April 15, 2008 (Vol. 28, No. 8)

New Product Line Designed to Represent Next Generation of Cell-Based Assays
Beginning this summer, Roche Applied Science will launch the first of three novel, cell-based assay systems under the xCELLigence™ brand name. The products are built upon and represent improved versions of the current impedance-based RT-CES technology Roche acquired from Acea Biosciences last November.

“The technology provides unique insights into the functions of the cell,” says Jeffrey Emch, marketing manager, Roche Diagnostics, Roche Applied Science USA.

“Genomics and proteomics research in the drug discovery environment has not, for the most part, led to the degree of new compound development that people had expected. A lot of assays are coming back to focus on the cell to address this issue.”

The first product, RTCA SP, will be released in July. This is a single-plate station that will interface with a 96-well microelectronic E-plate®. The plate station fits inside a standard tissue-culture incubator, while an analyzer and laptop computer with newly designed software will be on the outside.

In September Roche will launch the RTCA MP. The difference here (MP stands for Mult-E-Plate) is that the plate station accepts six 96-well E-plates inside the incubator.

The RTCA DP (dual plate) cell-based assay system will make its debut in December. This dual purpose offering can accomodate a 3 x 16 E-plate product. In the DP system, the plate station and analyzer are combined into one unit and connect to a computer outside the incubator.

“The RTCA DP can run standard 16-well E-plates as well as the invasion migration plates. The invasion migration device is basically a modified Boyden chamber that can detect directional movement of cells across a membrane,” explains Emch.

“As the cells move in response to a stimulus, they come into contact with the microelectrodes at the bottom of the plate, and we can detect that through impedance measurement. The product can be used in cancer research (e.g., studying metastases and chemotactic signaling).”

Initial Focus on Drug Discovery

The xCELLigence systems will have an initial focus on drug discovery, including applications in compound screening and profiling, assay development, and preclinical toxicology. Another important area will be functional receptor analyses, especially those involving GPCRs.

“The assays can detect a response to receptors that are expressed endogenously,” continues Emch. “There is no need to overexpress a given GPCR within a cell line which, in effect, changes the natural cellular condition to get a detectable response. You will be able to use primary cells.”

An important advantage of the xCELLigence system is the design of the electrodes, maintains Emch. While there are other types of impedance-based products, the xCELLigence system contains interdigitated microelectrodes that cover approximately 80% of the bottom surface area of the well, he says. This means that cells can be detected at low numbers and monitored from seeding on the plate through initial attachment and growth phase, through the point of challenge with some kind of chemical or biologic stimulus, and for as long as the researcher requires post challenge, continues Emch.

Major Features

The allure of this cell-based assay technology derives from two main features: it is label free and operates in real time, according to Yama Abassi, Ph.D., senior director of cell biology and assay development, Acea Biosciences, and one of the key players in developing the methodology. Labels can damage the cells and are often expensive, he points out, adding that radioactive labels also can be hazardous to your health and costly to dispose.

“The essence of impedance technology as a readout is that it is noninvasive and allows experiments to be done under physiological conditions,” says Dr. Abassi.

The real-time component of the assays provides a clear picture of how cells are behaving in each well, he explains. “Most cell-based assays are endpoint assays that measure only one data point per experiment,” claims Dr. Abassi. “Real-time capability means you can continuously monitor the cells in an experiment and obtain a number of data points. It gives you a kinetic profile of the experiment from beginning to end.”

Real time also offers a quality-control aspect, a point stressed by both Dr. Abassi and Emch. “You can detect any changes in the cell before the point of challenge,” says Emch.

Real-time readout lets you know exactly when to challenge cells based on where they are in their metabolic or growth cycle, adds Dr. Abassi. “This allows for a QC aspect that is difficult to achieve by standard assays.”

While Roche will be responsible for worldwide sales, marketing, and distribution of the xCELLigence system, Acea plans to develop other impedance-based products and other specialized applications such as diagnostics, says Dr. Abassi.

For its part, Roche will continue to add its expertise in design, engineering, and software functionality to further expand its cell-based assay-technology applications.

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