Implementing vertex dynamics models of cell populations in biology within a consistent computational framework

The dynamic behaviour of epithelial cell sheets plays a central role during development, growth, disease and wound healing. These processes occur as a result of cell adhesion, migration, division, differentiation and death, and involve multiple processes acting at the cellular and molecular level. Computational models offer a useful means by which to investigate and test hypotheses about these processes, and have played a key role in the study of cell–cell interactions. However, the necessarily complex nature of such models means that it is difficult to make accurate comparison between different models, since it is often impossible to distinguish between differences in behaviour that are due to the underlying model assumptions, and those due to differences in the in silico implementation of the model. In this work, an approach is described for the implementation of vertex dynamics models, a discrete approach that represents each cell by a polygon (or polyhedron) whose vertices may move in response to forces. The implementation is undertaken in a consistent manner within a single open source computational framework, Chaste, which comprises fully tested, industrial-grade software that has been developed using an agile approach. This framework allows one to easily change assumptions regarding force generation and cell rearrangement processes within these models. The versatility and generality of this framework is illustrated using a number of biological examples. In each case we provide full details of all technical aspects of our model implementations, and in some cases provide extensions to make the models more generally applicable

Finite element and mechanobiological modelling of vascular devices

There are two main surgical treatments for vascular diseases, (i) percutaneous stent deployment and (ii) replacement of an atherosclerotic artery with a vascular graft or tissue engineered blood vessel. The aim of this thesis was to develop computational models that could assist in the design of vascular stents and tissue engineered vascular grafts and scaffolds. In this context, finite element (FE) models of stent expansion in idealised and patient specific models of atherosclerotic arteries were developed. Different modelling strategies were investigated and an optimal modelling approach was identified which minimised computational cost without compromising accuracy. Numerical models of thin and thick strut stents were developed using this modelling approach to replicate the ISAR-STEREO clinical trial and the models identified arterial stresses as a suitable measure of stent induced vascular injury. In terms of evaluating vascular graft performance, mechanical characterisation experiments can be conducted in order to develop constitutive models that can be used in FE models of vascular grafts to predict their mechanical behaviour in-situ. In this context, bacterial cellulose (BC), a novel biomaterial, was mechanically characterised and a constitutive model was developed to describe its mechanical response. In addition, the interaction of smooth muscle cells with BC was studied using cell culture experiments. The constitutive model developed for BC was used as an input for a novel multi-scale mechanobiological modelling framework. The mechanobiological model was developed by coupling an FE model of a vascular scaffold and a lattice free agent based model of cell growth dynamics and remodelling in vascular scaffolds. By comparison with published in-vivo and in-vitro works, the model was found to successfully capture the key characteristics of vascular remodelling. It can therefore be used as a predictive tool for the growth and remodelling of vascular scaffolds and graft

Spectroscopic Studies and Mathematical Modeling of Laser Material Interaction for Development of Intelligent Quality Monitoring System.

This research investigates the fundamental physics of laser processing of multi-coated materials, through spectroscopic studies and a mathematical modeling of laser material interaction. This work focuses particularly on developing an in-situ quality monitoring system by detecting defects generated in the processing, understanding the effect of coated materials on defects formation, and further characterizing differences between newly developed lasers in regard to energy transfer. First, several welding defects generated in CO2 laser processing of a multi-coated material are monitored using Optical Emission Spectroscopy (OES). Tracking the specific constituent behaviors that induce the defects is proposed as a novel way to monitor the process. Second, in order to obtain promising results in both defect detection and defect classification, a machine learning algorithm, a Support Vector Machine (SVM), is adopted for the spectral data analysis using the richness of the available data. The richness is a major benefit in the use of the optical emission spectroscopy because the spectrometer can resolve and distinguish each spectral line of the constituents of the target materials. Third, a numerical simulation study is presented to investigate the effect of the coating material for understanding the interfacial phenomena in the laser processing of the multi-coated material. These interfacial phenomena are important because they determine the processed qualities of the target samples in the laser material interaction. The interfacial phenomena such as recoil pressure, capillary and thermo capillary force are investigated by comparing a coating free material with a coated material. Finally, characteristics of the energy transfer of the disk laser and the fiber laser are identified to provide users with insight into which laser might be more suitable for a given application. To assess the laser systems, two factors are considered: energy absorption by the laser induced plasma, which is an inevitable phenomenon in laser material interactions, and the penetration features of the samples irradiated by the attenuated laser beam after absorption by the plasma. The work presented in this study can be utilized to achieve the quality assurance, to understand energy transfer in the laser material processing, and thus eventually to control the process.PHDMechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/98014/1/iamshlee_1.pd

