A novel microfluidic chip integrated with Pt micro-thermometer for temperature measurement at the single-cell level

Noninvasive and sensitive thermometry of a single cell during the normal physiological process is crucial for analyzing fundamental cellular metabolism and applications to cancer treatment. However, current thermometers generally sense the average temperature variation for many cells, thereby failing to obtain real-time and continuous data of an individual cell. In this study, we employed platinum (Pt) electrodes to construct an integrated microfluidic chip as a single-cell thermometer. The single-cell isolation unit in the microchip consisted of a main channel, which was connected to the inlet and outlet of a single-cell capture funnel. A single cell can be trapped in the funnel and the remaining cells can bypass and flow along the main channel to the outlet. The best capture ratio of a single MCF7 cell at a single-cell isolation unit was 90 % under optimal condition. The thermometer in the micro-chip had a temperature resolution of 0.007 °C and showed a good linear relationship in the range of 20-40 °C (R² = 0.9999). Slight temperature increment of different single tumor cell (MCF7 cell, H1975 cell, and HepG2 cell) cultured on the chip was continuously recorded under normal physiological condition. In addition, the temperature variation of single MCF7 cell in-situ after exposure to a stimulus (4 % paraformaldehyde treatment) was also monitored, showing an amplitude of temperature fluctuations gradually decreased over time. Taken together, this integrated microchip is a practical tool for detecting the change in the temperature of a single cell in real-time, thereby offering valuable information for the drug screening, diagnosis, and treatment of cancer.