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May 15, 2011 (Vol. 31, No. 10)

Mass Spec Makes Its Way into the Clinic

Out-of-the-Box Solutions Ease Transition by Lowering Costs and Improving User Friendliness

  • Click Image To Enlarge +
    One-step enrichment of platelet-derived growth factor (PDGF) peptide (1930.0 Da) using Shimadzu Scientific’s Nanotrap particles: PDGF (60 ng) in the presence of albumin (600 ng) was processed with Nanotraps to sequester and enrich the extremely labile PDGF protein. Comparison of MALDI mass spectra of a control to a sample processed with Nanotraps demonstrates the capability to exclude abundant, high molecular weight proteins (e.g., albumin) and simultaneously amplify a low-level PDGF peptide (highlighted in blue), resulting in an eightfold increase in signal intensity (left).

    A significant shift in attitudes toward real-world use of mass spec in clinical settings was evident at this year’s meeting of The Association for Mass Spectrometry Applications to the Clinical Lab. Scientists at the San Diego conference agreed that implementing clinical use involves a great deal of expense and a daunting learning curve. A number of instrument vendors have responded by providing out-of-the-box solutions including training and support to get the system up and running.

    “This is the first year a high proportion of speakers were actually talking negatively about immunoassays and positively about chromatography and mass spec,” said Peter J. Stone, Ph.D., senior applications scientist at Agilent Technologies.

    Among those enthusiastic presenters was Brian Feild, Ph.D., life science applications chemist at Shimadzu Scientific Instruments. He presented work showing the use of core shell hydrogel particles called Nanotraps to enrich samples for biomarker discovery. Nanotraps are added to a biological fluid such as serum or plasma and incubated. After pelleting and washing, the captured proteins can be eluted. An additional benefit is that Nanotraps protect the trapped proteins from degradation by proteases.

    Shimadzu’s Nanotrap Biomarker Discovery Platform was developed to accelerate a biomarker discovery workflow by combining size exclusion and affinity capture to enrich for low molecular weight proteins, many of which are carried by high molecular weight excluded proteins. Dr. Feild scanned a set of non-small-cell lung carcinoma samples provided by George Mason University, using the Axima Performance MALDI-TOF MS. The analysis rapidly picked out differences between diseased and clear samples.

    “We also wanted to show that it is possible to screen for known biomarkers,” Dr. Feild said. Both the size-exclusion and affinity-capture components of the Nanotraps are tunable. “By screening a known biomarker against a panel of different Nanotrap baits, an assay can be developed to enrich and detect for diagnostic purposes.”

    Dr. Feild used the Nanotrap to capture and enrich prostate-specific antigen (PSA). “We showed the ability to enrich for a specific, known biomarker for prostate cancer, PSA, by first screening against a panel of different Nanotraps and determining which bait most effectively bound PSA.”

    The Nanotrap work flow could be applied to any disease where there is a need for lower abundant biomarkers.

  • Microbial Indentification

    Bruker Daltonics’ MALDI-TOF MS-based system for identification of microbes, the MALDI Biotyper, combines instrumentation, dedicated software, and a reference database of more than 2,000 microorganism species.

    In his conference presentation on the topic, Markus Kostrzewa, Sc.D., director of molecular biology, R&D, reviewed the introduction of the system in clinical microbiology laboratories. The MALDI Biotyper is now routinely being used as a diagnostic tool in many European laboratories because it shortens time to results, reduces costs, and increases accuracy compared to conventional biochemical assays.

    Bruker designed the instrument to optimize ease of use by technicians in the biomedical field. “The MALDI Biotyper is probably the first MALDI-TOF platform that can be successfully used by a medical technician after a one-day training course,” Dr. Kostrzewa said.

    Results presented by Dr. Kostrzewa showed that in order for a mass spectrometry system to be introduced into a clinical routine it must be robust, simple to use, and deliver superior clinical and diagnostic performance. The provider of the system needs to provide a complete, ready-to-use product, with full support for the clinical laboratory. Most companies that manufacture mass spec systems are accustomed to serving research scientists who are less interested in a turn-key solution and more interested in the absolute best technical specifications, so this required a different approach.

    Systems like the MALDI Biotyper have applications beyond microbiology. “The capabilities of the technology to unravel subspecies differences, for epidemiology, virulence and resistance detection, strain verification or other purposes, are not yet fully explored.”

    Bruker Daltonics will further develop MALDI-TOF technology to increase its uptake by clinical laboratories. It recently launched a kit to isolate and identify microorganisms from a positive blood culture called the MALDI Sepsityper, and it is working on further applications such as subtyping of strains, virulence detection, and antibiotic susceptibility. Dr. Kostrzewa sees a growing market for such applications, “Overall, mass spectrometry will move further into clinical laboratories. This will be driven by its analytical performance as well as its cost-effectiveness.”

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