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Piezoelectric bioMEMS cantilever for measurement of muscle contraction and for actuation of mechanosensitive cells

Abstract

A piezoelectric biomedical microelectromechanical system (bioMEMS) cantilever device was designed and fabricated to act as either a sensing element for muscle tissue contraction or as an actuator to apply mechanical force to cells. The sensing ability of the piezoelectric cantilevers was shown by monitoring the electrical signal generated from the piezoelectric aluminum nitride in response to the contraction of iPSC-derived cardiomyocytes cultured on the piezoelectric cantilevers. Actuation was demonstrated by applying electrical pulses to the piezoelectric cantilever and observing bending via an optical detection method. This piezoelectric cantilever device was designed to be incorporated into body-on-a-chip systems.

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References

  1. 1.

    J. Fritz. Cantilever biosensors. Analyst 133, 855 (2008).

    CAS  Article  Google Scholar 

  2. 2.

    C. Oleaga, C. Bernabini, A.S.T. Smith, B. Srinivasan, M. Jackson, W. McLamb, V. Platt, R. Bridges, Y. Cai, N. Santhanam, B. Berry, S. Najjar, N. Akanda, X. Guo, C. Martin, G. Ekman, M.B. Esch, J. Langer, G. Ouedraogo, J. Cotovio, L Breton, M.L. Shuler, and J.J. Hickman: Multi-organ toxicity demonstration in afunctional human in vitro system composed of four organs. Sci. Rep. 6, 20030 (2016).

    CAS  Article  Google Scholar 

  3. 3.

    M. Stancescu, P. Molnar, C.W. McAleer, W. McLamb, C.J. Long, C. Oleaga, J.-M. Prot, and J.J. Hickman: A phenotypic in vitro model for the main determinants of human whole heart function. Biomaterials 60, 20 (2015).

    CAS  Article  Google Scholar 

  4. 4.

    C. Oleaga, A. Riu, S. Rothemund, A. Lavado, C.W. McAleer, C.J. Long, K. Persaud, N.S. Narasimhan, M. Tran, and J. Roles: Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system. Biomaterials 182, 176 (2018).

    CAS  Article  Google Scholar 

  5. 5.

    A. Smith, C. Long, K. Pirozzi, S. Najjar, C. McAleer, H. Vandenburgh, and J. Hickman: A multiplexed chip-based assay system for investigating the functional development of human skeletal myotubes in vitro. J. Biotechnol. 185, 15 (2014).

    CAS  Article  Google Scholar 

  6. 6.

    J. Deng, Y. Qu, T. Liu, B. Jing, X. Zhang, Z. Chen, Y. Luo, W. Zhao, Y. Lu, and B. Lin: Recent organ-on-a-chip advances toward drug toxicity testing. Microphysiol. Syst 2, 8 (2018).

    Google Scholar 

  7. 7.

    K. Wilson, P. Molnar, and J.J. Hickman: Integration of functional myotubes with a Bio-MEMs device for non-invasive interrogation. Lab Chip 7, 920–922 (2007).

    CAS  Article  Google Scholar 

  8. 8.

    M.B. Esch, A.S. Smith, J.-M. Prot, C. Oleaga, J.J. Hickman, and M.L. Shuler: How multi-organ microdevices can help foster drug development. Adv. Drug Del. Rev. 69, 158 (2014).

    Article  Google Scholar 

  9. 9.

    J.H. Sung, B. Srinivasan, M.B. Esch, W.T. McLamb, C. Bernabini, M.L. Shuler, and J.J. Hickman: Using physiologically-based pharmacokinetic-guided “body-on-a-chip” systems to predict mammalian response to drug and chemical exposure. Exp. Biol. Med. 239, 1225 (2014).

    Article  Google Scholar 

  10. 10.

    J.H. Lee, K.S. Hwang, J. Park, K.H. Yoon, D.S. Yoon, and T.S. Kim: Immunoassay of prostate-specific antigen (PSA) using resonant frequency shift of piezoelectric nanomechanical microcantilever. Biosens. Bioelectron. 20, 2157 (2005).

