Joachim Koch

Material deposition during laser ablation in nitrogen was assessed and compared with the laser-induced fractionation in helium. In addition, the ICP-induced fractionation of a N ₂ -ICPMS was also compared to a conventional Ar-ICPMS.

The composition of laser generated aerosols produced during single spot ablation was analyzed by inductively coupled plasma time of flight mass spectrometry (LA-ICP-TOFMS) and compared to that if the corresponding material deposited on the sample surface. Differences between the signals recorded during single spot ablation and by analysis of the deposits allowed to study and describe non-stoichiometric processes at the ablation site. These measurements allowed for the determination of transport efficiencies for the elements measured in NIST SRM 610, which were element specific and always higher than 85 %. A mass balance of, e.g., ²³⁸U⁺/²³²Th⁺ signal intensity ratios allowed differentiation of laser-induced and ICP-induced elemental fractionation based on LA-ICP-TOFMS data only, i.e., without the need for off-line analysis of collected material. All phenomena reported here were studied using a range of laser fluences (7.4 – 25 J/cm²) and for single spot ablation (100 – 600 pulses per spot). The method presented here provided direct access to important parameters, which influence the accuracy of quantitative analysis in LA-ICPMS, such as the amount and composition of deposited material around the crater and information about the aforementioned transport efficiencies for individual elements. In addition, the proposed analysis and calculation procedure allowed distinguishing laser- and ICP-induced elemental fractionation for different LA and ICPMS operating conditions. Knowledge about these parameters will allow to study the ablation behavior of different matrices and may therefore improve non-matrix matched quantification in LA-ICPMS.

Bulk analysis in laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has commonly made use of large one-volume ablation cells of various geometries. These ablation cells offer significant dispersion of aerosols, resulting in stable signals but a loss of spatial and temporal resolution. In recent years, low dispersion ablation cells, most commonly two-volume cells, have been invented for the purposes of depth profiling and imaging due to their capabilities to resolve individual laser pulses. In this study, the differences between the two types of ablation cells were studied based on ICP-MS analysis, optical particle sizing and computational fluid dynamics. Differences in particle size distributions (PSD) and elemental ratios were investigated with respect to positional dependence within an ablation cell. 3D-gas flow patterns by CFD formed in a plain large one-volume cylindrical cell (30 cm³) revealed inhomogeneous gas flow patterns, where the location of ablation has an impact on the aerosol residence time within the cell. As a consequence, the mean particle size that is transported to the ICP varies from 80 nm to 150 nm for a cylindrical ablation cell. Correlating with the PSD, the ratio of ²³⁸U/²³²Th and ²³⁸U/²⁰⁸Pb varied by up to 15% using the same parameters but different ablation locations within the cell. As this deviation directly affects quantification, methods for matching in provenance studies, geochronology and forensics are especially vulnerable to these errors. For the low dispersion cell experiments, the recently described parallel flow ablation cell (PFAC) was used as an exemplary model. Mean particle sizes were significantly lower by a factor of more than 2, and the variation of the elemental ratios depending on the location within the cell was significantly reduced from 15% to 5%. Through use of longer transport tubing, it is possible to change from resolved laser pulses to continuous stable signal akin to large volume ablation cells, while still using the PFAC. This smoothing of the aerosol showed no effect on element ratios, resulting in comparable results as the resolved measurements. This work indicated that low dispersion ablation is more successful in achieving reproducible element ratios. It was also found that a decrease in aerosol dispersion within the ablation cell helps to suppress plasma induced fractionation effects originating from incomplete ionization.

