Stanford researchers have integrated an array of tiny magnetic sensors into a silicon chip containing circuitry that reads the sensor data. The magnetic biochip could offer an alternative to existing bioanalysis tools, which are costly and bulky.
“The magnetic chip and its reader can be made portable, into a system the size of a shoebox,” says Shan Wang, professor of materials science and electrical engineering at Stanford University, in Palo Alto, CA. Its small size, he says, could make it useful at airports for detecting toxins, such as anthrax, and at crime scenes for DNA analysis.
The Stanford biochip is one of a number of approaches being explored to replace the current bioanalysis technology. Today’s systems use florescent tags attached to molecules. The florescence is detected using optics–lenses, mirrors, and light detectors–that are fragile, bulky, and expensive.
Wang’s biochip employs silicon circuitry, made using standard silicon processes at National Semiconductor. To this chip, he added an array containing more than 1,000 sensors, each composed of two magnetic layers separated by a nonmagnetic spacer made of copper.
For his group’s most recent results, presented in November at the International Electron Device Meeting in San Francisco, the researchers built a chip that detects DNA sequences. They coated the sensor array with a polymer film and single-stranded DNA containing known sequences. The single-stranded DNA was used as a receptor, Wang explains, to attract complementary DNA strands from a test solution. “You’re looking for the matching molecule,” he says.
To detect the matching pair using the sensors, the strands of DNA in the test solution must contain a magnetic particle. Wang used magnetic nanoparticles, 15 nanometers in diameter, coated with a protein called streptavidin, which binds to a molecule added to the test strands of DNA, called biotin. When a test strand of DNA finds its complement on the sensor array, the nanoparticle and the sensor are in such close proximity that the entire sensor’s resistance signals a match.
It should be possible to detect toxins and cancer molecules with the magnetic biosensor using the same type of chip, Wang says. The trick is to bind a magnetic nanoparticle to the molecules so the electronic signature can be detected.
Because the chip has more than 1,000 sensors, Wang says, it is capable of monitoring many different types of molecules at one time. And integrating the electronic circuitry into the magnetic sensor array allows each sensor to provide a distinct output. The advantage here, he says, is that the chip design could be used to look for a number of different toxins, diseases, and DNA sequences.
With recent advances in high-density data storage, magnetic biosensors have become sensitive enough to use in biochips, says Lloyd Whitman a scientist at the U.S. Naval Research Laboratory in Washington, D.C. who is a pioneer in the field. Wang’s work, in particular, shows that the magnetic technology can be used to make large arrays of sensors on biochips, Whitman says. “It’s scalable,” he says, and each sensor can provide a distinctive electronic signature.
The biochip still needs to be tested with many non-DNA molecules to be useful for disease and toxin detection, Wang says. But within the next few years he expects that the technology will find its way into clinical trials.