Deng, XunLv, HuiZhang, QiangLai, Edmund Ming Kit2025-05-052025-05-052024-02-28Computers in Biology and Medicine, ISSN: 0010-4825 (Print); 0010-4825 (Online), Elsevier, 171, 108213-. doi: 10.1016/j.compbiomed.2024.1082130010-48250010-4825http://hdl.handle.net/10292/19143The nonlinearity and non-separability of the antithetic PID (aPID) controller have provided greater flexibility in the design of biochemical reaction networks (BCRNs), resulting in significant impacts on biocontrol-systems. Nevertheless, the dilution of control species is disregarded in designs of aPID controllers, which would lead to the failure of inhibition mechanism in the controller and loss of robust perfect adaptation (RPA)-the biological counterpart of robust steady-state tracking. Here, the impact of dilution processes on the structure of aPID is investigated in this study. It is discovered that the proportional and low-pass filters are altered when the dilution processes is present in control species, which increases the coupling between the controller parameters. Moreover, additional integrations for the reference signal and control output generated by control species dilution further leads to the loss of RPA. Subsequently, a novel aPID controller represented by BCRNs, termed quasi-aPID, has been designed to eliminate the detrimental effects of the dilution processes. In an effort to ameliorate the interdependencies among controller parameters, a degradation inhibition mechanism is employed within this controller. Furthermore, this work establishes the limiting relationship between the controller's reaction rates in order to guarantee RPA, while abstaining from the introduction of supplementary species and biochemical reactions. By using the quasi-aPID controller in both the Escherichia coli gene expression model and the whole-body cholesterol metabolism model, its effectiveness is confirmed. Simulation results demonstrate that, the quasi-aPID exhibits a smaller absolute steady-state error in both models and guarantees the RPA property.Copyright © 2024 Elsevier Ltd. All rights reserved. This is the author’s version of a work that was accepted for publication in (see Citation). Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. The definitive version was published in (see Citation). The original publication is available at (see Publisher's Version).Antithetic PID controllerBCRNsDegradation inhibition mechanismRobust perfect adaptationSpecies dilutionAntithetic PID controllerBCRNsDegradation inhibition mechanismRobust perfect adaptationSpecies dilution31 Biological Sciences3102 Bioinformatics and Computational Biology4203 Health Services and Systems42 Health Sciences46 Information and Computing Sciences4601 Applied Computing08 Information and Computing Sciences09 Engineering11 Medical and Health SciencesBiomedical Engineering3102 Bioinformatics and computational biology4203 Health services and systems4601 Applied computingJournal ArticleOpenAccess10.1016/j.compbiomed.2024.108213