A uniaxial bioMEMS device for imaging single cell response during quantitative force-displacement measurements David B. Serrell & Jera Law & Andrew J. Slifka & Roop L. Mahajan & Dudley S. Finch Published online: 22 July 2008 # Springer Science + Business Media, LLC 2008 Abstract A microfabricated device has been developed for imaging of a single, adherent cell while quantifying force under an applied displacement. The device works in a fashion similar to that of a displacement-controlled uniaxial tensile machine. The device was calibrated using a tipless atomic force microscope (AFM) cantilever and shows excellent agreement with the calculated spring constant. A step input was applied to a single, adherent fibroblast cell and the viscoelastic response was characterized with a mechanical model. The adherent fibroblast was imaged by use of epifluorescence and phase contrast techniques. Keywords Actin . BioMEMS . Fibroblasts . Micro-fabricated . Single-cell 1 Introduction We have developed a MEMS-based, single-cell measure- ment technique that allows mechanical force-displacement data to be taken while simultaneously imaging the living cell. Mechanical forces have profound effects on cellular function and behavior. Cells are nonlinear, viscoelastic, and constantly adaptive; they rapidly sense changes in their mechanical environment and adapt their internal structure and function in response. Mechanical stresses on cells can influence cellular processes such as growth, differentiation, apoptosis, contraction, division, spreading and the regula- tion of protein transduction (Chicurel et al. 1998; Maniotis et al. 1997; Janmey 1998; Lenormand and Fredburg 2006; Janmey and McCulloch 2007). Furthermore, several well known pathologies such as sickle cell anemia and asthma are related to the mechanical properties of cells. Despite the importance of forces on cell life, the underlying mechanisms for how these forces are transmitted and regulated within living cells are poorly understood. To quantify the relation- ship between mechanical force and cellular response, there is a need for accurate, physical metrology tools that can determine time-dependent, force-displacement responses in living cells and simultaneously integrate this data with imaging of subcellular structures. There are a wide variety of techniques available to quantify mechanical forces on single cells in vitro. Techniques such as atomic force microscopy (Hyonchol et al. 2002; Yamamoto et al. 1998; Mathur et al. 2001; Florin et al. 1994), magnetic traps (Wang et al. 1993; Chen et al. 2001; Lo et al. 1998; Alenghat et al. 2000; Lenormand and Fredburg 2006; Deng et al. 2006), optical traps (Svoboda and Block 1994; Yamada et al. 2000) and silicon cantilevers (Saif et al. 2003; Saif et al. 2002) have been used for studying local cellular phenomena as well as individual components of the cystoskeleton such as actin (Minajeva et al. 2001; Zaner and Valberg 1989). Other techniques used to study single-cell mechanics at the global level include micropipette aspiration (Evans and Yeung 1989; Evans and Hochmuth 1976; Hochmuth 1981; Hochmuth and Waugh 1987), flexible silicon substrates (Di Palma et al. 2003; Ignatius et al. 2004; Moretti et al. 2004; Park et al. 2004), shear flow devices (Ainslie et al. 2005; Rhodes et al. 1998; Biomed Microdevices (2008) 10:883–889 DOI 10.1007/s10544-008-9202-7 D. B. Serrell (*) : J. Law : A. J. Slifka National Institute of Standards and Technology, Boulder, CO, USA e-mail: david.serrell@colorado.edu D. B. Serrell University of Colorado, Boulder, CO, USA R. L. Mahajan : D. S. Finch Virginia Polytechnic Institute and State University, Blacksburg, VA, USA