Georges Slodzian

Scanning secondary ion analytical microscopy with parallel detection

The secondary ion microscope described here allows to obtain the simultaneous registration of chemical and isotopic distribution maps of several elements composing the sample. The instrument has been specially designed to optimize both sensitivity and selectivity: bombardment with primary Cs+ ions to increase the ionization yields of negative secondary ions, efficient collection of secondary ions at the target surface, matching of the secondary ion beam etendue with the acceptance of the mass spectrometer working at high mass resolution, spectrometer with parallel detection capabilities. The probe diameter can be made as low as 30 nm and ion induced electron images registered at the same time as ion images. Presently, four ion micrographs are obtained simultaneously over a field of view up to 20 × 20 μm2 containing up to 512 × 512 pixels. Examples are shown with an ion probe diameter of 0.1 μm.

Complementary advantages of fluorescence and SIMS microscopies in the study of cellular localization of two new antitumor drugs

Low light level fluorescence microscopy studies have been carried out on MCF7‐P human mammary tumor cells to localize the intracellular distribtion of two new anticancer drugs, Pazelliptine and Intoplicine, which are currently under clinical evaluation. These two molecules are thought to act at the nuclear level, through DNA topoisomerase interactions. Because fluorescence of these compounds appears strongly quenched by intercalation in double strand DNA, secondary ion mass spectrometry (SIMS) imaging was used to check the presence of the drugs in the nuclear compartment. In spite of chemical structure similitudes, pazelliptine and intoplicine appear to be distributed in quite different ways within the cells. Incubation for 1 and 24 hours also allowed us to bring to light strong differences in the distribution kinetics. Pazelliptine quickly enters into the nucleoli but is no longer present in the nucleus after 24 hours incubation. Intoplicine was not detected by fluorescence in the nucleus, however SIMS microscopy allowed us to show its accumulation within this cellular compartment as a function of time of exposure. This study shows the complementarity of fluorescence and SIMS microscopies. Microsc. Res. Tech. 36:287–295, 1997.

Detection and cartography of the fluorinated antimalarial drug mefloquine in normal and Plasmodium falciparum infected red blood cells by scanning ion microscopy and mass spectrometry

Summary— Due to the presence of fluorine atoms in its molecule, the antimalarial drug mefloquine (MQ) can be easily detected in normal and Plasmodium falciparum infected red blood cells (RBC) by scanning ion microscopy and mass spectrometry. The P falciparum infected RBC exhibited intense distribution of MQ inside the parasite. The main compartments of the parasite which accumulate the drug were the food vacuole and the cytoplasm. The correlation between fluorine (19F−) and phosphorus (31P−) as well as probes for the DNA synthesis (BrdU and IdU) emissions shows that the parasite nucleus is also accessible to the drug. This study demonstrates that SIMS technique on smear preparations is an efficient approach for the direct detection and cartography of fluorinated antimalarial drugs in normal and P falciparum infected RBC, without radioactive labelling.

Oxygen isotopic measurements on the Cameca Nanosims 50

Abstract The Cameca Nanosims 50 has been designed to provide for parallel detection along a focal plane over a large mass range but spacing between adjacent mass lines makes it necessary to use miniature electron multipliers (EMs). A new version of a miniature EM, designed to reduce aging effects, has been tested. Means to characterize aging effects are presented. Data are interpreted by simulations with a simple model. Consequences of aging on isotopic measurements in a parallel detection context are examined in the special case of oxygen. Measurements of the most abundant isotope with a Faraday cup (FC) and weak isotopes with EMs are reported. Advantages of FC are emphasized: no dead time correction and no quasi-simultaneous arrivals to account for in a situation where high collection efficiencies (8% for O− for instance) leads to large corrections.