The enormous diversity of genetic responses in living microbes to thei
r environment is an attractive resource on which to base biosensor des
igns. In particular, there is much interest in microbial sensors for e
nvironmental monitoring where toxicity can be ascertained directly by
its action on cellular physiology. However, due to the complexities of
living systems, the utility of genetic-based microbial sensors has be
en limited by the ability to accurately transduce the activities of sp
ecific genetic sensing systems into readily measurable signals. We pre
sent here a strategy for employing an additional signal in the sensor
design, to provide an internal baseline control upon which to reliably
interpret sensor responses. The strategy relies on using beetle lucif
erases capable of emitting optical signals of different wavelengths; t
he optical signals are a sensitive real-time indicator of genetic acti
vity within the cells. The different wavelengths allow both a target a
nd control signal to be incorporated into each cell, providing a means
of differentiating between specific effects of a genetic sensing syst
em and other non-specific interfering influences.