Enabling direct microcalorimetric measurement of metabolic activity and exothermic reactions onto microfluidic platforms via heat flux sensor integration

Signe L K Vehusheia; Cosmin Roman; Olivier Braissant; Markus Arnoldini; Christofer Hierold

doi:10.1038/s41378-023-00525-z

Enabling direct microcalorimetric measurement of metabolic activity and exothermic reactions onto microfluidic platforms via heat flux sensor integration

Microsyst Nanoeng. 2023 May 9:9:56. doi: 10.1038/s41378-023-00525-z. eCollection 2023.

Authors

Signe L K Vehusheia¹, Cosmin Roman¹, Olivier Braissant², Markus Arnoldini³, Christofer Hierold¹

Affiliations

¹ Tannenstrasse 3, 8092 Zurich, Switzerland Micro and Nanosystems, Department of Mechanical and Process Engineering, ETH Zurich.
² Hegenheimermattweg 167C, 4123 Allschwil, Switzerland Center of Biomechanics and Biocalorimetry, Department of Biomedical Engineering, University of Basel.
³ Otto-Stern-Weg 3, 8093 Zurich, Switzerland Laboratory for Food Immunology, Department of Health Sciences and Technology, ETH Zurich.

Abstract

All biological processes use or produce heat. Traditional microcalorimeters have been utilized to study the metabolic heat output of living organisms and heat production of exothermic chemical processes. Current advances in microfabrication have made possible the miniaturization of commercial microcalorimeters, resulting in a few studies on the metabolic activity of cells at the microscale in microfluidic chips. Here we present a new, versatile, and robust microcalorimetric differential design based on the integration of heat flux sensors on top of microfluidic channels. We show the design, modeling, calibration, and experimental verification of this system by utilizing Escherichia coli growth and the exothermic base catalyzed hydrolysis of methyl paraben as use cases. The system consists of a Polydimethylsiloxane based flow-through microfluidic chip with two 46 µl chambers and two integrated heat flux sensors. The differential compensation of thermal power measurements allows for the measurement of bacterial growth with a limit of detection of 1707 W/m³, corresponding to 0.021OD (2 ∙ 10⁷ bacteria). We also extracted the thermal power of a single Escherichia coli of between 1.3 and 4.5 pW, comparable to values measured by industrial microcalorimeters. Our system opens the possibility for expanding already existing microfluidic systems, such as drug testing lab-on-chip platforms, with measurements of metabolic changes of cell populations in form of heat output, without modifying the analyte and minimal interference with the microfluidic channel itself.

Keywords: Biosensors; Microfluidics; Sensors.