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Publications about 'antithetic feedback'
Articles in journal or book chapters
  1. M.K. Wafi, A.C.B de Oliveira, and E.D. Sontag. Boundedness of solutions in feedback systems with antithetic controllers. 2026. Note: ArXiv 2604.27290.Keyword(s): boundedness of solutions, nonlinear systems, antithetic controller, integral feedback, synthetic biology.
    Abstract:
    This paper studies whether solutions of a class of nonlinear feedback systems remain bounded over time. The systems we consider arise naturally in synthetic biology, where the antithetic feedback controller regulates a biological process through a delayed feedback loop. Our main result is that every trajectory of such a system is bounded. The key insight is simple: if the regulated state grows too large for too long, the feedback loop will eventually respond and push it back down. More precisely, we show that whenever the state exceeds a threshold and remains there long enough, the feedback signal becomes strong enough to force the state to decrease. We then show that once this happens, the feedback remains strong enough to keep the state from growing unbounded. The proof works directly with differential inequalities and does not require constructing a Lyapunov function, making the mechanism transparent and easy to interpret. The boundedness result can be understood as a time-domain small-gain effect, where the delayed feedback ultimately counteracts any persistent growth in the system.


Conference articles
  1. M. Margaliot, C. Wu, and E.D.Sontag. Compact attractors of an antithetic integral feedback system have a simple structure. In Proc. 64th IEEE Conference on Decision and Control (CDC), pages 2880-2885, 2025. [PDF] Keyword(s): Poincaré-Bendixson, synthetic biology, nonlinear control.
    Abstract:
    Since its introduction by Briat, Gupta and Khammash, the antithetic feedback controller design has attracted considerable attention in both theoretical and experimental systems biology. The case in which the plant is a two-dimensional linear system (making the closed-loop system a four-dimensional nonlinear system) has been analyzed in much detail. This system has a unique equilibrium~$e$ but, depending on parameters, it may exhibit periodic orbits. An interesting question is for what parameter values periodic orbits exist. Another open question is whether other dynamical behaviors, such as chaotic attractors, might be possible for some parameter choices. We show that, for any parameter choices, every compact omega-limit set that does not include~$e$ is a periodic solution. We also show that if the Jacobian of the vector field at the equilibrium is unstable then a (non-trivial) periodic orbit exists. The analysis is based on the theory of strongly~$2$-cooperative systems.


Internal reports
  1. M. Margaliot and E.D. Sontag. Compact attractors of an antithetic integral feedback system have a simple structure. Technical report, bioRxiv 2019/868000v1, 2019. [PDF] Keyword(s): Poincare-Bendixson, k-cooperative dynamical systems, sign-regular matrices, synthetic biology, antithetic feedback.
    Abstract:
    Since its introduction by Briat, Gupta and Khammash, the antithetic feedback controller design has attracted considerable attention in both theoretical and experimental systems biology. The case in which the plant is a two-dimensional linear system (making the closed-loop system a nonlinear four-dimensional system) has been analyzed in much detail. This system has a unique equilibrium but, depending on parameters, it may exhibit periodic orbits. This note shows that, for any parameter choices, every bounded trajectory satisfies a Poincare'-Bendixson property: the dynamics in the omega-limit set of any precompact solution is conjugate to the dynamics in a compact invariant subset of a two-dimensional Lipschitz dynamical system, thus precluding chaotic and other strange attractors.



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Last modified: Fri Jun 19 21:49:04 2026
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