2023 IMSAloquium

Welcome to IMSAloquium 2023. This is IMSA’s 36 th year of leading in educationalinnovation, and the 35th year of the IMSA Student Inquiry and Research (SIR) Program.https://digitalcommons.imsa.edu/archives_sir/1033/thumbnail.jp

Laser Surface Structuring of Alumina

Alumina ceramic is an important abrasive material for grinding wheels used for rough grinding/machining of materials in manufacturing industry. Purpose of this work is to explore laser surface structuring of alumina grinding wheels for precision machining/grinding of materials by modifying surface microstructure of wheels. Major objective of this work is to study the evolution of surface microstructure and depth of modification such that microstructures/properties of modified wheels can be efficiently tailored based on fundamental understanding of physical processes taking place during laser surface structuring. Surface structuring of alumina using a continuous wave Nd:YAG laser resulted in significant surface melting and subsequent rapid solidification. The surface modified alumina consisted of microstructure characterized by regular polygonal and faceted surface grains with well defined edges and vertices. Such multifaceted grains act as micro-cutting tools on the surface of grinding wheels facilitating micro-scale material removal during precision machining. The formation of faceted morphology is explained on the basis of evolution of crystallographic texture in laser modified alumina. Furthermore, complete crystallographic description of multifaceted morphology of surface grains is provided based on detailed analysis of surface micro-texture. Due to complexity of microstructure formed during laser surface structuring, a fractal analysisbased approach is suggested to characterize surface microstructures. Detailed analysis of the effects of laser interaction with porous alumina ceramic indicated that melt surface undergoes rapid evaporation resulting in generation of high (\u3e105 Pa) evaporationinduced recoil pressures. These pressures drive the flow of melt through underlying porous alumina during modification extending the depth of modification. An integrative modeling approach combining thermal analysis and fluid flow analysis resulted in better agreements between predicted and experimental values of depths of melting. Finally, improvements in microindentation fracture toughness of alumina ceramic are reported with increasing laser fluence. Such improvements in the fracture toughness seem to be derived from better surface densification and coarsening of grain structure. The understanding of the evolution of faceted morphology, depth of surface modifications and improvements in fracture properties in laser surface microstructured alumina ceramic reached in this work provides the foundation for tailoring of surface microstructures/properties of alumina grinding wheels for precision machining applications

Computational fluid dynamics techniques for fixed-bed biofilm systems modeling : numerical simulations and experimental characterization

