Sub-nanowatt microfluidic single-cell calorimetry

Sahngki Hong; Edward Dechaumphai; Courtney R Green; Ratneshwar Lal; Anne N Murphy; Christian M Metallo; Renkun Chen

doi:10.1038/s41467-020-16697-5

Sub-nanowatt microfluidic single-cell calorimetry

Nat Commun. 2020 Jun 12;11(1):2982. doi: 10.1038/s41467-020-16697-5.

Authors

Sahngki Hong^{1

2}, Edward Dechaumphai^#², Courtney R Green^#³, Ratneshwar Lal^{1

2

3}, Anne N Murphy⁴, Christian M Metallo³, Renkun Chen^{5

6}

Affiliations

¹ Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, 92093, USA.
² Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA, 92093, USA.
³ Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA.
⁴ Department of Pharmacology, University of California San Diego, La Jolla, CA, 92093, USA.
⁵ Materials Science and Engineering Program, University of California San Diego, La Jolla, CA, 92093, USA. rkchen@ucsd.edu.
⁶ Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA, 92093, USA. rkchen@ucsd.edu.

^# Contributed equally.

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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Basal Metabolism
Calorimetry / instrumentation
Calorimetry / methods*
Microfluidic Analytical Techniques / methods*
Microfluidics / instrumentation
Microfluidics / methods*
Mitochondria / metabolism
Oxygen Consumption
Single-Cell Analysis / instrumentation
Single-Cell Analysis / methods*
Temperature*
Tetrahymena thermophila / cytology
Tetrahymena thermophila / metabolism*
Thermal Conductivity