Nanocalorimetric sensor for ultra-low-volume biological measurements and calibration by chemical method

Abstract

Microcalorimetry is an established technique in the biological sciences for determining energy generation and consumption. With recent developments in microfabrication techniques, nanocalorimeters or even picocalorimeters are now possible. Measuring the biological thermal signal from cells is very difficult, however, due to both the cells’ low thermal activity level and the challenge of maintaining cell viability without undermining the sensitivity of the calorimeter. We have modified a commercial thermal sensor to acquire biological data. An integrative thermal shielding, evaporation prevention, and nanoliter sample-injection system was developed to deliver cells into the reaction chamber and preserve the sensitivity of the sensor. The modified nanocalorimeter has a power sensitivity of 7.6 nW/Hz1/2 and a temperature sensitivity of 136 ìK/Hz1/2. The heat production of the cardiomyocytes was measured when cells were stimulated with high K+ solution. The method may be useful for future development of high-speed parallel devices for drug screening or bioanalysis.