July 1, 2010 (Vol. 30, No. 13)

With Its Microfluidics Technology, Cellix Simulates In Vivo Conditions

As postgraduate students in the department of physics and clinical medicine at Trinity College, Dublin, Vivienne Williams and Dmitry Kashanin were working on a project to investigate microfluidics and develop biochips for cell-based experiments. They developed a technology to mimic human capillaries in plastic.

Williams and Kashanin realized that dynamic, continuous-flow experiments by simulating a blood vessel, would be more representative of the physiological condition than animal tests. The assay would mimic the flow of blood, thereby, providing a better simulation of how a new drug might react within the body. Researchers could use the system in tandem with, or just before, animal testing to determine the in vivo effect of drugs on the human body.

“By operating under continuous blood flow conditions, the Cellix platform simulates the human environment, providing researchers with powerful data far beyond that available via static conditions of the petri dish before advancing to costly animal trials,” Williams explains. “By using our solution, false leads can be eliminated earlier in the process and winning compounds can be chosen, increasing the success rate of clinical trials and giving researchers the competitive edge.”

As a result of this collaborative partnership supervised by professors Dermit Kelleher and Igor Shvetz, a prototype microfluidics screening tool for drug discovery was born, patents were issued, grants were procured, and Cellix was launched.

“Our solution contains everything a researcher requires to execute continuous-flow, cell-based assays and make informed decisions,” Williams explains. “The only fully integrated end-to-end microfluidics system on the market, the Cellix solution includes the platform, biochips, and cell analysis software. They give researchers reliable tools for investigation of cell adhesion under physiological shear stresses.”

In 2006, the company was formally established with a head office in Dublin. Williams joined as the CEO and was the first employee in March of that year with Kashanin and O’Dowd joining as CTO and design engineer, respectively, in November.

The company raised venture capital funding from OTC in Paris, NCB Ventures in Dublin, and Enterprise Ireland. “That $3.5 million in funding was not a huge amount, but we’ve grown the business on original revenue,” Williams explained.

According to Williams, the technology provides an assay for secondary drug screening in research labs and preclinical testing for drug discovery. Compounds can be investigated with isolated cells or whole blood samples from human donors “where cells act differently under flow conditions in a physiological sense.” In situations where no biomarkers are present, researchers have to use flow-based adhesion studies or flow cytometry to determine what happens in vivo, according to Williams, who said that cell-cell and cell-protein interactions can be studied in a fast, reliable, cost-effective manner.

“We don’t offer one-size-fits-all products. During the consultation phase, our team will run a demonstration and ensure that a customer’s team members are fully trained to get the most from the platform within the specialized disease area. Cellix provides customized solutions for all its clients depending on what is needed, e.g., changing flow rates or adhesion molecules to suit the application.”

According to Williams, one key area of research with Cellix systems is thrombosis studies, in which scientists determine how platelets attach to blood vessel walls. Inflammation studies are also “huge,” she said. Those experiments determine how cells attach to blood vessel walls and attack the site of inflammation. Another area of study is circulating tumor cells, which can create a secondary tumor.

The VenaFlux™ system is a fully integrated, automatic platform that enables researchers to carry out experiments in conditions that mimic physiological microenvironments. The microfluidics system is “preassembled, robust, and simple,” according to Williams, who points out that it reduces volume and cost and is “plug and play.”

Using the system, the adhesion profiles of cells can be studied to obtain information on the effects of drugs on receptor-ligand activation or on the effects of chemokines. Experiments have been carried out to study the adhesion profiles of cells such as monocytes, T cells, eosinophils, neutrophils, PBMCs, cancer cells, platelets, and cell lines including THP1s and CHOs. The adhesion of cells can be studied on endothelial cells or purified molecules such as rhVCAM-1, rhICAM-1, collagen, vWF, or fibrinogen.

Doing cell-based assays under flow with Cellix’ biochips does not have to mean an expensive investment in capital equipment, according to Williams, because the biochips are compatible with confocal microscopy, syringe pumps, and imaging systems.

“Pumping systems act like the heart pumping blood through capillaries, providing even flow through the samples,” Williams explains. Cellix’ Mirus Nanopump is capable of delivering accurate flow rates and shear stresses. It can be upgraded with the MultiFlow8 to enable the running of eight assays simultaneously in the Vena8 biochip.

Cellix offers two biochips, the Vena8  and the VenaEC, which contain capillaries. In these capillaries, cells or whole blood samples may be flowed over adhesion molecules (Vena8) or endothelial cells (VenaEC).

DucoCell™ is the software package supplied by Cellix for image analysis. It provides the researcher with information on cell number, cell shape, polarity, form-factor, and area. Graphs are automatically generated for the selected parameters. Readouts include cell count (i.e., number of cells adhered in the microfluidic channels of the biochips at a particular shear stress)  and morphological parameters including area or diameter of cell at a particular shear stress.

Williams believes that there is “a greater appetite for microfluidics technology now.” She adds that “there was a buzz about it five or 10 years ago, but very few commercial products came out of it. It’s taken a long time to make headway, but now there’s a change in the general mindset as people see good, solid products in the marketplace.” 

More areas are being studied with Cellix’ microfluidic technology, according to Williams. Early studies were in the areas of thrombosis, immunology, and oncology. “Now people are studying bacteriology with biofilms to determine how bacteria attack in different places. Companies are developing antibacterials and studying urinary tract infections under flow conditions. These kinds of studies will increase in importance in the next couple of years.”

The recessionary economy has produced another kind of trend as companies reduced their budgets, put projects on hold, or underwent mergers and acquisitions. “Cellix decided to diversify into the academic and government sectors when the funding started to dry up in companies,” Williams says.

The Vena8 biochip is used for studying cell receptor-ligand interaction. As cells flow through the microcapillary of the Vena8 biochip, the cell surface receptors may interact with adhesion molecules or ligands that coat the microcapillary walls.

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