Sensing array of radically coupled genetic biopixels

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While there has been significant progress in the development of engineering principles for synthetic biology, a substantial challenge is the construction of robust circuits in a cellular environment that is governed by noisy processes such as random bursts of transcription and translation. Such an environment leads to considerable intercellular variability in circuit behavior, which can hinder their functionality at the colony level. While quorum sensing is a promising design strategy for reducing variability through coordination across a cellular population, the length scales are limited by the diffusion time of the small molecule governing the intercellular communication. In this talk, I will discuss our recent progress in engineering the synchronization of thousands of oscillating colony “biopixels” over centimeter length scales through the use of redox signaling that is mediated by hydrogen peroxide vapor. We have used the redox communication to construct a frequency modulated biosensor by coupling the synchronized oscillators to the output of an arsenic sensitive promoter that modulates the frequency of colony‐level oscillations due to quorum sensing. For the detection of arsenic, we have developed thresholding and period modulation as sensing mechanisms. In the case of thresholding, oscillations arise when a pre‐determined low level of arsenic is present, while for period modulation the level of arsenic is proportional to the oscillatory frequency. In both cases, the coupling of thousands of colonies dramatically increases the signal to noise ratio and leads to the reliable detection of extremely low levels of arsenic. Given the repertoire of sensing capabilities of bacteria such as E. coli, the ability to coordinate their behavior over large length scales sets the stage for the construction of low cost genetic biosensors that are capable of detecting heavy metals and pathogens in the field.