News Release

Microscopic hydrogel chambers facilitate drug screenings

Peer-Reviewed Publication

Penn State

Microscopic chambers constructed of a hydrogel similar to Jell-O, may allow pharmaceutical chemists to screen chemical libraries of molecules rapidly for potential new drugs, according to a Penn State chemical engineer.

"Pharmaceutical companies doing drug discovery generate enormous libraries of molecules that must be screened to determine useful drug activity," says Michael Pishko, associate professor of chemical engineering. "The generation of hundreds of thousands of molecules makes screening a very large task." According to Pishko, the drug companies typically put the molecular libraries through a relatively fast, high throughput process and those chemicals that show activity are then tested further.

"If they put 100,000 chemicals through high throughput screening, then about 5,000 may show some promise," Pishko told attendees at the spring meeting of the Materials Research Society today (April 4) in San Francisco. "Testing that many molecules on animal models would be prohibitively expensive, so the pharmaceutical companies test chemical activity on cell cultures."

Pishko and Won-Gun Koh, graduate student in chemical engineering, developed a 3-dimensional biochip that contains tiny chemical reactor chambers where cells can grow combined with a microfluidics delivery system already in place. The chips start as glass or plastic substrates on which microchannels for the microfluidic delivery system are etched using conventional photo lithographic methods. Then the 3-dimensional poly (ethylene) glycol hydrogel microstructures are fabricated in the microfluidic channels using a photo mask and light, which sets the gel. Because the live cells are incorporated into the tiny cell culture chambers when the reaction chambers are created and the microfluidic channels are incorporated into the chip from the start, the chips are ready for attachment to an external fluidic system when they are fabricated.

Currently, the researchers produce 400 microstructures of between 50 and 100 microns in diameter on a millimeter square chip. Cells from a variety of organs including the nervous system, liver and connective tissue and both healthy and cancer cells can be incorporated into the chips. The high liquid content of the hydrogel creates an environment more closely matched to nature than the flat cell cultures currently available on 2-dimensional biochips.

Growing the cells and delivering components of the chemical library and nutrients to the living cells is only the first step. Once the potential new drugs and cells come together, some way to test the outcome is needed. Typically, pharmaceutical chemists wish to test for such activity as toxicity, uptake of calcium, initiation of apoptosis -- when cells kill themselves, production of nitrogen oxide, production of proteins or gene expression.

In many cases, incorporating a flourescent marker into the cells will monitor the results. To test for toxicity, when the cells are illuminated, the flourescent tag will glow green if the cell is alive, but red if it is dead. Another flourescent tag, which can be incorporated into the hydrogel, marks a change in acidity and can indicate that the cells are producing a product, such as a protein or enzyme. Because the hydrogel is transparent, a variety of optical sensors can also be used on chambers in the biochip. Using the microfluidic system, chemicals produced by the cells can also be sampled.

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Pishko, Koh and Alexander Revzin of Texas A & M have submitted a provisional patent application on this technology. The research was funded by NASA.


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