All-optical diamond heater-thermometer enables versatile and reliable thermal modulation of ion channels at the single-cell level.

A living cell is a nonequilibrium thermodynamic system where, nevertheless, a notion of local equilibrium exists. This notion applies to all micro- and nanoscale aqueous volumes, each containing a large number of molecules. This allows one to define sets of local conditions, including thermodynamic ones; for instance, a defined temperature requires thermodynamic equilibrium by definition. Once such a condition is fulfilled, one can control local variables and their gradients to theoretically describe the thermodynamic state of living systems at the micro- and nanoscale. Performing ultralocal experimental manipulations has become possible thanks to the patch-clamp technique, which controls the cell membrane potential, and fluorescence imaging, which monitors molecular concentrations and their intracellular gradients. However, precise temperature gradient control at the micro- and nanoscales has yet to be reliably realized in a living cell. Here, we present a new methodology-microscale control of a temperature gradient profile in aqueous media by a fully optical diamond heater-thermometer in a plug-and-play fiber configuration combined with the patch-clamp technique. In particular, we demonstrate applications of the combined diamond heater-thermometer-patch-clamp approach for fast, reproducible thermal modulation of ionic current from voltage-gated Na