Cell Inductively Coupled Plasma Mass Spectrometry Research Articles

Abstract 2988: Quantifying the Uptake of Metal Based Cancer Therapy Drugs Using Single Cell ICP-MS

Abstract Metallic based cancer therapy drugs have been around for several years, the most widely used being platinum-based drugs, however these come with severe side effects due to the non-specific targeting of these drugs. Recently a number of nanoparticle-based cancer therapeutics have been approved for clinical use or are currently under development. Advantages that engineered nanoparticles may offer over conventional small molecule drugs include: (i) prolonged circulation time in the body; (ii) reduction of nonspecific cellular uptake along with undesirable off-target and other side effects; and (iii) improvement in cellular interactions through specific cancer cell targeting moieties. The therapeutic effect of cancer treatment is related to the amount of drug that interacts with each individual cancer cell. Traditional drug research techniques, such as conventional inductively coupled plasma mass spectrometry (ICP-MS), have been limited to cell ensemble measurements, which require homogenization of a given cell population for quantitative analysis. All cells within this population are assumed to be similar and therefore assumed to interact with the same amount of drug, however, recent studies demonstrate that cell populations are heterogeneous, and differences exist even for cells from the same cell population and cell line. For example, gene expression measurements based on homogenized cell populations are misleading as they only provide averaged results and do not account for the small but critical changes occurring in individual cells such as size, protein levels, and expressed RNA transcripts. These variations are key aspects when answering previously unsolvable questions in cancer research, stem cell biology, immunology, developmental biology, and neurology. To overcome these limitations, PerkinElmer developed Single-Cell (SC) ICP-MS, which allows the rapid analysis of a large number of individual cells rather than a cell population as a whole or only a few cells. This allows for the quantification of the metal mass in individual cells, resulting in a histogram of the population showing not only the most frequent and mean masses of drug in the population but also the distribution throughout the population. Here we will show results for both cisplatin uptake and surface modified gold nanoparticle uptake into cancer cells. The first resulting in a wide distribution in the amount of platinum measured per cell over time with differences in resistant and non-resistant cancer cells. While the latter shows the ability of this technique to quantify the number for modified Au nanoparticles per cell as well as the number of cells containing the drug. Note: This abstract was not presented at the meeting. Citation Format: Chady Stephan, Ruth Merrifield, Stefan Wilhelm. Quantifying the Uptake of Metal Based Cancer Therapy Drugs Using Single Cell ICP-MS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2988.

Size and elemental distributions of nano- to micro-particulates in the geochemically-stratified Great Salt Lake

Abstract The characterization of trace elements in terms of their apportionment among dissolved, macromolecular, nano- and micro-particulate phases in the water column of the Great Salt Lake carries implications for the potential entry of toxins into the food web of the lake. Samples from the anoxic deep and oxic shallow brine layers of the lake were fractionated using asymmetric flow field-flow fractionation (AF4). The associated trace elements were measured via online collision cell inductively-coupled plasma mass spectrometry (CC-ICP-MS). Results showed that of the total (dissolved + particulate) trace element mass, the percent associated with particulates varied from negligible (e.g. Sb), to greater than 50% (e.g. Al, Fe, Pb). Elements such as Cu, Zn, Mn, Co, Au, Hg, and U were associated with nanoparticles, as well as being present as dissolved species. Particulate-associated trace elements were predominantly associated with particulates larger than 450 nm in size. Among the smaller nanoparticulates (

Copper determination using ICP-MS with hexapole collision cell

AbstractDetermination of copper using inductively coupled plasma mass spectrometry (ICP-MS) suffers from polyatomic overlays originating from Na+ and Mg2+ matrix elements due to the formation of 40Ar23Na+ and 40Ar25Mg+ in the mass-to-charge ratios of 63 and 65, respectively. The collision/reaction cell technology belongs to the most modern methods used to overcome polyatomic interferences. Gas-filled collision/reaction cell can cause an additional mass bias effect influencing analytical precision of the method. In this study, the additional mass bias effect of the hexapole collision/reaction cell ICP-MS was studied on an example of n(65Cu)/n(63Cu) isotope ratio. As a result, a method for suppressing polyatomic interference on the mass-to-charge ratio of 63 and 65 was introduced and additional mass bias of the collision/reaction cell was lowered to an acceptable level.

