Single-cell Expression and Microfluidics
Thu, 09/16/2010 - 8:16am
Mike May, PhD; Contributing Editor
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This microfluidics-based biochip from Fluidigm can be used more than once. (Source: Fluidigm) 

Microfluidics helps researchers study the gene expression in individual cells. “Reducing the volumes makes analyses much easier,” says Michael Clarke, MD, an oncologist at Stanford University in Palo Alto, Calif. “In fact, in some instances microfluidics is even enabling.” In addition, studying single-cell expression will drive many new discoveries.

Research is showing that single cells differ in their expression even in tissues once considered homogenous. This could be especially useful knowledge in medical research. For instance, finding the expression differences will provide deeper knowledge about the mechanisms behind diseases. Also, the expression in single cells could enhance drug discovery and development. “Toxicity is a prime example,” says Clarke. “If a drug target is expressed by certain cells in a tissue, it could be extraordinarily toxic; if the target is expressed in other cells, the toxicity might be irrelevant.”

The key to using microfluidics for such expression studies is the sample size. “We are developing dynamic microarray architectures,” says Gajus Worthington, president and CEO at Fluidigm in South San Francisco, Calif. “The sample volume is one-thousandth of that of a microtiter well. Also, this technology can run 100 samples across 100 assays—all simultaneously.”

Despite the advanced capabilities behind Fluidigm’s technology, researchers can quickly learn to use it. “People tend to be amazed by how simple it is,” says Worthington. “People expect these technologies to require very specialized training, but it’s a highly integrated device.” As he adds, “The chip itself does 99 percent of the liquid handling.”

Still, Worthington and his colleagues wanted more from microfluidics. “A year ago, we set out to figure out how to radically reduce cost,” he says. “Typically, you do that by increasing chip density.” Instead, Fluidigm developed reusable biochips. “People have been asking for this for as long as biochips have been invented,” Worthington says. This chip can be run five times, and it doesn’t cost five times as much as a single-use chip. The user loads the chip normally, then cleans and dries it between uses. In addition, this chip works fast. It takes about 30 minutes to load, 30 minutes to run PCR, and it can dry overnight to be used again the next day. Worthington adds: “There is zero performance compromise.”

From advances in single-cell expression to reuse, microfluidics keeps pushing assays ahead.

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Image-analysis software tracks cells under shear stress created in a microfluidics-based biochip from Cellix. (Source: Cellix)  

A Natural Flow
In Dublin, Ireland, Cellix uses microfluidics to simulate a natural human environment, such as creating shear flows for measuring adhesion between blood platelets. The Cellix platform includes biochips, pumping solutions, and analytical software. “With this system, you can use whole blood—in just microliters instead of the milliliters that other systems require,” says Vivienne Williams, CEO of Cellix. “We can create high shear stress or flow rates in the microfluidics biochips that we use.”

The biochip includes eight channels. “It has SBS standard spacing of a 384-well plate, so it integrates with other technology,” says Williams. She adds that it’s very easy to use: “You just pipette in the adhesion molecule for coating, take in the sample with the pumping system, and press start. Our chambers come preassembled and ready to go.” A computer collects images from the chip, and software provides a range of data, including cell count, morphology, elongation, and so on. Currently, Cellix focuses primarily on two disease areas: thrombosis and inflammation. “One very common side effect of many drugs is blood clotting,” says Williams. This makes the Cellix biochip useful for, among other things, screening new compounds for safety.

About the Author
Mike May is a publishing consultant for science and technology based in Houston, Texas.

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