Automated cell characterization by a nanohandling robot station

Krohs, F., Hagemann, S., Fatikow, S.
Current research work on the development of a nanohandling robot station for automated characterization of biological cells is presented. The station consists of a sample piezo scanning stage with three degrees of freedom (DoF) and a three-axes nanomanipulator that is equipped with a piezoresistive atomic force microscope (AFM) probe as an endeffector. Thus, the endeffector can be used both to measure mechanical properties of the sample and as a force sensor giving a feedback signal to the underlying control system. While the endeffector can be positioned coarsely by the nanomanipulator, fine positioning of the sample is performed by the piezo stage. As a visual sensor for the station an inverted optical microscope is utilized. The setup is enhanced by a second nano-manipulator equipped with a pipette for injection/extraction tasks or patch clamp purposes. Alternatively, a second piezoresistive AFM probe can be used as an endeffector for the second nanomanipulator. The station provides the opportunity to automatically determine a region-of-interest (i.e. a single cell) by means of object recognition in previously acquired images from the optical microscope. Next, the endeffector is brought into proximity to the sample, and an automated, mechanical characterization of the cell is performed. First experiments cover recordings of single force-distance curves to gain information on elasticity and adhesion of the cell. Using the fast piezo stage, complete adhesion or elasticity maps of the region-of-interest can be obtained. This mechanical characterization delivers valuable information about cell mechanics concerning cell to cell contact or cell motility. It is also of interest in oncology, since tumor cells tend to have a different elasticity than healthy cells. The use of a second nanomanipulator surpasses the capabilities of a standard AFM system, since it enables the station to cover areas as deoxyribonucleic acid (DNA) extraction, measurements of reactions to drug - injection or electrophysiological measurements of stress activated ion channels.
06 / 2007