We have developed high-sensitivity microfluidic calorimeters and are applying them to biological studies.

Figure 1. Polymer-based microfluidic calorimeter chip. (a) Device mounted on a vacuum chuck. (b) The central active region of the chip. (c) The Parylene microfluidics, the thermopile and the heater on the parylene membrane. (d) Magnified view of the Parylene measurement chamber.

High-sensitivity microfluidic calorimeters [1 ~3] have raised the prospect of achieving high throughput biochemical measurements with minimal sample consumption. To achieve these ends we have developed chip-based microfluidic calorimeters capable of characterizing the heat of reaction of sub-nanoliter scale samples and of small organisms with sub-nanowatt resolution. Our approach [4], based on a combination of Poly-dimethylsiloxane (PDMS) and Parylene microfluidics provides both exceptional thermal response and the physical strength necessary to construct high-sensitivity calorimeters that are readily scalable to automated, highly-multiplexed array architectures. PDMS microfluidic valves and pumps are interfaced to Parylene channels and reaction chambers to automate the control of analyte handling and fluid flow and, thereby, the control of chemical reactions with sub-nanoliter resolution. We attain excellent thermal resolution via on-chip vacuum encapsulation, which provides unprecedented thermal isolation of the minute microfluidic reaction chambers.

The device structure can be easily adapted to enable a wide variety of standard calorimeter operations, such as ITC, DSC and flow calorimetry. We are currently focusing on applications of microfluidic calorimetry devices to studies of cellular and organismal metabolism.

Personnel
Dr. Warren Fon, Prof. Michael Roukes and collaborators in Prof. Paul Sternberg's group at Caltech.

References

1. Torres F.E., et al. (2004) Enthalpy array. Proc. Natl. Acad. Sci. USA 101: 9517–9522.
2. Xu J., Reiserer R., Tellinghuisen J., Wikswo J.P., Baudenbacher F.J. (2008) A microfabricated nanocalorimeter: design, characterization, and chemical calibration. Anal. chem. 80:2728-2733.
3. Wang L., Sipe D.M., Xu Y., Lin Q. (2008) A MEMS thermal biosensor for  metabolic monitoring applications. J. Microelectromech. Sys. 17:318-327.
4. Lee W., Fon W., Axelrod B.W., Roukes M.L. (2009) High-sensitivity microfluidic calorimeters for biological and chemical applications, Proc. Natl. Acad. Sci. USA 106 (36), 15225-30.