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乳酸生物传感器的操作稳定性研究:建模、参数识别与稳定性分析。

Operational stability study of lactate biosensors: modeling, parameter identification, and stability analysis.

作者信息

Martsenyuk Vasyl, Soldatkin Oleksandr, Klos-Witkowska Aleksandra, Sverstiuk Andriy, Berketa Ksenya

机构信息

Department of Computer Science and Automatics, University of Bielsko-Biala, Bielsko-Biala, Poland.

Department of Biomolecular Electronics, Institute of Molecular Biology and Genetics of NASU, Kyiv, Ukraine.

出版信息

Front Bioeng Biotechnol. 2024 Jul 16;12:1385459. doi: 10.3389/fbioe.2024.1385459. eCollection 2024.

Abstract

INTRODUCTION

This paper investigates the operational stability of lactate biosensors, crucial devices in various biomedical and biotechnological applications. We detail the construction of an amperometric transducer tailored for lactate measurement and outline the experimental setup used for empirical validation.

METHODS

The modeling framework incorporates Brown and Michaelis-Menten kinetics, integrating both distributed and discrete delays to capture the intricate dynamics of lactate sensing. To ascertain model parameters, we propose a nonlinear optimization method, leveraging initial approximations from the Brown model's delay values for the subsequent model with discrete delays.

RESULTS

Stability analysis forms a cornerstone of our investigation, centering on linearization around equilibrium states and scrutinizing the real parts of quasi-polynomials. Notably, our findings reveal that the discrete delay model manifests marginal stability, occupying a delicate balance between asymptotic stability and instability. We introduce criteria for verifying marginal stability based on characteristic quasi-polynomial roots, offering practical insights into system behavior.

DISCUSSION

Qalitative examination of the model elucidates the influence of delay on dynamic behavior. We observe a transition from stable focus to limit cycle and period-doubling phenomena with increasing delay values, as evidenced by phase plots and bifurcation diagrams employing Poincaré sections. Additionally, we identify limitations in model applicability, notably the loss of solution positivity with growing delays, underscoring the necessity for cautious interpretation when employing delayed exponential function formulations. This comprehensive study provides valuable insights into the design and operational characteristics of lactate biosensors, offering a robust framework for understanding and optimizing their performance in diverse settings.

摘要

引言

本文研究乳酸生物传感器的运行稳定性,该传感器是各种生物医学和生物技术应用中的关键设备。我们详细介绍了专为乳酸测量定制的安培型传感器的构造,并概述了用于实证验证的实验装置。

方法

建模框架纳入了布朗动力学和米氏动力学,整合了分布延迟和离散延迟以捕捉乳酸传感的复杂动态。为确定模型参数,我们提出一种非线性优化方法,利用布朗模型延迟值的初始近似值来为后续的离散延迟模型提供参数。

结果

稳定性分析是我们研究的基石,重点是围绕平衡态进行线性化并仔细研究准多项式的实部。值得注意的是,我们的研究结果表明离散延迟模型表现出临界稳定性,处于渐近稳定性和不稳定性之间的微妙平衡。我们引入了基于特征准多项式根来验证临界稳定性的标准,为系统行为提供了实际见解。

讨论

对模型的定性研究阐明了延迟对动态行为的影响。我们观察到随着延迟值增加,从稳定焦点到极限环以及倍周期现象的转变,使用庞加莱截面的相图和分岔图证明了这一点。此外,我们确定了模型适用性的局限性,特别是随着延迟增加解的正性丧失,强调在使用延迟指数函数公式时谨慎解释的必要性。这项全面研究为乳酸生物传感器的设计和运行特性提供了有价值的见解,为理解和优化其在不同环境中的性能提供了一个强大的框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf0/11292224/32538fcc281d/fbioe-12-1385459-g001.jpg

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