This thesis is focused on the development of one-phase and multiphase models using computational fluid dynamics (CFD) techniques to analyze biosystems behavior at mesoscale. In the first part, the operation of a fixed-bed biofilm reactor was simulated using Eulerian one-phase models, coupling fluid flow dynamics with biokinetics. The results reproduced accurately bioreactor performance, being experimentally verified hydrodynamics and species transport. However, the models had to be adapted to reproduce real scenarios where the biofilm motion can play a key role. On further consideration, this thesis suggested the development of Eulerian two-phase models using volume of fluid (VOF) method, defining the biofilm as an independent fluid phase by means of a comprehensive analysis of its rheological properties. This characterization became essential for accurately reproducing the fluid-biofilm interaction, describing the biofilm as a non-Newtonian fluid, which parameters were strongly dependent on its density. Thus, in the second part of this thesis, this novel continuum approach for biosystems modeling was tested, considering the required implementations to reproduce the species transfer at the interface (liquid-biofilm), and the possible growth of the biofilm phase. This new approach coupled fluid dynamics under laminar conditions with biochemical phenomena and/or biofilm mechanical behavior, so being able to reproduce the fluid stress over the biofilm, and its motion. The simulated results were experimentally verified evaluating transport mechanisms under different hydrodynamic conditions, and the model capability to reproduce shear-induced deformation and detachment, and recoil in biofilms was stated. In the third part of this thesis, the capacities of the new approach of continuum model were further tested, in order to reproduce wide range of hydrodynamic conditions to which biosystems can be exposed. Particularly, Eulerian multiphase models were developed and solved to characterize turbulent gas flows behavior over biofilms attached to walls. A coupled method of VOF and level-set, and shear stress transport (SST) k-omega model were used, reproducing accurately gas-biofilm interactions, turbulence and near-wall treatment. The simulated results were experimentally verified to confer identity to developed CFD approach, correctly describing the interfacial instabilities on the fixed-bed biofilm, such as ripples formation, and biofilm displacement and removal from its original position. The results also revealed that biofilm fluidization was the mechanisms behind the impact of turbulent air flows. Finally, in the last part of this thesis, the work was focused on the accurate analysis of fluid-biofilm interface, and on the necessity of acquiring local experimental data to verify models. The applicability of needle-probes as an innovative technique for in-situ biofilm layer and fluid interfaces detection was examined. The sensor probe performance was calibrated and verified in multiphase systems, revealing its practicability for interface detection, depth measuring, and surface reconstruction. So, a feasible tool for the experimental characterization of biosystems and models verification at mesoscale was provided. Therefore, the Eulerian multiphase approach proposed in this thesis, together with the experimental analyses, revealed the potential of CFD techniques as an alternative tool for fixed-bed biofilm systems modeling, allowing to reproduce simultaneous spatial and temporal, physical and biochemical phenomena under different operating conditions and biosystems configurations. The proposed approach helped to address key aspects of biofilm modeling such as its deformation and detachment under laminar and turbulent conditions.El estudio y modelización de los sistemas biológicos o biosistemas sigue siendo un reto que requiere explorar los fenómenos físicos y bioquímicos desde diferentes niveles de resolución espacial y temporal. Incluso para el régimen de flujo laminar más simple, las interacciones fluido- biopelícula deben ser investigadas en detalle. La dinámica de fluidos computacional (CFD, del inglés computational fluid dynamics) es una herramienta prometedora y extendida para modelar rigurosamente la hidrodinámica en reactores, la cual recientemente ha surgido como un enfoque alternativo para el modelo de biorreactores. Sin embargo, las complicadas interacciones entre la biopelícula y las fases fluidas (gas y líquido), aún no han sido descritas utilizando este tipo de técnicas. En esta tesis, se diseñaron y desarrollaron modelos monofásicos y multifásicos utilizando códigos comerciales CFD para analizar el comportamiento de los biosistemas a nivel de mesoescala. En la primera parte, se simuló la operación de un reactor de biopelícula de lecho fijo utilizando modelos monofásicos Eulerianos, acoplando la dinámica del flujo de fluido con la biocinética, e implementando un modelo de pérdidas de presión hidráulica para considerar las características físicas de la biopelícula. Esta técnica permitió obtener resultados precisos