Uncertainty modelling and stability robustness analysis of nucleic acid-based feedback control systems

Nuno Paulino, Mathias Foo, Jongmin Kim, Declan Bates

    Research output: Chapter in Book/Report/Conference proceedingConference proceedingpeer-review

    2 Citations (Scopus)
    38 Downloads (Pure)


    Recent advances in nucleic acid-based chemistry have highlighted its potential for the implementation of biomolecular feedback circuits. Here, we focus on a proposed design framework, which is able to approximate the inputoutput behaviour of key linear operators used in feedback control circuits by combining three elementary chemical reactions. The implementation of such circuits using DNA strand displacement introduces non-linear internal dynamics due to annihilation reactions among different molecular species. In addition, experimental implementation of in silico designs introduces significant levels of uncertainty and variability in reaction rate constants and equilibrium concentrations. Previous work using this framework has overlooked the practical
    implications of these issues for the construction of nucleic acidbased feedback control circuits. Here, we analyse the impact of these nonlinearities and uncertainties on the stability of a biomolecular feedback loop.We show that a rigorous analysis of its nucleic acid-based implementation requires an investigation of the associated non-linear dynamics, to decide on realisable
    parameters and acceptable equilibrium concentrations. We also show how the level of experimental uncertainty that is tolerated by the feedback circuit can be quantified using the structured singular value. Our results constitute a first step towards the development of a rigorous robustness analysis framework for nucleic acid-based feedback control circuits.
    Original languageEnglish
    Title of host publicationIEEE Conference on Decision and Control
    Number of pages6
    ISBN (Electronic)978-1-5386-1395-5
    ISBN (Print)978-1-5386-1396-2
    Publication statusPublished - 17 Dec 2018
    EventIEEE Conference on Decision and Control - Florida, Miami Beach, United States
    Duration: 17 Dec 201819 Dec 2018

    Publication series

    NameProceedings of the IEEE Conference on Decision & Control / IEEE Control Systems Society. IEEE Conference on Decision & Control
    ISSN (Print)0743-1546
    ISSN (Electronic)2576-2370


    ConferenceIEEE Conference on Decision and Control
    Country/TerritoryUnited States
    CityMiami Beach


    • Uncertainty
    • Feedback control
    • Robustness
    • Stability analysis
    • Chemicals
    • Analytical models


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