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Millikelvin Intracellular Nanothermometry with Nanodiamonds.

Maabur Sow1, Jacky Mohnani2, Genko Genov1

  • 1Institute for Quantum Optics, Ulm University, D-89081, Ulm, Germany.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 29, 2025
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Summary

Nanothermometry using nanodiamonds in cells revealed that apparent temperature changes were electrical artifacts, not real heat diffusion. This study establishes a precise method for intracellular temperature measurement, finding no significant changes during metabolic stimulation.

Keywords:
diamondnanothermometrynitrogen‐vacancyquantum sensingthermodynamics of life

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Area of Science:

  • Physics and Biophysics
  • Cellular Biology
  • Nanotechnology

Background:

  • Nanothermometry in living cells is crucial for understanding heat diffusion dynamics.
  • Previous studies reported controversial temperature variations (up to several Kelvins) during cellular metabolic activity.
  • These reported variations contradicted heat diffusion laws at physiological heating rates.

Purpose of the Study:

  • To investigate intracellular temperature changes during metabolic stimulation using nanodiamond nanothermometry.
  • To address and correct for artifacts in nanothermometry measurements within living cells.
  • To establish a precise and reliable method for measuring intracellular temperatures.

Main Methods:

  • Utilized nanodiamonds with nitrogen-vacancy centers for optically detected magnetic resonance (ODMR) spectroscopy.
  • Measured ODMR spectra in macrophages during metabolic stimulation and post-mortem.
  • Developed optimized nanodiamonds and a robust sensing protocol to mitigate electrical field artifacts.

Main Results:

  • Identified electrical field changes on nanodiamond surfaces as a source of artifactual spectral shifts, misinterpreted as temperature changes.
  • Achieved high-precision temperature measurements down to 100 mK (intracellular) and 52 mK (extracellular).
  • Found no significant intracellular temperature changes upon metabolic stimulation in macrophages.

Conclusions:

  • Electrical field variations, not temperature changes, were responsible for previous controversial nanothermometry findings.
  • The developed nanodiamond nanothermometry protocol provides accurate intracellular temperature measurements.
  • Results align with the law of heat diffusion and expected physiological heating rates, resolving prior discrepancies.