Whole transcriptome profiling was examined in E. coli K12 when cultured on the surface of a pure polysiloxane coating (Sil) and a polysiloxane coating containing a tethered quaternary ammonium compound (QSil) shown to inhibit biofilm formation. An optimized protocol was developed for isolating high quality RNA from the surface of these coatings prepared in multi-well plates. DNA microarray data obtained from the Sil and QSil coatings revealed that 222 genes were differentially expressed between these two surfaces by a factor of at least 2-fold and with a 90% level of confidence. Several genes of the lsr operon, which encode the various components of the AI-2 based quorum sensing system, were repressed on the QSil coating surface. The QSil coatings ability to effectively interfere with the AI-2 based quorum sensing system was most likely the primary factor that contributed to the impairment of E. coli K12 biofilm formation on that surface.