Published online by Cambridge University Press: 15 February 2011
We have constructed an oblique-incidence reflectivity difference (OI-RD) microscope for fluorescent label-free imaging of DNA and protein microarrays on standard glass substrates. Using both OI-RD and fluorescence images, we demonstrate a difference in wetting behavior of labeled and unlabeled IgG protein molecules deposited on an aldehyde-derivatized glass surface. The potential of fluorescent labeling agents to influence the properties of proteins highlights the need for label-free microarray detection techniques to supplement existing fluorescence methods. We also present OI-RD images of an oligonucleotide microarray after printing and washing procedures to demonstrate the use of OI-RD for non-destructive monitoring of changes in the optical properties of microarrays during processing.