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This paper proposes and demonstrates a novel microcalorimetric sensor for detecting Neisseria meningitidis. To eliminate additional heating structures and calibration steps, a split-flow microchannel is integrated into the microcalorimeter. The split-flow microchannel constantly maintains the output of the microcalorimeter near a zero level without the use of any heating elements when there is no biochemical reaction. With the use of the split-flow microchannel, an active heating element such as a heater is no longer required. In addition, to improve the sensitivity of the microcalorimeter, a thermal sensing component, which is a thermopile in this case, has been fabricated on a high thermal resistivity layer, which reduces the parasitic heat transfer to the silicon substrate and concentrates the released thermal energy to the thermopile. The characteristics of the proposed microcalorimeter were investigated by measuring the reaction heat of the biotin-streptavidin pairs. The sensitivity of the microcalorimeter was measured to be 0.21 V/cal. Then, a biological reaction between Neisseria meningitidis group B (NMGB) and its antibody was detected by using the proposed microcalorimeter. In order to verify the reliability of the measurement, exactly the same number of NMGB was reacted with its antibody and an optical density was measured by an enzyme-linked immunosorbent assay as a known reference.