The potential successor to the microarray looks a lot like glitter. It’s a handful of tiny silicon integrated circuits termed microtransponders, each smaller than the head of a pin. Each microtransponder contains 50 bits of memory, and transmits radio signals through a wispy antenna when activated by light.
Scientists at Monmouth Junction, NJ, startup PharmaSeq have turned these microtransponders into DNA probes by covalently binding different oligonucleotides to each one.
“It’s as if you took a microarray on a glass slide and diced it into individual cubes, then put a label on each cube to indicate the probe’s position on the cube,” said Wlodek Mandecki, the microtransponder’s inventor and the CEO of PharmaSeq. “It’s a lot faster and the handling is greatly simplified.”
Mandecki said that these microtransponder arrays can be produced at “significantly less cost” than traditional microarrays, since they involve individual chips, each coated with a single DNA probe, and not arrays. Additionally, they can be used with or without PCR amplification, depending upon the concentration of the target molecule in the sample.
These particle assays are also more flexible than microarrays, Mandecki said. With microarrays, “if a new gene is discovered, you need to manufacture a new array. Not so with microtransponders. You simply add a new microtransponder to the mix.”
In a typical assay, sample cDNA tagged with a fluorescent molecule is added to a vial of these particles. Next, the particles in a liquid medium are shot rapidly through a tube in an instrument similar to a flow cytometer. At a single point, a beam of light shines on each particle as it zips by, activating the microtransponder. The microtransponder emits its unique radio frequency (identification number), which is picked up by a detection instrument. At the same time, if any fluorescently tagged cDNA has hybridized to the microtransponder’s oligonucleotide probe, this light beam activates the tag to fluoresce brightly.
Next, a computer attached to the detection instrument matches the identification number of the fluorescent tags to the identity of the sequence on them (which is recorded in its database), and then produces a precise readout of the number of hybridizations to each oligonucleotide probe.
Mandecki sought to commercialize this technology for biological applications after working as a biochemist for 12 years in R&D at Abbott Labs and two years at DGI Biotech.
In 1999, he launched PharmaSeq through $2.25 million in government grants. Soon after, the electronics manufacturer Sarnoff agreed to help the company design and manufacture the microtransponders. Most recently, in January 2001, the Japanese trading giant Mitsui & Company made an equity investment in the company estimated at over $2 million.
But PharmaSeq, which has 12 employees and occupies a modest office and laboratory suite, is still seeking additional financing and “strategic partners,” Mandecki said.
The company initially aims to develop instruments and ready-to-ship prepackaged DNA-based assays. Mandecki envisions eventually applying the microtransponder technology to DNA diagnostics, proteomics, and combinatorial chemistry.
In proteomic applications, antibodies could be immobilized on the microtransponder, and could query for antigens in patient samples; the opposite scenario could also be applied. In combinatorial chemistry applications, small organic molecules could be synthesized on microtransponders. “The idea is that microtransponder technology will be used for high-throughput screening,” Mandecki said.
These microtransponders could even fill non-life sciences applications, for example being used as anti-theft and tracking devices.
Although the microtransponder probes are what Pharmaseq vice president Michael Pappas calls “leapfrog technology,” the startup still faces the challenge of transforming a vision into a viable product. The company still needs to finish developing its instrumentation and publish proof-of-principle studies for its technology.
PharmaSeq is in fact one of a cluster of companies that have broken the microarray mold and developed particle-based arrays. Others, including Lynx, Illumina, and Luminex, are all seeking to develop bead-based arrays that would also escape the spatial and design limitations confining the microarray. While PharmaSeq’s transponders have the additional feature of being “smart” probes that can transmit radio frequencies, the company still faces significant hurdles to commercialization, which others, such as Luminex and Lynx, are already beginning to clear.
“We face challenges typical of small companies with a unique technology,” Mandecki said. “To perfect the technology, manufacture the products and market them, convincing the customers of the benefits of the approach is essential.”
Whether the microtransponder technology takes off is in fact based not only on its performance, but also on how clearly (and loudly) PharmaSeq transmits the message about the advantages of its nano- transponders for DNA detection.