMs) in gases was used and the suitability of the TOF mass analyzer for multielemental speciation analysis and multi-isotope ratio determinations was studied in terms of accuracy and precision. Isotope ratios 118Sn/120Sn and 121Sb/123Sb have been determined in in-house gas standard atmospheres in Tedlar bags at two different levels (100 pg and 1 ng) for different elemental species (SnH4, MeSnH3, Me2SnH2, Me3SnH, BuSnH3, SbH3, and MeSbH2). A limitation arising from counting statistics in both detection modes could be shown. A solution containing rhodium (10 ng mL(-1)) and cadmium (40 ng mL(-1)) was introduced simultaneously to the GC outlet. Rhodium acts as a continuous internal standard and Cd is used for mass-bias correction (by measuring the 111Cd/113Cd ratio). The detection system in both pulse counting and analog mode was examined. The best attainable precision was established for Me2SnH2 (analog mode, 12 replicates, 1 ng, RSD 0.34%, accuracy 0.31%) whereas most other species ranged between 0.4 and 0.5% RSD if higher concentrations were used. The limitations of the pulse counting system are clearly seen, with peak heights of more than 2000 counts reaching saturation (for an integration time of 100 ms), which reduces the accuracy of isotope ratio determinations. A dozen VOM could be detected in an aged landfill gas sample; several unidentified Sn compounds were present. Although their isotope ratios are within the confidence value of the standards, it is not yet clear if the acquired precision is good enough to identify isotopic fractionation of metal(loid)s through biovolatilization processes. With the precision achieved, the combination of cryotrapping GC and ICP-TOFMS is a powerful tool for monitoring volatile multi-element species in multi-tracer experiments and isotope dilution methodology.

Preliminary investigation of electrothermal vaporization sample introduction for inductively coupled plasma time-of-flight mass spectrometry.

The coupling of an electrothermal vaporization (ETV) apparatus to an inductively coupled plasma time-of-flight mass spectrometer (ICP-TOFMS) is described. The ability of the ICP-TOFMS to produce complete elemental mass spectra at high repetition rates is experimentally demonstrated. A signal-averaging data acquisition board is employed to rapidly record complete elemental spectra throughout the vaporization stage of the ETV temperature cycle; a solution containing 34 elements is analyzed. The reduction of both molecular and atomic isobaric interferences through the temperature program of the furnace is demonstrated. Isobaric overlaps among the isotopes of cadmium, tin, and indium are resolved by exploiting differences in the vaporization characteristics of the elements. Figures of merit for the system are defined with several different data acquisition schemes capable of operating at the high repetition rate of the TOF instrument. With the use of both ion counting and a boxcar averager, the dynamic range is shown to be linear over a range of at least 6 orders of magnitude. A pair of boxcar averagers are used to measure the isotope ratio for silver with a precision of 1.9% RSD, despite a cycle-to-cycle precision of 19% RSD. Detection limits of 10-80 fg are calculated for seven elements, based upon a 10-microL injection.

Isotope ratios and abundance sensitivity obtained with an inductively coupled plasma-time-of-flight mass spectrometer

Isotope ratios and abundance sensitivities have been determined with an inductively coupled plasma-time-of-flight mass spectrometer (ICP-TOFMS). Abundance sensitivities are at least in the 10(6) range for low abundance ions that precede high abundance ions. Three methods of detection for isotope-ratio measurement have been compared. The three systems involve gated detection followed by analog integration, analog averaging, or ion counting. Gated ion counting offers excellent precision-between 0. 64 and 1. 00% relative standard deviation (RSD). These values approach those predicted from counting statistics and are comparable to those reported for other inductively coupled plasma-mass spectrometry (ICP-MS) instruments. In addition, a greater number of accumulated counts or longer analysis times would afford precisions of 0. 1% with stable gating electronics. The accuracy of the counting method is in the 1-10% range if no correction for mass bias is performed. However, this ion counting method suffers from a limited dynamic range due to pulse pileup. Constant-fraction discrimination gated integration and commercial boxcar averager techniques offer a broader dynamic range because of their analog nature, but the attainable RSD values are limited by drift in the detection systems and by the methods employed to calculate an accurate ratio. Overall, mass bias in the ICP-TOFMS is more severe than previous work in ICP-MS due primarily to detection system bias.

An inductively coupled plasma-time-of-flight mass spectrometer for elemental analysis. Part II: Direct current quadrupole lens system for improved performance

An electrostatic quadrupole lens has been substituted for a cylindrical lens system used in the original inductively coupled plasma-time-of-flight mass spectrometer (ICP-TOFMS). With an improved vacuum system also installed, the cylindrical and quadrupole lenses are compared to each other and to the performance of the prototype ICP-TOFMS. The quadrupole lens requires no tradeoff between ion throughput and resolving power as was encountered with cylindrical lenses. The background noise in both ion-optical systems is within the same order of magnitude. Images of the ion beam formed by each ion-optical system have been obtained on a microchannel plate-phosphor screen. The quadrupole lens shows a higher ion-beam flux and produces a slitlike focus required in the orthogonal ICP-TOFMS instrument. Signal-to-noise ratios in the ICP-TOFMS can be improved by using a technique called pulsed-ion injection that is particularly convenient with the quadrupole lens. In this technique, one quadrupole electrode is pulsed to prevent ions from entering the extraction zone except when an ion packet is to be extracted for mass analysis. This technique significantly reduces the noise over continuous ion injection. In the orthogonal ICP-TOFMS with pulsed-ion injection, 0.5 frnol of analyte could be detected in 1.4 ms with a proper data acquisition system. Overall, the combination of a quadrupole lens and pulsed-ion injection may provide detection limits for the ICP-TOFMS that are competitive with those of quadrupole inductively coupled plasma-mass spectrometry instruments.

An inductively coupled plasma—time-of-flight mass spectrometer for elemental analysis. Part I: Optimization and characteristics

An inductively coupled plasma—time-of-flight mass spectrometer (ICP-TOFMS) has been constructed and evaluated for elemental analysis. The instrument produces analog spectra similar to those from quadrupole inductively coupled plasma mass spectrometers. The large abundance of Ar ions is deflected away from the microchannel plate detector to reduce detector dead time and space-charge complications. The ICP-TOFMS, operated in a linear (nonreflecting) mode, currently has a resolving power of 500 (full width at half maximum). Present ion optics employed in the instrument require a trade-off between signal-to-noise ratio and resolving power. In addition, mass-dependent kinetic energies in the supersonic beam created in the ICP mass spectrometer interface cause a mass bias in the right-angle TOFMS because the ions must be steered to the detector to compensate for their velocity in the supersonic beam direction. In the current design the sampling duty cycle is only approximately 3%, thereby limiting sensitivity. However, positive potentials applied to the right-angle extraction region can increase sensitivity by a factor of 2–4 by slowing down the ions that enter the extraction zone. The transmission efficiency of the TOFMS is approximately 20% and is limited by divergence of the ion packet in the drift tube.