Tuesday July 8, 14h
ISMO Amphitheater
Microfluidic devices to detect bacteria / SEPSIS by nanoluminescence
The World Health Organization (WHO) recently reported that Antimicrobial resistance (AMR) represents a growing threat to global public health and security’. At least 50000 annual deaths, across Europe and the US alone, are due to antimicrobial-resistant infections. New resistance mechanisms continue to emerge and spread, undermining the world’s ability to treat common infectious diseases. The need for new antimicrobial agents is essential. Surveillance to monitor the emergence and spread of drug resistance is another crucial component of the global strategy to combat AMR. Thus physicians need to propose the best therapy to patients through (i) identification of the presence or not of bacterial infection and if yes (ii) identification of the bacteria strains involved and their eventual antibiotic resistance profile. Consequently, development of novel rapid, low cost and reliable assays for Antimicrobial Susceptibility Testing (AST) has thus become an urgent priority. Up to now, the gold standard diagnosis methodology for severe infections is done by blood culturing requiring 2-5 days with a low sensitivity (30 to 50% with regard to clinical outcome). Alternative methods have been developed to reduce the amount of time and sample necessary for a reliable measurement by detecting the presence of whole cells by quantifying the oxygen levels or the presence of specific nucleic acid sequences. The use of microfluidic devices has been developing rapidly because of the low sample volumes required, the possibility for multiplexing and the increased growth rate of bacteria due to the high O2 availability. Yet, the detection of the resulting small number of cells remains a challenge since current methods are either expensive (impedance spectroscopy) or lack robustness and reproducibility (SPR). A first generation of bacteria-sensitive (but non-specific) nanoparticles has been developed and can rapidly detect (typically 2-6 h, depending on the initial concentration) low bacterial growth (<1000 CFU / ml) [Biosensors and Bioelectronics, 2016, 75, 320]. These nanoparticles are not only more sensitive than the molecular sensors currently in use, but also more sensitive and reliable than conventional optical density measurements. They allow continuous and real- time monitoring of bacterial growth over long periods of time and on small volumes and can thus be used for high throughput applications such as screening for the presence of antibiotic-resistant strains. Ratiometric particles for pH-sensing and bacteria growth detection are currently under development. New molecular probes and/or QDs selective for certain strains have to be developed and characterized (for instance by targeting peptides or carbohydrates from bacteria membranes). First-generation fluidic microdevices shall be designed. This thesis project focuses on the development of highly sensitive devices thanks to fluorescent molecular probes or nano-luminescent objects (organic or inorganic).