Sabrina Gschwind

Capabilities of inductively coupled plasma mass spectrometry for the detection of nanoparticles carried by monodisperse microdroplets

Recently, first analyses of single sub-micrometre particles, embedded in liquid droplets, by inductively coupled plasma optical emission spectrometry (ICP-OES) with a size-equivalent detection limit of several hundred nanometres were reported. To achieve lower detection limits which might allow for the analysis of particles in the nanometre size range a more sensitive technique such as mass spectrometry (MS) is required. Various modifications of particle delivery and data acquisition systems commonly used were carried out to install a setup adequate for ICP-MS detection. These modifications enabled us to supply droplets generated by a commercial microdroplet generator (droplet size: 30–40 µm) with nearly 100% efficiency and high uniformity to the ICP. Analyses were performed using both standard solutions of dissolved metals at concentrations of 1 (Ag), 2 (Au), 5 (Au), or 10 (Cu) mg L−1 and highly diluted suspensions of gold and silver nanoparticles with sizes below 110 nm. In doing so, detection efficiencies of 10−6 counts per atom could be achieved while size-related limits of quantification were found to be 21 nm and 33 nm for gold and silver, respectively. Furthermore, the advantages of utilizing microdroplet generators vs. conventional nebulizers for nanoparticle analyses by ICP-MS are discussed.

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.

Mass quantification of nanoparticles by single droplet calibration using inductively coupled plasma mass spectrometry.

Utilization of metallic engineered nanoparticles (ENP) is progressing rapidly; therefore, characterization of their most important properties, e.g., size/mass, elemental composition, and number concentration, is inevitable and currently uses a set of different techniques. In this work, a new setup is proposed for the quantitative size and mass determination of ENPs employing a monodisperse microdroplet generator (MDG) with transport efficiencies >95% coupled to an ICPMS. Two different MDG sample introduction configurations (vertical and horizontal) were tested, and their performance characteristics were evaluated. Due to a 5-fold reduced temporal jitter resulting in a shorter measurement time, the horizontal droplet introduction approach was used for the analysis of ENPs. With this setup, the quantification of Au, Ag, and CeO2 nanoparticles of different sizes and polydispersities was achieved. Results are compared to complementary techniques such as transmission electron microscopy (TEM) and asymmetric flow field flow fractionation (AF4), and advantages as well as limitations of this newly proposed technique are discussed.

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.

Nanomagnet-based removal of lead and digoxin from living rats

In a number of clinical conditions such as intoxication, bacteraemia or autoimmune diseases the removal of the disease-causing factor from blood would be the most direct cure. However, physicochemical characteristics of the target compounds limit the applicability of classical filtration and diffusion-based processes. In this work, we present a first in vivo magnetic blood purification rodent animal model and demonstrate its ability to rapidly clear toxins from blood circulation using two model toxins with stable plasma levels (lead (Pb(2+)) and digoxin). Ultra-strong functionalized metal nanomagnets are employed to eliminate the toxin from whole blood in an extracorporeal circuit. In the present experimental demonstration over 40% of the toxin (i.e. lead or digoxin) was removed within the first 10 minutes and over 75% within 40 minutes. After capturing the target substance, a magnetic trap prevents the toxin-loaded nanoparticles from entering the blood circulation. Elemental analysis and magnetic hysteresis measurements confirm full particle recovery by simple magnetic separation (residual particle concentration below 1 μg mL(-1) (detection limit)). We demonstrate that magnetic separation-based blood purification offers rapid blood cleaning from noxious agents, germs or other deleterious materials with relevance to a number of clinical conditions. Based on this new approach, current blood purification technologies can be extended to efficiently remove disease-causing factors, e.g. overdosed drugs, bacteria or cancer cells without being limited by filter cut-offs or column surface saturation.

Visualization, velocimetry, and mass spectrometric analysis of engineered and laser-produced particles passing through inductively coupled plasma sources

Velocities of particles passing through the load coil region of an inductively coupled plasma (ICP) attached to a quadrupole mass spectrometer (MS) were measured by particle image velocimetry (PIV). Particles were produced either by laser ablation (LA) of solid targets or from drying analyte-spiked microdroplets ejected by a piezoelectrically actuated quartz capillary. For instance, velocities determined under conditions typically applied to LA-ICP-MS analyses were found to range between 10 and 20 m s−1, depending on the axial position. Our data, furthermore, evidence significant changes of the gas velocity upon modifications of the ICP operating conditions such as plasma power, gas flow rate, and torch injector diameter if helium is admixed in excess of >50% of the total gas flow passing through the injector. For instance, an increase of the ICP RF power from 800 to 1600 W resulted in particle velocity gradients up to 15 m s−1 kW−1 measured after the third turn of the RF-coil. Temporal changes in velocity, i.e. particle accelerations over the axis of the load coil region were specified to 300–1000 m s−2. In addition, ICP-MS analyses of laser-produced aerosols carried out at constant volumetric flow rates but reduced injector diameters made signal intensities of elements such as Y, Ce, or U drop by up to two orders of magnitude suggesting incomplete particle evaporation as well as notably different aerosol penetration depths. Sensitivities measured in this case turned out to correlate with boiling points of the respective oxides rather than the element-specific ionization potentials commonly observed. The mechanisms controlling gas velocity and sensitivity variations are discussed and consequences on LA-ICP-MS analyses are drawn.

