A pico calorimeter with a highly sensitive sensor for detecting heat from a biological cell is developed and evaluated, and also the heat detection of a single brown fat cell has been demonstrated. The measurement principle relies on resonant frequency tracking of a resonator in temperature variation due to the heat from the sample; the resonator is placed in vacuum, and heat is conducted from the sample in the microfluidic channel via a heat guide. This configuration can prevent heat loss from the resonator to the surroundings and damping in water. The heat resolution of the fabricated sensor is 5.2 pJ. Heat emissions from single cells are detected as pulsed or continuous in the absence and presence of stimulation, respectively.