In this paper we report a calorimetrie sensing system for the detection of clinically relevant biomolecules. The calorimetrie biosensor consists of a thin (∼20 μm) micromachined Y-cut quartz crystal resonator (QCR) placed in close proximity to a fluidic chamber packed with an immobilized enzyme in alginate beads. This configuration enables a detection mechanism physically separated from the solution of interest and is thereby free from fouling. The performance of this biosensor is demonstrated by detection of urea, creatinine and hydrogen peroxide in phosphate buffer via a flow injection analysis (FIA) technique. This work demonstrates a sensing modality in which the sensor itself is not fouled or contaminated by the solution of interest. Such a system enables reuse and reliability for long term sampling measurements. Further, the immobilized enzyme is easily discarded and replaced with a new reaction column. We envision a biosensing system which can perform rapid measurements to detect biomarkers such as glucose, creatinine, urea and lactate in urine and blood continuously over extended periods of time.