Main navigation | Main content
Office: 2101C Mechanical Engineering
Ph.D. 1989, M.S. 1985, Mechanical Engineering,
Massachusetts Institute of Technology
B.S. 1983, Mechanical Engineering, Iowa State University
Biological cells are molecular machines that are workhorses of modern biotechnology and medicine. It is common for cells to be collected in one location and used at a later time in another location. Thus, certain critical biological properties of the cells need to be preserved in order for the cells to be useful for the anticipated downstream application.
Molecular Mechanisms of Damage
Raman spectroscopy is a powerful imaging technique that has become very instrumental in our understanding of the response of the cell to freezing environment. The spatial resolution of Raman (~300 nm) permits us to image single cells during freezing and even subcellular structures inside the cell. This technique permits identification of a wide range of molecules based on their unique scattering characteristics. One freezing experiment on a single cell can provide many distinct pieces of information on the freezing response of a cell and this multiplexed information brings us closer to understanding how and at what point cells are damaged during freezing.
Technology to improve preservation
Preserving cells requires the use of specialized solution containing cryoprotective agents that help the cells survive the stresses of freezing and thawing. For many applications, the specialized solutions must be removed prior to downstream use of the cells. Current methods of removing the specialized solutions are labor intensive, require special equipment and highly trained personnel capable of washing cells. Even with all of those elements in place, cell losses can be very high (25-60%). We have developed a vertically oriented microfluidic device for washing cells. The microfluidic technology developed is being commercialized and applications beyond cell washing are being developed.
Novel approaches to preservation
Nature uses molecules called osmolytes to stabilize biological systems during environmental extremes. For example, trees that survive Minnesota winters produce osmolytes in the fall that help stabilize the tree’s cells when temperatures drop below freezing. As in nature, combinations of osmolytes are needed to stabilize cells and a computational algorithm was developed to accelerate development of multicomponent solutions.
Corneal tissue engineering
The cornea is the most commonly transplanted tissue in the United States with over 46,000 transplants performed annually. Worldwide, the supply of corneal tissue suitable for transplantation has never matched the demand (generally, a total of 120,000 transplants are available for 10,000,000 patients as reported by the World Health Organization, and a similar situation may present itself in United States in the next few years. We are developing a tissue-engineered cornea with favorable optical and biomechanical properties and capable of integration into the eye.
Integrated Training in Development and Clinical Practice of Cell Based Therapies