relacionados con el rendimiento del bioreactor, verificando experimentalmente la hidrodinámica y el transporte de las especies. Sin embargo, estos modelos necesitaron ser mejorados para poder reproducir escenarios reales donde el movimiento de la biopelícula puede jugar un papel importante. Por ello, se sugirió el desarrollo de modelos Eulerianos de dos fases utilizando el método de volumen de fluido (VOF, del inglés volume of fluid), donde la biopelícula se definió como una fase líquida independiente. Para desarrollar estos modelos, la caracterización experimental de las propiedades de la biopelícula fue imprescindible para adquirir un conocimiento profundo de los fenómenos implicados, especialmente para reproducir con precisión la interacción fluida sobre la biopelícula, ya que tiene un efecto directo sobre la estructura de la biopelícula. Como resultado, se desarrolló un análisis reológico integral bajo flujos de cizallamiento estables, oscilatorios y transitorios, para obtener las propiedades mecánicas macroscópicas y analizar los mecanismos de unión entre los componentes estructurales a microescala. Los resultados experimentales señalaron que las biopelículas mostraban un carácter gelatinoso, y teniendo un comportamiento de adelgazamiento del cizallamiento con una tensión de fluencia. Así, la biopelícula se caracterizó como un fluido no Newtoniano, cuyos parámetros dependían en gran medida de la densidad de la biopelícula estudiada. En la segunda parte de esta tesis, se propuso, implementó y probó un nuevo enfoque continuo para el modelado de biosistemas. Esto incluyó la definición de biopelícula como una fase fluida no Newtoniana, y otras implementaciones para reproducir la transferencia de especies en la interfaz (líquido-biopelícula), y para vincular el posible crecimiento de la fase de biopelícula con las especies transportadas y transferidas, entre otras consideraciones. Este nuevo enfoque combinó la dinámica de fluidos en condiciones laminares con fenómenos bioquímicos y/o comportamiento mecánico de la biopelícula, calculando con precisión la fracción volumétrica de las fases a lo largo del dominio, pudiendo así reproducir la interacción fluido-biopelícula en caso de movimiento de la biopelícula. Los resultados simulados fueron verificados experimentalmente evaluando los mecanismos de transporte bajo diferentes condiciones hidrodinámicas. Adicionalmente, se mostró la capacidad del modelo desarrollado para reproducir deformaciones y desprendimientos inducidos por cizallamiento y el retroceso (o recuperación) en las biopelículas, estando los resultados simulados en concordancia cualitativa con las observaciones experimentales. Con el fin de reproducir una amplia gama de condiciones hidrodinámicas a las que pueden estar expuestos los biosistemas, las capacidades del nuevo enfoque del modelo continuo se probaron más a fondo. En particular, se desarrollaron y resolvieron modelos Eulerianos multifásicos para caracterizar el comportamiento de los flujos de gas turbulento sobre biopelículas adheridas a la pared, utilizando un método acoplado de VOF y de conjunto de nivel (en inglés level-set) y el modelo SST k-ω, con el fin de reproducir con precisión las interacciones gas-biopelícula, la turbulencia y el tratamiento cercano a la pared. Los resultados simulados fueron verificados experimentalmente para conferir identidad al enfoque de CFD desarrollado, describiendo correctamente las inestabilidades interfaciales en la biopelícula de lecho fijo, tales como la formación de ondulaciones, y el desplazamiento y desprendimiento de la biopelícula de su posición original. Los resultados también revelaron que la fluidización del biopelícula era el mecanismo que se encontraba detrás del impacto de flujos de aire turbulentos. Finalmente, en la última parte de esta tesis, el trabajo se centró en el análisis preciso de la interfase fluido-biopelícula, y en la necesidad de adquirir datos experimentales locales para verificar modelos, como se había comentado en los capítulos anteriores. Se examinó la aplicabilidad de las sondas de aguja como técnica innovadora para la detección in-situ de la capa de biopelícula y de las interfases de los fluidos. El comportamiento de las sondas fue calibrado y verificado en sistemas multifásicos, mostrando su practicidad para la detección de interfases, medición de profundidad y reconstrucción de superficies. Así pues, se proporcionó una herramienta viable para la caracterización experimental de biosistemas y la verificación de modelos a mesoescala. Por lo tanto, el enfoque multifase Euleriano propuesto en esta tesis, junto con los análisis experimentales, reveló el potencial de las técnicas CFD como una herramienta alternativa al modelo de sistemas de biopelícula de lecho fijo, permitiendo reproducir simultáneamente fenómenos físicos y bioquímicos en espacio y tiempo, y bajo diferentes condiciones de operación y configuraciones de los biosistemas. El enfoque propuesto ayudó a abordar aspectos clave del modelado de biopelículas como su deformación y desprendimiento bajo condiciones laminares y turbulenta

