Thermoelectric Nanofluidics Probing Thermal Heterogeneity inside Single Cells

Area of Science:

• Biophysics
• Cell Biology
• Nanotechnology

Background:

• Accurate intracellular temperature measurement is crucial for understanding cellular functions and regulation.
• Existing methods lack the required sensitivity and spatiotemporal resolution for real-time single-cell analysis.

Purpose of the Study:

• To develop a novel nanopipet electric thermometer (NET) for precise, real-time intracellular temperature monitoring.
• To investigate thermal dynamics within single cells, including responses to stimuli and during immunotherapy.

Main Methods:

• Development of a nanopipet electric thermometer (NET) based on temperature-controlled ion migration and thermoelectric responses.
• Utilizing a galvanostatic configuration for sensitive voltage measurements.
• Achieving high spatiotemporal resolution (100 nm, 0.9 ms) and thermal resolution (25 mK).

Main Results:

• The NET demonstrated highly sensitive thermoelectric responses (up to 11.1 mV K⁻¹), significantly exceeding previous methods.
• Successfully monitored thermal fluctuations in steady-state cells and heat changes upon drug administration.
• First report of thermal heterogeneities in single cancer cells during immunotherapy, correlating increased temperature with survival and resistance.

Conclusions:

• The NET provides a reliable and highly sensitive method for microscopic temperature monitoring.
• Revealed critical insights into cancer cell thermal behavior during immunotherapy, potentially explaining immune evasion and therapeutic resistance mechanisms.