摘要
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 46µl 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/m^(3),corresponding to 0.021OD(2·10^(7) 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.
基金
This work is a part of and was partially funded by the ETHeart initiative of the Swiss Federal Institute of Technology(ETH Zurich).M.A.was supported as a part of NCCR Microbiomes,a National Centre of Competence in Research,funded by the Swiss National Science Foundation(grant number 180575).We would like to especially acknowledge the support of Prof.Dr.Volkmar Falk and Nikola Cesarovic for the project.We would also like to acknowledge Prof.Emma Wetter Slack of the Laboratory for Food Immunology in the Department of Health Sciences and Technologies at ETHZ for support and the use of equipment.We would also like to acknowledge Lavinia Recchioni for her help in the work on the lumped element model.Furthermore,we would like to acknowledge the help of Alyson Hockenberry for all of her support regarding the microfluidics.Lastly,we would like to acknowledge all of the support by the members of the Micro-and Nanosystems at ETH Zürich.
