In our experiments, we observed that solution pH, a key experimental variable, could have a significant and yet underappreciated impact on the magnitude of the measured optical modulations. The influence of pH on SWCNT optical properties is well documented, with a general increase in brightness noted for most SWCNT solutions as pH increases. However, the effect of pH on analyte-induced optical modulation is not well understood. We found that changing solution pH by just two units could dramatically attenuate optical response for some analytes (Fig. ). These analytes have substituents with pKA values that allow deprotonation to occur in this range. To probe pH effects more systematically, we measured the optical responses of a subset of analytes while ranging solution pH from 2 to 13 units (Fig. , fig. ). At high pH levels (> 8), optical responses were greatly diminished for all analytes. This reduction is partly a consequence of the fact that nanotube fluorescence (i.e., brightness) increases with increasing pH, reducing the dynamic range of the optical response that can be elicited by the analytes. In other words, the baseline fluorescence (F0) is higher, making the change in fluorescence (∆F/F0) lower.