Accelerated evaporation of microdroplets at ambient conditions for the on-line analysis of nanoparticles by inductively-coupled plasma mass spectrometry

The helium-assisted evaporation of pure, saline, and nanoparticle (NP)-containing microdroplets (∅droplet = 40–50 μm) at ambient conditions was studied. To quantify the liquid-to-gas mass transfer water droplets experience during evaporation, their sizes were monitored in different sections of a custom-made transport system, corresponding to increasing residence times after production. Drying times specified this way turned out to be approximately three times faster than values achievable by heavier gases such as argon which is commonly chosen as the carrier gas for subsequent NP analysis by inductively-coupled plasma mass spectrometry (ICP-MS). Furthermore, residues of saline droplets doped with well-defined amounts of an acidified calcium standard solution were classified by light scattering (LS) and scanning electron microscopy (SEM) indicating nearly complete desolvation over transport distances of a few tens of centimeters if helium or argon–helium mixtures were supplied. Mass transfer rates along droplet trajectories simulated on the basis of computational fluid dynamics (CFD) were found to be consistent with measured ones which proved the applicability of the evaporation model used, thus allowing an optimization of user-defined transport systems without the need for a time-consuming adaptation by trial-and-error. The analytical capabilities of helium-assisted evaporation as an alternative to conventional approaches employing argon-only-based set-ups operated at elevated temperatures were, in addition, demonstrated by ICP-quadruple (Q)MS of gold NPs. Therefore, NP-containing droplets were delivered through an either horizontally or vertically arranged transport assembly both resulting in over-all throughputs of 90 to 100%.

Role of arginine in chemical cross-linking with N-hydroxysuccinimide esters

In order to clarify whether arginine has a promoting effect on the acylation of hydroxyl groups of serine, threonine, or tyrosine by homobifunctional cross-linking agents in aqueous solution, we carried out systematic experiments with model peptides, comparing relative reaction yields with covalently protected and unprotected arginines by MALDI-MS. The guanidinium group could be demonstrated to contribute to the reactivity of hydroxyl groups toward N-hydroxysuccinimide esters and catalyze the nucleophilic substitution, probably via hydrogen bonds.

In vivo risk evaluation of carbon-coated iron carbide nanoparticles based on short- and long-term exposure scenarios

BACKGROUND While carbon-encapsulated iron carbide nanoparticles exhibit strong magnetic properties appealing for biomedical applications, potential side effects of such materials remain comparatively poorly understood. Here, we assess the effects of iron-based nanoparticles in an in vivo long-term study in mice with observation windows between 1 week and 1 year. MATERIALS & METHODS Functionalized (PEG or IgG) carbon-encapsulated platinum-spiked iron carbide nanoparticles were injected intravenously in mice (single or repeated dose administration). RESULTS One week after administration, magnetic nanoparticles were predominantly localized in organs of the reticuloendothelial system, particularly the lung and liver. After 1 year, particles were still present in these organs, however, without any evident tissue alterations, such as inflammation, fibrosis, necrosis or carcinogenesis. Importantly, reticuloendothelial system organs presented with normal function. CONCLUSION This long-term exposure study shows high in vivo compatibility of intravenously applied carbon-encapsulated iron nanoparticles suggesting continuing investigations on such materials for biomedical applications.

Capabilities of sequential and quasi-simultaneous LA-ICPMS for the multi-element analysis of small quantity of liquids (pl to nl): insights from fluid inclusion analysis

Three configurations of inductively coupled plasma mass spectrometers (ICPMS), namely: a quadrupole (QMS) and a sector-field (SFMS), both equipped with a standard cylindrical ablation cell, and an orthogonal time-of-flight (TOFMS), equipped with a fast washout ablation cell, were coupled with the same 193 nm Excimer laser ablation system in order to evaluate their capabilities for measurement of multiple minor and trace elements in small quantities of liquids (pl to nl), such as fluid inclusions. Analyses were performed with different objects: (i) multi-element solutions sealed in silica capillaries of internal diameter of 20 μm serving as synthetic analogues of natural fluid inclusions; (ii) natural two-phase (liquid + vapour) fluid inclusions with low salinity (ca. 4.8 wt% NaCl eq.) and homogeneous compositions, trapped in quartz crystals from the Alps; (iii) natural multi-phase (liquid + vapour + multiple solids) fluid inclusions with high salinity (ca. 13–15 wt% NaCl eq.) and homogeneous compositions, trapped in quartz crystals from the Zambian Copperbelt. This study demonstrates that the SFMS and TOFMS provide improvements, particularly in term of limits of detection (LODs) and precision, compared to the QMS traditionally used for the measurement of fluid inclusions. SFMS leads on average to lower LODs within one order of magnitude compared to QMS and TOFMS, but precision and accuracy are lower due to longer acquisition cycle times. TOFMS presents both advantages of having rapid and quasi-simultaneous acquisition for all isotopes from 6Li to 238U in a very short cycle time down to 30 μs, with higher precisions and lower LODs than for QMS for isotopes with m/Q > 11. Its use, coupled to a fast washout cell, leads to (i) the improvement in the analysis of small-size (<10 μm) and multi-phase fluid inclusions and (ii) detection of higher number of isotopes compared to QMS and SFMS, which are both limited by the number of measured isotopes from short transient signals of fluid inclusions. Consequently, the tested TOFMS, coupled with a fast washout ablation cell, appears to be a promising instrument for the analysis of natural fluid inclusions by LA-ICPMS, especially for small, multi-phase and/or low salinity fluid inclusions.