A High-Precision Micropipette Sensor for Cellular-Level Real-Time Thermal Characterization

We report herein development of a novel glass micropipette thermal sensor fabricated in a cost-effective manner, which is capable of measuring steady thermal fluctuation at spatial resolution of ∼2 μm with an accuracy of ±0.01 °C. We produced and tested various micrometer-sized sensors, ranging from 2 μm to 30 μm. The sensor comprises unleaded low-melting-point solder alloy (Sn-based) as a core metal inside a pulled borosilicate glass pipette and a thin film of nickel coating outside, creating a thermocouple junction at the tip. The sensor was calibrated using a thermally insulated calibration chamber, the temperature of which can be controlled with an accuracy of ±0.01 °C, and the thermoelectric power (Seebeck coefficient) of the sensor was recorded from 8.46 to 8.86 μV/°C. We have demonstrated the capability of measuring temperatures at a cellular level by inserting our temperature sensor into the membrane of a live retinal pigment epithelium cell subjected to a laser beam with a focal spot of 6 μm. We measured transient temperature profiles and the maximum temperatures were in the range of 38-55 ± 0.5 °C.