Hallam, Stephanie (2025). The development of an in vitro model of microvascular collapse. University of Birmingham. Ph.D.
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Hallam2025PhD.pdf
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Abstract
Trauma conditions affecting the microvasculature in humans such as Acute Compartment Syndrome (ACS) lack reliable and fast diagnosis methods. Advances in “Lab-on-a-chip” technology through the use of microfluidics have allowed for in vitro models of microvascular dysfunction and collapse to be created. Their design is complex, with variables such as biological compatibility, geometry, and the ability of the hydrodynamics to be experimentally measured at the microscale competing with the creation of a design that maintains physiological relevance.
Various microfluidic models of blood vessels and blood vessel networks were developed to investigate the effect of microvascular collapse on wall shear stress using soft lithography methods and PDMS. The flow within the models over a physiologically relevant range of applied upstream pressures 2000 to 4700 Pa was measured using Ghost Particle Velocimetry (GPV), an optical method. Changes in wall shear stress are known to affect cell behaviour which could be used in creating diagnostic criteria for conditions such as ACS. It was found that small changes in the geometric design, using models with channel widths of 200, 300 and 400 μm, could be used to mimic the resistance changes seen as the microvasculature collapses and mimic shear stress ranges seen in vivo, 1-9.5 Pa in the 200 μm model. Flows within the models had Reynolds numbers of 1-23 in the non-stenosed region and a maximum of 38 in the stenotic region at the highest pressure, 4700 Pa. Increased resistance to flow was observed when a stenosis, an area of decreased cross-sectional area, is incorporated into the design mimicking increased resistance in the channel during collapse, at the physiologically relevant pressures of 2000, 3200 and 4700 Pa. Using ANSYS Fluent, laminar steady-state Computational Fluid Dynamics (CFD) models were created to replicate the experiments and were validated using GPV data and via analytical solutions, supporting claims of increasing resistance, decreasing flow rate and detecting a peak range in wall shear stress.
Experimental models incorporating side branches following Murray’s law, side branching with one branch at 45° from the main channel and even branching, where the main channel branches into two channels both at 45° to the main channel; were found to increase resistance further and display variation of shear stress in different locations within the device, with values of 0.1-3.5 Pa at Reynolds numbers of 0.3-1. These branched models also mimicked shear stress ranges seen in vivo, creating suitable models for studying cell behaviour under physiologically relevant conditions. Models with deformable side walls, controlled by fluid bladders (referred to as micropumps) on the sides of the channel, were created through modification of the initial 200 μm designs using a 25:1 ratio of PDMS base to curing agent. Additionally, the inclusion of micropumps into the device design allowed for dynamic studies of up to 100% deformation of the channel width at the point of maximum stenosis. These models highlighted how the channel cross-section affects the in vitro resistance increase and the resultant shear stress ranges, maintaining suitable shear stress values for the study of cell behaviour, 0.3-2.4 Pa at flows with Reynolds numbers of 0.02-0.06.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||||||||
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| Licence: | All rights reserved | |||||||||||||||
| College/Faculty: | Colleges > College of Engineering & Physical Sciences | |||||||||||||||
| School or Department: | School of Chemical Engineering | |||||||||||||||
| Funders: | Engineering and Physical Sciences Research Council | |||||||||||||||
| Subjects: | T Technology > TA Engineering (General). Civil engineering (General) T Technology > TP Chemical technology |
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| URI: | http://etheses.bham.ac.uk/id/eprint/16251 |
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