Millennium Pharmaceuticals has adopted Bioscale's acoustics-based ViBE protein analytics system as part of its drug development workflow, using it as an alternative to conventional methods like AlphaScreens and LI-COR Western blot assays.
The drugmaker, which purchased a system in August after several months of trying out a beta version, is primarily using the platform to quantitate pharmacodynamic biomarkers, Michael Bembenek, associate director of lead discovery at Millennium, told ProteoMonitor, and has found it cuts run times for such assays down to a little as one day – compared to a week for traditional LI-COR Western blot approaches.
This week, results of a Millennium-led study investigating the use of the ViBE system for PD biomarker analysis were published in the online edition of Analytical Biochemistry. In the study, the researchers used the ViBE platform to measure the PD protein biomarkers Gadd34 and Akt2 in cell culture and tumor lysates, comparing the instrument's effectiveness to AlphaScreens and LI-COR Western blot assays.
According to the study's results, the BioScale platform compared favorably with the conventional methods in terms of sensitivity, and avoided interference issues that limited the usefulness of the AlphaScreen and LI-COR techniques when applied directly to tumor xenograft samples.
Millennium's day-to-day experience with the platform backs up the study's outcome, Bembenek said, noting that "everyone here likes the data that they get from the Bioscale instrument."
While the degree of adoption varies by project team, he said that at least one of the company's teams has made it their primary assay for PD biomarker work.
"[The ViBE platform] is still being evaluated," Bembenek said, "but one project team has adopted it solely. They check [its results] every now and then with Western [blots], but they use it to get their main dataset for PD [biomarker] studies."
Founded in 2002 by CEO Mark Lundstrom, Bioscale operated largely under the radar until launching the ViBE system – the company's first commercial release – in June. In May it secured $25 million in a round led by Morningside Venture to fund commercialization of the platform (PM 6/18/2010).
The ViBE system relies on Bioscale's proprietary Acoustic Membrane MicroParticle, or AMMP, technology – an acoustical, rather than an optical, detection system for protein analytics. A capture agent like an antibody is attached to a resonating membrane and then exposed to a sample containing the analyte of interest. The analyte is captured by the affinity agent bound to the membrane, which adds mass to the membrane and in turn changes the frequency of the membrane's oscillations. The system detects and quantitates the analyte of interest by measuring these changes in frequency.
Because of its relatively straightforward protein capture step, and its use of acoustical rather than optical detection, the platform has proven useful for protein detection work in complex matrices, like the tumor xenografts in the Millennium study, where interference can present a problem for conventional methods, Brett Masters, Bioscale's chief technology office, told ProteoMonitor.
One potential drawback to the system is its use of antibody pairs, which limits the assay to proteins for which there exist two antibodies. Some of Millennium's project teams have been unable to use it for this reason, Bembenek said. However, he noted, the company has come up with a quick AlphaScreen-based method of developing antibody pairs that will ease this constraint somewhat.
Chip Leveille, Bioscale's chief operating officer, told ProteoMonitor that the company wasn't currently able to discuss sales numbers or identify its customers, but he said the company was doing multisite demonstrations of the system with "in essence 10 of our systems out at any one time" for evaluation by potential clients.
The ViBE line comprises two products – a lower-throughput manual unit called the ViBE Bioanalyzer and an automated high-throughput unit called the ViBE Workstation. Prices for the units range from $50,000 for the Bioanalyzer up to $100,000 for the Workstation. The two units are designed to work as a modular system, meaning that pre-existing Bioanalyzer units can be upgraded to Workstations. According to Leveille, the Workstation has thus far accounted for the lion's share of customers.
In addition to PD biomarker work like Millenium's, the platform has also drawn interest from bioprocessing labs, and the company has developed predefined kits for running the three major bioprocessing purity assays on the ViBE system, Leveille said. The majority of Bioscale's recent work, he noted, has revolved around phosphoproteins.
"There still seems to be a very big gap in what people want to do [in phosphoproteomics] and what they can do. So we've been at many sites that have addressed us with that," he said.
"When you're looking for phosphoproteins, you're looking for a very little bit of modified proteins in a whole lot of total [protein]," Masters said. "So you've got to be very efficient and very kind to your capture agents in terms of being able to select out that very small amount when everything looks the same. So that's what we're able to do."
He added that the company is able "to go into samples and select out those very specific phosphoproteins using those capture agents that are designed for them, and then bring further specificity through the secondary antibodies that we deploy and sense with our system."
While Bioscale hopes eventually to move the device into the clinic, for the time being it's focused on the preclinical space, Leveille said.
"We're seeing adoption across the board from [work aimed at] a basic understanding of tumor biology all the way through to people saying 'I've got a set of markers I want to evaluate in a mouse model or a preclinical setting,'" he said. "It's moved into becoming a platform that could be used in the preclinical area and then eventually into discussion of the clinical [area], but we're holding off from that language right now until we prove ourselves in the development space."
The company also envisions possible point-of-care devices based on the technology, but, again, Leveille said, that's something that will come down the road.
"There has been work going on in that direction thinking through it on a prototype basis, but a lot of that has been superseded by focusing on what we can do to make sure we have the most robust performance across the board from consumables and reagents to the assays we're engaged in," he said. "A lot of the focus this year specifically will be around assays and performance [of the current device]."
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