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Breaking the Speed Limit

April 14, 2006 | Mass spec and high throughput are not often found in the same sentence, except perhaps as antonyms. This is the problem RTC researchers and MIT’s Ian Hunter joined forces to solve, eventually leading to the formation of BioTrove.

“There are a whole lot of enzymes that are involved in various biology processes that you just don’t have any assays for,” says Ralph Lambalot, RTC director of protein biology. There are also many screens biologists would like to run without using radioactive labels, which can complicate both processing and interpreting results. Moreover, traditional HPLC sample preparation is also generally slow.

What emerged from the collaboration was a computer-controlled fluidic robotic interface to a triple-quad mass spectrometer, which eliminated the need for HPLC and was able to feed samples into the mass spec very fast.

“You end up pushing the processing limits of the mass spec. We’re able to push as fast as one second per sample, which is now in the realm of high throughput,” says Lambalot. “We can run 15 384-well plates in a standard operating scientist’s day. That’s 30-fold faster than anything that was currently available on the market.”

“When we scoped the system out, we expected that we’d be running a couple of screens a year. As soon as it came online, we suddenly had targets queuing up, targets that were running at very slow speed in the biology laboratories out in the therapeutics areas because they were running very low throughput assays, using lots of radioactivity in many cases.”

Demand grew such that Pfizer’s internal capacity often proves insufficient, and it now uses BioTrove’s screening services to fill in where needed. BioTrove, of sell services commercially in two flavors, RapidFire Lead Discovery and RapidFire XC-MS.

In an interesting turn of fate, BioTrove has since shifted emphasis. The company still supports and sells mass-spec-based services but is making its biggest bet on offering genotyping services based on a proprietary through-hole technology called OpenArray. The company sees this as a bigger market opportunity.

As described in BioTrove literature, “One OpenArray has 3,072 through-holes in a microscope-slide-sized plate. In our current generation of products, each through-hole is 300 µm in diameter with a depth of 300 µm. The through-holes are arranged in 48 sub-arrays of 64 holes. Proprietary processes are used to coat the surfaces of the arrays so that they are hydrophobic, while rendering the interiors hydrophilic and biocompatible. Thus, 3,072 separate assays containing 33-nL of fluid may be loaded into the OpenArray plate using the OpenArray Sample Loading Device. Liquid is held in the through-holes by means of surface tension. No cross-talk between the through-holes is observed because of the hydrophilic and hydrophobic coatings.”—J.R.

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