Integrating silicon microchip technology with a
network of tiny fluid channels, some thinner
than a human hair, researchers at Johns Hopkins have
developed a thumb-size micro-incubator to
culture living cells for lab tests.
In a recent edition of the journal IEEE
Transactions on Biomedical Circuits and Systems, the
researchers reported that they had successfully used the
micro-incubator to culture baby hamster
kidney cells over a three-day period. They said their
system represents a significant advance over
traditional incubation equipment that has been used in
biology labs for the past 100 years.
"We don't believe anyone has made a system like this
that can culture cells over a period of days
autonomously," said Jennifer Blain Christen, lead author of
the journal article. "Once it's set up, you
can just walk away."
The incubator's microchannels, fabricated in soft
silicone polymer material, allow 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. The
tiny incubator's 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.
Blain Christen spent the past three years working on
the device as the focus of her doctoral
dissertation in the Whiting School's Department of
Electrical and Computer Engineering. She received
her degree in May and has continued to fine-tune the device
while working as a postdoctoral fellow.
Andreas G. Andreou, a professor in Electrical and Computer
Engineering who was Blain
Christen's doctoral adviser, said, "This device represents
a unique blend of two technologies, and we
believe it will have a great impact on biology lab testing
and research." Andreou was co-author on the
journal article.
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 are placed inside a traditional
incubator, a heating compartment that is 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 — 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," said Blain Christen, "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."
The device was designed not only to provide these
capabilities but to do so in an ecofriendly
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 reused
in other devices. Blain Christen and Andreou said the
impact on the environment 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," said Blain Christen. "But we also believe
this approach is one that all engineers should be
adopting."
Blain Christen and Andreou are continuing to refine
and enhance the micro-incubator. They say
they hope to enable it to image the cells and tissue using
optical light guides, and that they wish to
give it the ability to stimulate and gather information
about the electrical activity of cells.
This research was supported by the National Science
Foundation and the National Institutes of
Health.
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