A high-precision thermometry microfluidic chip for real-time monitoring of the physiological process of live tumour cells.

ABSTRACT

Temperature changes in cells are generally accompanied by physiological processes. Cellular temperature measurements can provide important information to fully understand cellular mechanisms. However, temperature measurements with conventional methods, such as fluorescent polymeric thermometers and thermocouples, have limitations of low sensitivity or cell state disturbance. We developed a microfluidic chip integrating a high-precision platinum (Pt) thermo-sensor that can culture cells and monitor the cellular temperature in situ. During detection, a constant temperature system with a stability of 0.015 °C was applied. The temperature coefficient of resistance of the Pt thermo-sensor was 2090 ppm/°C, giving a temperature resolution of the sensor of less than 0.008 °C. This microchip showed a good linear correlation between the temperature and resistance of the Pt sensor at 20-40 °C (R2 = 0.999). Lung and liver cancer cells on the microchip grew normally and continuously. The maximum temperature fluctuation of H1975 (0.924 °C) was larger than that of HepG2 (0.250 °C). However, the temperature of adherent HepG2 cells changed over time, showing susceptibility to the environment most of the time compared to H1975. Moreover, the temperature increment of non-cancerous cells, such as hepatic stellate cells, was monitored in response to the stimulus of paraformaldehyde, showing the process of cell death. Therefore, this thermometric microchip integrated with cell culture could be a non-disposable and label-free tool for monitoring cellular temperature applied to the study of physiology and pathology.