With the integration of renewable energies such as offshore wind farms and the constraints of development of transmission grids, High-Voltage Direct Current (HVDC) are developing. The concept of HVDC Meshed grid has emerged in the past decade to increase reliability and strengthen interconnections between different countries. Grid interconnections of existing HVDC lines are inherently complex for technical and technological reasons related to different voltage levels caused by a staggered grid design and ongoing technological evolution. It is necessary to introduce static converters to ensure interconnection. The operating principles of early HVDC DC/DC converter topologies are now well known but deeper analysis is still required to improve transient behaviour, and other promising topologies remain untapped. Moreover, no extensive work has been done on the integration and control of DC/DC converters in mesh DC grids, a key decisive factor for their wider deployment.

The emergence of Additive Manufacturing (AM) is disrupting design practices to respond to the increased developments of Industry 4.0. However, few designers have sufficient knowledge of AM to use it effectively (possibilities, constraints and limits). Thus, our research objective is the enrichment of the designer in the preliminary phase thanks to the integration of knowledge related to tolerancing by taking the example around the LPBF (Laser Powder Bed Fusion) process. Indeed, this knowledge is necessary to ensure the functionality of the manufactured parts. To do this, we propose to describe these entities using logical concepts (based on mereotopology) as a function of space and time. The AM process seems perfectly suited to this theory because of its layer-by-layer construction. The description will be associated with the skeletons and surfaces of the part or an assembly. It will then be used to analyse and check the consistency of the proposed design with the specifications. This verification will be done through an ontology in which rules will be added as well as a database corresponding to quantitative values associated with geometrical dispersions. The description and the ontology will also be integrated into a global design methodology making it possible to link the knowledge of the designer, the method expert (metrologist) and the manufacturer (AM expert). For example, this enables checking that the functional surfaces of the product comply with the tolerancing for a given specification and a chosen manufacturing orientation. Consequently, the HECATE project will enrich the preliminary design phase with GD&T knowledge related to a given additive manufacturing process.

Tablets are the most popular pharmaceutical dosage form. They are manufactured in the industry using a die compaction process and the compacted powders have typical grain size around 100µm. Tablets must fulfill a lot of requirements. Among them, the mechanical strength is of particular importance as it makes it possible to maintain the integrity of the tablet during all the post-compaction processes (coating, etc.) until its delivery to the patient. By adjusting the process parameters, e.g. the compaction force, it is possible to obtain tablets with different porosities. Moreover, the powders used to make tablets can have very distinct mechanical behaviors. As a consequence, by changing the kind of powder and the process parameters, it is possible to obtain tablets with different apparent mechanical properties. Moreover, a better understanding of why a tablet may break under a certain load, would also make it possible to foresee problems of capping/lamination that are among the most frequent problems encountered during the manufacture of tablets. They correspond to a sudden breakage of the tablet during its ejection from the die or during its post-compaction relaxation. Lamination corresponds to a breakage of the tablet in layers whereas capping corresponds to the separation of the top of the tablet. The aim of this project is the study of capping (or lamination) which is a well-known problem since more than a century but still remains not fully understood. Thanks to a global approach, the goal is to identify the causes and to understand their respective contribution to the phenomenon. For this, we develop an original approach both experimental and numerical based on material and fracture mechanics. For the moment, this approach has not been fully developed in the pharmaceutical field but it is the only one that can make it possible to have a fundamental understanding of the phenomenon. This understanding can only be obtained by studying the stresses applied to the tablet during the whole compaction cycle (especially during the unloading phase) and by defining a failure criterion suited to pharmaceutical tablets. These two aspects are necessary to be able to predict the breakage of the tablet as a function of the applied stresses. This project is separated into two parts that will be developed simultaneously. In the first part, we would like to work on the mechanical models that are used to describe the behavior of the tablet during FEM modelling. An improvement of these models is necessary to make it possible to obtain, in the FEM simulations, stress distributions quantitatively realistic. For this purpose, time dependent properties like viscoelasticity and viscoplasticity (that are not taken into account until now) must be characterized, modeled and implemented in a finite element method (FEM) code. Non-linear elasticity for high elastic deformations will also be studied. The other part of this project deals with the definition of a failure criterion for pharmaceutical tablets to be able to predict the failure under a certain load. Two approaches will be developed. The first one will be to define a failure criteria taking into account the stress distribution especially in the case of local stress concentrations. The second one will use the formalism of fracture mechanics in order to define a criteria based on fracture energy.

