Isothermal titration calorimetry in a 3D-printed microdevice
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Isothermal titration calorimetry in a 3D-printed microdevice Yuan Jia 1,2 & Chao Su 2,3 & Maogang He 4 & Kun Liu 5 & Hao Sun 6 & Qiao Lin 2
# Springer Science+Business Media, LLC, part of Springer Nature 2019
Abstract Isothermal titration calorimetry (ITC) can benefit from operating in miniaturized devices as they enable quantitative, low-cost measurements with reduced analysis time and reagents consumption. However, most of the existing devices that offer ITC capabilities either do not yet allow proper control of reaction conditions or are limited by issues such as evaporation or surface adsorption caused inaccurate solution concentration information and unintended changes in biomolecular properties because of aggregation. In this paper, we present a microdevice that combines 3D-printed microfluidic structures with a polymer-based MEMS thermoelectric sensor to enable quantitative ITC measurements of biomolecular interactions. Benefitting from the geometric flexibility of 3D-printing, the microfluidic design features calorimetric chambers in a differential cantilever configuration that improves the thermal insulation and reduces the thermal mass of the implementing device. Also, 3D-printing microfluidic structures use non-permeable materials to avoid potential adsorption. Finally, the robustness of the polymeric MEMS sensor chip allows the device to be assembled reversibly and leak-free, and hence reusable. We demonstrate the utility of the device by quantitative ITC characterization of a biomolecular binding system, ribonuclease A (RNase A) bind with cytidine 2′-monophosphate (2’CMP) down to a practically useful sample concentration of 0.2 mM. The thermodynamic parameters of the binding system, including the stoichiometry, equilibrium binding constant, and enthalpy change are obtained and found to agree with values previously reported in the literature. Keywords 3D-printed microfluidic structures . Isothermal titration calorimeter . MEMS thermoelectric sensor . Polymer substrate
1 Introduction Three-dimensional (3D) printing can bring about potentially ground-breaking changes to the field of microfluidics. It has Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10544-019-0444-3) contains supplementary material, which is available to authorized users. * Qiao Lin [email protected] 1
School of Mechanical Engineering, Southeast University, Nanjing 211189, China
2
Department of Mechanical Engineering, Columbia University, New York, NY, USA
3
School of Mechanics, Civil Engineering and Architecture, Northwestern Polytechnical University, Xi’an, China
4
Key Laboratory of Thermo-Fluid Science and Engineering, Ministry of Education, Xi’an Jiaotong University, Xi’an, China
5
School of Mechanical Engineering and Automation, Northeastern University, Shenyang, China
6
School of Mechanical Engineering and Automation, Fuzhou University, Fuzhou 350116, China
the capability of fabricating a microfluidic device in a single step, thus enabling rapid, cost-efficient prototyp
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