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Natural sciences
- Infectious diseases
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Medical and health sciences
- Clinical microbiology
- Bacteriology
- Pharmaceutical analysis and quality assurance not elsewhere classified
- Microbial diagnostics
Rapid and accurate detection of microorganisms is of utmost importance in clinical and pharmaceutical microbiology. However, current methods often lack speed and/or the ability to detect low numbers of organisms. My project addresses this, by proposing a novel approach based on isothermal microcalorimetry (IMC), a technique that measures the very small amounts of metabolic heat produced by low numbers of microorganisms. In the clinical context, I have chosen urinary tract infections, where IMC will be combined with the use of culture media resembling the in vivo microenvironment in order to increase sensitivity. An optimal synthetic urine medium will be selected and validated, and subsequently used in combination with IMC. The information obtained from the resulting thermograms will allow to detect, quantify and potentially even identify microorganisms considerably faster than with current methods. To provide a complete workflow, the antimicrobial susceptibility of the organism will then be assessed with IMC. For the pharmaceutical part, the use of IMC will be evaluated for quality control of advanced therapy medicinal products (ATMP) (e.g. CAR T-cells), where rapid sterility testing is essential for fast batch release. The high amount of T-cells in these drugs will be mimicked using Jurkat cell suspensions, that will be spiked with dilution series of relevant microorganisms. This way, I will determine the optimal approach for IMC-based rapid sterility testing of these ATMP.