Frequent blood glucose monitoring is vital for effective diabetes management, given the global diabetic population surpassing half a billion (according to WHO). The traditional method of using finger pricks, involving painful blood drop extraction, raises infection risks and discourages regular monitoring, impacting overall care. Though implantable patch microneedles offer a promising alternative, they do not eliminate infection risks. Additionally, they measure glucose in interstitial fluid, not directly in the blood, which is the clinically relevant measure for effective diabetes management. Making life with diabetes easier is the goal of the GLUMON project. To detect glucose in the blood without blood extraction, we developed a novel biosensor called “Depth-gated mid-IR Optoacoustic Sensor” (DIROS). This biosensor uses a combination of mid-infrared light and optoacoustic technology to measure glucose levels in small blood vessels under the skin. By enabling measurements beyond 100 µm, DIROS can access the human microvasculature layers in the skin at the junction between the epidermis and dermis, typically located at depths of 20 to 80 µm. DIROS utilizes a smart algorithm to concentrate on specific tissue areas, disregarding signals from the outer skin layers. In mouse experiments, DIROS demonstrated heightened sensitivity in detecting glucose in blood-rich areas compared to the fluid around cells. During a glucose tolerance test, DIROS more accurately reflected changes in glucose levels than traditional methods. Notably, DIROS enhanced accuracy by mitigating the influence of factors such as humidity and lipids, common challenges for other glucose sensors. DIROS could transform how we measure glucose, offering accurate and sensitive detection directly in the blood, which is more precise than methods focusing on less specific fluids like interstitial fluid. This breakthrough holds transformative potential for the future of diabetes care, offering a more comfortable and convenient alternative to traditional methods. Transitioning from successful laboratory testing, the next crucial phase involves conducting clinical studies to validate its efficacy.