    CAS  Article  Google Scholar 

  11. 11.

    D. Isarakorn, M. Linder, D. Briand, and N.F. De Rooij: Evaluation of static measurement in piezoelectric cantilever sensors using a charge integration technique for chemical and biological detection. Meas. Sci. Technol. 21, 075801 (2010).

    Article  Google Scholar 

  12. 12.

    V. Mohammadi, S. Mohammadi, and F. Barghi: Piezoelectric Materials and Devices-Practice and Applications. In Piezoelectric Materials and Devices-Practice and Applications, edited by Farzad Ebrahami (IntechOpen, Rijeka, Croatia, 2013).

    Google Scholar 

  13. 13.

    J. Ali, J. Najeeb, M.A. Ali, M.F. Aslam, and A. Raza: Biosensors: their fundamentals, designs, types and most recent impactful applications: a review. J. Biosens. Bioelectron. 8, 235 (2017).

    Article  Google Scholar 

  14. 14.

    P. Sangeethaand A.V. Juliet: MEMS cantilever based immunosensorsfor biomolecular recognition. Int. J. Comput. Technol. Electron. Eng 2(1), 109–114.

  15. 15.

    B.N. Johnson and R. Mutharasan: Biosensing using dynamic-mode cantilever sensors: a review. Biosens. Bioelectron. 32, 1 (2012).

    CAS  Article  Google Scholar 

  16. 16.

    S. Tadigadapa and K. Mateti: Piezoelectric MEMS sensors: state-of-the-art and perspectives. Meas. Sci. Technol. 20, 092001 (2009).

    Article  Google Scholar 

  17. 17.

    M. Das, C.A. Gregory, P. Molnar, L.M. Riedel, K. Wilson, and J.J. Hickman: A defined system to allow skeletal muscle differentiation and subsequent integration with silicon microstructures. Biomaterials 27, 4374 (2006).

    CAS  Article  Google Scholar 

  18. 18.

    A. Colón, X. Guo, N. Akanda, Y. Cai, and J.J. Hickman: Functional analysis of human intrafusal fiber innervation by human γ-motoneurons. Sci. Rep. 7, 17202 (2017).

    Article  Google Scholar 

  19. 19.

    J.W. Rumsey, M. Das, A. Bhalkikar, M. Stancescu, and J.J. Hickman: Tissue engineering the mechanosensory circuit of the stretch reflex arc: sensory neuron innervation of intrafusal muscle fibers. Biomaterials 31, 8218 (2010).

    CAS  Article  Google Scholar 

  20. 20.

    S. Barkam, S. Saraf, and S. Seal: Fabricated micro‐nano devices for in vivo and in vitro biomedical applications. WIRES Nanomed. Nanobi. 5, 544 (2013).

    CAS  Article  Google Scholar 

  21. 21.

    M.T. Chorsi, E.J. Curry, H.T. Chorsi, R. Das, J. Baroody, P.K. Purohit, H. Ilies, and T.D. Nguyen: Piezoelectric biomaterials for sensors and actuators. Adv. Mater. 31, 1802084 (2019).

    Article  Google Scholar 

  22. 22.

    C. Frias, J. Reis, F.C. e Silva, J. Potes, J. Simões, and A. Marques: Piezoelectric actuator: searching inspiration in nature for osteoblast stimulation. Compos. Sci. Technol. 70, 1920 (2010).

    CAS  Article  Google Scholar 

  23. 23.

    C. Mota, M. Labardi, L. Trombi, L. Astolfi, M. D’Acunto, D. Puppi, G. Gallone, F. Chiellini, S. Berrettini, L. Bruschini, and S. Danti: Design, fabrication and characterization of composite piezoelectric ultrafine fibers for cochlear stimulation. Mater. Design. 122, 206 (2017).

    CAS  Article  Google Scholar 

  24. 24.

    M. Das, K. Wilson, P. Molnar, and J.J. Hickman: Differentiation of skeletal muscle and integration of myotubes with silicon microstructures using serum-free medium and a synthetic silane substrate. Nat. Protoc. 2, 1795 (2007).

