Modeling Genetic Circuitry of Cell-To-Cell Communication with Integrated Fluid Circuit Technology

Utilizing integrated fluidic circuits (IFCs), researchers have discovered a much larger spectrum of differences between individual cells than has previously been demonstrated. Among these differences are the communication capabilities that emerge from the interactions of genetic circuitry that mediates cell-to-cell communication.

Stanford University (Palo Alto, CA, USA) investigators used Fluidigm Corporation's (South San Francisco, CA, USA) Dynamic Array and Digital Array technology in addition to support instrumentation for its cell culture chip as part of this innovative analysis and modeling on how biologic systems operate at the cellular level.

Stanford University School of Medicine found that, "Cells don't all act in a uniform fashion, as was previously thought. Think of cells as musicians in a jazz band,” said Marcus Covert, Ph.D., assistant professor of bioengineering and senior author of the study, published online in the journal Nature June 27, 2010. Dr. Covert's lab studies complex genetic systems. "One little trumpet starts to play, and the cells go off on their own riffs. One plays off of the other.”

Up to now, most of the scientific data collected on cell signaling has been obtained from populations of cells using bulk assays due to technologic limitations on the ability to examine each individual cell. The new study, using an imaging system developed at Stanford based on microfluidics, revealed that scientists have been misled by the results of the cell-population-based studies, according to the researchers.

"This study represents a triple-play of Fluidigm capabilities. Steve, Markus, and their teams used Fluidigm's Dynamic Arrays and Digital Arrays chips for a large portion of their work and some of our analytical instrumentation in operating the cell culture chip. Their work with cell culture coincides with development work that Fluidigm has underway to develop a Stem Cell Culture Chip for the commercial market under a grant from CIRM [California Institute of Regenerative Medicine],” said Gajus Worthington, president and chief executive officer of Fluidigm.

Fluidigm provides commercially available technology on the market to examine individual cells. This technology enabled these Stanford researchers to look at thousands of individuals cells and conduct a multitude of tests on each cell. Fluidigm researchers said, "Population studies have not revealed the intricate network of information one observes at the single-cell level.

"This really surprised us,” said study coauthor Stephen Quake, Ph.D., a professor of bioengineering at Stanford, and a leader in the field of microfluidics. "It sends us back to the drawing board to figure out what is really going on in cells.”

The study used a combination of Fluidigm 48.48 Dynamic Array IFCs to perform 2,304 quantitative polymerase chain reactions (qPCR) in parallel per chip. The cycle thresholds measured during qPCR reactions were converted into relative expression levels and those expression levels were calibrated for total mRNA molecules per cell using Fluidigm Digital Array IFCs performing digital PCR measurements on a single gene.

"These results highlight the value of high-throughput, quantitative measurements, with single-cell resolution in understanding how biological systems operate. We couldn't agree more,” said Fred Walder, Fluidigm's chief business officer. "The Fluidigm platform is uniquely matched to this emerging and critical biological research reality. As more scientists discover that single-cell understanding is key to life science research, we anticipate dramatically increasing interest and demand for our IFC platform products.”

Fluidigm develops, manufactures, and markets proprietary IFC systems that significantly improve productivity in life science research. Fluidigm IFCs enable the simultaneous performance of thousands of sophisticated biochemical measurements in extremely minute volumes. These "integrated circuits for biology” are made possible by miniaturizing and integrating liquid-handling components on a single microfluidic device.

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