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Biocompatible Optically Transparent MEMS for Micromechanical Stimulation and Multimodal Imaging of Living Cells

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Abstract

Cells and tissues in our body are continuously subjected to mechanical stress. Mechanical stimuli, such as tensile and contractile forces, and shear stress, elicit cellular responses, including gene and protein alterations that determine key behaviors, including proliferation, differentiation, migration, and adhesion. Several tools and techniques have been developed to study these mechanobiological phenomena, including micro-electro-mechanical systems (MEMS). MEMS provide a platform for nano-to-microscale mechanical stimulation of biological samples and quantitative analysis of their biomechanical responses. However, current devices are limited in their capability to perform single cell micromechanical stimulations as well as correlating their structural phenotype by imaging techniques simultaneously. In this study, a biocompatible and optically transparent MEMS for single cell mechanobiological studies is reported. A silicon nitride microfabricated device is designed to perform uniaxial tensile deformation of single cells and tissue. Optical transparency and open architecture of the device allows coupling of the MEMS to structural and biophysical assays, including optical microscopy techniques and atomic force microscopy (AFM). We demonstrate the design, fabrication, testing, biocompatibility and multimodal imaging with optical and AFM techniques, providing a proof-of-concept for a multimodal MEMS. The integrated multimodal system would allow simultaneous controlled mechanical stimulation of single cells and correlate cellular response.

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Acknowledgments

The authors thank the staff of the Nano3 facilities at Calit2 at UCSD for the valuable support during the microfabrication process, Dr. Stefano Maggiolino at the University of Trieste for brainstorming. The authors also thank members of Nano-bio-imaging and Devices Laboratory at UCSD, especially Brian Meckes and Srinivasan Ramachandran for their input. F.M. acknowledges her advisor, Dr. Farooq Azam, and support from the Gordon and Betty Moore Foundation MMI initiative. This work was supported by NIH Grants R01DA025296 (R.L.) and R01DA024871 (R.L.), and MISE-ICE-CRUI Grant 16-06-2010 Project 99 and FVG Region LR 26/2005 Art. 23 (O.S.).

Author information

Authors and Affiliations

  1. Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA

    Raffaella Fior & Ratnesh Lal

  2. Department of Aerospace and Mechanical Engineering, University of California, San Diego, La Jolla, CA, 92093, USA

    Jeanie Kwok & Ratnesh Lal

  3. Materials Science and Engineering Program, University of California, San Diego, La Jolla, CA, 92093, USA

    Jeanie Kwok & Ratnesh Lal

  4. Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, 92093, USA

    Francesca Malfatti

  5. Department of Engineering and Architecture, University of Trieste, 31400, Trieste, Italy

    Raffaella Fior & Orfeo Sbaizero

  6. University of California, San Diego, Powell-Focht Bioengineering Hall (PFBH) Rm 217, 9500 Gilman Drive MC 0412, La Jolla, CA, 92093, USA

    Ratnesh Lal

Authors
  1. Raffaella Fior
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  2. Jeanie Kwok
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  4. Orfeo Sbaizero
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  5. Ratnesh Lal
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Correspondence to Ratnesh Lal.

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Associate Editor Konstantinos Konstantopoulos oversaw the review of this article.

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Fior, R., Kwok, J., Malfatti, F. et al. Biocompatible Optically Transparent MEMS for Micromechanical Stimulation and Multimodal Imaging of Living Cells. Ann Biomed Eng 43, 1841–1850 (2015). https://doi.org/10.1007/s10439-014-1229-8

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  • DOI: https://doi.org/10.1007/s10439-014-1229-8

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