Really Flowing

In February 2011, PharmaChemical Ireland, which represents the country's chemical and pharmaceutical industry, urged the government to endorse policies, such as R&D tax credits, that would drive biotechnology success. One Irish company already paving the way to success is Dublin-based Cellix, founded in 2006, whose ground breaking screening system has changed the way researchers study cells in motion.

The Cellix VenaFlux platform mimics venous, arterial or microcapillary structures and gives scientists a window through which to observe how cells behave in the body. The process starts with an eight-channel chip coated with adhesion molecules, such as collagen, fibrinogen, von Willebrand factor, vascular cell adhesion molecules, ligands and seeded endothelial cells. The chip is secured on a microscope frame. Samples of whole blood or separated fractions of blood, such as platelets or monocytes, are then aspirated from Eppendorf tubes by a nanopump set at the rate of normal human blood flow. As the samples flow across the channels, cells adhere to the chip wall, just as they would in vivo, in some cases causing a thrombosis, or clot, which is then recorded by a camera.

The Cellix system also allows researchers to watch interactions between cells or between cells and ligands. It even reveals morphological traits that could alter blood flow. A computer attached to the system analyzes the form, speed and direction of migrating cells.

This technology represents a major leap forward in blood analysis, because viewing cells in motion, as if they were in situ, is more realistic and thorough than the usual observations with static experiments. "Since platelets are known to become activated under shear-flow conditions resulting in different adhesion and thrombi-formation profiles, it is essential to conduct such assays with a continuous flow platform, instead of static, in order to obtain physiologically relevant results," explains Vivienne Williams, chief executive officer of Cellix.

Pharmaceutical companies often use VenaFlux to investigate treatments for thrombosis. The system is reliable, simple to use and reduces the number of animal model studies—which saves time and money during the pre-clinical trial phase. In addition, it requires only microliters of sample, making tests easy to repeat. Williams adds that since the samples are observed as if they were moving through the body, researchers are better able to make informed decisions about a lead candidate, and whether or not it should proceed to clinical trials.

Scientists also use the Cellix system for inflammation assays, such as in atherosclerosis. "Flow is extremely important when modeling the first steps to the build-up of an atherosclerotic plaque in a blood vessel," Williams explains.

Cellix is currently developing a new pump so that researchers can look at long-term cell culture under shear flow. With this advance and others, Cellix will help to keep Ireland's biotech industry surging ahead.