Monday, June 19, 2006

A Better Toxicity Test for Drugs

A device that can reveal if compounds are toxic to living cells could be a fast and accurate way to detect liver toxicity.

By Prachi Patel-Predd

Rat liver cells placed on a porous silicon chip light up (b) as they die from a toxic dose of acetaminophen (Tylenol). (Courtesy of Sara Alvarez, Austin Derfus and Michael Schwartz, UCSD.)

A new method of sensing slight changes in the structure of liver cells, based on the way they scatter light, could provide a faster, more efficient way to test the toxicity of drugs and the harmful effects of environmental pollutants.

Liver toxicity is the most common reason for manufacturers to withdraw drugs and for the Food and Drug Administration to refuse approval of new drugs. Indeed, one-third of all drugs fail clinical trials because of such toxicity. What's more, current in-vitro toxicity tests are tedious and complicated, because researchers have to periodically look at the cells under a microscope or insert a fluorescent dye into the cells genetically. Moreover, existing tests frequently use chemicals that kill the cells, so that researchers have to use a number of different cell cultures during a study, which affects the result.

The new device was developed by Michael Sailor, professor in the department of chemistry and biochemistry at the University of California, San Diego, and Sangeeta Bhatia, associate professor in the department of health sciences and technology and the department of electrical engineering and computer science at MIT. It consists of a porous silicon chip on which cells can live for days, and an inexpensive charged-coupled-device detector like those found in digital cameras. It can continuously monitor living cells and indicate earlier than current tests whether a compound is harming the cells, based on how much light they reflect (paper abstract).

The researchers create the porous substrate by placing silicon chips in hydrofluoric acid and passing an electric current through the solution. This forms cylindrical wells a few hundred nanometers in diameter on the surface. The tiny wells make the porous silicon reflect light at a sharp frequency, a well-known property not seen in regular silicon. The researchers can engineer the pores to control the frequency.

Next, the researchers cover the chip with polystyrene to make a surface similar to a Petri dish. When cells are placed on the surface, they scatter the reflected light, decreasing the intensity of light falling on the detector. As the cells wither or die, their structure changes, which increases the intensity of light at the detector. "The cells light up like little lighthouses when they die," says Sailor.

In the lab, the researchers placed rat liver cells on the chip and treated them with toxic doses of cadmium and the pain-killer acetaminophen. They found that the sensor detected changes in the cells at least two hours before conventional tests. They plan to test the device with human liver cells soon.