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Design and optimization of a chip calorimeter for cell metabolism detection

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Abstract

Basal heat production is an important feature of cell metabolic activity detection. The chip calorimeter can monitor cell metabolism by non-invasively detecting changes in cell temperature. In this paper, we developed a numerical model of an open type calorimeter based on a thin film thermopile for cell and microbial metabolism detection applications. We optimized the system through finite element analysis and design rules to determine the key performance of the calorimeter, such as sensitivity, time constant, power resolution, and signal-to-noise ratio (SNR) depending on the sample size (50 nL–1 μL). For example, ideally, when the sample volume is 200 nL, the specific volume thermal power detection limit of 1.264 mW/L is achieved. This is a prerequisite for a promising application of microorganisms or cells. In addition, due to the mutual constraints between various aspects of calorimeter performance, the simulation results of our calorimeter model can be used to guide the design and optimization of the calorimeter.

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References

  • Chancellor EB, Wikswo JP, Baudenbacher F, Radparvar M, Osterman D (2004) Heat conduction calorimeter for massively parallel high throughput measurements with picoliter sample volumes. Appl Phys Lett 85(12):2408–2410

    Article  Google Scholar 

  • Cooke DW, Michel KJ, Hellman F (2008) Thermodynamic measurements of submilligram bulk samples using a membrane-based “calorimeter on a chip”. Rev Sci Instruments 79(5):053902

    Article  Google Scholar 

  • Falconer RJ, Penkova A, Jelesarov I, Collins BM (2010) Survey of the year 2008: applications of isothermal titration calorimetry. J Mol Recognit 23(5):395–413

    Article  Google Scholar 

  • Garden J-L, Richard J (2007) Entropy production in ac-calorimetry. Thermochim Acta 461:57–66

    Article  Google Scholar 

  • Hansen LD, Fellingham GW, Russell DJ (2011) Simultaneous determination of equilibrium constants and enthalpy changes by titration calorimetry: methods, instruments, and uncertainties. Anal Biochem 409(2):220–229

    Article  Google Scholar 

  • Hartmann T, Barros N, Wolf A, Siewert C, Volpe PLO, Schemberg J, Lerchner J (2014) Thermopile chip based calorimeter for the study of aggregated biological samples in segmented flow. Sensors and Actuators B 201:460–468

    Article  Google Scholar 

  • Higuera-Guisset J, Rodríguez-Viejo J, Chacón M, Muñoz FJ, Vigués N, Mas J (2005) Calorimetry of microbial growth using a thermopile based microreactor. Thermochim Acta 427(1–2):187–191

    Article  Google Scholar 

  • Johannessen EA, Weaver JMR, Bourova L, Svoboda P, Cobbold PH, Cooper JM (2002) Micromachined nanocalorimetric sensor for ultra-low-volume cell-based assays. Anal Chem 74(9):2190–2197

    Article  Google Scholar 

  • Krenger R, Lehnert T, Gijs MAM (2018) Dynamic microfluidic nanocalorimetry system for measuring Caenorhabditis elegans metabolic heat. Lab Chip 18(11):1641–1651

    Article  Google Scholar 

  • Lee W, Fon W, Axelrod BW, Roukes ML (2009) High-sensitivity microfluidic calorimeters for biological and chemical applications. Proc Natl Acad Sci 106(36):15225–15230

    Article  Google Scholar 

  • Lee, W., Lee, & Koh (2012) Development and applications of chip calorimeters as novel biosensors. Nanobiosensors in Disease Diagnosis 17.

  • Lerchner J, Wolf A, Wolf G, Fernandez I (2006) Chip calorimeters for the investigation of liquid phase reactions: design rules. Thermochim Acta 446(1–2):168–175

    Article  Google Scholar 

  • Lerchner J, Maskow T, Wolf G (2008a) Chip calorimetry and its use for biochemical and cell biological investigations. Chem Eng Process 47(6):991–999

    Article  Google Scholar 

  • Lerchner J, Wolf A, Buchholz F, Mertens F, Neu TR, Harms H, Maskow T (2008b) Miniaturized calorimetry—a new method for real-time biofilm activity analysis. J Microbiol Methods 74:74–81

    Article  Google Scholar 

  • Lerchner J, Wolf A, Schneider H-J, Mertens F, Kessler E, Baier V, Krügel M (2008c) Nano-calorimetry of small-sized biological samples. Thermochim Acta 477(1–2):48–53

    Article  Google Scholar 

  • Lerchner J, Volpe POL, Lanaro C, Fertrin KY, Costa FF, Albuquerque DM, Mertens F (2018) A chip calorimetry-based method for the real-time investigation of metabolic activity changes in human erythrocytes caused by cell sickling. J Therm Anal Calorim 136(2):771–781

