January 15, 2015 (Vol. 35, No. 2)

To Gain a Systems Perspective, Explore the Genomic Heterogeneity of Cell Populations

Fluidigm, a pioneer of single-cell biology, has announced a new technology that enables individual cells to be analyzed in situ, enabling greater understanding of systems biology at the cellular and subcellular levels.

“We want to ignite a revolution in biology through the relentless pursuit of scientific truth,” says Gajus Worthington, Fluidigm’s president, CEO, and co-founder. The company’s role, he says, is to dramatically simplify complex jobs to enable scientists to understand the workings of single cells and then apply that knowledge to entire systems.

Fluidigm introduced its first integrated fluidic circuit (IFC)-based system in the early 2000s, and in 2012 the company brought the C1 Single-Cell Auto Prep system to market. The C1 could capture, process, and prep up to 96 individual cells in parallel.

The C1 system has since acquired additional capabilities. It now supports single-cell whole genome sequencing, whole exome sequencing, targeted gene expression, mRNA sequencing, miRNA expression profiling, and targeted DNA sequencing.

The Fluidigm instrumentation that served the production genomics market before the redesign.

New System, New Set of Tools

A new IFC prototype, expected to be released in the first half of 2015, can capture and process up to 750 single cells per run for high-throughput mRNA sequencing. This makes individual studies of 100,000 cells practical, Worthington tells GEN. “There’s nothing like it in the industry,” he boasts.

“There are between 40 and 100 trillion single cells in a human being—more if you include bacteria,” Worthington points out. “We realized we needed to build tools that could process a lot more cells, so the new IFC can handle nearly an order of magnitude increase from our initial device, which is a pretty dramatic change.”

Fluidigm also is developing a new set of tools to interrogate single cells within their biological niche, which enables cellular responses to be analyzed in a systems biology approach. The first product, an imaging mass cytometer, was distributed to early-access customers at the end of 2014. “It lets researchers take tissue and analyze their proteins in parallel, at the cellular and subcellular levels,” Worthington asserts. Subsequent products will build on that theme.

From Cellular to Systems Biology

“As a life sciences industry, we don’t understand to a high degree what happens to individual cells,” Worthington acknowledges. “We get surprised a lot.” Yet surprises or misapprehensions could become less common if our understanding of biology at the cellular and subcellular levels could be improved.

Worthington, with degrees in physics and electrical engineering, compares the aerospace industry to the life sciences: “The aerospace industry used equations for motion to accurately predict the behavior of spacecraft decades before they flew, but we can’t do that in biology yet. We can’t even understand how an individual cell works, much less predict its behavior.”

The equivalent of “equation of motion” studies must be performed for single cells before accurate predictions become routine. The ability to conduct such studies is a necessary precursor to understanding biology at the systems level.

To explain the relationship between cellular and systems biology, Worthington uses the analogy of a crowded room: “Say something provocative and you will hear a cacophony of voices. Likewise, stimulating a biological system creates a cascade of reactions. Cells provoke their neighbors and absorb the stimulation at different rates. But if you could listen to each reaction independently, you could tease apart what’s happening.”

This sort of listening, Worthington suggests, will complement “equation of motion” studies, deepening our understanding of cellular behavior. The chatter of biological systems could start to become audible (in a sense) this year, with the most meaningful chatter emerging from intact systems, that is, systems consisting of cells that have not been sequestered.

Design Sparks Creativity

Fluidigm recently began a two-year rebranding initiative to infuse customer-centric thinking into all aspects of its business, including technology definition; industrial design; marketing and communications; and  education and response. The company applies what Worthington calls an industrial design approach for the look, shape, and user interface of its equipment.

“We seek to transform the entire experience biologists have with us, through sleek, approachable industrial design and intuitive interfaces,” Worthington explains. “The user interface should add value to the product.”

Beyond functionality and ease of use, he says, instruments also should be aesthetically pleasing. “Some scientific machines cost as much as the nicest of sports cars, so there’s no excuse for them not to look amazing.”

Because scientists are emotional beings, insists Worthington, they can be inspired. By designing equipment that not only “does amazing things” but also “looks amazing,” companies may “bring life to an aesthetically depressing lab environment,” adding an “extra spark” that may help spur creativity.

Juno is the first product to incorporate the new industrial design elements that are part of Fluidigm’s rebranding. The instrument, like its predecessors, serves production genomics.

Changing the Customer Dialog

Worthington says he considers Fluidigm’s new website a springboard for collaboration rather than just a way to stimulate the usual vendor/customer relationship.

“Every word from the company should be impactful. Our website should be a teaching portal, not just a place to sell products,” maintains Worthington. “Therefore, the company’s website includes magazine-like elements that showcase customers’ work, profile innovative scientists, and highlight new techniques and scientific advances in single cell biology.”

Content includes insights and profiles from the Sanger Institute, the Broad Institute, the Genome Institute of Singapore, Kyoto University, and other Fluidigm partners. The goal, Worthington says, is for visitors to say, “Wow! Look at that interesting science!”

Customers and Fluidigm each benefit by gleaning important insights about the direction of science. With such insights and collaborations, Worthington says, “We can continue to kick-start the new field of single-cell biology and make contributions to the deeper understanding of cancer, HIV, stem cell biology, and neuroscience.”


Location: 7000 Shoreline Court, Suite 100, South San Francisco, CA 94080

Phone: (650) 266-6000

Website: www.fluidigm.com

Principal: Gajus Worthington, President, CEO, and co-founder

Number of Employees: 500

Focus: Fluidigm leverages its pioneering work on integrated fluidic circuits to continue innovating its core microfluidic and mass cytometry technologies for single-cell analysis and industrial-scale genomics applications.

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