Micromechanical cantilever based surface stress sensors have demonstrated tremendous sensitivity to
non-labeled detection of chemical and biochemical compounds. The sensing strategy involves coating
one surface of a microcantilever with a receptor species that has high affinity for the analyte molecule of
interest. The presence of the analyte is detected by resolving the surface stress change associated with
absorption/adsorption of analyte molecules on the sensitized surface. While a number of studies have
been undertaken to explore potential uses of the cantilever sensors, their widespread application is
severely limited due to: 1) lack of integration of all the components in a single miniature device; and 2)
incomplete understanding of the molecular mechanisms governing the sensor response. We address these
limitations through development of an interferometry based surface stress sensing approach and
multiscale models to identify mechanism governing surface stress generation. I will discuss our results on
surface stress changes associated with two model systems: 1) formation of monomolecular alkanethiol
films on gold surfaces; and 2) hybridization of surface immobilized DNA molecules. Insight gained from
the results on the model systems is currently being used to investigate aptamer-modified microcantilevers
for detection of controlled substances and novel approach on immobilizing receptor molecules that
maximizes the surface stress changes.