Background The redirected optimized cell platform (ROCK®) enables the generation of customizable innate cell engagers (ICE®) of varying valency, affinity, and pharmacokinetic profiles. Preclinical and clinical studies have demonstrated the advantage and unique features of this first-in-class ICE® antibodies across a multitude of cancers and its differentiation to monoclonal antibodies. ICE® are tetravalent, bispecific antibodies that bivalently bind to a unique epitope on CD16A, which is selectively expressed on natural killer (NK) cells and macrophages, while the other domains target a tumor antigen. In addition to promoting antibody-dependent cellular cytotoxicity (ADCC) of NK cells, ICE® can also promote tumor targeting of macrophages eventually inducing antibody-dependent cellular phagocytosis (ADCP). Methods ADCP and ADCC assays were performed using monocyte-differentiated macrophages and NK cells derived from healthy donor PBMCs. Target tumor lines and patient-derived xenograft line-derived spheroids were labelled and co-cultured with macrophages or NK cells. Live-cell imaging (IncuCyte®) was used to measure ADCP and ADCC events. Results We show that ICE® molecules can enhance ADCP of tumor cells mediated by various functional/phenotypic subsets of macrophages derived from in vitro differentiation of human monocytes. ICE®-induced ADCP of tumor target cells was seen across different macrophage subtypes (M1 and M2). We further investigated the expression of immune-suppressive checkpoint programmed death-ligand 1 (PD-L1) on macrophages upon ICE® treatment that could be a key anti-tumor molecule within the suppressive tumor microenvironment. Based on patient-derived xenograft line-derived spheroids (3D) generated from primary tumor samples of patients suffering from various malignancies, we could demonstrate robust ADCC and ADCP mediated by NK cells and macrophages, respectively. Conclusions ICE® molecules are able to mount robust NK cell- and macrophage-mediated anti-tumoral innate immune responses. This combined immune activity has the potential to not only fight tumor cells directly but also to initiate a full immune response comprised of innate and adaptive components of the immune system.

The effects of He + X (X = H₂O or O₂) carrier gases on the ²⁰⁶Pb/²³⁸U system bias and down-hole fractionation in LA-ICPMS of natural zircon and NIST SRM610 are reported.

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%.

This paper is a review of the basic principles and recent developments of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) as a method for the element- and isotope-selective trace analysis of solid materials. In the course of this review, the aerosol formation/transportation process, quantification issues, as well as technical aspects concerning the system configuration and ICP operating conditions are outlined. Furthermore, the performance of femtosecond (fs) LA-based analyses as one of the most important advancements made over the past years is discussed. The benefits offered by fs-LA in comparison to LA using nanosecond (ns) laser sources are demonstrated on the basis of oxide layer and silicate glass analyses with different applied calibration strategies.

The transport phenomena of laser-produced aerosols prior to analysis by inductively coupled plasma mass spectrometry (ICPMS) were examined. Aerosol particles were visualized over the cross section of a transport tube attached to the outlet of a conventional ablation cell by light scattering using a pulsed laser source. Experiments were carried out under laminar or turbulent in-cell flow conditions applying throughputs of up to 2.0 L/min and reveal the nature of aerosol transportation to strongly depend on both flow rate and carrier gas chosen. For instance, laser ablation (LA) using laminar in-cell flow and helium as aerosol carrier resulted in stationary but inhomogeneous dispersion patterns. In addition, aerosols appear to be separated into two coexisting phases consisting of (i) dispersed particles that accumulate at the boundary layer of several vortex channel flows randomly arranged along the tube axis and (ii) larger fragments moving inside. The occurrence of these fragments was found to affect the accuracy of Si-, Zn-, and Cd-specific ICPMS analyses of aerosols released by LA of silicate glass (SRM NIST610). Accuracy drifts of more than 10% were observed for helium flow rates of >1 L/min, most probably, due to preferential evaporation and diffusion losses of volatile constituents inside the ICP. The utilization of turbulent in-cell flow made the vortex channels collapse and resulted in an almost complete aerosol homogenization. In contrast, LA using argon as aerosol carrier generally yielded a higher degree of dispersion, which was nearly independent of the flow conditions applied. To illustrate the differences among laminar and turbulent in-cell flow, furthermore, the velocity field inside the ablation cell was simulated by computational fluid dynamics.