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UNM-Luminex Alliance, NIH Link May Promote Flow Cytometry as Option for HT Drug Screening


QUEBEC CITY, Canada — An ongoing collaboration between Luminex and the University of New Mexico at Albuquerque may lead Luminex to start selling ultra-high-throughput versions of its xMAP assays, a Luminex official told CBA News at the International Society for Analytical Cytology meeting, held here this week.

Luminex has been working with the research group of Larry Sklar at UNM to investigate the compatibility of Luminex's flow cytometers and bead-based xMAP assays with HyperCyt, a system Sklar invented that enables the high-throughput delivery of liquid samples from well plates to commercial flow cytometers, which greatly increases the overall throughput of flow-based screening applications.

The Luminex alliance, along with UNM's membership in the National Institutes of Health's Molecular Libraries Screening Centers Network, may help validate HyperCyt's ability to increase the throughput of flow cytometers to the point where big pharma would find them attractive options for high-throughput drug screening.

It also aims to "demonstrate the feasibility of compatibility between Luminex's technology and [HyperCyt]," James Jacobson, vice president of R&D for Luminex, told Cell-Based Assay News. "There is the potential for commercialization of a very high-throughput version of our technology based on this."

"There is the potential for commercialization of a very high-throughput version of our technology based on this."

Jacobson said that terms of the collaboration give Luminex an option to license the technology from UNM for commercialization. Luminex is considering this option, Jacobson said. He declined to elaborate.

Luminex's xMAP technology is bead-based and used for a variety of highly multiplexed biochemical assays including gene- and protein-expression profiling, SNP detection, cytokine profiling, and diagnostic testing. The assays are performed on Luminex's 200, 100 IS, or HTS flow cytometry systems, to which HyperCyt could be coupled to significantly enhance assay throughput.

According to Jacobson, the collaboration between Luminex and UNM's Small Molecule Screening Center started some two years ago, even before UNM's involvement in the MLSCN. Sklar had been using a Luminex platform to conduct specific bead-based protein-protein interaction, protein-nucleic acid interaction, and kinase assays. Finding the throughput of the Luminex platform inadequate for his needs, Sklar realized it was a prime opportunity to test the HyperCyt device, which he had invented several years earlier, as a front-end add-on to increase the platform's sampling rate.

"It was a natural evolution of some work that he had done on our platform in the past, but to move his assays on to the beads provided by Luminex," Jacobson said. "So the collaboration exists to build a technology that will provide higher-throughput screening capabilities for his center."

Sklar and colleagues are also exploring routes to commercialize HyperCyt to enable high-content, cell-based drug-discovery assays for flow cytometry, as opposed to bead-based assays. Sklar, who holds multiple professorships within UNM's School of Medicine, is also principal investigator on the grant for the New Mexico Molecular Libraries Screening Center, one of 10 members of the NIH's MLSCN.

The MLSCN is a nationwide consortium of NIH-funded centers charged with producing innovative chemical tools for use in biological research. It is also supposed to contribute data from cell-based and biochemical screening assays to the PubChem database. Of the 10 centers comprising the MLSCN, UNM's is the only one using flow cytometry as its basic discovery platform.

However, UNM's MLSC is one of a growing number of academic and commercial entities currently investigating flow cytometry — traditionally thought of as a clinical and basic research tool — as a platform for highly multiplexed cell-based drug screening (see related story, "Is Flow Cytometry…", in this issue).

To further assist with the commercialization of HyperCyt, Sklar and colleagues at UNM's Science and Technology Corporation have enlisted the help of an Albuquerque-based startup called Sage Sciences, headed by Terry Dunlay, co-founder and former vice-president of informatics of Cellomics. According to Sklar and Dunlay, Sage Sciences is a very early-stage enterprise that is primarily concerned with making HyperCyt available to early-access partners.

"Twenty-plex or, theoretically, even 100-plex assays per second are within the realm of possibility."

"There is a [HyperCyt] platform that's been licensed by a biotech company, and a platform for which there is a purchase order right now," Sklar said. "We're talking to people about distribution, and my expectation is that Sage Scientific will be involved in distribution.

"[Luminex] also has an interest in using this as a front end for its instruments," Sklar added. "Distribution arrangements between OEMs and those who want to install the front end on already-purchased flow cytometers — those are things that are going to have to be worked out between [Sage], the [UNM] Science and Technology Corporation, and the OEMs. And those things are going on right now."

According to Dunlay, flow cytometry has been well-validated on a wide range of biochemical and cell-based assays, but hasn't been used as a high-throughput platform primarily due to limitations on front-end sample handling and back-end data analysis.

Various flow cytometry vendors such as Beckman Coulter, Becton Dickinson, and Dako have developed methods for increasing the rate with which samples can be drawn from well plates into the flow tube. At their very best, some of these instruments can analyze a 96-well plate in 10 to 15 minutes, using a sampling rate on the order of one sample every 5 to 10 seconds.

HyperCyt uses a peristaltic pump to continuously draw samples from well plates and intersperse the samples with air bubbles to keep them separated in flow. Compared with current commercial technologies, HyperCyt can draw one to two samples per second, allowing an entire 96-well plate to be sampled in about 2.5 minutes.

Validation of HyperCyt as a front-end device for increasing the sampling rate and overall throughput of the Luminex systems, or other flow cytometry platforms being used by UNM's MLSC or other biotech partners, could go a long way toward increasing the drug-discovery community's interest in flow cytometers as high-throughput drug-screening tools.

In particular, the Luminex platform already has highly multiplexed capabilities due to its use of differently coded beads, of which there are about 100. Sklar and colleagues have presented data demonstrating a 20-plex assay of particles on a Luminex system with the HyperCyt front end.

"The mathematics are actually quite straightforward," Sklar said. "Our sampling volumes are about a microliter, and to do a 20-plex assay we need something like 200 particles of each population, which comes to about 4,000 particles in a microliter.

"This figure is not an unreasonable density to run through a flow cytometer," Sklar added. "It is certainly reasonable in a second, because some flow cytometers can do 10,000 to 50,000 particles per second. So 20-plex or, theoretically, even 100-plex assays per second are within the realm of possibility."

The Luminex partnership may prove to be one of the faster routes to commercialize HyperCyt, but not for cell-based assays, as Luminex will, for the time being, continue to play primarily in bead-based biochemical assays.

"Luminex has a unique niche, and their interest in this platform has to do with what their market position is," Sklar said.

Luminex's Jacobson agreed with Sklar, but acknowledged the importance of eventually incorporating cell-based assay data into the fold.

"Our current product focuses very narrowly on bead-based assays right now," Jacobson said. "Certainly the cellular aspect of that is very important. Biochemistry doesn't happen in a tube, it happens in a cell, so integrating the information from the bead-based assays with the cell information is very important for the drug-discovery process."

When asked whether Luminex was currently working on ways to incorporate cell-based assay data with its xMAP technology, Jacobson said, "Never say never."

It remains to be seen whether UNM and Sage will have to partner with a large flow cytometer vendor to commercialize HyperCyt for cell-based assays, or whether it will be able to validate HyperCyt through MLSCN or other studies, and then market the platform itself to core flow cytometry labs.

"I think Sage Scientific could succeed in sort of a retrofitting business model, and that is likely to be a component of what we do initially," Sklar said. "One way or another, I expect we're going to retrofit, install, support, develop a network, and what happens after that is really up to the other guys."

— Ben Butkus ([email protected])

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