Exploiting Polymer Theory to Simulate the Rheology of Micellar Solutions and Polymer Glasses

Exhibiting different rheological (viscoelastic) behaviors, micellar solutions and polymeric glasses are at the center of many applications. For micellar solutions, I have developed a mesoscopic simulation model, drawing from concepts developed for entangled polymer melts, to account for linear rheology of different micelle structures (linear and branched micelles). Through a “pointer” algorithm I developed, this new model tracks boundaries between relaxed and unrelaxed parts of micelles that are diffusing in entanglement tubes, and uses polymer-like mechanisms along with intermicellar reactions (breakage and reformation) to compute rheology, which allows, for the first time, not only quantitative prediction of flow behaviors but also estimation of important micelle properties from rheological measurement with much greater accuracy than ever before. For polymeric glasses, by treating the short glassy segments as “solvent” for the slow-relaxing polymeric part, a hybrid model has been developed that combines a constitutive model of the glassy solvent with Brownian dynamics simulations of polymers, whose relaxation is coupled to the glassy dynamics through the drag coefficient. This hybrid model successfully captures numerous behaviors of polymeric glass (yielding, strain hardening, recovery, physical aging, and flow rejuvenation) under various types of deformations as well as the effects of polymer pre-orientation, whose results prove to be consistent with observations from both experiments and molecular level simulations.PHDChemical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/143963/1/weizhong_1.pd

Design optimisation for stent manufacture

Intravascular stents of various designs are currently used to prop open diseased arteries and there is evidence that different stent geometries have different in-stent restenosis rates. The majority of commercially available stents are designed generically to fit all individuals. Recent advances in imaging and catheter technologies, however, allow measurement of lesion shape and stiffness. Incorporating patient specific data into the stent design process could enable the development of customised stents. Considering the variety of lesion types, it is envisaged that better outcomes will be achieved if a stent is custom designed in such a way that it has variable radial stiffness longitudinally to hold the varying pressure of plaque and healthy artery at the same time while maintaining an acceptable lumen diameter. This type of operation is suitable for topology optimisation potentially allowing for optimal material distribution of a stent. The primary aim of this research is to develop new stent designs for a set of plaque types and investigate the final radius of the lumen after stent implantation. Stent geometries were obtained by topology optimisation for minimised compliance under different stenosis levels and plaque materials. Three types of stenosis levels by area, i.e. 30%, 40% and 50% with each type having three different plaque material properties i.e. calcified, cellular and hypocellular were studied. The optimisation results were transformed to clear design concepts and their performance was evaluated by implanting them in their respective stenosed artery types using finite element analysis. The results were compared with a generic stent in similar arteries, which showed that the new designs showed less recoil. In the hardest (calcified) of plaques studied, topology optimised designs overall resulted in 2%, 2% and 6% residual area stenosis compared to 10%, 29% and 35% from the generic design in arteries with 30%, 40% and 50% stenosis respectively. It was shown that higher material distribution resulted in the central region of the stent in order to resist implantation recoil due to higher plaque compressive loads. Additive manufacturing (AM) was utilised to validate the computational approach used in this thesis. This work provides a proof of concept for stents tailored to specific lesions in order to minimise recoil and maintain a patent lumen in stenotic arteries