DNA detectors get smaller, faster

Television coverage of the O.J. Simpson trial could possibly be credited with introducing DNA analysis and polymerase chain reactions (PCR) to the general public. But if the engineers at Cepheid (Sunnyvale, CA) have their way, this powerful tool might soon emerge from the courtroom and crime lab and appear in your local doctor's office, pharmacy, or even grocery store.

Cepheid is working on developing miniaturized, fast, disposable DNA analysis systems. Their products--still in the prototype stage--are a combination of a silicon microfluidic PCR chip developed by Lawrence Livermore National Laboratory's Allen Northrup, now Cepheid's chief technical officer, and a DNA Purification Chip conceived in collaboration with micromachining pioneer Kurt Petersen, the company's president and former founder of NovaSensor (now Lucas Novasensor), and the rest of the Cepheid team.

DNA extraction is tedious and time consuming, requiring an entire morning for a technician to extract and purify the DNA for perhaps half a dozen samples. "Sample preparation is the difficult part of PCR," says Petersen.

Cepheid's DNA Purification Chip is a MEMS device made with deep reactive ion etching. It consists of a cavity containing thousands of pillars 200 microns tall, 10 microns in diameter, with 20 micron spacing. The pillars are oxidized to form a thin layer of SiO2 to which DNA will naturally bind. Several milliliters of prepared fluid containing DNA can be flowed through the chip. Afterwards, the trapped DNA can be eluted from the chip by passing through a chemical solution. This has shown in tests the ability to increase the DNA concentration tenfold.

The unique flow-through design of the chip is the key to making the device disposable. It can process milliliters of fluid, even though its volume is on the order of nanoliters. "Without the flow-through the chip would be enormous and too expensive," says Petersen.

Once extracted, the DNA is passed to the microfluidic PCR device. It's said to be ten times faster at DNA replication than current PCR instruments.

It also offers greater sensitivity and specificity than other disease detection methods. In HIV testing, for example, patients with less than 500 virus particles per ml of blood are asymptomatic. Current tests detect down to around 1,000 particles per ml. "We think we can get down to 100 or less," says Petersen.

Cepheid engineers intend to combine the extraction and PCR technologies into one microDiagnostics(TM) product. Medical applications of the device will target such things as testing for sexually transmitted diseases. "Right now, it takes 24 to 48 hours to get back results from such tests," says Petersen. "Something like 60% of the people never come back for the results."

Why? It's inconvenient. Petersen expects Cepheid's technology to cut the wait to 20-30 minutes.

While the medical market is lucrative, Petersen sees potential in everything from food processing to poultry ranches, fruit orchards, or even biological weapons detection on the battlefield.

Another trend: "There is going to be a real move towards home health monitoring and analysis," says Roger Grace, a San Francisco based sensor-industry analyst and consultant. Cepheid's technology might open doors to this area with inexpensive but powerful consumer health products.