    Article  Google Scholar 

  • Lerchner J, Sartori MR, Volpe POL, Lander N, Mertens F, Vercesi AE (2019) Direct determination of anaerobe contributions to the energy metabolism of Trypanosoma cruzi by chip calorimetry. Anal Bioanal Chem 411:3763–3768

    Article  Google Scholar 

  • Lubbers B, Baudenbacher F (2011) Isothermal titration calorimetry in nanoliter droplets with subsecond time constants. Anal Chem 83(20):7955–7961

    Article  Google Scholar 

  • Lubbers B, Kazura E, Dawson E, Mernaugh R, Baudenbacher F (2019) Microfabricated calorimeters for thermometric enzyme linked immunosorbent assay in one-Nanoliter droplets. Biomedical Microdevices 21(4).

  • Maskow T, Lerchner J, Peitzsch M, Harms H, Wolf G (2006) Chip calorimetry for the monitoring of whole cell biotransformation. J Biotechnol 122(4):431–442

    Article  Google Scholar 

  • Maskow T, Schubert T, Wolf A, Buchholz F, Regestein L, Buechs J, Lerchner J (2011) Potentials and limitations of miniaturized calorimeters for bioprocess monitoring. Appl Microbiol Biotechnol 92(1):55–66

    Article  Google Scholar 

  • Mekonen Buzuayene (2008) Rise Time vs. Bandwidth and applications, interference technology

  • Torra V, Auguet C, Lerchner J, Marinelli P, Tachoire H (2001) Identification of micro-scale calorimetric devices I Establishing the experimental rules for accurate measurements. J Therm Anal Calorim 66(1):255–264

    Article  Google Scholar 

  • Torres FE, Kuhn P, de Bruyker D, Bell AG, Wolkin MV, Peeters E, Williamson JR, Anderson GB, Schmitz GP, Recht MI, Schweizer S, Scott LG, Ho JH, Elrod SA, Schultz PG, Lerner RA, Bruce RH (2004) Enthalpy arrays. Proc Natl Acad Sci USA 101(26):9517–9522

    Article  Google Scholar 

  • Verhaegen K, Simaels J, Driessche WV et al (1999) A Biomedical Microphysiometer Biomed. Microdevices 2:2

    Article  Google Scholar 

  • Wadsö I (1986) Bio-calorimetry. Trends Biotechnol 4:45–51

    Article  Google Scholar 

  • Wang S, Yu S, Siedler MS, Ihnat PM, Filoti DI, Lu M, Zuo L (2016) Micro-differential scanning calorimeter for liquid biological samples. Rev Sci Instrum 87(10):105005

    Article  Google Scholar 

  • Wang S, Yu S, Siedler M, Ihnat PM, Filoti DI, Lu M, Zuo L (2018) A power compensated differential scanning calorimeter for protein stability characterization. Sens Actuat 256:946–952

    Article  Google Scholar 

  • Wang S, Sha X, Yu S, Zhao Y (2020) Nanocalorimeters for biomolecular analysis and cell metabolism monitoring. Biomicrofluidics 14(1):011503

    Article  Google Scholar 

  • Wiseman T, Williston S, Brandts JF, Lin L-N (1989) Rapid measurement of binding constants and heats of binding using a new titration calorimeter. Anal Biochem 179(1):131–137

    Article  Google Scholar 

  • Zhang Y, Tadigadapa S (2004) Calorimetric biosensors with integrated mi-crofluidic channels. Biosens Bioelectron 19:1733–1743

    Article  Google Scholar 

Download references

Acknowledgement

The authors thank the Fundamental Research Fund from Central University (No. 2023012).

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Author notes

  1. Shuyu Wang and Xin Lv authors contributed equally to this work

Authors and Affiliations

  1. School of Control Engineering, Northeastern University at Qinhuangdao, Qinhuangdao, 066004, China

    Shuyu Wang, Xin Lv & Jianning Hua

  2. Department of Mechanical Engineering, Columbia University, New York City, NY, 10027, USA

    Shifeng Yu

Authors
  1. Shuyu Wang
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  2. Xin Lv
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  3. Shifeng Yu
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  4. Jianning Hua
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Correspondence to Shuyu Wang.

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Wang, S., Lv, X., Yu, S. et al. Design and optimization of a chip calorimeter for cell metabolism detection. Microsyst Technol 27, 921–928 (2021). https://doi.org/10.1007/s00542-020-05014-1

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  • DOI: https://doi.org/10.1007/s00542-020-05014-1

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