Isothermal titration calorimetry in a polymeric microdevice

Abstract

Microelectromechanical systems (MEMS) technology can enable the integration of isothermal titration calorimetry (ITC) on a single chip for direct thermodynamic characterization. However, existing ITC microdevices either do not yet allow proper control of reaction conditions for thermodynamic characterization of biomolecular reaction systems or do not yet suitable for practical applications because of a lack of reliability, high costs, and other issues. This paper aims to address these limitations with polymeric MEMS-based quantitative ITC measurements. The polymer-based ITC device design eliminates the use of silicon and exploits the low thermal conductivity of the polymer substrate to achieve thermal isolation of reaction samples in the absence of any complex or fragile freestanding structures. The low-cost availability of polymers and the elimination of the freestanding structures simplify the fabrication process, increase the fabrication yield, reduce the device cost, and improve the device reliability. During the ITC device operation, reactants and reference solutions are introduced to their respective measurement chambers, and the reaction-induced differential thermal power is measured and used to compute the thermodynamic binding parameters associated with the reaction. The potential utility of the device has been demonstrated with quantitative ITC measurements of a model reaction system in which the ligand BaCl₂ is titrated into the receptor 18-C-6 at a concentration of 2 mM.