Researchers have developed a modular system that combines chemical and biological sensing tools capable of providing…

Researchers at the Georgia Institute of Technology
and the Vienna University of Technology have developed a modular system that
combines chemical and biological sensing tools capable of providing simultaneous,
nano-level resolution information on cell topography and biological activity.
The tools integrate micro and nanoscale electrodes into the tips of an atomic
force microscope (AFM). A veritable Swiss army knife of sensors, the patented
technique is currently being tested to combine other sensing methods to give
scientists a more holistic view of cellular activities. The research is
published in Vol 44, 2005 of the chemistry journal Angewandte Chemie.

By adding electrodes to the tip of an atomic
force microscope, researchers created a tool that can monitor many activities
at the same time. (Image courtesy of Georgia Institute Of Technology)

‘Usually people image topography and then measure the biological
activity,” said Christine Kranz, research scientist at Georgia Tech. “But
if you think about having biological material, it’s changing with time.
So scanning for these sequentially may mean that the structure and activity
level of your sample has changed and you’re not looking at the same condition
of your sample anymore.”

Using an AFM as the base, researchers added micro and
nano-electrodes into the tip. This allows researchers to get biological and
chemical information via scanning electrochemical microscopy (SECM) simultaneously
with topographical information provided by AFM.

‘The problem with conventional AFM imaging is that you
get topographical information, but only limited information on the chemical
processes occurring at the cell surface,” said Kranz. “With SECM, you can
get information on electro-activity, but this information may be convoluted
with the topographical information. Also SECM still suffers from limited resolution.
We combined the two techniques to give us high resolution topography as well
as the chemistry that’s going on at the cell surface.”

Researchers tested their new technique by integrating biosensors
for glucose into AFM tips. They imaged, as a synthetic model, glucose transport
through track-etched membranes. In another test, a biosensor based on horse
radish peroxidase was integrated into the AFM tip. They were able to faithfully
measure the chemical activity and image the process to a resolution of 200

The tool promises to be valuable for a wide range of biomedical
and biotechnological applications. In an NIH-funded project in collaboration
with Emory University, Kranz and Boris Mizaikoff are currently using this
technique to study cystic fibrosis and the role errors in regulating adenosine
triphosphate (ATP), a chemical involved in transporting energy to cells, might
play in the disease.

‘The system’s modular design allows it to be adapted for
many uses,” said Kranz. Researchers at the Applied Sensors Laboratory at Georgia
Tech are testing integrating optical microscopy with the AFM. Another project
adds an infrared sensor, while yet another adds a pH sensor. These sensors
could also be combined to have three or more sensors on a single instrument
because the technology is in the modified AFM tip.

‘The technology is very flexible and can be adapted to
sense for a wide range of biological systems and processes. Using this technique,
we can get a more complete picture of what is going on in a given biological
system,” said Kranz.

The research team consisted of Kranz, Mizaikoff, and
former postdoc Angelika Kueng from Georgia Tech. Focused ion beam milling
was done by Alois Lugstein and Emmerich Bertagnolli from the Vienna University
of Technology. Since January 2005, Georgia Tech has established a Focused
Ion Beam Center led by Mizaikoff enabling tip fabrication, characterization,
and measurements on campus.

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