MEMS Technology Creates Cheaper DNA Chips

Ruth DeJule, Associate Editor -- Semiconductor International, 2/1/2000

Ruth DeJule, Associate Editor

Oligonucleotide microarrays, known as DNA chips, allow scientists to study organisms as a system, rather than a mixture of dissected parts. The chips consist of short strands of DNA. Some chips contain just a few features, others hundreds of thousands; each feature holds millions of copies of a specific piece of DNA that acts like a probe, corresponding to a particular gene under test. Some speculate DNA chips will be used to diagnose disease.

DNA is made up of four bases: A, C, T and G monomers. Like an alphabet with four letters, DNA probes contained on a DNA chip can be 18 to 25 bases long. DNA is a double helix consisting of two strands. It is purified from a drop of blood to be analyzed by essentially removing one of the strands. The DNA is then labeled with a fluorescent molecule and spread on a chip's surface. The fluorescently labeled DNA will find its complement on the DNA chip and hybridize. The identity of the sample DNA and the presence of known genetic diseases can then be deduced by indexing the fluorescence signal to the DNA probes on the DNA chip. DNA chip technology has notable potential, but processing costs have been prohibitive.

Similar to semiconductor device manufacturing, DNA chip processing requires photolithography to synthesize small regions on the chip and define specific DNA probes. Photomasks for DNA chips originally were developed in the early 1990s in collaboration between IBM Almaden and Affymetrix (Santa Clara, Calif.). A mask is required for each option A, C, T and G and for each position on the probe. Therefore, a probe 25 bases long requires 100 masks. These numbers soon multiply as the number of probes contained on a DNA chip increases; an array n bases long requires as many as 4n masks.

Researchers at the University of Wisconsin in Madison, led by Professor Franco Cerrina, have found a better way of synthesizing the chips (Fig. 1). Their maskless array synthesizer (MAS) is based on a projection technology developed at Texas Instruments (TI, Dallas). The digital micromirror device (DMD) consists of an array of nearly 500,000 mirrors (Fig. 2). Like a digital direct write scheme, the micromirrors reflect light onto particular regions of a DNA chip by tilting the mirrors ±10deg, thus eliminating the need for any photolithographic masks. The DMDs are microelectromechanical structures (MEMS) built on SRAMs. A final aluminum layer forms the micromirrors that cover 90% of the surface. DMDs originally were designed for TI's Digital Light Processing (DLP), a projection system, noted for its high-quality images.

These new DNA chips can analyze thousands of genes at once at ~$100/chip, an order of magnitude less than current DNA microarrays. In addition to the economics, MAS is fast. Typically, new DNA chips can take months to produce because of the number of mask sets involved. According to Dr. Roland Green, vice president and chief technical officer at NimbleGen Systems (Madison, Wis.), researchers potentially can make their own DNA chips at their lab bench. Currently, DNA microarrays containing more than 300,000 discrete features are being synthesized. Plans are underway to synthesize a second-generation MAS capable of creating DNA chips containing more than 2 million discrete features.