Multi-time-scale biomolecular 'quasi-integral' controllers for set-point regulation and trajectory tracking

• Main Authors: Qian, Yili (Contributor), Grunberg, Theodore Wu (Contributor), Del Vecchio, Domitilla (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Mechanical Engineering (Contributor)
• Format: Article
• Language: English
• Published: Institute of Electrical and Electronics Engineers (IEEE), 2018-11-16T21:27:07Z.
• Subjects: Article
• Online Access: Get fulltext

 Recent trends in synthetic biology to move from prototypes to applications have triggered higher expectations on the robustness, predictability and responsiveness of biomolecular circuits. Therefore, a systematic approach to designing biomolecular controllers for regulating gene expression is needed. Although a number of integral control motifs (ICMs) have been proposed for set-point regulation, their performance in vivo is challenged by integration leakiness due to dilution, which cannot be neglected in growing cells. In this paper, we study a class of quasi-integral controllers designed based on existing ICMs and multiple time-scale separations. We demonstrate that by engineering all controller reactions to be much faster than dilution, set-point regulation can be achieved even in the presence of a leaky integrator. Furthermore, by engineering controller parameters for a second layer of time-scale separation, arbitrarily small tracking error can be achieved under certain technical conditions. We demonstrate a realization of our design principle through a small RNA feedback circuit.