The suspension bridge structure for bio-thermal detection based on single thermocouple structure is proposed for the design of silicon-based micro-calorimeter. Due to the use of silicon-based electrodes and the suspended bridge structure by Micro-machining technology, the fabricated micro-calorimeter has a high bio-detection sensitivity, which allows monitoring the heat changes during enzyme reactions by massive enzymes fixed on the surface of micro-beads within the reaction chamber. With high thermal characterization accuracy, the micro-calorimeter can simultaneously achieve ultra-high accuracy of 0.38 V/W sensitivity and fast response time of under 200 ms. The micro-calorimeter shows great potential for health detection and thermal detection of biological reactions, providing potential opportunities and possibilities for countless applications of the sensor.