Fabrication and characterization of thermocouple probe for use in intracellular thermometry

Measuring temperatures within a biological cell requires a sensor with small thermal mass and microscale or smaller size that is electrically and chemically inert to the cell's environment, and is thermally isolated from the surroundings. We investigate how such requirements can be satisfied in a microscale thermocouple probe that is fabricated using the techniques of silicon-based microelectromechanical systems. Previous reports of invasive probes lacked either the required spatial resolution (< 5 mu m) or response time (<4 ms). Here, we report 1 mu m thick silicon nitride supported probes with a 5 mu m tip that has a response time of 32 mu s. These figures enable future transient thermometry of cell organelles. To reduce calibration errors, we devise an on-chip calibration in a vacuum cryostat. We find that the accuracy of our measurements is +/- 54 mK for 300 +/- 10 K. This work paves the way toward future thermometry at a subcellular level. (C) 2018 Elsevier B.V. All rights reserved.