Purdue uses nanomaterials for drug discovery
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.
In 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-tumour chemotherapy drugs.
These proteins act as tiny pumps that quickly remove chemotherapy drugs from tumour 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.
The researchers, from Perdue university, created a trip approximately 1cm squared 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 vessels.
The vessels are cylindrical cavities that are open at the top and sealed at the bottom with a material called alumina. The alumina contains pores smaller than 100 nanometres, and the total volume of the reactors varies from 1-10 nanolitres.
The 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.
"What's unique about this device is that the surface has nanometer-scale pores in it," Gil Lee, the project's leader and an associate professor of chemical engineering said. "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 to pass."
"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."
Such a technology could be used to quickly screen millions of untested drug compounds that exist in large pharmaceutical "libraries." The chips could dramatically increase the number of experiments that are possible with a small amount of protein.
"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 Lee.
"Drugs that deactivate the pumps, would make chemotherapy drugs more effective. The researchers 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," he said.
Researchers tested the devices with an enzyme that produces a blue colour 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.
Currently, it is extremely difficult to study these proteins because they are difficult to produce in large quantities. The devices are set to 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.
The work is part of overall research being carried out by an interdisciplinary team of scientists and engineers who are members of a Centre for Membrane Protein Biotechnology. The paper that details new findings appear in the current issue (Feb. 15) in the journal Langmuir.
