Date of Award
Doctor of Philosophy (PhD)
Tong , Chenning
Miller , Richard S
Zumbrunnen , David A
Cell printing is an emerging technology that uses droplets to deliver cells to desired positions with resolution potentially comparable to the size of single cells. In particular, ink–jet based cell printing technique has been successfully used to build simple bio–constructs and has shown a promise in building complex bio–structures or even organs. Two important issues in ink–jet based cell printing are the moderate survival rate of delicate cells and the limited cell placement resolution. Resolving these issues is critical for the ink–jet based cell printing techniques to realize their full potential.
In this work, we use numerical simulations to reconstruct the impact of a droplet loaded with a single cell onto a pool of viscous fluids to gain insights into the droplet and cell dynamics during cell printing. We developed a mathematical model for this process: the droplet, pool and air are modeled as Newtonian fluids, and their flow is modeled as a laminar flow governed by the Navier–Stokes equation. The cell is modeled as an axisymmetric solid object governed by the neo–Hookean law and also has a shear viscosity that is the same as that of its host droplet. To numerically solve the coupled fluid and cell motion, we used a hybrid method in which fluid flow is solved on a fixed Cartesian grid and the deformation of solid body is solved on a Lagrangian mesh. We also developed a new full Eulerian method, termed the solid level set (SLS) method, to simulate cell printing. The key idea is to track the deformation of the solid body using four level set functions on a fixed Cartesian grid instead of using a Lagrangian mesh. The SLS method is easy to implement and addresses several challenges in simulations of fluid–tructure interactions using hybrid Eulerian/Lagrangian meshes. Using codes developed based on the above methods, we systematically investigated the fluid and cell dynamics during the cell printing process. We studied how the droplet penetration depth, droplet lateral spreading, cell stress and cell surface area change are affected by printing conditions such as impact velocity, pool depth, and cell stiffness. Our simulations indicate that cell experiences significant stress (∼20kPa) and local surface area dilation (∼100%) during the impact process. The latter suggests that cell membrane is temporally ruptured during the printing process, and is consistent with the gene transfection observed during cell printing. We speculate that the survival of cell through the rather violent cell printing process may be related to the briefness of the impact process, which only lasts about 0.1 milliseconds. Based on our simulation results, several strategies have been proposed to reduce the stress and membrane dilation of cells during cell printing.
He, Ping, "Fluid Dynamics of Cell Printing" (2011). All Dissertations. 727.