Sepsis, an extreme and deregulated immune response to an infection that then spreads through the bloodstream, can lead to organ dysfunction and death (11 million deaths worldwide every year). The patented GMR (Giant MagnetoResistance) sensor-based biochip we have developed has real potential for the early detection of pathogens involved in sepsis or biomarkers of the disease, present in very small quantities in the blood, without the need for a culture step. The innovative approach we are proposing is cross-disciplinary, since it is based on the use of magnetic nanoparticles (NPM), functionalized by monoclonal antibodies produced in the LERI laboratory, directed against target biological objects (cells, bacteria, yeasts, etc.) which are detected dynamically and simultaneously one by one by GMR sensors arranged on either side of a microfluidic channel in which they flow. Proof of concept for this biochip was obtained on a murine myeloma cell model.We were able to achieve a sensitivity and specificity with this model that makes our technique highly competitive with existing Point-of-Care tests. However, we still need to validate these results on pathogens.

During the course of the thesis, two objectives will be defined. Following on from the current thesis, the first objective of the student at the LNO will be to adapt the biochip (sensors, microfluidics and signal processing) so that it is sensitive and rapid for the detection of bacteria and yeasts involved in sepsis in blood samples. At LERI, he will optimize the magnetic labeling of bacteria and yeasts in this clinical matrix using commercial NPM functionalized with one or more antibodies directed against the target. This stage of the thesis will be carried out in close collaboration with the Service de Bactériologie et Hygiène at Hôpital Béclère (also a member of the IHU), which will recommend and supply relevant bacterial and yeast strains for detection, as well as clinical samples.One of the GMR biochips will be installed at Hôpital Béclère for measurements under real-life conditions. The second objective will be to use the GMR biochip to quantify the reduction in monocyte expression of mHLA-DR molecules, which is an indicator of the immunosuppressed state of sepsis associated with increased infectious risk and mortality.