Wednesday, 13 January 2016

What do Fludigms problems with the C1 IFCs mean for users?

Fluidigm President and CEO Gajus Worthington sent a message to C1 users today that reported problems with their C1 IFCs, particularly those for medium-size cells (10–17µm), The issue is an unacceptably high level of doublets i.e. two-cells in a capture site rather than one. The medium size C1 96 IFC has approximately 30% doublets with a standard deviation of 10%; the HT IFC has approximately 44% doublets with a standard deviation of 23%; and even the small and large size 96 IFCs (not the focus of the message to customers) have approximately 10% doublets with a standard deviation of 4%...single-cell this is not.

Fluidigm will have had a tough Christmas deciding how to handle this. Whilst painful I'm glad they've contacted users and put out this message. A white paper is available that describes what Fluidigm have done to investigate the problems, and it has recommendations for doublet detection: Doublet Rate and Detection on the C1 IFCs. They have already said that development of new IFCs designed to reduce the incidence of doublets should be available by spring, i.e. April.
 
 
Validation, validation, validation: Single-cell data are complicated to analyse and have thrown up some very new and interesting biological surprises. As with any new method there is real excitement at what else we'll learn, but also concern over claims that might turn out to be technical artefact's. Good validation experiments are key, but so is a good understanding of the technology - and this fundamental check of cell doublets should be a standard QC in our experiments. It should also have been picked up as a standard QC by Fluidigm's manufacturing team.

What does this mean for your C1 experiments: None of this is what we customers want to hear, the C1 is effectively out of action for people planning on using the medium 96 and HT IFC. Fludigm are contacting customers somewhat proactively, announcing issues that will affect users experiments, but potentially before some of those experiments are started. We might get a little hot under the collar at not being able to run projects as planned, but this is a lot better than finding projects are ruined after the event. For now our C1 work is on hold.

The recommendations in Fluidigm's whitepaper are for higher magnification imaging, and cell staining to detect doublets. However this significantly increases the time and complication of doing what are already time consuming and complicated experiments.

What does this mean for Fludigm: On GenomeWebs financial index report for 2015 they reported a 68% drop in Fludigm's stock. And just today Fluidigm coverage on GenomeWeb was all about their beating market expectations on sales for Q4 after what was described as a "challenging start [2015]" by CEO Gajus Worthington. Fluidgm's stock has gone from a high of $50 to around $9. With the focus very much on single-cell, and the headline product not performing in the labs, stock are likely to drop further without strong signals that Fluidigm are on top of this and their solutions have a bright long-term future. Don't forget their other very innovative products, which enable experimental biology that is difficult or impossible to do in a traditional lab.

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