Lab on a chip? Cheap, disposable UD biosensor uses gold-on-plastic design

July 08, 1999

Coated with gold and sandwiched between tiny electrodes, specially designed polymer beads provide a cheap, disposable device for detecting disease, University of Delaware scientists say.

A prototype, "gold-on-plastic" biosensor, protected by a provisional patent and described in the May 25 issue of Langmuir, also may prove useful for analyzing food and environmental samples.

With a detection region about the size of a living cell, multiple biosensors can be placed on a single chip, reports Eric W. Kaler, the University's Elizabeth Inez Kelley Professor of Chemical Engineering.

"Our biosensor detects targeted molecules and rapidly generates an objective, electrical readout," says Kaler, chairperson of the UD Department of Chemical Engineering. "We believe it may eventually be sensitive enough to detect as few as 30 targeted molecules in a sample."

The new technology represents an alternative to a popular, but more indirect and subjective, laboratory procedure known as the latex agglutination test (LAT), according to Kaler and his coinventor, Research Assistant Prof. Orlin D. Velev.

The widely used LAT procedure, first developed in 1956, makes it possible to screen bodily fluids for a host of diseases--from Lyme disease and tuberculosis to human immunodeficiency virus (HIV), Velev explains. Latex agglutination tests also detect antibiotics in foods and pregnancy-related hormones in urine. The tests use latex coated with specific antigens, or foreign particles, to detect antibodies through a biochemical "clumping" process called agglutination, Velev says.

While the agglutination approach is "fast and robust," Velev says, it also requires a relatively large sample. Moreover, he says, "The resulting optical readout may be complex, and it is subject to interpretation by a clinician."

Simple, automated and robust electronic biosensors may be a better option for many types of tests, Velev says. The UD invention requires only a microscopic drop of sample material, according to Kaler, and it provides an automatic, clearcut response. It also could be refined to detect fragments of DNA and other genetic markers, the UD researchers say.

Building a better biosensor

To create their biosensor, Kaler and Velev deposited gold electrodes onto a slim, inch-wide square of glass, using a photolithography technique. Next, they introduced a drop of the same product used in agglutination tests: Various biospecific molecules bound to latex particles.

Suspended in liquid and subjected to an alternating electrical field, the latex particles coagulate, forming a "bridge" between the electrodes, Velev says. The latex particles can then pick up any targeted molecules in a sample. If the latex is coated with Protein A, for example, it binds with part of the human immunoglobulin.

Adding coated gold particles to the sample turns the latex bridge into a conductor, thereby short-circuiting the electrodes. (To achieve results at lower frequencies, the researchers currently add a silver stain, too.)

Wires link the electrodes to an off-the-shelf generator and a resistance meter, which produces a rapid, yes-or-no (quantitative) response. In the future, Velev says, the technology could be fine-tuned to measure concentration levels of various molecules.

Other chip-based options

Before the UD researchers invented their biosensor, Velev says, they first examined previous efforts to develop a "lab on a chip" for analyzing medical, industrial and environmental samples.

Specifically, they evaluated existing immunosensors based on surface plasmon resonance/total internal reflection (SPR/TIRF), as well as devices using piezoelectric oscillators. When targeted molecules latch onto surface binding sites on these two types of sensors, Velev explains, "It changes their optical properties, or the frequency of oscillations by transducers."

But, Velev says, such devices are "prone to errors" because many molecules may unspecifically adsorb on their surface. Their sensing elements are expensive, too. "You can't say, for certain, that these devices are the wave of the future," Velev concludes. "They've been around for 10 years and they still aren't in practice."

By comparison, the UD biosensor more specifically targets key biomolecules, Kaler says. And, a single $150 bottle of coated latex particles, combined with "electronics you could pick up at a Radio Shack store," could produce thousands of disposable biosensors, Velev says.

"Our goal was to introduce a completely novel technology to the field of biosensing," Kaler says. "We're still grappling with unknowns. But, we have demonstrated the viability of a new technological option, and we believe that it's an important one."

University of Delaware

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