IMTC 2006 - Instrumentation and Measurement Technology Conference Sorrento, Italy 24-27 April 2006 An Hybrid Micro-Force Sensing Device for Mechanical Cell Characterization Maxime Girot 1 , Mehdi Boukallel 1 , Stéphane Régnier 1 1 Laboratoire de Robotique de Paris Université Pierre et Marie Curie - Paris 6 CNRS - FRE 2507 18, route du Panorama - BP 61 92265 Fontenay-aux-Roses Cedex, France Phone: +33 1 46 54 92 39, Fax: +33 1 46 54 72 99, E–mail: girot, boukallel, regnier@robot.jussieu.fr. Abstract – This paper presents a fully automated microrobotic system based on force/vision referenced control designed for cell mechan- ical characterization. The design of the prototype combines Scan- ning Probe Microscopy (SPM) techniques with advanced robotics approaches. As a result, accurate and non-destructive mechanical characterization based on soft contact interactions mechanics are achieved. The in vitro working conditions are supported by the exper- imental setup so that mechanical characterizations can be performed in biological environmental requirements as well as in cyclical op- erating mode during several hours. The design and calibration of the different modules which compose the experimental setup are de- tailed. Experimentation on the mechanical cell characterization un- der in vitro conditions on human adherent cervix Epithelial Hela cells are presented to demonstrate the viability and effectiveness of the pro- posed setup. Keywords – In vitro mechanical cell characterization; Scanning Probe Microscopy (SPM) techniques; Human adherent cervix Epithe- lial Hela cells mechanical characterization. I. INTRODUCTION Robotics and microrobotics techniques can play an im- portant role for addressing the study of mechanical cell re- sponse. Up to date, several experimental setups have been developed to identify the control mechanisms of the mechan- ical cells response [1]-[5]. These significant research efforts make possible the measurement of relevant mechanical prop- erties (Young’s modulus, bulk modulus, surface roughness, ...). However, most of these studies have been performed in non- biological clean room environment. Since elementary biologi- cal functions and mechanical properties of biological cells are widely affected by the experimental conditions, some identi- fied properties may not be relevant. In fact, due to the structural complexity of various adherent cells (such as the deformable cytoskeleton formed by a three dimensional intercellular net- work of interconnected filamentous biopolymers), significant differences on the cell mechanical responses can be observed. Furthermore, there is recently a great interest in the field of biopolymers, for the quantification of the viscoelastic behavior of biological samples. To suite this need it is necessary to per- form an accurate automatic mechanical characterization pro- cess as well as supervised micromanipulation tasks in a cycli- cal operating mode. Moreover, since the reaction of the bio- logical samples to stress vary greatly in a given lapse time, it is important to monitor the characterization process continuously in an in vitro environment. In the next section, the context and motivations of these works are presented. The experimental device produced, called Force Bio-Microscope (FBM), is presented and detailed in the sec- tion III. The cantilever spring constant calibration is explained in section IV. Section V is devoted to the description of our preliminary experimentation and analysis of cell mechanical characterization using the automated FBM under in vitro con- ditions on human adherent cervix Epithelial Hela cells. Finally, planned future work on the cell mechanical characterization using the autonomous force sensing and measurements capa- bilities of the (FBM) are introduced in section VI. II. SPM TECHNIQUES FOR THE CELL MECHANICAL CHARACTERIZATION Among the robotics and microrobotics systems developed during the last decade to perform mechanical characterization of biological samples, the most promising ones involves Scanning Probe Microscopy (SPM) techniques for nanoscale. These techniques have the potential to give an accurate quantitative information on local forces and mechanical interactions at the nanoscale. The Atomic Force Microscope (AFM) has become a commonly used microindenter tool to measure mechanical properties of the biological samples [6]-[11]. Despite the AFM’s multiple operating modes, the mechanical characterization of biological samples is mainly performed in contact mode. In this case, a flexible cantilever with low spring constant and an atomic sharp tip is brought in contact with the biological sample. Deflection of the cantilever which results of the interaction between the microindenter and the sample is monitored by a split pho- todiode and a laser beam reflected on the back of the cantilever. 501 0-7803-9360-0/06/$20.00 ©2006 IEEE