Personalized antibiotherapy: development and evaluation of a microfluidic biosensor platform for non-invasive, multianalyte on-site diagnostics

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Antibiotherapy achieves constantly increasing importance in human medicine. Herein, an individualized antibiotherapy, comprising the antibiotic dose and the dosing interval as well as the duration, plays a decisive role in the efficacy of the anti-infective therapy. However, due to the lack of the methods for bedside concentration monitoring, antibiotic dosages are, if at all, adapted only to the body weight of the patients. In this context, a major problem is the in-hospital development of multidrug resistance as a consequence of suboptimal antibiotic use.A non-invasive approach, enabling such diagnostics in non-invasively collected body fluids such as exhaled breath condensate (EBC), urine and saliva, would be highly desirable for a personalized antibiotherapy. In this respect, microfluidic lab-on-a-chip (LOC) platforms provide an acceleration of the specific and sensitive quantification of various analytes along with a low sample consumption, faster sample-to-result times and an easy integration of complex laboratory functions. Therefore, the goal of the proposed project is the implementation and pre-clinical evaluation of a microfluidic multiplexed biosensor platform for the non-invasive, on-site quantification of a panel of parameters, comprising various ß-lactam antibiotics, as well as renal and inflammation biomarkers, in order to allow a personalized antibiotherapy.In this project, various endogenous biomarkers including creatinine and cystatin C for renal function, and interleukin-6 and acute phase proteins (e.g., serum amyloid A, C-reactive protein and procalcitonin) for bacterial inflammation will be evaluated regarding their sensitivity and selectivity. Furthermore, in large animal experiments, investigating various antibiotic dosages, the quasi real-time surveillance of inflammation markers and antibiotic pharmacokinetics will be carried out in blood, tissue and non-invasively collected EBC samples. Hence, this project includes the realization of an EBC sampling device for rapid and non-invasive specimen collection.A successful implementation of the planned microfluidic LOC device in combination with a performant biomolecular sensing system could be a game-changer in the antibiotherapy. Since it would enable the (non-invasive) profiling of the inflammation progress and the antibiotic pharmacokinetics and thus, could pave the way for a personalized antibiotherapy. Furthermore, this could be a significant landmark on the global combat against the antibiotic resistance.