The continuous monitoring of the concentration of glucose provides an essential tool for the improved glycemic control for people with diabetes. Most of the present approaches of transcutaneous, continuous glucose monitors are based on chemical detection and require the insertion of reagents into the body. In contrast, we aim at the reagent-free monitoring of glucose by means of mid-infrared spectroscopy. A quantum cascade laser provides narrow band radiation at wavelengths around the absorption bands of glucose (≈ 10 μm). At the same time it yields sufficient energy to allow for a good signal-to-noise ratio in transmission measurements despite the strong background absorption of water. We investigated various concepts for the sensor head based on the light-guiding properties and handling of materials such as AgCl/AgBr or silicon. In-vitro experiments were performed using a custom-made, temperaturestabilized measurement flow chamber. In preparation for future in-vivo applications first results of biotoxicity tests of the fiber sensors are given.© (2010) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.