Stefan Thalhammer

Department for Geoand Environmental Sciences, GeobioCenter and Center for Nanoscience, Ludwig-Maximilians-Universität, Theresienstrasse 41, 80333 München, Germany *E-mail: [email protected] URL: www.nanobiomed.de Over the last 15 years, the use of atomic force microscopy (AFM) has spread from the materials science of hard matter to the fields of biology and biomolecular research. Nowadays, AFM can be used not only as a high-resolution imaging tool for precise cytogenetic studies, but also for the mechanical measurement and manipulation of genetic material. This combination allows, for the first time, identification of sample area, microdissection, and nanoextraction of genetic material for further biomedical and biochemical studies. Here, we show combined AFM and laser-based microscopy techniques, like cutting, gripping, and extracting at the submicron scale, under high-resolution image control and their potential applications in cytogenetics. Shortly after the 1986 Nobel Prize in Physics was awarded for the invention of the scanning tunneling microscope (STM), Nobel laureate Gerd Binnig, Calvin Quate, and Christoph Gerber built the atomic force microscope (AFM) in order to avoid the limitations of the STM in only imaging conductive matter or thin layers of organics1 (Fig. 1a). Using the principle of a miniaturized record player, similar to a stylus profilometer, it is possible to image the surface of biological (nonconducting) objects, such as DNA and chromosomes, down to the molecular scale2-4. The most important fact in the development of the AFM as a universal instrument for bionanotechnology applications is that the tip of the cantilever used for imaging can also be used for measuring forces at the nanoscale, and, moreover, as a nanoscale tool, down to the single-atom level5. Here, we show how techniques like cutting, gripping, and extracting biomaterial at the submicron scale under highresolution image control has been developed into a useful tool, especially in cytogenetic studies (Fig. 1b). The combination of the nanomechanics tool box and modern biochemical techniques like the polymerase chain reaction (PCR) has immense potential in the future development of singlemolecule techniques ranging from applications in DNA mechanics to cytogenetic studies and the development of biochips. genetic material