The emergence of biological threats became a reality, when the world witnessed the Anthrax attacks in 2001. This subsequently led in October, 2001 to the implementation of the Biotox plan (completing the ORSEC plan) of venture management and crisis in the face of such situations. Biological hazards, like ionising radiation and many chemical hazards cannot be directly detected by human senses and therefore can go unnoticed. Moreover, similar to radioactivity and many chemical hazards, biological hazards rely on the notion of absorbed pathogen dose. Consequently, quickly understanding an individual’s exposure can make the difference between life or death as this knowledge is mandatory to define as earlier as possible the adapted medical countermeasures. Achieving this requires a continuous, local means of monitoring this exposure at individual level. Individual biological aerosol collectors integrated for example into clothing of those placed in harms way (i.e. first responders) could permit early discovery of airborne biohazards at the individual level. Periodic reading of these aerosol collectors can then provide evidence of biological incidents that would have been unnoticed or unexpected and lead to appropriate protective actions. To date, such a device does not exist and in this context, the development of a biological aerosol collector (small and lightweight design) with the appropriate level of performance represents a significant advance in individual protection. Its conception requires the combination of break-trough technologies and knowhow, which has lead to the choice of the different partners in the present consortium: system conception (Bertin Technologies), sample collection (ENSL), and integration into protective clothing (Paul Boyé). Specifically, this proposal is aimed at the development of electrostatic cyclone systems for improved sampling of airborne contaminates. The final objective of this industrially driven research project is to provide a small, portable and robust device that can be integrated into the suit of first responders’ so that biological aerosol exposure can be assessed during an intervention. The fundamental advantages of cyclone separation and electrostatic precipitation will be used to overcome the short-comings of present day technologies. Specific synergies sought include, increased intrinsic efficiency, higher treatment throughputs, improved pressure-drop profiles and improved energy consumption-effectiveness.

The aim of the project proposed by Bertin Technologies, CEA and ISL is to develop a system to assist in the detection, recognition and identification of threats in the visible and infrared domains. The algorithm developed during this project is intended to be embedded in optronic systems used in the battlefield. It will therefore be subject to material and energy frugality constraints. The proposed approach will rely on artificial intelligence solutions based on deep neural networks. This technology is very promising for detection, recognition and identification applications. However, it requires supervised learning with a lot of annotated data representative of the usecases, which is difficult to obtain for military applications, as well as a high computing power during use. ISL, CEA and Bertin Technologies will bring their expertise to bear in data acquisition, AI training and optimisation, hardware integration and optronics to overcome the three technical hurdles of learning from a frugal dataset, joint exploitation of visible and infrared data, and frugality in computing power. A demonstration model based on Bertin Technologies' existing optronic solutions will be produced in order to validate the solution developed. This project is in line with French and European strategies to pursue research efforts in the field of AI, which has major economic and strategic implications. From a military point of view, it addresses strong tactical and operational challenges, in particular for surveillance, reconnaissance, identification and intelligence gathering applications. Embedded in optronic systems, artificial intelligence can facilitate the processing of information transmitted by sensors, limit the risks of human error, facilitate rapid decision-making and optimize the consumption of sensor batteries. Threat detection, recognition and identification functions are also of interest in civilian areas, particularly in the surveillance of sensitive areas (ports, borders) or industrial sites, as well as self driving cars.

