BCG detection based on a split-flow microcalorimetric biosensor for the diagnosis of tuberculosis

This paper proposes and demonstrates a novel microcalorimetric sensor for detecting BCG (Bacillus Calmette-Guerin). In order to eliminate additional heating structures and calibration steps, a split-flow microchannel is integrated with the microcalorimeter. The split-flow microchannel keeps the output of the microcalorimeter constantly near a zero level without any heating elements when there is no biochemical reaction. By using the split-flow microchannel, an active heating element such as a heater is no longer required. And, in order to improve the sensitivity of the microcalorimeter, a thermal sensing component, a thermopile in this case, has been fabricated on a high thermal resistivity layer, which reduces a parasitic heat transfer to the silicon substrate and makes released thermal energy concentrated to the thermopile. The characteristics of the proposed microcalorimeter were investigated by measuring the reaction heat of the biotin-streptavidin pairs. The sensitivity was measured to be 0.8 Whsec/cal. Then, a biological reaction between BCG and its antibody was detected using the proposed microcalorimeter. In order to verify the reliability of the measurement, exactly the same amount of BCG was reacted with its antibody, and the optical density was measured using an enzyme-linked immunosorbent assay as a known reference.