Application of enriched stable isotopes as tracers in biological systems: a critical review

The application of enriched stable isotopes of minerals and trace elements as tracers in biological systems is a rapidly growing research field that benefits from the many new developments in inorganic mass spectrometric instrumentation, primarily within inductively coupled plasma mass spectrometry (ICP-MS) instrumentation, such as reaction/collision cell ICP-MS and multicollector ICP-MS with improved isotope ratio measurement and interference removal capabilities. Adaptation and refinement of radioisotope tracer experiment methodologies for enriched stable isotope experiments, and the development of new methodologies coupled with more advanced compartmental and mathematical models for the distribution of elements in living organisms has enabled a broader use of enriched stable isotope experiments in the biological sciences. This review discusses the current and future uses of enriched stable isotope experiments in biological systems.

Determination of sulfur and selected trace elements in metallothionein-like proteins using capillary electrophoresis hyphenated to inductively coupled plasma mass spectrometry with an octopole reaction cell.

The determination of sulfur in biologically relevant samples such as metalloproteins is described. The analytical methodology used is based on robust on-line coupling between capillary electrophoresis (CE) and octopole reaction cell inductively-coupled plasma mass spectrometry (ORC-ICP-MS). Polyatomic ions that form in the plasma and interfere with the determination of S at mass 32 are minimised by addition of xenon to the collision cell. The method has been applied to the separation and simultaneous element-specific detection of sulfur, cadmium, copper, and zinc in commercially available metallothionein preparations (MT) and metallothionein-like proteins (MLP) extracted from liver samples of bream ( Abramis brama L.) caught in the river Elbe, Germany. Instrumental detection limits have been calculated according to the German standard procedure DIN 32645 for the determination of sulfur and some simultaneously measured trace elements in aqueous solution. For sulfur detection limits down to 1.3 microg L(-1) ((34)S) and 3.2 microg L(-1) ((32)S) were derived. For the other trace elements determined simultaneously detection limits ranging from 300 ng L(-1) ((58)Ni) to 500 ng L(-1) ((66)Zn, (55)Mn) were achieved. For quantification of sulfur and cadmium in a commercially available MT preparation under hyphenated conditions the use of external calibration is suggested. Finally, the need for proper sample-preparation technique will be discussed.

Comparison of different nebulisers and chromatographic techniques for the speciation of selenium in nutritional commercial supplements by hexapole collision and reaction cell ICP-MS

A detailed comparison of the performance of different nebulisation (Meinhard, hydraulic high pressure and microconcentric nebulisers) and chromatographic (reversed-phase and ion-pair) systems for the speciation of selenium by hexapole collision and reaction cell inductively coupled plasma mass spectrometry (ICP-MS) was carried out. The relative limits of detection for the seleno compounds under study (selenite, selenate, selenocystine, selenomethionine and selenoethionine) monitoring isotope 80Se were in the range 100–200 pg mL−1 (Meinhard nebuliser), 80–150 pg mL−1 (microconcentric nebuliser) and 35–90 pg mL−1 (hydraulic high pressure nebuliser). Selenium species separation was carried out by both reversed-phase and ion-pair high-performance liquid chromatography (HPLC). More seleno compounds could be separated and a slight improvement in the limits of detection was obtained with the ion-pair HPLC system. Different commercial nutritional selenium supplements were analysed by both chromatographic techniques after extraction with hot water. The efficiency of this extraction was in the range 80–95% for selenate and selenomethionine and 10–25% for selenoyeast-based supplements. Identification of some seleno compounds and quantification in supplement samples were easily and rapidly realised with the MassLynx™ software.