University of Silesia in Katowice

Twenty two years ago, the seven experiments on CERN’s Heavy Ion programme at the Super Proton Synchrotron (NA44, NA45/CEREA,NA49, NA50,NA52/NEWMASS, WA97/NA57 and WA98) combining their data were able to characterise a new state of matter, verifying an important prediction of the theory of fundamental forces between quarks.

This talk briefly reviews studies of the phase diagram of strongly interacting matter with relativistic nuclear collisions at the CERN Super Proton Synchrotron which followed the observation of the quark-gluon plasma. The first ten years of this period was mostly influenced by the results of the NA49 experiment, the second period was dominated by NA61/SHINE. I will close by suggesting priorities for future measurements.

This lecture will introduce astroparticle physics focusing on cosmic rays and astrophysical neutrinos. It covers the cosmic speed limit (Greisen Zatsepin-Kuzmin Cutoff), gigantic avalanches of elementary particles (air showers), 3000 km² large particle detectors (Pierre Auger Observatory), cosmic neutrinos (and how to find them) and astrophysical accelerators achieving 10,000,000 times larger beam energies than the Large Hadron Collider at CERN.

Thes scattering of X-rays at small angles (SAXS) is a unique technique to study emulsion phases and nanoparticles. The lecture will present the method with practical details and applications to modern pharmaceutics. 

Continuous production of drug delivery systems (DDS) assisted by microfluidics has drawn a growing interest because of the high reproducibility, low batch-to-batch variation of formulations, narrow and controlled particle size distribution and scale-up facilities induced by this process. Besides, microfluidics offers opportunities for high throughput screening of process parameters and the implementation of Process Analytical Technologies (PAT) as close to the product. 

In this context, we propose to spotlight the GALECHIP concept [1] through the development of an instrumented microfluidic pilot considered as a Galenic Lab-on-Chip to formulate nanomedicines, such as Lipid Nano-Emulsions (LNE), under controlled process conditions which are essential to obtain DDS with controlled sizes and properties. 

With this microfluidic pilot, we conducted: 

1. an in operando Small Angle X-ray Scattering (SAXS) investigation along the microfluidic channels in order to understand the physicochemical and hydrodynamical mechanisms involved in the formation of well controlled LNEs (25, 50 and 100 nm in size). Starting at the mixing point of pure water and non-ionic surfactants in a pharmaceutical oil, we studied the phase inversion process that occurs during the Lipid Nano Emulsion formation and the DDS maturation pathway. The mapping of the SAXS signal from the chip in continuous production, was obtained with sufficient time and spatial resolution, by combining a tailored silicon/glass chip, high speed SAXS “fly-scans” and the use of X-ray Compound Refractive Lenses,
2. a technological development of affordable 3D printed plastic microfluidic chips (PEEK & ABS) in order to encourage the use of such formulation platforms at low costs; and,
3. the application to the formulation in sterile production of loaded-LNE for medical treatments involving hydrophobic drugs. 

To understand the physical properties of materials or nanomaterials we need to know perfectly their structure properties. In some cases, X-ray diffraction, Neutron diffraction and even DFT calculations cannot specify certain structural properties. One of the solutions is to use large instruments facilities like the synchrotron SOLEIL. We will give some examples of intermetallic nanomaterials for which the use of the synchrotron is essential.

Twenty two years ago, the seven experiments on CERN’s Heavy Ion programme at the Super Proton Synchrotron (NA44, NA45/CEREA,NA49, NA50,NA52/NEWMASS, WA97/NA57 and WA98) combining their data were able to characterise a new state of matter, verifying an important prediction of the theory of fundamental forces between quarks.

This talk briefly reviews studies of the phase diagram of strongly interacting matter with relativistic nuclear collisions at the CERN Super Proton Synchrotron which followed the observation of the quark-gluon plasma. The first ten years of this period was mostly influenced by the results of the NA49 experiment, the second period was dominated by NA61/SHINE. I will close by suggesting priorities for future measurements.

Thes scattering of X-rays at small angles (SAXS) is a unique technique to study emulsion phases and nanoparticles. The lecture will present the method with practical details and applications to modern pharmaceutics. 

Continuous production of drug delivery systems (DDS) assisted by microfluidics has drawn a growing interest because of the high reproducibility, low batch-to-batch variation of formulations, narrow and controlled particle size distribution and scale-up facilities induced by this process. Besides, microfluidics offers opportunities for high throughput screening of process parameters and the implementation of Process Analytical Technologies (PAT) as close to the product. 

In this context, we propose to spotlight the GALECHIP concept [1] through the development of an instrumented microfluidic pilot considered as a Galenic Lab-on-Chip to formulate nanomedicines, such as Lipid Nano-Emulsions (LNE), under controlled process conditions which are essential to obtain DDS with controlled sizes and properties. 

With this microfluidic pilot, we conducted: 

1. an in operando Small Angle X-ray Scattering (SAXS) investigation along the microfluidic channels in order to understand the physicochemical and hydrodynamical mechanisms involved in the formation of well controlled LNEs (25, 50 and 100 nm in size). Starting at the mixing point of pure water and non-ionic surfactants in a pharmaceutical oil, we studied the phase inversion process that occurs during the Lipid Nano Emulsion formation and the DDS maturation pathway. The mapping of the SAXS signal from the chip in continuous production, was obtained with sufficient time and spatial resolution, by combining a tailored silicon/glass chip, high speed SAXS “fly-scans” and the use of X-ray Compound Refractive Lenses,
2. a technological development of affordable 3D printed plastic microfluidic chips (PEEK & ABS) in order to encourage the use of such formulation platforms at low costs; and,
3. the application to the formulation in sterile production of loaded-LNE for medical treatments involving hydrophobic drugs. 

To understand the physical properties of materials or nanomaterials we need to know perfectly their structure properties. In some cases, X-ray diffraction, Neutron diffraction and even DFT calculations cannot specify certain structural properties. One of the solutions is to use large instruments facilities like the synchrotron SOLEIL. We will give some examples of intermetallic nanomaterials for which the use of the synchrotron is essential.