“Sudden death” or out-of hospital cardiac arrest is a major public health issue. Only a few patients can be resuscitated and further survive, often with severe neurological sequels and a high socioeconomic cost. Implementation of a moderate therapeutic hypothermia (i.e., 32°C) is known to improve the survival and neurological recovery of those patients. However, this benefit primarily depends upon the rapidity to achieve the target temperature following cardiac arrest. Currently, most of the strategies used in critical care units provide a rather slow cooling rate (~-2°/h). Therefore, the need to dispose of specific devices inducing faster cooling rates is widely admitted. In previous preclinical studies, INSERM U955-3 (partner of this project) investigated an original strategy to induce such an ultra-fast cooling through total liquid ventilation (TLV) with temperature-controlled perfluorocarbons (PFC) since these liquids can use the lungs as a heat exchanger while maintaining normal gas exchanges. Using experimental devices, this laboratory has established the solid proof of concept that hypothermic TLV can dramatically improves cardiac and neurological outcomes following focal myocardial ischemia and cardiac arrest in rabbits (pending US patent application). This demonstration also confirmed the innocuity of PFC. The next mandatory step for a translation of hypothermic TLV in humans is to further investigate this approach in large animals. It accordingly requires a TLV device with two major features: (1) to be adapted for large animals (~80 kg) and (2) to accurately match both inspiratory and expiratory volumes to prevent volo/barotraumatism, while monitoring/controlling the corresponding pressure levels, flows and PFC temperature. Such a device does not exist on the market, and the experimental devices previously used cannot be modified to achieve the requested features. Accordingly, the main goal of this project is to develop and validate such a TLV prototype in large animals. It will be designed to work with PFC already used in human therapeutic. The development and validation of this TLV prototype will be permitted through a Consortium of four partners including an industrial company dedicated to technological innovations (BERTIN TECHNOLOGIES) and three academic laboratories specialized in the pre-clinical investigation of liquid ventilation (INSERM U955-3), in lung biomechanics (INSERM U955-13) and in lung imaging (CNRS UMR8081), respectively. The Consortium will be supervised by an Advisory Committee involving representatives from the medical community (expert clinicians), from “INSERM Transfert” and from the “ITMO Technologies pour la Santé” (AVIESAN). Depending upon the functional needs addressed by this Advisory Committee, the Consortium will produce a TLV prototype with a supervisor using an algorithm permitting to optimize lung filling/emptying as well as PFC-blood thermal exchanges. This algorithm will be constructed on the basis of a mathematical and physical modelization of PFC flows and thermal transfer thoroughly validated by fluorine imaging (MRI) of lungs filled with PFC. A first prototype will be adjusted to fit the size of small laboratory animals (3 kg), in order to validate the overall design, processes and safety/efficiency in rabbits. Then a second prototype will be dedicated and tested in a large animal model (pig) to further demonstrate its safety, efficiency and ability to induce faster cooling rates than other hypothermic strategies. This should provide the first proof of concept of the feasibility of hypothermic TLV in human-sized animals. In the ultimate phase of the project, the Advisory Committee will allow to determine the expectations regarding a TLV device for pre-hospital ultra-fast cooling in human adults, and will make a synthesis step to determine the final inputs and regulatory experiments required to obtain a medical approval. The total duration of the project is 36 months.

The frame of the STREAM project is focused on the most achieved field of cell therapy: Hematopoietic Stem Cells (HSC) Transplantation for bone marrow reconstitution in patients with malignant hemopathies (acute leukemias, lymphomas, myelomas) and other types of cancers. This project intends to bring an innovative, efficient and less expensive method for improvement of graft products preparation. The targeted step is the selection of HSC and progenitors from heterogeneous cell population sources: (i) in vivo : peripheral blood mobilized with G-CSF or not, bone marrow or Umbilical Cord Blood (UCB), (ii) ex vivo : after various expansion processes. Today, clinical grade selection can only be achieved using Magnetic Assisted Cell Sorting (MACS). The STREAM proposal aims to overcome the limitations of this technology and to improve the cell selection – yield, purity, accessibility and cost – by: 1) Developing an alternative principle: the differential retention of cells in controlled flow on optimized surfaces. Selectivity will be obtained trough biological ligands (antibodies, lectines…) and/or differential mechanical properties; 2) Automating the process with an appropriate device and consumable to ensure potential clinical grade and reproducibility; 3) Optimizing the quality of the purified cell product – cell viability, purity, functionality – as a main objective. The selected cells will undergo several in vitro (phenotyping, functionnal assays) as well as in vivo (using the NOD/SCID mouse model) quality control tests. The efficacy of the cell selection process will also be tested on in vitro expanded cells, which, if demonstrated, would highly facilitate their subsequent clinical use. Such a goal can only be achieved through the multidisciplinary skills of the STREAM consortium. Each of the three axis mentioned above relies on the expertise of particular members of the consortium, respectively composed of: 1) Physicists, with expertise in physical chemistry of cell adhesion: the UMR 7195 PECSA/ Laboratoire des Colloïdes et Matériaux Divisés (LCMD) , 2) Specialists in biotech process automation: Bertin Technologies; 3) Stem cell & Cell therapy specialists: the UMR_S 938 Proliferation and differentiation of stem cells-Application to Cell Therapy & the private non-profit research institute IRHT, which also represents the end-user of the developed process. The members of the consortium have already worked together on several R&D projects, one of them leading to a mature product commercialized by Bertin (KIM analyzer). This positive collaborative background will ensure maximal synergy during the STREAM project. The STREAM project aims at setting the basis for a new technology that could be launched by the industrial partner of the consortium.