Logo: University of Southern California

Making Chips with a Snap!

Viterbi Investigator Patenting New Path to Making Gene Chips
Eric Mankin
April 26, 2007 —
Eun Sok Kim in his lab.
DNA microarrays, also known as gene chips, are a basic tool for modern medicine and biology.  They allow someone to detect whether a certain message sequence is present or absent in a given DNA sample.

A University of Southern California researcher, who with his team won a prize last year for demonstrating a new way to create DNA microarrays, has improved the technique to make it much more powerful.

Usually, gene chips are made to order by specialty companies, using extremely expensive equipment. But the directional soundwave technique invented by the research group of Eun Sok Kim, a professor at the USC Viterbi School's Ming Hsieh department of electrical engineering, potentially allow researchers to have their own gene chip making machines in their own labs.

The Kim group's machine consists of an array of a quartet of ejectors, depressions in which small drops of DNA bases -- the genetic chemical letters A, T, C, and G -- sit on top of thin membranes that can be given acoustical snaps generated electronically by an activator.

The snap is directional and extremely precise, so that droplets emerge at exactly the same predetermined angle from the vertical. The paths from the four different ejectors converge at a single point about two millimeters above the quartet package, adhering there to the surface of a slide. (see diagram below right) For each snap, only one of the four ejectors fires.

Directional ejection: each reservoir contains a different base of 'letter' in the DNA alphabet. When activated, an acoustic membrane located underneath the membrane aims a tiny droplet of the desired letter to a point above the center of the array, to the surface of a slide (not shown). Successive activations build up a DNA sample on the slide. (click on image to see a .wmv file of the system in action.)
Supply lines from four central reservoirs refill the injectors after each snap.

Construction of quartet array system, described as a "nozzleless, heatless, lensless" machine, is a complex process. Kim and his former students, Jae Wan Kwon, now at the University of Missouri/Columbia and Sanat Kamal-Buhl, now at Intel, first described it in an April 2006 paper in the IEEE Transactions on Automation Science and Engineering.

That paper won the journal's "Best New Application Paper Award" for 2006, based on the criteria of  "technical merit, originality, potential impact on the field, clarity of presentation, practical significance for applications, and the novelty of the new application." The honor carries a cash prize and certificate to be awarded at a conference this fall.

In the paper Kim and his co-authors discussed the advantages of the system over existing techniques, which include photomask and inkjet-like printing systems and also painstaking contact transfer.

Inkjet systems also eject droplets, and "the smallest droplet size depends on the size of the nozzle. But the small nozzles are difficult to construct with uniformity and tend to get clogged," the paper notes.

Manufacturers in the field include Affymetrix, Agilent, and Rosetta.

Photograph of a packaged ejector array (Click on photo for non-stroboscopic .wmv file)

In the 2006 paper, the authors said that they were working on a way to synthesize sequences longer than three DNA bases that the pilot machine produced.

They have now done so. A new paper accepted for publication in IEEE/ASME Journal of Micro-Electro-Mechanical Systems, details how the system has been improved to allow synthesis of 15 DNA bases. Kim and his co-workers have patents pending on the process.

A working commercial machine is still at least 3-5 years away, says Kim. "It would require better integration of the ejectors, microchannels, and interconnecting ports, miniaturization of the driving electronics and wash/dry station, and packaging of the whole system."

He estimates that the first models would cost in the neighborhood of $100,000.

The National Science Foundation funded the work.