Isospin dependence of the Ar+Ni fusion-evaporation cross section

The fundamental goal of this thesis is the determination of the isospin dependence of the Ar+Ni fusion-evaporation cross section. Three Ar isotope beams, with energies of about 13AMeV, have been accelerated and impinged onto isotopically enriched Ni targets, in order to produce Pd nuclei, with mass number varying from 92 to 104. The measurements have been performed by the high performance 4pi detector INDRA, coupled with the magnetic spectrometer VAMOS. Even if the results are very preliminary, the obtained fusion-evaporation cross sections behaviour gives a hint at the possible isospin dependence of the fusion-evaporation cross sections.

Measurement of the atmospheric muon charge ratio with the OPERA detector

The atmospheric muon charge ratio, defined as the number of positive over negative charged muons, is an interesting quantity for the study of high energy hadronic interactions in atmosphere and the nature of the primary cosmic rays. The measurement of the charge ratio in the TeV muon energy range allows to study the hadronic interactions in kinematic regions not yet explored at accelerators. The OPERA experiment is a hybrid electronic detector/emulsion apparatus, located in the underground Gran Sasso Laboratory, at an average depth of 3800 meters water equivalent (m.w.e.). OPERA is the first large magnetized detector that can measure the muon charge ratio at the LNGS depth, with a wide acceptance for cosmic ray muons coming from above. In this thesis, the muon charge ratio is measured using the spectrometers of the OPERA detector in the highest energy region. The charge ratio was computed separately for single and for multiple muon events, in order to select different primary cosmic ray samples in energy and composition. The measurement as a function of the surface muon energy is used to infer parameters characterizing the particle production in atmosphere, that will be used to constrain Monte Carlo predictions. Finally, the experimental results are interpreted in terms of cosmic ray and particle physics models.

Development and applications of hollow fiber flow field-flow fractionation in the bioanalytical field. Studies of aggregation phenomena in complex protein samples

Recent advances in the fast growing area of therapeutic/diagnostic proteins and antibodies - novel and highly specific drugs - as well as the progress in the field of functional proteomics regarding the correlation between the aggregation of damaged proteins and (immuno) senescence or aging-related pathologies, underline the need for adequate analytical methods for the detection, separation, characterization and quantification of protein aggregates, regardless of the their origin or formation mechanism. Hollow fiber flow field-flow fractionation (HF5), the miniaturized version of FlowFFF and integral part of the Eclipse DUALTEC FFF separation system, was the focus of this research; this flow-based separation technique proved to be uniquely suited for the hydrodynamic size-based separation of proteins and protein aggregates in a very broad size and molecular weight (MW) range, often present at trace levels. HF5 has shown to be (a) highly selective in terms of protein diffusion coefficients, (b) versatile in terms of bio-compatible carrier solution choice, (c) able to preserve the biophysical properties/molecular conformation of the proteins/protein aggregates and (d) able to discriminate between different types of protein aggregates. Thanks to the miniaturization advantages and the online coupling with highly sensitive detection techniques (UV/Vis, intrinsic fluorescence and multi-angle light scattering), HF5 had very low detection/quantification limits for protein aggregates. Compared to size-exclusion chromatography (SEC), HF5 demonstrated superior selectivity and potential as orthogonal analytical method in the extended characterization assays, often required by therapeutic protein formulations. In addition, the developed HF5 methods have proven to be rapid, highly selective, sensitive and repeatable. HF5 was ideally suitable as first dimension of separation of aging-related protein aggregates from whole cell lysates (proteome pre-fractionation method) and, by HF5-(UV)-MALS online coupling, important biophysical information on the fractionated proteins and protein aggregates was gathered: size (rms radius and hydrodynamic radius), absolute MW and conformation.

Flow Field–Flow Fractionation for size analysis and characterization of nanoparticles for applications in Life Sciences

Nanotechnologies are rapidly expanding because of the opportunities that the new materials offer in many areas such as the manufacturing industry, food production, processing and preservation, and in the pharmaceutical and cosmetic industry. Size distribution of the nanoparticles determines their properties and is a fundamental parameter that needs to be monitored from the small-scale synthesis up to the bulk production and quality control of nanotech products on the market. A consequence of the increasing number of applications of nanomaterial is that the EU regulatory authorities are introducing the obligation for companies that make use of nanomaterials to acquire analytical platforms for the assessment of the size parameters of the nanomaterials. In this work, Asymmetrical Flow Field-Flow Fractionation (AF4) and Hollow Fiber F4 (HF5), hyphenated with Multiangle Light Scattering (MALS) are presented as tools for a deep functional characterization of nanoparticles. In particular, it is demonstrated the applicability of AF4-MALS for the characterization of liposomes in a wide series of mediums. Afterwards the technique is used to explore the functional features of a liposomal drug vector in terms of its biological and physical interaction with blood serum components: a comprehensive approach to understand the behavior of lipid vesicles in terms of drug release and fusion/interaction with other biological species is described, together with weaknesses and strength of the method. Afterwards the size characterization, size stability, and conjugation of azidothymidine drug molecules with a new generation of metastable drug vectors, the Metal Organic Frameworks, is discussed. Lastly, it is shown the applicability of HF5-ICP-MS for the rapid screening of samples of relevant nanorisk: rather than a deep and comprehensive characterization it this time shown a quick and smart methodology that within few steps provides qualitative information on the content of metallic nanoparticles in tattoo ink samples.