When ViaLogy CEO Doug Lane wrote the company's business plan two years ago, market forecasts, he said, projected that microarrays would be a $5 billion business by 2005.
Some of these market forecasts admittedly contained more hype than hard facts, but only the most conservative naysayers among the forecasters [see BAN 06-19-01] projected that the market would be anywhere near as small as where it is leading up to 2004: an estimated $800 million.
Lane believes, though, that his company has the technology to drive the market for arrays up toward that $5 billion mark. The core of this technology is quantum resonance interferometry, which takes the techniques used in advanced radar detection and applies them in silico to microarray data analysis.
The company has this month launched a service based around this technique for the Affymetrix platform, and announced this week that it plans to launch a similar service in January around the chips made by Swiss array startup Zeptosens; but the technology, according to Lane, can make any microarray platform orders of magnitude more sensitive, specific, and reproducible.
"As I go out and talk to heads of research at 8 to 10 of the major pharma companies, they list the same five issues as to why they have not adopted that technology as people thought they would have adopted that technology three years ago," said Lane, himself a former SmithKline Beecham R&D manager. "Number one of the issues is sensitivity. They just do not believe these microarray devices are showing all of the genes that are present in an experiment." The other issues include a lack of reproducibility, false-positive results, scale, and informatics, he said.
"So we look at our technology and we see the performance improvements that we have on the sensitivity, the specificity, the reproducibility, [and] we absolutely believe that pharma companies will adopt these microarray devices as one of the front line tools to begin to discriminate optimal targets for drug discovery."
Skeptics might balk at the idea that a data analysis tool alone could do this much for microarrays. After all, data can only be massaged so much. In fact, the collaboration with Witterswill, Switzerland-based Zeptosens, in which Qiagen is also participating, aims to go beyond just computation. Qiagen has been working to optimize the mRNA extraction, purification, and labeling protocols for Zeptosens' SensiChip DNA microarrays, while Zeptosens has been working on optimizing sensitivity of the chips themselves. The companies have reported that the combination of technologies enables them to detect mRNA levels from as few as 1,000 cells with reproducible results.
"This is really a breakthrough that we could demonstrate [the ability] to measure RNA or cDNA from about 1,000 cells without amplifications," Markus Ehrat, Zeptosens' CEO, told BioArray News. "We were quite happy to see that we could have a major improvement of our already high sensitivity system with the ViaLogy software."
The team achieved full detection of signal down to 20 picograms of starting sample, and absolute quantitation of expression (rather than the relative expression levels microarrays generally provide) down to 20 nanograms of starting material, according to Sandeep Gulati, CSO of ViaLogy
The partners in this collaboration are preparing an article for submission to a peer-reviewed journal that demonstrates their results, and "we hope to get it out really quickly," Ehrat said.
Technologies That Push the Limit
The combination of QRI with the SensiChip is a marriage of like-minded souls: Both technologies contain special features designed to push the limits of detection for gene expression beyond the current state of the art.
The SensiChip (which is only being sold in Europe at present) uses planar waveguide technology, which creates a thin layer of light above the chip surface to excite only fluorophores bound to the surface of the chip, while leaving those in solution dark -- thus decreasing background fluorescence, and in doing so enabling users to skip enzymatic amplification steps [For more details on this technology, [see BAN 08-02-02].
Similarly, QRI "allows us to detect signals that are up to ten thousand times lower than background noise," said Lane. The technology is a software application that uses algorithms the company calls "active signal processing" to detect signal on microarray images by injecting specific pulses of mathematical noise into the data from the images, then seeing how the signal interferes with that noise.
"We start with the same image [that other analysis does], then we have transformations and reduce it to the spectral regime," said Gulati. "What we are looking [for] is after we do these transformations, that in our representation or in our spectral transformations, if signal is present we see spectrum which is different than from what the noise is doing." [For a full explanation of the technology, see Lab Report, p. 6.]
"What we are doing with our technology is like taking a very powerful magnifying glass and applying it to the DNA microarray systems and getting substantially better performance than what [users] can get with their own analyses from software," added Lane.
ViaLogy's strategy is to make the QRI system available as a data processing service, the ViaLogy Microarray Service, for the major microarray platforms. In addition to the current Affymetrix service, which processes U95 and U133 human chips, the company has also adapted its software to read images from glass slide arrays, and has a plan in the works to make its service compatible with Agilent chips.
But with Zeptosens, and its focus on detection in tiny samples, the company sees an opportunity to make microarray systems sensitive enough for clinical applications. "We recognized in advance of the start of the collaboration that if we could get the performance to the point where we could do very high-quality analyses on a few genes, that would allow researchers to do simple fine-needle aspirations almost at the bedside or at the clinic to do differential expression experiments, and begin to get an expression profile that can be used to determine the type and possibly the advancement of a specific tumor or tumor therapy," Lane said.
Ehrat was more cautious, though, in his estimation of the Zeptosens platform's applicability to clinical diagnostic applications. Currently, he said, the company is focusing on other applications. "This is not meaning that we could not move into clinical evaluation of compounds," he added.
In the near term, ViaLogy will be selling European users of the Zeptosens system its microarray service, on a fee-for-service basis. For all platforms, the company charges a $5,000 one-time setup fee per client, and then a flat fee of $250 per microarray experiment. Five pharma companies are already using the technology, Lane said.
As might be expected of a company CEO, Lane is optimistic about getting more pharma business. "What [pharma customers] tell us initially is that the ability to have our service means they can very quickly scroll through their microarray experiments," he said. "They continue to tell us that they have hundreds and thousands of microarray experiments that they would like to do, but because of the performance degradation that they see today, it's impractical and doesn't make sense for them to do that. So we see ourselves very much as an enabling technology."
The coming months will reveal whether this new microarray service becomes more than a bleep on pharma's radar screen.