Sub-nanowatt microfluidic single-cell calorimetry

Sahngki Hong, Edward Dechaumphai, Courtney R. Green, Ratneshwar Lal, Anne N. Murphy, Christian M. Metallo and Renkun Chen ()
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Sahngki Hong: University of California San Diego
Edward Dechaumphai: University of California San Diego
Courtney R. Green: University of California San Diego
Ratneshwar Lal: University of California San Diego
Anne N. Murphy: University of California San Diego
Christian M. Metallo: University of California San Diego
Renkun Chen: University of California San Diego

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Non-invasive and label-free calorimetry could become a disruptive technique to study single cell metabolic heat production without altering the cell behavior, but it is currently limited by insufficient sensitivity. Here, we demonstrate microfluidic single-cell calorimetry with 0.2-nW sensitivity, representing more than ten-fold enhancement over previous record, which is enabled by (i) a low-noise thermometry platform with ultralow long-term (10-h) temperature noise (80 μK) and (ii) a microfluidic channel-in-vacuum design allowing cell flow and nutrient delivery while maintaining a low thermal conductance of 2.5 μW K−1. Using Tetrahymena thermophila as an example, we demonstrate on-chip single-cell calorimetry measurement with metabolic heat rates ranging from 1 to 4 nW, which are found to correlate well with the cell size. Finally, we perform real-time monitoring of metabolic rate stimulation by introducing a mitochondrial uncoupling agent to the microchannel, enabling determination of the spare respiratory capacity of the cells.

Date: 2020
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DOI: 10.1038/s41467-020-16697-5

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