— A novel technology that can test cells in minutes
for responses to any stimulus, including antibiotics,
pathogens, toxins, radiation or chemotherapy, has
been developed by scientists at the University at
The paper describing the sensor
will appear in the Feb. 15 issue of Analytical Chemistry,
and currently is available as an "ASAP"
article on the American Chemical Society Web site
Susan Z. Hua, Ph.D., UB assistant
professor of mechanical and aerospace engineering
and physiology and biophysics, is the lead researcher.
The technology is based on
the universal connection between cell volume and the
cell environment, or cell volume cytometry. It is
particularly useful because it eliminates the need
to culture bacteria to assess their sensitivity to
"Now, in a matter of minutes,
we can tell if particular antibiotics are active against
specific bacteria," said Frederick Sachs, Ph.D.,
professor of physiology and biophysics at UB, co-director
of UB's Center for Single Molecule Biophysics and
a coauthor on the paper.
"We have measured the
sensitivity to antibiotics of different strains of
E. Coli in less than 10 minutes at room temperature.
We will get results even faster at higher temperatures."
Hua and her students created
the tiny silicon chip that is the heart of the sensor
chamber in which the cells are encased for testing.
"The new technique is
so sensitive it can detect changes in cell dimensions
never seen before in living cells," she said.
"The necessary power can be supplied even by
a watch battery and the sensor is so small it could
fit into a pencil eraser."
Sachs said the assay can be
used on any biological component that is enclosed
by a membrane. "It doesn't have to be cells.
We can use lipid bilayer vesicles containing a single
protein, mitochondria, chloroplasts (plant cells)
or cell nuclei, as well as whole cells. We can screen
for just about anything."
For example, this technique
could be used to rapidly scan cancer cells obtained
from biopsies to evaluate the effectiveness of chemotherapy
or radiation protocols. The chip has obvious application
to measuring toxins relevant to bioterrorism, Sachs
Cell volume and physiological
function are intimately intertwined, the authors note
in their paper. Normal biological activity, such as
metabolism, apoptosis (programmed cell death) or cell
division affect cell volume, as does abnormal activity,
such as exposure to toxic agents. Sachs and Hua call
the sensor a "canary on a chip," to highlight
its versatility as a first-line indicator of activity.
There are many methods used
to measure changes in cell volume, said Hua, but electrical
impedance, the resistance to flow of electric current,
is the key to this sensor's simplicity.
Cells are electrical insulators,
she noted. "When immersed in salt water, which
conducts current, the cells displace some of the water
and reduce the electrical current. If cells swell,
as commonly would happen in the presence of a toxin,
the resistance would increase and the current would
become smaller, indicating a cellular response."
In addition to being simple
to use, the chip is inexpensive, low power, portable
and provides real-time results, said Sachs. "The
assay is applicable to an enormous number of problems,
and is a particularly powerful tool for drug screening,"
Additional authors on the study
are Daniel A. Ateya, a UB mechanical engineering student;
Philip A. Gottlieb, Ph.D., research associate professor
in the UB Center for Molecular Biology and Immunology,
and Steve Besch, Ph.D., research assistant professor
of physiology and biophysics. The authors have filed
a patent on the technology.
The work was supported by grants
to Hua and Sachs from the National Science Foundation
and the National Institutes of Health, respectively.
The microfabrication was done primarily in the Nanofabrication
Facility at Cornell University.