Often the performance of a material is governed by how its surface interacts with its environment, and this frequently depends upon the structure and composition of that surface at the molecular scale. This basic fact has driven the development of surface analytical instrumentation for decades. An ideal tool would allow the researcher to know the surface composition of their sample with molecular resolution and in a realistic environment, and even to monitor these molecular processes directly as the sample interacts with its environment. While the search for the perfect instrument is still ongoing, in 1982 this effort was significantly enhanced by the invention of the scanning tunneling microscope (STM), allowing the direct spatial imaging of conductive surfaces with atomic resolution under a wide range of environments. This invention sparked the imagination of scientists and engineers worldwide, and the ensuing years witnessed the development of a regular alphabet soup of different techniques that are broadly known as scanning probe microscopy (SPM). Of these techniques, none is so pervasive and broadly applicable as atomic force microscopy (AFM). Briefly, AFM operates by placing a sharp tip in such close proximity to a sample that their interaction can be measured. Unlike traditional spectroscopic surface analytical instruments, the high resolution afforded to AFM is offset by the remarkably low data content, which is largely mechanical and physical in nature with little chemical or compositional information. Initial efforts to enhance the data content of AFM focused on increasing the number of modes. Atomic force microscopy (AFM) has revolutionized surface characterization by allowing the researcher to examine the molecular structure of virtually any sample under virtually any environmental condition. The AFM is used to produce information about surface topography, elasticity, friction, adhesion, charge density, magnetic structure, or even long- range effects. Compared to traditional spectroscopic surface analytical tools, the AFM suffers from a remarkably low data content. Chemical modification of the tip incorporates chemical information within the measurements. In this way, researchers have obtained compositional maps of heterogeneous materials, measured single-molecule interaction forces between biopolymers, and even differentiated some nuances of cell membranes. by John-Bruce D. Green, Ademola Idowu, and Sandra S. F. Chan Modified tips: molecules to cells Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2 Canada Email: john.green@ualberta.ca ISSN:1369 7021 © Elsevier Science Ltd 2003 February 2003 22