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Pending Products May Increase Corning s Play In Cell-Based Assays, High-Content Screening


Corning's Life Sciences division plans two product releases next year that may increase the company's play in the emerging cell-based assay and high-content screening market, various company officials said recently.

First, Corning hopes to release the Epic label-free biological detection system in the fourth quarter of 2006, representatives for the company told CBA News last week. Although originally designed with high-throughput biochemical assays in mind, the system is expected to enable several types of label-free high-throughput cellular assays, as well, Corning said.

In addition, Corning is collaborating with Fisher's high-content screening subsidiary Cellomics to develop a specialized microplate for high-content cell-based assays, which would stand to be one of the first such products on the market, a company representative told CBA News at IBC's High-Content Analysis meeting held two weeks ago in Washington, DC. However, this project is only in the development phase, and Corning has no specific timeline for the product, he said.

Corning's Epic system is a "marriage of many of Corning's core competencies," such as materials science, photonics, and surface chemistry, Dana Moss, marketing communications manager for the product line, told CBA News last week. Despite this, it would be Corning's first major attempt at a full-scale instrumentation platform, relatively unfamiliar territory for the company.

"The response is directly proportional to the amount of compound that the cell sees, and we can determine IC50 values for compounds that agree well with what is known in the literature."

The platform features a label-free detection method in which each well of a 384-well microplate contains a resonant waveguide optical sensor. According to the company's website, "when illuminated with a broadband light source, these sensors reflect a specific wavelength that is a function of the combined indices of refraction related to the materials composing the waveguide; this includes the biomolecules within 200 nm of the sensor surface."

When biomolecules are bound to the surface of the sensors, a baseline reading can be taken; then, when additional molecules are added that bind to or alter the original molecule in some way, a shift in wavelength can be detected and quantified by a plate-reading instrument that Corning will market along with the plates.

The molecules bound to the sensor surface can be proteins for high-throughput biochemical binding assays; or, they can be intact, live cells for assays such as GPCR activation, cell proliferation, cell toxicity, and the activation of other cell-signaling pathways.

Like other label-free cell-based assay technologies, a change in the physical attributes of a cell close to the sensor can be translated into a significant biochemical event of some sort occurring in or around the cell.

"We're sensitive to either changes in cell shape, or the vertical distribution of mass within the cell," Tony Frutos, a biochemical research manager at Corning, told CBA News. When, for example, a cell-surface receptor such as a GPCR is activated, it can trigger events that cause mass within the cell to move toward the cell surface. This, in turn, would manifest itself as an increase in signal, Frutos said.

"It can be quantified," Frutos said. "We can measure the magnitude of the increase or decrease in signal, and we can also measure the amount of time it takes to reach maximal signal.

"All of those are important characteristics, and we've actually demonstrated in several papers that we can measure dose-dependent binding," he added. "In other words, the response is directly proportional to the amount of compound that the cell sees, and we can determine IC50 values for compounds that agree well with what is known in the literature."

Corning would join a growing number of companies marketing label-free cellular detection platforms, though all are based on different concepts. For instance, MDS Sciex, ACEA Biosciences, and Applied Biophysics are all marketing instruments based on electrical impedance sensing; Blueshift Biotechnologies is developing an instrument based on fluorescence anisotropy; and several others are selling or developing instruments that use surface plasmon resonance.

Moss said that when Corning rolls out the platform late next year, it will do so as an instrument for biochemical, cell-based, or hybrid assays. The company will sell specially designed 384-well plates along with an optical reader, which will be manufactured in partnership with Jena, Germany-based instrument maker CyBio.

Currently, Corning has several undisclosed beta testers at pharmaceutical and biotech companies, and one at an academic institution. Moss said that one of the pharma companies and the academic institution plan to evaluate the cell-based assay capabilities of Epic in the coming months. The cost of the microplates will translate to approximately $0.40 per well, while the instrument will be in the $350,000 to $400,000 range, she said.

Corning may have had a commercial instrument on the market sooner were it not for recent litigation involving the technology's core US patent, No. 4,815,843. Corning had licensed the original IP for the sensing technology from Swiss firm Artificial Sensing Instruments.

In 2003, Corning and ASI sued Woburn, Mass.-based SRU Biosystems, claiming that SRU had infringed the patent by developing a similar instrument platform and testing that platform with an early-access partner. Earlier this month, Corning said it had won the litigation.

Familiar Territory

The other product that Corning is working on is more familiar territory: microplates. Although the company already has many products for cell culture and cell-based assays, it is currently developing a multi-well plate designed specifically for high-content screening.

At IBC's High-Content Analysis meeting, James Buttarazzi, an instrument and automation manager for Corning Life Sciences, said that Corning has partnered with Cellomics to develop the plate.

Buttarazzi declined to provide details about the collaboration, as the partnership hasn't been "officially" established; however, he did provide some details potential product, and showed off an early beta version.

The well plate will attempt to solve the very simple but disruptive problem of thermal fluctuations that occur in cells that are in the border wells of a typical plate. As these wells are not bordered by other wells that also contain cells and a liquid volume of some sort, they are subject to minute temperature fluctuations that can completely disrupt readouts from a high-content screening instrument.

The new Corning plate would have a channel surrounding the outer wells of the plate and containing the same insulating liquid found in each of the wells on the plate, thus stabilizing the temperature in the outer wells. It sounds simple, but Buttarazzi said that nothing is on the market to address this problem.

Corning does not yet have a timeline for the development of this product.

— Ben Butkus ([email protected])

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