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Modeling the PARC nanocalorimeter using COMSOL

 

To enable measuring heats of biomolecular interactions in parallel using small sample volumes and short measurement times, we have been developing enthalpy arrays, which are arrays of nanocalorimeters. The technology provides a new tool for both biochemical screening in drug discovery and fundamental biochemical research. The measurements do not require labeling or immobilization of reactants, an attractive feature compared with surface-based methods such as Surface Plasmon Resonance and methods requiring fluorescent tagging. Today, isothermal titration calorimetry (ITC) on large samples (¡Ö1.5 mL) is used to characterize the thermodynamics of biomolecular interactions, but the level of use is hampered by the need for a large amount of material and long measurement times. The enthalpy array technology addresses this problem by enabling measurements with 250 nL drops that only take a few minutes. For assays in which sample size and measurement time are of primary importance, such as are used in drug discovery, enthalpy arrays are an attractive technology. We describe our use of COMSOL in designing and optimizing the nanocalorimeters. For each detector, heat is generated by a reaction and dissipates, the dissipation occurring by thermal conduction and evaporative heat transfer. The evaporative heat transfer depends on a vapor pressure that is itself dependent on temperature, further coupling the heat and mass transport. Each detector has both a sample region and a neighboring reference region to enable common mode rejection through a differential measurement, so the COMSOL simulation must accurately describe the coupling of these two regions. Furthermore, some of the elements of the detectors have a large aspect ratio (as large as 300:1), providing further challenges in the modeling. Using COMSOL, we successfully simulate our detectors and study their behavior, whereas earlier efforts using other modeling tools, such as ANSYS, failed. Of course, the outcome that matters the most is having detectors that work. Therefore, we conclude by showing hexokinase and trypsin enzymatic data that reveal substrate specificity and enzyme inhibition, demonstrating the capabilities and current sensitivity of the enthalpy array technology. In presenting this data, we discuss how we use COMSOL simulations in deconvoluting the reaction enthalpy, which is the property that a biochemist really wants, from the temperature data.

 
citation

Torres, F. ; Recht, M. I. ; Bell, A. G. ; de Bruyker, D.; Wolkin, M. V. ; Peeters, E. ; Anderson, G. B. ; Kuhn, P.; Bruce, R. H. Modeling the PARC nanocalorimeter using COMSOL. COMSOL Users Conference; 2006 October 26-27; Las Vegas; NV.