September 1, 2008 (Vol. 28, No. 15)

Cellix’ Drug Discovery System Strives to Reproduce In Vivo Microenvironments

Researchers working in drug discovery “have to think outside the box to insure a higher success rate for their clinical trials and gain a competitive edge,” says Vivienne Williams, CEO and cofounder of Cellix. The company offers life scientists a drug screening tool that aims to bridge the gap between the Petri dish and mouse models, taking them one step closer to in vivo conditions.

By simulating continuous blood flow, Cellix’ platform gives researchers “a physiological snapshot of how a potential lead candidate will affect cells in a human capillary,” says Williams. The technology uses VenaEC™ biochips, cell-based assays that mimic human capillaries, which provides data early in the screening process to make informed decisions and eliminate false leads. Customers include AstraZeneca, Amgen, Pfizer, Sanofi-Aventis, and the NIH.

Drug companies are currently seeking cell-based systems to monitor monocyte adhesion to endothelial cells to study plaque formation in heart disease. The alternative to biochips is using animal models to recreate plaque buildup, which is difficult, time-consuming, and often not representative of the human condition. “To be able to quantify the first step in plaque buildup in a microcapillary is amazing,” Williams says. “Our technology can bridge the gap between human and animal models in an in vitro setup.”

Beyond Microplates

In January, Cellix launched the VenaFlux™ platform, a semiautomated, high-throughput, microfluidic cell-based assay for measuring cell adhesion under conditions that mimic physiological flow. The inspiration for the new system came from customers who asked for a semiautomated version of the earlier Microfluidic SP1.0 system.

VenaFlux uses Vena8 and VenaEC biochips with eight and two microchannels, respectively, that are coated with antibodies or endothelial cells. The manual SP1.0 system uses similar biochips with eight channels.

Each channel is about 400 microns wide, 100 microns deep, 20 millimeters long, and holds 1 to 15 µL of fluid. The small volume makes the system ideal for studying rare cell types or low sample volumes, Williams says. Shear stress, delivered with Cellix’ Mirus™ Nanopump, ranges from 0.05 to 100 dyne/cm2 applied in steps of 0.05 dyne/cm2.

The VenaFlux system can run eight microchannels in 15 minutes, allowing 32 assays to be performed in one hour or about 1,000 assays a week, Williams notes. The relatively rapid analysis reduces drug development costs by eliminating false leads early in the research and development stage, she adds.

Moreover, the company insists, VenaFlux is simple to use, and it cuts down on costly experiments in animal models. The VenaFlux Platform includes a patented nanopump, software, automated robotic arm, digital camera, and Carl Zeiss Axiovert™ 40 CFL inverted microscope.

Traditionally, researchers have performed cell-based assays in isolated 96-well microplates. Each isolated microwell, however, gives only a limited view of an in vivo microenvironment in which cells are in constant communication with each other. Scientists at Cellix strive to reproduce the multitude of interactions occurring in local microenvironments as cells migrate within microchannels.

The effects of drugs on cell adhesion, proliferation, and transmigration are examined under well-defined shear stress protocols with the Cellix techology. Researchers can observe how disease processes control cell migration from the bloodstream to sites of infection and injury by analyzing cells under flow rates that replicate physiological conditions. Additionally, examination of cells under flow permits the exploration of how drugs, pathogens, changes in blood gases, and toxic compounds impact cells, Williams explains.

A range of suspension cell samples can be used with the VenaEC biochips, including T cells, monocytes, neutrophils, eosinophils, platelets, and heparinized whole blood, the company reports. Validated samples include human coronary artery endothelial cell monolayers for investigating monocyte adhesion in cardiovascular diseases and human microvascular endothelial cell monolayers for investigating eosinophil adhesion in respiratory diseases.

Protocols for Clients

Application scientists at Cellix develop protocols to show researchers how to use the patented biochips to different disease situations. The protocols available so far involve using lymphocytes to investigate inflammation in autoimmune disorders, platelets to investigate thrombosis in cardiovascular disease, and eosinophils for exploring respiratory inflammation. Now customers are asking for methods to look at cell-cell interactions in obesity and diabetes, such as ways to knock down certain cell surface receptors with inhibitors.

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