Startups aim to realize potential of cytometry

SAN JOSE, CA—Flow cytometry—the use of light-based techniques (light scattering, light emission, or fluorescence) for sorting and classifying small particles and cells on the micron scale—is imminently useful.

SAN JOSE, CA—Flow cytometry—the use of light-based techniques (light scattering, light emission, or fluorescence) for sorting and classifying small particles and cells on the micron scale—is imminently useful. But despite its many benefits and the recent advancements of flow cytometers, the tools have not reached their potential, says Rosa Chang, co-founder of Stratedigm, a company launched to address a gap in the market.

Stratedigm is not offering new technology per se, but is packaging its tools in such a way as to make high-end capabilities available even at much lower cost—and to enable modular upgrades as customers need them.

Chang is an alumnus of BD Biosciences (also in San Jose, CA), a heavy hitter in flow cytometry. While there, she helped design BD FACSCanto’s flow cytometer—a benchtop, high-fluorescence sensitivity flow cytometer for immunology, cell biology, and drug discovery introduced in May 2004. Chang says that most high-performance units—that is, cytometers with resolution under 2%CV (coefficient of variance) and superior sensitivity—are large, difficult to use, and configured for high-end applications. Those that are configurable are typically expensive because of their architecture. Low-cost instruments, on the other hand, lack the performance of their high-end counterparts. And because of their limited capabilities, the instruments must be replaced as the researchers’ needs change.

Chang and Shervin Javadi launched Stratedigm in late 2004 to provide high performance (that is, high resolution and sensitivity) at all levels (that is, no matter the number of colors and lasers). Stratedigm’s initial offering, the S1000 flow cytometer, is designed to offer scalability in terms of both price and performance. The company is attracting customers who need configurability. For instance, Chang notes that one of Stratedigm’s first customers configured their unit to have blue, red, green, and violet lasers. The design had the green and blue lasers share the same detectors, and spatially separated the signals from the red and violet lasers. The configuration was required in the customer’s lab, but their existing high-end analyzer could not provide that need: only the Stratedigm configurable system would do.

Expansion to 3-D

Another startup that is stretching the capabilities of cytometry is TissueVision (Cambridge, MA), which is based on work Tim Ragan did for his post-doctoral studies at MIT. “The project required that I develop a new sort of microscope that made it possible to quantitatively find cellular mutations with tissues,” which was challenging because these mutations occur so rarely—in about one in a million cells, says Ragan. He needed an instrument that, like a flow cytometer, processes large cell populations to find rare cells. But, says Ragan, “We had to do it inside the 3-D tissue, something current cytometers couldn’t do (and still can’t).”

“As powerful as cytometry has proven,” Ragan notes, “instrument limitations have generally restricted its use to cells outside their native 3-D tissue environment. This limits the range of diseases or processes that can be studied.” He explains that once a cell is removed from its native 3-D tissue, its morphology is dramatically altered and all inputs from cell-matrix and cell-cell interactions are gone.

So Ragan worked to develop a fast, sensitive “tissue cytometer” able to investigate many biological and medical problems that were difficult to address with traditional cytometry. Word got out, and other research groups expressed interest in using the instrument for their work in cancer, vascular biology, heart disease, and neurobiology. “This broad interest got us pretty excited,” he said, so he and partner Karsen Bahlmann decided to start the company.

In 2005 TissueVision received $900,000 in National Institute of Health Small Business Innovation Research grant money—and also became a finalist in an MIT business plan competition, which gave the company great exposure. TissueVision recently sold its first entire system, and has been awarded a third SBIR grant, this one for incorporating fluorescence lifetime detection.
—Barbara Goode

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