Since its invention over ten years ago, the scanning tunneling microscope, STM, (and more recently the whole family of scanning probe microscopes such as the atomic force microscope, AFM) has received great attention in the physics and chemistry communities because of its Angstrom resolution in three dimensions for metal and semiconductor samples. Some time later a broader community, including the biological community, began to envision the use of this new technology to image and eventually solve real problems in structural biochemistry, including the sequencing of DNA. In the last three years there has been a large expansion in the number of experimenters who have tried to use these technologies in the realm of biology, with mixed success. Some spectacular claims have been made and published. Perhaps as a result of these claims the field is suffering from a credibility problem, stemming largely from difficulties, of reproducibility, the experimental approach used, and the rush to publish results which are only preliminary. The general goal of this project is to investigate the feasibility of using this technology (that is, STM and AFM) to determine the sequence of bases in DNA, in a systematic, credible, and non-spectacular way. The approach will address some of the major problems which the community generally agrees are limiting the success of these kinds of experiments. In particular, this work will focus on the surface chemistry which is lacking and needed to adsorb DNA molecules in a fashion which is appropriate for these experiments. This includes the use of additional surface-sensitive methods for independent verification, an element which has been entirely lacking in studies to date.
