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Blueshift Scores Biotech, Academic Partners for Dynamic Fluorimetry Platform; SBIR Grant Pending

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SOUTH SAN FRANCISCO, Calif. — Blueshift Biotechnologies, the Sunnyvale, Calif.-based startup attempting to commercialize cell-based screening technology based on what it calls “dynamic fluorimetry,” has recently signed on at least three beta-testers or collaborators for IsoCyte, its flagship screening platform, Blueshift said at Select Biosciences’ EmTech conference held here last week.

In addition, Blueshift anticipates to receive a Small Business Innovation Research grant for an undisclosed amount from the National Institutes of Health sometime in the next month, Chris Shumate, Blueshift’s vice president of business development told Cell-Based Assay News. As it would be Blueshift’s first NIH grant, the award would likely be a Phase I SBIR — which are typically worth around $100,000.

Blueshift’s first partnership, which it announced in January, is with Carlsbad, Calif.-based biotech Active Motif. In that collaboration, Blueshift and Active Motif will jointly develop assay kits to be used on the IsoCyte platform. The companies will co-market the kits and share revenues, and the first jointly developed assay kit will be available later this year, according to a joint statement by the companies.

Meanwhile, Shumate told Cell-Based Assay News, Blueshift has also initiated a previously unannounced collaboration with Academia Sinica in Taiwan. The IsoCyte customer in that collaboration, Shumate said, is Chi-Huey Wong, a professor of chemistry at the Scripps Research Institute in La Jolla, Calif., and director of the Genomics Research Institute at Academia Sinica.

“As the director of that center, he is always interested in genotyping,” Shumate said. “But there are a variety of other opportunities within Academia Sinica as well as the [affiliated] Taiwan University for other applications.”

Both partnerships, according to Shumate, will serve to validate specific applications for IsoCyte, which Blueshift believes can be used for array-, bead-, and cell-based assays.

Blueshift’s instrument platform exploits the well-characterized notion that detailed measurements of a fluorescent tag’s activity can provide a great deal of information about an attached molecule in a controlled assay. The majority of these measurements relates to fluorescence polarization, anisotropy, and lifetime, and can provide a so-called high-content assay without actually taking pictures of a cell, as is the case with most high-content screening platforms on the market.

Now, the company is determining which applications are best-suited to the concept.

“This is the time that we’re proving that we can deliver a product,” Shumate said. “We have our noses to the grindstone now, building and shipping instruments to our current customers, and prospecting for people who are interested in turning the capabilities of anisotropy imaging into applications.

“I think it’s been accepted that the hardware is somewhat mature in that it’s been used in the semiconductor inspection field,” Shumate added. “The beta partners are really application betas, not hardware betas.”

Shumate declined to disclose a third beta tester.

The pending SBIR grant, meanwhile — for which Shumate said Blueshift has already received a confirmation letter and only awaits finalization — will also be for developing genotyping applications on IsoCyte, although Shumate characterized these as “highly multiplexed genotyping” applications.

The grant will provide much-needed income for Blueshift, which has to this point depended primarily on an early-2004 financing round that garnered the company somewhere between $1 million and $5 million (see Inside Bioassays, 10/19/2004).

FRETting Away

At the EmTech conference, Shumate presented data obtained in collaboration with Vanderbilt professor David Piston, a Blueshift scientific advisory board member and pioneer in the field of dynamic fluorimetry.

Specifically, Shumate presented data that appears in recent issue of Biophysical Journal [2005 Feb; 88(2): L14-6.], in which Piston demonstrated a strategy for conducting FRET (fluorescence resonance energy transfer) in high-throughput in living cells by exploiting fluorescence polarization measurements similar to those that are performed on IsoCyte.

“In the absence of FRET, we show that fluorescence emission from a donor fluorescent protein is highly polarized,” the paper’s abstract states. “Depolarization of fluorescence emission is observed only in the presence of energy transfer. A simple detection strategy was adapted for fluorescence microscopy using both laser scanning and wide-field approaches. This approach is able to distinguish FRET between linked and unlinked Cerulean and Venus fluorescent proteins in living cells with a larger dynamic range than other approaches.”

According to Shumate, the significance of the data is that “it appears to be a high dynamic range for FRET, so doing object-based high-throughput versions of that looks like a good opportunity,” for IsoCyte, he said.

In fact, Shumate added, Piston and other Blueshift scientists were working on duplicating the data using IsoCyte on the very same morning of Shumate’s presentation.

“This actually describes FRET in cells — high-speed, object-based FRET by anisotropy,” Shumate said. “And that’s one that the world hasn’t seen, and the majority wouldn’t quite understand yet.

“We’ve been working on proving unique aspects that we can measure with anisotropy in cells,” he added. “And we have made models that were bead-based and surface-based to prove the kind of readouts that were possible. So [we did] some obligatory cytotoxicity assays to show … how the data is manipulated, and hopefully how easy it is to develop an assay.”

Although Blueshift is still seeking to hammer out the details regarding the use of IsoCyte in high-throughput cell-based assays, it is already eyeing the next-generation version of IsoCyte: TauCyte, a platform that would incorporate lifetime fluorescence measurements into the fold.

“We still have in our plans TauCyte, which will probably be in a beta-phase at the end of this year, and we hope to release it in the first quarter or second quarter next year,” Shumate said. “That will add imaging in the lifetime frequency domain, so every picture will be an average lifetime — it’s not a time-gated system, it’s a true lifetime imager.”

— BB

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