Progress towards rapid and simple characterization of biomolecular samples by scanning probe microscopy (SPM) is impeded considerably by limitations of the current approach to sample preparation. The group at Arizona State University, with which BioForce Laboratory has started a collaboration, pioneered a simple and versatile approach based on chemical functionalization of mica. Keeping in mind the positive results obtained under Phase I with AP-mica, methylated mica and in particular chemically reactive iodopropyl mica, we propose in Phase II to develop further chemical modification procedures of surfaces with silanes. The ultimate goal of these studies is to obtain surfaces with almost any desirable characteristics. These include negatively and positively charged surfaces having different controlled charge densities and surfaces with a selective binding affinity towards specific groups of macromolecules. The last feature is extremely important for making easier the use of AFM as the instrument for studies of intermolecular interactions, a very attractive application of AFM for future pharmaceutical studies and in particular for drug design. In this connection, a significant part of our efforts will also be devoted to the development of technologies for preparation of functionalized tips. Functionalized substrates may also be useful in optical and near-field scanning optical microscopy and for preparation of biomolecular chips. PROPOSED COMMERCIAL APPLICATION: Sales of functionalized substrates and probes to scanning probe microscope and high resolution optical microscopy users. Availability of functionalized substrates and probes will satisfy an important market, as imaging is made easier through the widespread availability of these new materials. Functionalized surfaces can be used in biomolecular chip (biochip) or biomolecular array industry.