Over a decade of rapid advances in biology has swept an avalanche of genetic information into scientists' laps. But analysis of so vast an input, whether to deduce the inner workings of cells or to diagnose diseases, would be impractical without high-throughput technologies. Of these, DNA microarrays are in the lead. These gene chips or biochips, to use their popular name, allow scientists to look for the presence, productivity, or sequence of thousands of genes at a time. Just five years ago, no practical method could do that.
Analysts predict the US $300 million market in DNA microarrays will leap ahead by about 50 percent per year through 2005. Currently, one company, Affymetrix Inc., Santa Clara, Calif., dominates the market. But as microarrays have caught on among others, Affymetrix has found itself embroiled in patent disputes with a host of other life science firms.
Competition from other technologies may also challenge the company's lead. The potential of various devices for genetics research and drug discovery caught the eye of established high-tech firms like Motorola, Hitachi, Corning, and Agilent Technologies. In often novel ways, each of these firms is adapting existing tools--semiconductors, inkjet printers, flat panel displays--to the manufacture of microarrays, and are developing high-volume manufacturing techniques using fine printing pins and inkjet nozzles to challenge the leading technology, photolithography. Motorola and a few of its rivals are also putting active electronic elements into their microarrays to manipulate and sense DNA.
The tagged DNA is washed over a micro-array that has single-stranded DNA fixed to its surface in known locations. This DNA represents important genes or parts of genes. If a gene has been expressed in a cell, it will bind to a copy of itself on the array; those with no complementary site on the array will wash off.
A light source scans the array, causing the dyes to fluoresce. The glow is picked up by a sensor, and a computer interprets the pattern of spots, indicating for each cell which genes are active and the relative abundance of the RNA. Click on the image to enlarge.
Few of these companies are typically identified with the life sciences, and some, like Motorola, are outright newcomers. All are hoping, though, that their technology will compete hard with Affymetrix' and smaller competitors' approaches.
Even with novel technologies, rivals of Affymetrix will need to target its weaknesses or markets it does not serve. "Affymetrix is in a solid position," said Ken Rubenstein, chief executive officer of the Lion Consulting Group in Emeryville, Calif., and author of a recent microarray technology analysis. He expects the company to hold onto most of the research market for the foreseeable future, because of the manufacturing and market infrastructure it has already built up. But there are parts of the market where others might compete. "Agilent is going to be cutting in on the market for customized arrays, and Motorola hopes to make inroads into [low-density arrays], what is now being largely done on a home-brew basis," he said.
The potential profits are huge, because pharmaceutical firms are in a rush to translate the human genome results into new products. First, though, they must figure out what the genes do, how they interact, and how they relate to disease. This is too tall an order for experiments that focus on one gene at a time, but microarrays can perform experiments with thousands of genes simultaneously. Arrays can take snapshots of which subset of genes in a cell is actively making proteins--the term biologists use is "which genes are expressed." Other types of arrays can indicate where mutations lie that might be linked to a disease. Still others could be used to determine if a person's genetic profile would make him or her more or less susceptible to drug side effects.