Nano-Quakes

Courtesy of Advalytix The Advacard is used instead of a conventional coverslip during microarray hybridization in the ArrayBooster instrument. Many microfluidics-based lab-on-a-chip devices use external pumps and micromachined parts to move liquids through tiny channels.1 Brunnthal, Germany-based Advalytix, however, takes a different approach: Its programmable microfluidic biochips dispense with micromechanics and instead employ a technology found in cellular phones to move sample volumes along the chip's surface. The heart of Advalytix's technology is a "nanopump" that has no moving parts and never comes into contact with reagents or samples. The pump is based on surface acoustic waves (SAW)--a technology used in communications electronics--which are generated on a piezoelectric substrate via specially designed electrodes to which a radio frequency signal is applied. The waves propagate along the surface of the substrate like a "nanoearthquake" that transfers momentum to any substance applied to the chip's surface. "This mechanical wave that's traveling on the surface of our chips really works as a kind of tiny conveyor belt," explains Jürgen Scriba, chief operating officer. Reagents are moved to specific spots on the chip via microfluidic tracks defined by surface chemistry--for example, a hydrophilic track surrounded by hydrophobic boundaries. Scriba contrasts Advalytix's lab-on-a-chip technology to conventional alternatives, which contain interconnected channels etched into glass or silicon. "These approaches have the big physical problem that as you decrease feature size, the surface tension of the solutions you're trying to move really becomes a major force, which it is not in the macroscopic world. So if you try to flood a channel that's just a couple of microns wide with a liquid, you will find it either fills the channel instantly due to capillary forces or you will need substantial pressure to feed the system," he says. As a result, these systems require external pumps to control the movement of the sample through the chip, as well as small mechanical parts that can become contaminated or wear out. Advalytix's SAW-driven nanopumps eliminate these problems, because the pumps are integral to the chips themselves. "These pumps don't wear out ... simply because they don't move," Scriba says. COMMERCIAL DEBUT Advalytix's first commercial product is the ArrayBooster™, an instrument that agitates the hybridization solution via SAW during the incubation of DNA or protein microarrays. The ArrayBooster consists of a microagitation card, or AdvaCard™, that covers the spotted area on the microarray and agitates the sample throughout the entire incubation period. Courtesy of Advalytix ArrayBooster employs a novel microagitation technology based on surface acoustic waves that agitate the hybridization solution during the entire incubation process without adding any dead volume. Scriba explains that hybridizations that rely on diffusion are inefficient. "If you're looking for rare genes that are present in your hybridization solution and you're looking for the fluorescent signal of one specific spot [that contains the target molecule] ... during the normal overnight incubation most of the sample never even comes near to this specific spot," he says. Agitating the solution permits the target molecules to pass over all the spots on the microarray, leading to higher sensitivity and potentially decreasing the necessary incubation time. Several instruments are currently installed in the United States and Europe. Boulder, Colo.-based SomaLogic, for example, has been testing the ArrayBooster as a possible addition to its photoaptamer-based protein-detection platform. Helen Petach, senior director of scientific affairs, says that early studies show that the ArrayBooster enhances protein binding but that it is too soon to tell precisely how much the instrument improves array performance. Hybridization signals, she adds, are enhanced "a lot" by the ArrayBooster--more than twofold, according to SomaLogic's studies. Advalytix is currently working with several healthcare companies to develop point-of-care diagnostic tests based on the programmable biochip platform, miniaturizing assays that would normally be performed by a trained laboratory technician. Scriba explains that the platform's simplicity, speed, and cost-effectiveness make it ideal for such applications. "Our microfluidic processor is mechanically an extremely simple system," he says. "It's manufactured by standard semiconductor process technology ... Basically a mobile phone today contains all the circuitry you'd need to operate one of our fluidic processors." --Aileen Constans 1. D. Fitzgerald, "Riding the microfluidics wave," The Scientist, 16[23]:40, Nov. 25, 2002.

Nano-Quakes

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	Courtesy of Advalytix
	The Advacard is used instead of a conventional coverslip during microarray hybridization in the ArrayBooster instrument.