It is the goal and vision of this joint project between groups in Bordeaux and Siegen to mount a high-density array of probes, which themselves constitute multianalyte sensoric units (called: lab-on-molecule), at the 6000 nanotips of a multi-fiber optical bundle, thus enabling n-dimensional (bio)chemical analysis in spatially confined settings by electrochemiluminescence (ECL) and photoluminescence (PL). As ECL has become a powerful quantitative analytical technique for immunoassays, food/water testing and many individual analytes, the present endeavor seeks to establish a full analytical laboratory at the global tip of a 300 ?m optical waveguide with its 6000 individual fibers (lab-on-nanotips). The relevance of this project, in comparison to other endeavors, is thus to set up a full analytical laboratory, suited for all kind of invasive diagnostics in microenvironments, on the basis of the ?sensor array in a sensor array? concept: several distinct lab-on-molecules (array no. 1: using two-channel detection with ECL and PL) will be combined on 6000 nanotips (array no. 2). It is the ?sensor array in a sensor array? concept that will provide the required high resolution analytics. To accomplish this goal, the fiber optical nanotips (diameter: 3 µm; apex: 30 nm curvature radius) need to be addressed in an individually guided and spatially highly defined electropolymerization/functionalization process, such that each individual tip may be equipped with a distinct sensoric lab-on-molecule ECL system conductively connected to the electroactive surface by an electropolymeric backbone. In this respect, the concept additionally opens options for all kind of applications requiring the functionalization of individual fiber optical nanotips, while keeping intimate electric contact with the functional unit through the ITO cover and the electropolymer. In order to solve the above challenges new organic and technological tools need to be established that allow to implement the required multidimensional sensoric arrays at the 6000 individual tips of a multifiber optical system using electrochemiluminescence (ECL) and photoluminescence (PL) as the detection techniques. This venture will necessitate (1) the development of a hitherto unknown photoresponsive electropolymer that can be functionalized after photodeprotection, and (2) the development of an array of lab-on-molecules. So far only two lab-on-molecules are known in the literature. Furthermore, it will require important parallel technological developments, such as (3) the controlled electropolymerization at the conductive ITO-coated nanotips, and (4) the development of controlled single fiber light injection to allow for the well-directed functionalization with ECL sensoric units at each of the 6000 fiber tips. Clearly, the more individual ECL/PL sensors are mounted, the more it should be possible to analyze even utmost complex analyte mixtures in a quantitative manner, in particular after use of training methods based on probabilistic neural networks. The combination of a lab-on-nanotips with a spatially defined array of lab-on-molecules is without precedence and requires ? as enumerated above ? from both groups the development of complementary technologies mostly unsolved so far in the literature.

Enantiodiscrimination is one of the major challenges in contemporary chemistry. Chiral molecules exist in two non-superimposable mirror image forms, which induce different effects in biological systems. Thus, they need to be produced in a stereoselective way, especially for pharmaceutical use. The motivation and societal relevance of this project is based on the fact that if the wrong enantiomers are present in pharmaceuticals, their effects can be toxic or even lethal, as has been exemplified by the scandal around the use of racemic mixtures of thalidomide in the 1960ies. Subsequently, it became obvious, and strongly recommended by the FDA and European legislation, that medication should contain pure enantiomers. Therefore, there is a strong and constantly increasing need to develop advanced technologies that allow a selective production of enantiomers by new synthesis strategies. This challenge is at the heart of the AMEN project. We plan to follow an unconventional concept, developed during the ERC Advanced grant ELECTRA, in order to obtain single enantiomers instead of racemic mixtures. This is achieved by directing the transformation of molecules towards one of the two possible enantiomers with the help of autonomously moving chiral microreactors. The fundamental strategy has been already validated with proof-of-principle experiments during the ERC Advanced project and showed extremely high selectivity, efficiency, and controllability, however only at the laboratory scale. Therefore, we plan as a next logic step with technology transfer character, to investigate in detail the possibility of scaling up this process and to evaluate its commercial viability and competitivity.