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Seahorse’s Newly Launched XF96 Analyzer Measures O2 Consumption in 96-Well Plates

Seahorse Biosciences this week launched its XF96 extracellular flux analyzer, which it claims is the first instrument that can measure kinetics of mitochondrial oxygen consumption and cytoplasmic glycolysis in a 96-well microplate.
The XF96, which is a higher-throughput version of Seahorse’s XF24 instrument, is designed to enable researchers to measure cellular bioenergetics, which previously was possible only with great difficulty, using an obsolete, decades-old technology, a company official told CBA News this week.
“I do not know the dollar value” of the potential market for the XF96, “but I know that we see it as probably having an upside of 5,000 labs worldwide,” said Steve Chomicz, vice president of sales and marketing for Seahorse.
In the 18 months since it was launched, the XF24 has gained more than 200 users, the number of users has grown each quarter, and sales are significantly greater than the preceding quarter, Chomicz said, though he did not elaborate.
The XF technology, which was developed “specifically with pharma in mind,” is currently being used to measure cellular bioenergetics in both the glycolysis and mitochondrial pathways. Another application for the technology is using those bioenergetic parameters to evaluate cells’ health before assays are run on them. Therefore, XF technology can be applied to specific disease states and to more general cell health-quality control studies.      
As the powerhouse of the cell, the mitochondria has been implicated in many human diseases. Although researchers want to study mitochondrial function, that is difficult to do, because the most widely used tools until now, the Warburg apparatus, invented in 1932 and the Clark electrode, which debuted in 1959, are obsolete.
“With our XF instruments, you can do some very sophisticated experiments to better understand” mitochondrial function and cellular bioenergetics, said Chomicz, whose company, based in North Billerica, Mass., was founded in 1984.
He added that Seahorse is currently focused on developing applications for the XF technology, including enabling the platform to analyze tissue sections in a 96-well format. “We expect to be able to do that within the next year, because we have had a lot of requests for that,” Chomicz said.
He said Seahorse developed the XF technology with pharmas in mind for doing obesity drug discovery work. “What we found was that when the academics got it in their hands, they started applying it to a variety of different research areas.”

“We are now seeing that [the XF technology] has applications in many other areas, and we are currently trying to develop each of those other areas into a suite of application assays.”

At the same, the pharmas who bought the instrument for obesity drug discovery reported that, for example, their cancer drug research group or their cardiovascular drug research group had expressed an interest in the XF.
So although Seahorse did not develop the XF instruments for all of these different applications, “we are now seeing that it has applications in many other areas, and we are currently trying to develop each of those other areas into a suite of application assays that scientists can use,” Chomicz said.  
For the past 75 years, tools for measuring cellular bioenergetics have remained unchanged since the invention of the Warburg apparatus and the Clark oxygen electrode. However, the Clark electrode only works with cells in suspension, and requires approximately 100 times as much material as the XF. In addition, it cannot be run for an extended period because it uses up oxygen.
Before Seahorse developed its XF technology, it was difficult for scientists to measure cellular respiration, said David Nicholls, a professor and director of the morphology core at the Buck Institute for Age Research in Novato, Calif.
“I spent a lot of effort developing a machine that would do one or two experiments a day, and in the XF technology, we now have a machine that will do 96 experiments in a couple of hours,” he told CBA News this week.
Nicholls’ research focuses on two main research areas: the role of mitochondria in neurodegenerative diseases, such as Parkinson’s disease, and also in stroke, and he also has a new interest in diabetes, and “I am using the XF24 for these studies.”
“I have been very favorable” about the XF technology, Nicholls said. “I give maybe 15 or 20 talks per year, and at most of them I have given unsolicited praise about the Seahorse Bioscience technology, and that was before I became a consultant to Seahorse.”
Nicholls said that he feels the XF technology is very important for two reasons: basic research into mitochondrial function in cells, and the XF96 will be an “extremely important” machine for drug screening.  
The XF24 allows researchers to “conveniently measure oxygen consumption in cells growing on plates, which we have not really been able to do before, and that opens up a whole new range of stuff that we can do,” said Martin Brand, a professor at the Buck Institute.
Brand’s lab looks atmitochondrial function in cells, “so we are looking at coupling efficiency and uncoupling by uncoupling proteins” primarily in a beta cell line to try and understand regulation of insulin secretion by mitochondrial efficiency. In addition, more generally, the researchers are looking at mouse models of various neurological diseases in humans, such as Parkinson’s, Huntington’s, and Alzheimer’s diseases, also using the XF24 to try and understand the role of mitochondria.
Brand said his lab could probably find use for the XF96. “There is certainly an advantage to being able to do more wells, because we currently are running three 24-well plates per day for some experiments, and that is hard work to do that for an entire day,” he said.
Brand also mentioned that his lab provided Seahorse with “extensive” feedback regarding the XF24. “We have basically redesigned the software for the oxygen measurements, with different assumptions and different corrections in it. It now works a lot better than it did, and Seahorse is currently in the process of putting that together and issuing it as the standard software,” he said.

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