Closed ampoule isothermal microcalorimetry for continuous real-time detection and evaluation of cultured mammalian cell activity and responses.

Closed ampoule isothermal microcalorimetry (IMC) is a simple, powerful, nondestructive, and convenient technique that allows continuous, real-time detection and evaluation of cultured cell activity and responses. At a selected set temperature, IMC measures the heat flow between a sample and a heat sink and compares it to the heat-flow between a thermally inactive reference and the heat sink. Since heat flow rates are proportional to the rates of chemical reactions and changes of state, IMC provides a means for dynamically following these processes in any type of specimen - including ones containing cultured cells. The ability of IMC instruments to provide measurements in the microwatt (μJ/s) range allows one to detect and follow the activity (including replication) of low numbers of cells in culture (ca. 10(3)-10(5), depending on cell type). Closed ampoule IMC is increasingly being used in medical and environmental sciences. While a closed ampoule imposes limitations, it conversely provides simplicity and excellent control. Also, it is still usually possible with closed ampoules to follow mammalian cell activity and replication for several days. This chapter provides an overview of IMC measurement principles and provides examples of the use of IMC for evaluating cultured human and other mammalian cell activity and responses.