James Bird
Linking Cell Viability and Stress Events Using a Microfluidic Platform
PROJECT DESCRIPTION
Cells are used in bioreactors to manufacture therapeutic drugs. Gas bubbles are injected to keep the cells alive; yet when these bubbles coalesce or rupture, the rapid deformations is believed to damage and kill nearby cells. This project aims to better understand the connection between flow profiles and cell damage. Measurement of the viability of a mammalian cell can be accomplished in many different ways. To asses a mammalian cell’s degree of function the measurement of certain reaction products can be carried out either by direct or indirect testing. The starkest measure of viability is whether a cell is alive or dead; this cell state can be determined through the use of an exclusion dye which is kept out by a cell that is alive, and taken up by a dead cell. Typically a certain volume of cells is subjected to a particular process and then that sample is mixed to a uniform distribution after which a cell concentration and viability analysis is conducted. We believe that this method introduces additional uncertainty in the transfer stage. Our goal is to measure viability directly in a microfluidic device using a combination of optical microscopy and high speed videography. In shortening the time and distance between a catastrophic event and the measurement of viability, we believe the uncertainty in the viability measurement can be significantly reduced. Upon completion of this phase, we would next explore the physical tracking of individual cells and each cell’s viability to its stress history.
LABORATORY ASSISTANT
Oliver McRae
RESEARCH GOALS
• Fabricate microfluidic devices in which cells pass through various stress profiles and relate the stress history to the cell viability.
• Use particle tracking to measure flow profiles within a device to calculate stress fields.
• Track the stress history of individual cells within a single device and relate these histories to spatial variability in viability.
LEARNING GOALS
• To learn how to design (CAD) and fabricate a microfluidic device.
• To learn how to carry out systematic experiments with a microscope and high-speed camera.
• To learn image process techniques to analyze high-speed videos.
TIMELINE
Weeks 1-2: Learn how to design (CAD) and fabricate a microfluidic device with safety training.
Weeks 3-4: Carry out systematic experiments to change average stress profile and link to cell viability on device.
Weeks 5-7: Carry out particle tracking to calculate velocity, accelerations, and estimate stress of individual cells and track cells to directly link viability with the stress profile of single cell.
Weeks 8-9: Use knowledge to determine how bubbles might directly damage cells.
Last days: Prepare poster.
Learn more about Professor Bird on his faculty page.