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Isothermal titration calorimetry in a 3D-printed microdevice

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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.

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Acknowledgments

This work was jointly supported by the Natural Science Foundation of Jiangsu Province (Grant No. BK20180384); the National Natural Science Foundation of China (Grant No. 61604042); Fundamental Research for the Central Universities of China (Grant No. N160302001); the Natural Science Foundation of Fujian Province (Grant No. 2017 J01501).

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Authors and Affiliations

  1. School of Mechanical Engineering, Southeast University, Nanjing, 211189, China

    Yuan Jia

  2. Department of Mechanical Engineering, Columbia University, New York, NY, USA

    Yuan Jia, Chao Su & Qiao Lin

  3. School of Mechanics, Civil Engineering and Architecture, Northwestern Polytechnical University, Xi’an, China

    Chao Su

  4. Key Laboratory of Thermo-Fluid Science and Engineering, Ministry of Education, Xi’an Jiaotong University, Xi’an, China

    Maogang He

  5. School of Mechanical Engineering and Automation, Northeastern University, Shenyang, China

    Kun Liu

  6. School of Mechanical Engineering and Automation, Fuzhou University, Fuzhou, 350116, China

    Hao Sun

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  1. Yuan Jia
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  2. Chao Su
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  3. Maogang He
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  4. Kun Liu
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Correspondence to Qiao Lin.

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Jia, Y., Su, C., He, M. et al. Isothermal titration calorimetry in a 3D-printed microdevice. Biomed Microdevices 21, 96 (2019). https://doi.org/10.1007/s10544-019-0444-3

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