AFM-Based Single Molecule Force Spectroscopy of Polymer Chains: Theoretical Models and Applications Haizhen Wei and Theo G. M. van de Ven Department of Chemistry, Pulp & Paper Research Centre, McGill University, Montreal, Canada Abstract: In recent years, remarkable advances in research of the mechanical and structural properties of single polymer chains have been achieved thanks to atomic force microscope (AFM)-based single molecule force spectroscopy (SMFS). This technique offers great possibilities to investigate the mechanical properties of a single polymer chain by static/dynamic force-extension measurements at the mesoscale level. Data are analyzed with the help of appropriate theoretical models, such as statistical mechanics models for freely jointed chains (FJC) or worm-like chains (WLC), which can well describe the moderate entropy-controlled stretch of most polymers, and with semiclassical models, which are being modified using quantum mechanics principles to account for entropic and enthalpic contributions to stretching in the high-force Hookean regime. In this article we review the theoretical models of single chain stretching, the latest progress in force-extension measurements by static and dynamic AFM modes for polymer chains dispersed in different solvents and subjected to a force that may induce their conformational transformations, as well as relevant applications. Keywords: AFM-based SMFS, theoretical models, single polymer chain stretching, advances in force-extension measurements Address correspondence to Prof. Theo G. M. van de Ven, Department of Chemistry, Pulp & Paper Research Centre, McGill University, 3420 University Street, Montreal, QC, H3A 2A7, Canada. E-mail: theo.vandeven@mcgill.ca Applied Spectroscopy Reviews, 43: 111–133, 2008 Copyright # Taylor & Francis Group, LLC ISSN 0570-4928 print/1520-569X online DOI: 10.1080/05704920701831254 111