Quantum sensing FOR Early SEpsis dEtection

Objective

Affecting 50 million people globally per year, sepsis is a leading cause of death in Europe. There is an urgent need for early diagnosis of sepsis to enable the timely start of treatment. However, early symptoms are difficult to diagnose, may be non-specific and vary per individual. One of the earliest responses in sepsis is production of free radicals by neutrophils and monocytes which precedes by hours or even days production of cytokines and other inflammatory markers currently used in clinical diagnosis of sepsis. Our preliminary data suggest that sepsis diagnosis can be improved by measuring the production of free radicals by circulating neutrophils and monocytes. However, free radicals are difficult to detect because of their high reactivity and low concentration. The detection challenge has recently been overcome with the use of diamond-based quantum sensing. This method relies on a fluorescent defect in a nanodiamond, the NV center, which changes its optical properties according to the magnetic surroundings. This purely optical technique enables measurement of free radicals at nanoscale resolution. The proposed research will establish when and where free radicals are generated in neutrophils and monocytes, identify those few radicals that play a role in sepsis and thus provide a proof of principle for diagnosing sepsis. Our findings will be compared and benchmarked with standard diagnostic tools. Further, a new fiber-based instrument will be developed that can read out the nanodiamond sensor via an optical fiber, which could be attached to an intravenous line. This instrument will enable online monitoring of free radical generation during sepsis in vivo. The new instrument will be applied in a mouse model in which sepsis is induced to determine when and where free radicals are generated. As well as providing these fundamental insights, this instrument could be further developed for use in monitoring sepsis development in patients in intensive care.