Corning Life Sciences is the oldest operating business of its parent company, Corning (www.corning.com). It has been supplying scientific laboratory products for more than 90 years, starting with the invention of Pyrex® glassware. Since then, 6,000 scientific products have been added, largely for researchers working with cell cultures.
About five years ago, Corning Life Sciences tapped the 1,500 scientists at its R&D center to find ways to improve drug discovery. A major result was the Epic® System, a high-throughput, label-free screening platform that was launched in September 2006.
Epic Changes for Drug Screening
The Epic System grew out of talks with drug discovery researchers about the limitations of current high-throughput screening (HTS) methods. “We heard over and over again that screens give a high rate of false negatives and false positives,” says Mark Beck, vp and general manager of Corning Life Sciences located in Corning, NY, and Lowell, MA. With companies screening millions of potential drug compounds, “it is not acceptable to miss a potential winner or invest months or years in a false hit,” he adds.
Most drug targets are proteins involved in a disease process, yet about 25% of these targets are not addressable through traditional screening technologies. “We learned that all these problems had the same root cause,” says Beck, namely, that all HTS technologies rely on fluorescent or radioactive labels. The addition of labels to tag molecules creates unnatural conditions that contribute to false information. In other cases, targets are difficult to label.
The Epic System identifies drug leads by using changes in the refractive index of light. The interaction of drugs with target proteins is observed in a natural way, so false information is reduced. Moreover, the Epic System works with previously unscreenable targets.
The system monitors two types of assays: biochemical assays such as binding reactions and cell-based assays such as signal transduction or toxicity. The next Epic System will allow users to measure kinetics in flow cells, according to Beck.
Researchers in optics, materials science, and the life sciences helped to develop the Epic System. The two basic components consist of a disposable 384-well microplate with integrated biosensors and an HTS-compatible microplate reader that permits screening of up to 40,000 wells in eight hours.
Epic is sensitive enough to detect the binding of a 300-dalton compound to a 70-kilodalton target, according to Corning. It uses an industry standard microplate format, making it easy to combine with existing facilities and instruments.
Because the concept behind the Epic System is so new, customers can take it for a test drive at two new Epic Applications Centers that Corning operates in Big Flats, NY, and Fontainebleau, France. The facilities allow pharmaceutical and biotech researchers to evaluate the technology before purchasing the platform.
Several Epic Systems have already been installed in laboratories across the U.S. and Europe. After purchasing an Epic System, researchers stay in contact with Corning’s internal applications scientists who provide protocols. In addition, field applications scientists work closely with customers in their own laboratories to design and optimize new assays.
In Vivo-like Cell Growth
Corning’s R&D experts have also made advances in methods to improve the growth of primary cells and stem cells. The company launched the Ultra-Web™ synthetic surface technology in April 2007.
“We’ve heard from hundreds of cell biologists that most cells used today are grown in sterile environments, and they are no longer predictive of how cells react in the body,” says Beck. The Ultra-Web surface technology offers in vivo-like growth conditions that can lead to improved outcomes in cell culture and cell-based assays.
This artificial, 3D matrix consists of electrospun nylon fibers that resemble structural components within the basement membrane or extracellular matrix.
Corning developed Ultra-Web with two collaborators, Donaldson (www.donaldson.com) and SurModics (www.surmodics.com). The former company created the underlying nanofiber structure, and chemistry experts at SurModics treated the synthetic nanofiber with special polymers to facilitate cell growth. Corning then integrated the pieces and applied it to 96-well microplates and 100-mm tissue culture dishes to mimic in vivo cell growth conditions.
“When cells are placed on the treated nanofiber in our vessels, they think it is extracellular matrix,” notes Beck. Unlike other biological coatings, the fibrous topography of Ultra-Web is more stable, more consistent from lot to lot, and is made from animal-free components, reports Beck.
Higher density cell cultures can be grown in Corning’s new HYPERFlask™ vessel that grows 10 times more cells than a standard T175 flask, according to the company. A multilayer design has 10 equivalent layers, or flaskettes, each containing a gas-permeable cell growth layer. An air gap is incorporated between each flaskette for cells to obtain oxygen and expel carbon dioxide.
Each flaskette is treated with the Corning CellBIND® Surface to optimize cell attachment and growth. HYPERFlask vessels can be used manually or in the Automated Partnership SelecT™ cell culture system.
Another in vivo-like technology aims to systematically identify growth conditions for cell lines that refuse to be cultured or grow poorly in culture.
Cells are exposed to thousands of polymer blends, while scientists observe their ability to seed themselves. Then more polymer combinations are generated, and after several iterations, a tailor-made growth surface for a cell line is selected. “It’s a very elegant approach for cells to select what works for them instead of us intuiting what cells like,” says Beck.
In the past five years, Corning’s materials scientists, biophotonics researchers, and biologists have solved several major problems that hamper drug discovery and cell culture researchers. Feedback from customers helps to drive the innovations. “We are open to collaborations and ideas that other folks may have,” says Beck, “and we urge them to seek us out.”