LAFAYETTE, Ind. - Researchers at Purdue University
have built and demonstrated a prototype for a new
class of miniature devices to study synthetic cell
membranes in an effort to speed the discovery of new
drugs for a variety of diseases, including cancer.
The researchers created a chip
about one centimeter square that holds thousands of
tiny vessels sitting on top of a material that contains
numerous pores. This "nanoporous" material
makes it possible to carry out reactions inside the
The goal is to produce "laboratories-on-a-chip"
less than a half-inch square that might contain up
to a million test chambers, or "reactors,"
each capable of screening an individual drug, said
Gil Lee, the project's leader and an associate professor
of chemical engineering.
"What we are reporting
now is a proof of concept," said Lee, one of
three researchers who wrote a paper that details new
findings in the current issue (Feb. 15) of the journal
Langmuir. The two other researchers are Zhigang Wang,
a postdoctoral fellow at Purdue; and Richard Haasch,
a research scientist at the University of Illinois
The work is part of overall
research being carried out by an interdisciplinary
team of scientists and engineers who are members of
a Center for Membrane Protein Biotechnology. The center
was created at Purdue in 2003 through a grant from
the Indiana 21st Century Research and Technology Fund,
established by the state of Indiana to promote high-tech
research and to help commercialize innovations.
The vessels discussed in the
research paper are cylindrical cavities that are open
at the top and sealed at the bottom with a material
called alumina, which contains numerous pores measured
in nanometers, or billionths of a meter.
Researchers are working to
duplicate how cell membranes function on chips in
order to test the potential effectiveness of new drugs
to treat diseases. Membranes, which surround cells
and regulate the movement of molecules into and out
of the cells, contain a variety of proteins, some
of which are directly responsible for cancer's ability
to resist anti-tumor chemotherapy drugs. These proteins
act as tiny pumps that quickly remove chemotherapy
drugs from tumor cells, making the treatment less
effective. Cancer cells exposed to chemotherapy drugs
produce a disproportionately large number of the pumps,
causing the cells to become progressively more resistant
to anticancer drugs.
Engineers and scientists in
the Purdue center are trying to find drugs that deactivate
the pumps, which would make the chemotherapy drugs
more effective. The researchers are developing synthetic
cell membranes to mimic the real thing and then plan
to use those membranes to create chips containing
up to 1 million test chambers. Each chamber would
be covered with a membrane containing the proteins,
and the chambers could then be used to search for
drugs that deactivate the pumps, Lee said.
Such an advanced technology
could be used to quickly screen millions of untested
drug compounds that exist in large pharmaceutical
The chips could dramatically increase the number of
experiments that are possible with a small amount
"It's been very hard to
study these proteins because they are difficult to
produce in large quantities," Lee said. "The
devices we have created offer the promise of making
chips capable of running thousands of reactions with
the same amount of protein now needed to run only
about 10 reactions."
Findings being reported in
the paper detail how researchers created the device
with the same "microfabrication" techniques
used to make computer chips. The reactors range in
diameter from about 400 to 60 microns, or millionths
of a meter. Human hairs are about 100 microns wide.
"You can think of it as
a micro-petri dish for studying biochemical reactions,"
The alumina contains pores
smaller than 100 nanometers, and the total volume
of the reactors varies from 1-10 nanoliters.
"What's unique about this
device is that the surface has nanometer-scale pores
in it," Lee said. "The concept is fairly
simple - there is an inorganic porous membrane - in
this case alumina, which separates the reaction chamber
from a solution. The pores in this membrane are nanometer
in scale, so they do not allow proteins to readily
pass through the membrane but will allow smaller molecules
"This allows us to do
separation right in the reactor, which means we can
do reactions that could not be done before in such
a small device.
We can study membrane proteins in a fundamentally
new way, which is very important because many future
drugs to treat diseases will likely work by controlling
proteins in cell membranes."
Researchers tested the devices
with an enzyme that produces a blue color when combined
with a liquid that contains molecules small enough
to easily pass through the pores. The enzyme, which
is a protein, was placed inside the vessels - on the
inner surface of the alumina membranes - and the liquid
was placed outside each vessel so that it covered
the opposite side of the membranes. When the liquid
diffused through the membrane's pores, it mixed with
the enzyme, causing a reaction and turning blue in
the process, which demonstrated that the device works.
The Center for Membrane Protein
Biotechnology combines a diverse range of researchers,
from engineers to chemists, and pharmaceutical scientists
to physicists. The research is supported by the Bindley
Bioscience Center, which is part of Discovery Park,
Purdue's hub for interdisciplinary research.
Writer: Emil Venere, (765)
Source: Gil Lee, (765) 494-0492, firstname.lastname@example.org
Related Web sites:
Gil Lee: http://atom.ecn.purdue.edu/~gl/home
Indiana 21st Century Research
and Technology Fund:
Journal Langmuir: http://pubs.acs.org/journals/langd5/index.html