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Agilent Acquires MassCode IP for Multiplex PCR, Plans to Commercialize Infectious Disease Panels

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By Bernadette Toner

This story was originally posted Nov. 24.

Agilent Technologies' recent acquisition of the MassCode Tag assets from Eurofins MWG Operon gives it a labeling technology for multiplexed PCR that should appeal to the basic research market, as well as an opportunity for the firm to launch its own line of panels for infectious disease screening, a company official told PCR Insider.

Agilent last week said that it had acquired all assets related to the MassCode technology, including four families of patents, for an undisclosed amount. Under the terms of the agreement, Eurofins MWG Operon will continue to manufacture certain reagents for the MassCode product line.

The key application for the technology, called MassTag PCR, was developed by Ian Lipkin and colleagues at the Center for Infection and Immunity at Columbia University's Mailman School of Public Health. In MassTag PCR, small-molecule tags with known molecular weights are attached to DNA primers. After PCR, the tags are released by applying UV irradiation, and they are then identified via mass spectroscopy.

The sensitivity of the approach is similar to that of standard real-time PCR, but the multiplexing capability is much higher — on the order of 30 analytes per sample as opposed to a handful with qPCR.

With standard qPCR, "the level of multiplexing in a single well is about four reactions — it's limited by the number of colors, so it's generally a four-analyte question that you can ask at one time," Gustavo Salem, vice president and general manager of Agilent's Biological Systems Division, told PCR Insider.

With the MassTag technology, however, "the level of multiplexing that you can achieve is in the neighborhood of a 30-plex," he said.

As a result, MassTag PCR should be a cost-effective and quick method for screening a wide range of potential analytes quickly, as in the case of infectious disease screening and other pathogen-detection applications. While the setup costs for the single-quadrupole mass spectrometer required for the approach may be higher than that of a typical PCR implementation, the multiplex format enables more samples to be run at a time and at lower cost per sample.

In one of the first papers to describe the approach, published in the Journal of Infectious Diseases in 2006, Lipkin and co-authors note that the instrumentation costs for MassTag PCR are on the order of $80,000 to $120,000, as opposed to $30,000 to $100,000 for real-time PCR, but the reagents for single-plex qPCR assays cost around $30 per target, while MassTag PCR cost $12 per sample.

Salem explained that MassTag PCR doesn't require a high-end mass spec, which would cost in the range of several hundred thousand dollars and require a skilled operator. "The mass spectrometer required to execute this application is a very low-complexity instrument," he said. The single-quadrupole instrument is "routinely used in all kinds of applications" and "quite simple to run."

Furthermore, he noted that the workflow isn't as complicated as that of many mass spec experiments, which require a liquid chromatography-based separation step on the front end. "For this particular application, we don't need the LC separation at all. It's flow injection directly into the instrument, so that helps further reduce the complexity of the instrumentation associated with doing the work."

Salem acknowledged that the mass spec-based method is "a little more complex than qPCR," but noted that it is better suited for certain applications.

"If you're really trying to identify a specific pathogen, qPCR may still be the right choice for the customer. … But, for example, in the case of infectious disease screens, you really want to be able to quickly screen them across the much broader range of pathogens than just one or two. So the ability to quickly analyze whether [a] person's been exposed to one of 30 different pathogens is significantly enhanced by doing it with this technology than by doing it with just traditional qPCR."

Salem said that Agilent has identified two "core" markets for MassTag PCR. The first is the basic research market, "where people would be able to use this labeling technology to develop their own quantitative methods where qPCR didn't provide the level of multiplexing or the cost per analysis that they might be looking for to make that work."

The second key market segment is global public health labs that would be interested in purchasing ready-made MassTag PCR panels for infectious disease screening. The company is currently collaborating with the Lipkin lab to co-develop a set of infectious disease panels that it plans to commercialize some time in the next year, though Salem said it is still too early to discuss specific diseases that would be included in the panels.

"We expect that these will be marketed for public health screening and not as a diagnostic," he said.

Agilent is also looking into the use of the technology for other pathogen applications, such as food testing, but Salem noted that work is still in the research stage. "We've demonstrated true feasibility. Technically it works just fine. What we need to do is validate how it differentiates itself from the other technologies that are out there. In the case of the infectious disease panel, we know where it does better, but I can't make the same statement for food yet."

Salem said that the MassCode assets are a good fit for Agilent's life science business, which is aiming "to develop full customer solutions, as opposed to just selling instrumentation for instrumentation's sake."

Given that the company offers a full range of PCR products through its Stratagene business, as well as a line of mass spectrometers, Agilent expects the MassCode labeling technology to give its customers more options for bundling those components into broader solutions.

"We can provide the PCR, we can provide all of the nucleic acid sample prep tools required to isolate the DNA, we can provide this tagging technology itself, we can provide the mass spectrometer, we can provide all of the software and informatics necessary to analyze the data," Salem said.

"So we can really enable the customer from beginning to end in developing these kinds of PCR-based quantitative screening assays," he added. "And we believe that without this, we'd be relegated to selling them just the detectors — the mass spec."

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