Fluid dynamics of aggregation and attachment

在工业、生物和药理学过程中，从外科植入物的细菌定植到生物材料的制造，流动介导的微尺度物种聚集和附着在表面是普遍存在的。由于流体应力和边界可以改变细菌细胞和蛋白质的形状、游动方向和生物功能，流体流动可以促进或减少聚集。连续体模型非常适合在与工业系统和生物功能相关的长度尺度和时间尺度上捕捉这些过程。然而，不以微尺度过程为基础的连续统模型往往无法提供定量预测。在这项研究中，我将开发一个框架，将流体响应物种的精确流动介导的微观动力学纳入聚合系统的宏观模型。我将运用这种方法来研究与工业和医疗保健及时相关的两个系统：多孔介质中的生物膜形成和注射过程中的治疗性蛋白质聚集。该框架将在理论上发展，首先在动力学微尺度连续体模型中模拟剪切下的附着，然后探索在哪些参数制度下可以达到微尺度动力学的平均场描述。然后，我将使用均质化和渐近多尺度分析将这些微尺度连续动力学纳入宏观流体模型。这些模型将在微观尺度和宏观尺度上使用实验和微观尺度模拟数据进行验证，然后通过控制流量参数和设备设计来预测最小化两个系统堵塞的方法。这项工作将在连续体建模方面取得新的理论进展，以及定量预测，以指导耐抗生素感染的治疗、治疗药物的生产和疫苗的提供，从而对全世界数百万人产生有益影响。

Flow-mediated aggregation and attachment of microscale species to surfaces is pervasive in industrial, biological and pharmacological processes, ranging from bacterial colonisation of surgical implants to biomaterial manufacture. Since fluid stress and boundaries can alter the shape, swimming direction and biological function of bacterial cells and proteins, fluid flow can either promote or reduce aggregation. Continuum modelling is well suited to capture these processes over the length scales and timescales relevant to industrial systems and biological functions. However, continuum models which are not grounded in microscale processes are often unable to provide quantitative predictions. In this fellowship, I will develop a framework to incorporate accurate flow-mediated microscale dynamics of fluid-responsive species into macroscale models of aggregating systems. I will apply this methodology to study two systems with timely relevance to industry and healthcare: biofilm formation in porous media and therapeutic protein aggregation during injection. This framework will be developed theoretically by first modelling attachment under shear in kinetic microscale continuum models, then exploring under which parameter regimes a mean-field description of the microscale dynamics can be reached. I will then incorporate these microscale continuum dynamics into macroscopic fluid models using homogenisation and asymptotic multiple scales analysis. These models which will be validated using experimental and microscale simulated data both at the microscale and macroscale and will then be used to predict ways of minimising clogging in both systems through control of flow parameters and device design. This work will produce new theoretical advances in continuum modelling, as well as quantitative predictions to guide the treatment of antibiotic-resistant infections, manufacturing of therapeutic drugs and the delivery of vaccines, with beneficial impacts on millions of people worldwide.