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. This application  addresses this, by proposing a novel approach based on the use of growth media resembling the infection site and/or isothermal microcalorimetry (IMC), a technique that measures the very small amounts of metabolic heat produced by low numbers of microorganisms. For clinical applications, IMC will be combined with the use of culture media resembling the in vivo microenvironment of prosthetic joint and urinary tract infections, in order to increase speed and sensitivity. For each type of infection, an optimal disease-specific 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. The use of IMC will also be evaluated for quality control of advanced therapy medicinal products (e.g. CAR T-cells), for which 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 will allow us to determine the optimal approach for IMC-based rapid sterility testing of these advanced pharmaceutical products.