PITA Fiscal Year 2007 Projects

Biomedical and Health Engineering

A Lab-on-a-Chip Device for Controlling the Cellular Environment
The development of a lab-on-a-chip device is proposed that will ultimately be used to explore the effect of gradual and continuous changes to the cellular environment, including both solution and thermal properties. Applications for this device range from cryopreservation to hyperthermia, thermal ablation, toxicity, and drug delivery. In particular a long-term goal of this work is to explore cryobiology effects in models ranging from stem cells to pancreatic islets, ultimately to develop knowledge and technology to advance cryopreservation via vitrification (vitreous in Latin means glassy). To illustrate the need for the device, we can describe a cryopreservation application as the combination of four key protocols: (1) loading the specimen with a cryoprotective agent (CPA), (2) cooling the specimen to a cryogenic storage temperature, (3) rewarming the specimen to a normal room temperature, and (4) washing out the CPA from the specimen. It is well established that a sequential execution of these protocols leads to a poor cryopreservation outcome, primarily due to the hazardous effects associated with crystal formation, the potential toxicity of the CPA, and the dramatic changes in the specimen surrounding, which impose severe stress on the cell membrane. However, it is evident that the execution of the above protocols in concert can lead to superior cryopreservation results.

The hypothesis that drives the proposed study is that the design concept of gradual and continuous changes in surrounding parameters will lead to far superior cryopreservation results. The proposed work seeks to develop a microfluidic chip that can accomplish these goals in a generic fashion and that will thus be useful for a wide range of biotechnology applications including cryopreservation. The major advantage in the proposed lab-on-a-chip setup is the ability to study an individual cell history throughout the entire process of cryopreservation, or more generally, throughout the process of gradually changing the environment. This ability increases the certainty in experimental results, decreases the dependency on cell population statistics, and is expected to yield close to real-time results. Another major advantage of the lab-on-a-chip technology is derived from its inherently superior process control, which increases repeatability and enables standardization of cryobiology studies performed at different sites. Consequently, the lab-on-a-chip setup enables cost-efficient studies, where sampling size is much smaller and the labor associated with its operation becomes minimal.