Coupled biophysical simulations of cell-cell interaction and drug delivery microrobots

Open Access
- Author:
- Gaskin, Byron Jerrod
- Graduate Program:
- Bioengineering
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- May 01, 2018
- Committee Members:
- Robert Francis Kunz, Dissertation Advisor/Co-Advisor
Robert Francis Kunz, Committee Chair/Co-Chair
Cheng Dong, Committee Member
William O Hancock, Committee Member
Robert Lee Campbell, Outside Member
Sean Michael Mcintyre, Special Member - Keywords:
- computational mechanics
personalized medicine
computational fluid dynamics
computational structural mechanics
biochemistry
fluid dynamics
solid mechanics
continuum mechanics
blood flow
blood cells
drug delivery
drug targeting
microrobotics
flowing bodies
hyperelasticity
rigid body motion - Abstract:
- A computational tool has been developed to model flowing cellular systems and has been applied to direct numerical simulation of microvascular flows with a vision towards personalized medicine. This tool couples computational fluid dynamics (CFD), computational structural mechanics (CSM), six degree-of-freedom (6DOF) motion, and surface biochemistry (SB), in the context of interface-resolved cell geometry, to provide a detailed model of the heterogeneous blood flow microenvironment. This tool can be used to study drug-mediated cellular interactions in the vasculature and design magnetically-actuated drug delivery microrobots (DDMRs) with targeting capabilities. The research hypothesis of this dissertation was that applying direct numerical simulation to study drug-mediated cellular interactions and DDMR dynamics can lead to protocols for patient-specific drug treatments, including use of DDMRs. The goal of this dissertation work was to validate the individual components of this tool and explore the capabilities and limitations of the tool being developed. The specific aims of this research were to develop a new coupled interface-resolved fluid-structure-biochemistry interaction (FSBI) numerical scheme for low Reynolds number vascular flows and perform direct numerical simulations of cell-cell interactions and DDMRs undergoing magnetic actuation. The first specific aim is crucial as the fluid-solid interface must be handled with care when solving fluid-structure interaction (FSI) problems. This is due to the inconsistency that arises from solving for velocity in the fluid subdomain and displacement in the solid subdomain. Several coupling procedures have been developed, implemented, and evaluated to determine an appropriate coupling strategy for handling relevant problems of interacting bodies in vascular flow. The FSI formulations have been implemented into a robust, production-ready flow solver capable of modeling interactions between cells. For the second specific aim, complete FSBI problems with multiple cell types and DDMR designs are presented to show the capabilities of the developed scheme. The input parameters for these problems include initial cell locations, biochemical reaction constants, solver time step, blood cell structural properties, DDMR geometry, and flow shear rate. This work provides key innovations over current state-of-the-art, namely an approach to solve the full flow-structure-biochemistry system by modifying readily available vascular flow solvers, demonstrated ability of finite-volume discretization of hyperelastic constitutive models for large motion and large strain systems, and design and evaluation capabilities for magnetically actuated DDMRs in microvascular flow. Collectively, the developed tool can be used in future work to use patient-specific biomarker data to develop personalized drug treatments protocols, design magnetically-actuated drug delivery microrobots for optimal tissue targeting, and educate a reduced-order-model with decreased runtime for greater feasibility of clinical deployment.