    CAS  Article  Google Scholar 

  25. 25.

    A. Natarajan, M. Stancescu, V. Dhir, C. Armstrong, F. Sommerhage, J.J. Hickman, and P. Molnar: Patterned cardiomyocytes on microelectrode arrays as a functional, high information content drug screening platform. Biomaterials 32, 4267 (2011).

    CAS  Article  Google Scholar 

  26. 26.

    K. Wilson, M. Das, K.J. Wahl, R.J. Colton, and J.J. Hickman: Measurement of contractile stress generated by cultured rat muscle on silicon cantilevers for toxin detection and muscle performance enhancement. PLoS ONE 5, e11042 (2010).

    Article  Google Scholar 

  27. 27.

    C. Oleaga, A. Lavado, A. Riu, S. Rothemund, C.A. Carmona-Moran, K. Persaud, A. Yurko, J. Lear, N.S. Narasimhan, and C.J. Long. Long‐term electrical and mechanical function monitoring of a human‐on‐a‐chip system. Adv. Funct. Mater. 29, 1805792 (2019).

    Article  Google Scholar 

  28. 28.

    C. McAleer, C. Long, D. Elbrecht, T. Sasserath, L. Bridges, J. Rumsey, C. Martin, M. Schnepper, Y. Wang, F. Schuler, A. Roth, C. Funk, M. Shuler, and J. Hickman: Multi-organ system for the evaluation of anti-cancer therapeutics on efficacy and off-target toxicity. Sci. Trans. Med 11(497), eaav1386 (2019).

    Article  Google Scholar 

  29. 29.

    K. Pirozzi, C. Long, C. McAleer, A. Smith, and J. Hickman: Correlation of embryonic skeletal muscle myotube physical characteristics with contractile force generation on an atomic force microscope-based bio-microelectromechanical systems device. Appl. Phys. Lett. 103, 083108 (2013).

    CAS  Article  Google Scholar 

  30. 30.

    C.W. McAleer, A.S. Smith, S. Najjar, K. Pirozzi, C.J. Long, and J.J. Hickman: Mechanistic investigation of adult myotube response to exercise and drug treatment in vitro using a multiplexed functional assay system. J. Appl. Physiol. 117, 1398 (2014).

    CAS  Article  Google Scholar 

  31. 31.

    A. Grosberg, P.W. Alford, M.L. McCain, and K.K. Parker: Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip. Lab Chip 11, 4165 (2011).

    CAS  Article  Google Scholar 

  32. 32.

    W. Liu, Z. Feng, R. Liu, and J. Zhang: The influence of preamplifiers on the piezoelectric sensor’s dynamic property. Rev. Sci. Instrum. 78, 125107 (2007).

    CAS  Article  Google Scholar 

  33. 33.

    A.P. Haring, H. Sontheimer, and B.N. Johnson: Microphysiological human brain and neural systems-on-a-chip: potential alternatives to small animal models and emerging platforms for drug discovery and personalized medicine. Stem Cell Rev. Rep. 13, 381 (2017).

    CAS  Article  Google Scholar 

  34. 34.

    C. Luni, E. Serena, and N. Elvassore: Human-on-chip for therapy development and fundamental science. Curr. Opin. Biotech. 25, 45 (2014).

    CAS  Article  Google Scholar 

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Acknowledgements

This work was funded by the National Institutes of Health (Grant numbers 1R44TR001326, 2R44TR001326, and 5R01NS050452). This work was performed in part at the Cornell NanoScale Science & Technology Facility (CNF), a member of the National Nanotechnology Coordinated Infrastructure (NNCI), which is supported by the National Science Foundation (Grant NNCI-1542081).

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Correspondence to James J. Hickman.

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The supplementary material for this article can be found at https://doi.org/10.1557/mrc.2019.129.

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Coln, E.A., Colon, A., Long, C.J. et al. Piezoelectric bioMEMS cantilever for measurement of muscle contraction and for actuation of mechanosensitive cells. MRS Communications 9, 1186–1192 (2019). https://doi.org/10.1557/mrc.2019.129

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