Fluidigm microfluidics used in stem cell research

Induced pluripotent stem (iPS) cells have been one of the hottest areas of recent stem cell research, because iPS cells may offer the same therapeutic potential as embryonic stem cells, but without embryo destruction. Ever since the development of human iPS cells by theYamanaka lab, researchers have been working to establish whether iPS cells are truly equivalent to embryonic stem cells (so far they seem to be) and to demonstrate their clinical potential.

This summer Fluidigm announced that the Yamanaka lab will be using one of Fluidigm’s devices, the BioMark System, to analyze genes in iPS cells. Fluidigm’s microfluidic platform applies familiar methods such as qPCR, SNP genotyping, and gene expression analysis to the tiny volumes involved in single-cell analysis. These techniques, although not conceptually new, are cumbersome to execute on single cells using traditional methods. Recently Martin Pieprzyk and Howard High of Fluidigm published a Nature Methods article documenting the performance of the system in analyzing gene expression in single cells.

So why is single-cell analysis useful? Megan Scudellari’s article in Nature Reports Stem Cellsgives an overview:

…even after careful sorting, a single population of stem cells is dynamic: some divide rapidly and others more slowly; some differentiate, others self-renew; some can give rise to more lineages than others. Because of this variation, population studies of stem cells are unable to accurately address essential questions, such as defining discrete steps from a single stem cell to a complex population of cells.

This summer Fluidigm also announced that prominent stem cell researcher Toshio Suda will be using the system to investigate hematopoetic stem cells.

Although Fluidigm has been reporting growing revenue, apparently it is not yet profitable. The success of the Fluidigm platforms may depend on scientific perception as well as on cost issues. Biologists are familiar with many aspects of the systems, which may speed adoption; the microfluidic assays are the same ones biologists already perform, but at a smaller scale, and researchers are no strangers to microchips, having used DNA microarrays (e.g., Affymetrix devices) for years. Adoption by leading scientists such as Yamanaka and Suda is also likely to encourage uptake.

In addition to enabling more convenient single-cell assays, cost savings have also emerged as a potential motivation for adoption, as Justin Petrone reports in BioArray News:

Suda, who plans to use Fluidigm’s Digital and Dynamic Arrays in his study, toldBioArray News in an e-mail this week that prior to adopting BioMark, he had used quantitative PCR and microarrays to perform gene-expression profiling of HSCs and iPS cells. He said that he decided to adopt BioMark because the cost of running arrays is “expensive” so his lab “cannot repeat the experiments.” In the past, Suda used Affymetrix’s mouse genome 430 2.0 array.

Fluidigm says the advantages of their systems are cost savings and higher throughput, typical arguments used to motivate microfluidic research. During my academic work, I alwayswondered how realistic such arguments were. I’m excited that the proposed savings (in time, labor, and materials) seem to be for real. Suda’s comment implies that the Fluidigm system may provide direct competition to standard gene arrays, such as those by Affymetrix; Hoover’slists Affymetrix as one of Fluidigm’s key competitors.

Another advantage of the Fluidigm platforms is that if Fluidigm develops new assays, scientists may be able to use the same controller system, needing to buy only the new chips. I would be surprised if new chips were not in the works. Although the current Fluidigm chips are direct extensions of experiments that biologists already perform, microfluidics could enable a vast array of novel assays, allowing biologists to probe and measure in ways they currently cannot.