In this work, a novel standardization strategy for quantitative elemental bioimaging is evaluated. More specifically, multi-element quantification by laser ablation-inductively coupled plasma-time-of-flight mass spectrometry (LA-ICP-TOFMS) is performed by multi-point calibration using gelatin-based micro-droplet standards and validated using in-house produced reference materials. Fully automated deposition of micro-droplets by micro-spotting ensured precise standard volumes of 400 ± 5 pL resulting in droplet sizes of around 200 μm in diameter. The small dimensions of the micro-droplet standards and the use of a low-dispersion laser ablation setup reduced the analysis time required for calibration by LA-ICPMS significantly. Therefore, as a key advance, high-throughput analysis (pixel acquisition rates of more than 200 Hz) enabled to establish imaging measurement sequences with quality control- and standardization samples comparable to solution-based quantification exercises by ICP-MS. Analytical figures of merit such as limit of detection, precision, and accuracy of the calibration approach were assessed for platinum and for elements with biological key functions from the lower mass range (phosphorus, copper, and zinc). As a proof-of-concept application, the tool-set was employed to investigate the accumulation of metal-based anticancer drugs in multicellular tumor spheroid models at clinically relevant concentrations.

In this work, a combination of routine clinical practice and state-of-the-art laser ablation-inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) imaging is presented for multielement analysis of single cells on clinical samples. More specifically, routinely drawn blood thin films of a patient undergoing treatment with the anticancer drug cisplatin were studied. The presented label-free approach enabled rapid analysis of hundreds of cells at the single-cell level within a few minutes without additional tailored sample preparation. The employed low-dispersion LA setup is based on the tube-type COBALT ablation cell in combination with the aerosol rapid introduction system (ARIS) providing pixel-resolved imaging at 250–500 Hz for biological sample material. In order to cope with the short transient signals of only a few milliseconds delivered by the laser ablation setup, an icpTOF 2R TOF-based ICP-MS instrument was used for analysis, which has a mass coverage of m/z = 14–256. Leukocytes and erythrocytes, imaged with a laser beam of 4 μm and pixel interspacing of 2 μm, were differentiated on the basis of their intrinsic trace-elemental pattern. Overall, red blood cells displayed high iron intensities, whereas individual white blood cells were characterized by their high phosphorus content and increased sulfur signal. Unsupervised multivariate statistical analysis was applied to the data set. Principal component plots showed a clear clustering of leukocytes versus erythrocytes. The approach allowed studying not only the drug distribution between plasma and cells but also, for the first time, the preferential accumulation of platinum in different blood cell types without the need of cell fixation and labeling. Extracellular hotspots of platinum were observed, whereas only a small fraction of platinum was associated with erythrocytes. The investigation demonstrates the potential of low-dispersion LA-ICP-TOFMS as a rapid and powerful tool for label-free single-cell imaging in the clinical context.

The capabilities of flow injection inductively coupled plasma time-of-flight mass spectrometry (FI-ICP-TOFMS) were evaluated for accurate multi-element analysis addressing water and serum reference materials with a sample intake of 5 μL in comparison to FI-ICP-MS/MS analysis.

A high-throughput ICP-TOFMS method is presented for multi-element quantification in CSF material requiring low sample volume.

A series of six highly lipophilic Cp‐substituted molybdenocenes bearing different bioactive chelating ligands was synthesized and characterized by NMR spectroscopy, mass spectrometry and X‐ray crystallography. In vitro experiments showed a greatly increased cytotoxic potency when compared to the non‐Cp‐substituted counterparts. In vivo experiments performed with the dichlorido precursor, (Ph2C−Cp)2MoCl2 and the in vitro most active complex, containing the thioflavone ligand, showed an inhibition of tumour growth. Proteomic studies on the same two compounds demonstrated a significant regulation of tubulin‐associated and mitochondrial inner membrane proteins for both compounds and a strong metabolic effect of the thioflavone containing complex.