A novel MEMS device for the multidirectional mechanical stimulation of single cells: Preliminary results Francesca Antoniolli, Stefano Maggiolino, Nicola Scuor, Paolo Gallina ⁎, Orfeo Sbaizero Department of Architecture and Engineering, University of Trieste, via A. Valerio 10, 34127 Trieste, Italy article info abstract Article history: Received 6 September 2011 Received in revised form 19 December 2013 Accepted 21 March 2014 Available online 18 April 2014 In recent years, understanding cell mechanics has gained increasing importance, with significant implications for human health. Currently, different technologies have been developed to perform the mechanical stimulation of living cells. However, they often show some limitations. Here we present the development and characterization of a novel microelectromechanical system (MEMS), designed to perform a multidirectional mechanical stimulation of single living cells: in this way, in vitro cell behavior is closely simulated. The proposed device employs a new compliant spring linkage to move a twelve-slice sectioned plate that works as a seating platform for the cell under study. The whole platform is moved by means of four series of bimorph thermal actuators, which allow displacements in 12 directions in the x–y plane. Results show the workability of the device under certain conditions, with important implications for a better understanding of cell mechanics and related disease. © 2014 Elsevier Ltd. All rights reserved. Keywords: MEMS Linkage mechanism Cell stretching Single cell Mechanical stimulation 1. Introduction Living cells can sense mechanical forces and convert them into biological responses. Similarly, biological and biochemical signals are known to influence the abilities of cells to sense, generate and bear mechanical forces [1]. Studies in the mechanics of single cells have rapidly evolved in the past decade with important implications for biotechnology and human health. Many systems have been created to stretch and study the mechanical properties of single cells. According to Bao and Sures, these can be classified into three main categories: the first is constituted by local probes, such as the tip of an AFM, which performs the local stimulation of a single cell [2,3]; the second is represented by devices that can exert the mechanical loading of an entire cell. This category includes optical tweezers [4,5] and microplates [6]. In the third category, the simultaneous mechanical stretching of an entire population of cells is performed [7,8]. Unfortunately these systems are often very complicated and present some limitations: for example, they fail to allow the stimulation of an entire cell (such as the AFM), they cannot be used to study adherent cells [9], they exert forces only in the pN range (such as the optical tweezers), and they give an average response on a huge number of cells (such as the stretching devices). An alternative and novel approach is represented by MEMS, an acronym for microelectromechanical systems. Microfabricated MEMS have already found a niche in the biology community: they can be used to sense, stimulate, manipulate or control cells and biomolecules [10]. In a certain sense they are superior to the technologies described above since they have suitable dimensions for single-cell studies, they can exert forces in the range of nN–μN [11] and they can be applied to whole and adherent cells. They can work in a liquid environment, have biocompatible surfaces and can be easily integrated in other instruments such as fluorescence microscopes or spectroscopic devices, thus obtaining details on the structure and morphology of the whole cell, too. We believe that this approach is superior to current atomic force microscopy methods that cannot measure the properties of the whole cell and optical trap methods that cannot be applied to cells adhered to a substrate. Using our MEMS approach, it is possible to both Mechanism and Machine Theory 78 (2014) 131–140 ⁎ Corresponding author. E-mail address: pgallina@units.it (P. Gallina). http://dx.doi.org/10.1016/j.mechmachtheory.2014.03.009 0094-114X/© 2014 Elsevier Ltd. All rights reserved. Contents lists available at ScienceDirect Mechanism and Machine Theory journal homepage: www.elsevier.com/locate/mechmt