Johns Hopkins applies microelectronic technology to biology research
By Ann Steffora Mutschler, Senior Editor -- 10/4/2007
Researchers at Johns Hopkins University in Baltimore, Maryland have developed a thumb-size micro-incubator to culture living cells for lab tests by integrating silicon microchip technology with a network of tiny fluid channels, some thinner than a human hair.
The development is chronicled in a recent issue of the journal IEEE Transactions on Biomedical Circuits and Systems, and reports that the Johns Hopkins researchers successfully used the micro-incubator to culture baby hamster kidney cells over a three-day period. The system is believed to mark a significant advance over traditional incubation equipment that has been used in biology labs for the past 100 years.
Jennifer Blain Christen, lead author of the article said in a statement, “We don't believe anyone has made a system like this that can culture cells over a period of days autonomously. Once it’s set up, you can just walk away,” due to the incubator’s microchannels, which are fabricated in soft silicone polymer material and allows researchers to easily insert and guide cells and nutrients during experiments, while the computer-controlled electronics keep the cells at the precise temperature that enables them to multiply and thrive. Also, the transparent design makes it easy to view the cells through a microscope or camera equipment without disrupting the conditions that help the cells to flourish, the researchers noted.
Blain Christen spent the past three years working on the device as the focus of her doctoral dissertation in the department of electrical and computer engineering in Johns Hopkins’ Whiting School of Engineering. She received her degree in May and has continued to fine-tune the device while working as a postdoctoral fellow.
Historically, since the early 20th century, cell culture techniques in biology labs have remained largely unchanged: Living cells and nutrients are put into a lab dish and then placed inside a traditional incubator, which is a heating compartment typically the size of a small refrigerator. Within the unit, the researcher must maintain a constant temperature, an environment free of contaminants and the proper levels of humidity, oxygen and carbon dioxide. Whenever the lab dish is removed for observation or experiments, however, these optimal conditions are disrupted, and the cells begin to die.
In contrast, the thumb-size system developed by the Johns Hopkins engineers is self-contained and requires no external heating source. A drop of liquid containing living cells is injected into a port and flows through one of the microfluidic channels. A nutrient solution of the cells' food is also added in this manner.
The cells gravitate toward and stick to the surface of the microchip. The chip contains a simple heating unit - a miniature version of the type found in a common toaster - and is equipped with a sensor that continually checks to make sure the proper temperature is maintained. For human cells, this is usually 37 degrees Celsius or 98.6 degrees Fahrenheit. The chip is connected to a computer that controls the sensing and heating process. The prototype is connected to a computer via a hard wire, but the inventors say a wireless version would be the next step.
A gas-permeable membrane on the incubator allows the microsystem to exchange carbon dioxide and oxygen but keeps out bacteria that could contaminate the cell culture. If a cell colony grows too large, an enzyme can be injected into one of the microfluidic ports to detach and flush away surplus cells without destroying the primary cell culture.
The incubator's small size provides several advantages, the researchers say. The unit can easily be moved to different microscopes, imaging devices or other experimental tools without jeopardizing the health of the cell culture.
Its size and relatively low cost should allow biologists to run numerous experiments simultaneously in a small space. Because it can be powered by batteries, the micro-incubator could be used outside a traditional lab for field tests. “Also, because it's so small, we can change the temperature of the cell culture environment very quickly. We can go from room temperature to 98.6 degrees in less than a 10th of a second,” Blain Christen noted.
The device was designed not only to provide these capabilities but to do so in an eco-friendly manner. This was achieved by minimizing the size of components whose fabrication affects the environment in an adverse way. These components were also designed so that they can easily be re-used in other devices.
Blain Christen and Andreou said environmental impacts should be an important consideration in all types of research. “In our own field, among researchers who are working at the interface between electronics and biology, we believe our approach -making ecological considerations integral to our design - is rather uncommon. But we also believe this approach is one that all engineers should be adopting,” Blain Christen said.
Blain Christen and Andreou said they are continuing to refine and enhance the micro-incubator and hope to allow it to image the cells and tissue using optical light guides. They also would like to give it the ability to stimulate and gather information about the electrical activity of cells.
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