July 1, 2009 (Vol. 29, No. 13)

Major Players Compete for Lucrative Market Share with New Product Introductions at ASMS

At the ASMS conference held last month in Philadelphia, Waters launched the Synapt™ G2 quadrupole TOF-MS system, which incorporates QuanToF™ and High Definition MS™ technologies and is designed for use with Waters’ Acquity UPLC-MS and MS/MS applications.

According to Alan Millar, senior product manager for TOF MS at Waters, the Synapt G2 has a “resolution >40,000 FWHM at acquisition rates (20 spectra/second) compatible with ultra-HPLC,” a mass accuracy of 1 ppm RMS, and a dynamic range of up to five orders of magnitude. Waters expects to deliver the first Synapt G2 unit in 4Q09.

“When it comes to proteomics, metabolite identification, or biopharmaceutical studies, the cost of missing potentially crucial pieces of information can be a show stopper,” says Millar. “With the Synapt G2 system, a patented data-acquisition method—what we call Mse—provides high-speed, high-resolution, exact mass precursor and fragment ion data over a wide dynamic range on virtually every ion present to provide a comprehensive ‘digital catalog,’ if you like, of the sample. Once you have that catalog, you can interrogate it and reinterrogate it with different questions as many times as you like. This is a tremendous advantage.” 

The system’s new QuanToF technology incorporates a high field pusher and a novel ion-detection system that combines an electron multiplier and hybrid ADC detector electronics. A dual-stage reflectron improves focusing of high-energy ions. The system’s second-generation Triwave™ technology yields up to fourfold higher ion mobility resolving power than the original Synapt instrument.

Waters also introduced eight enhancements to its MassLynx™ workflow, designed to expand MS applications. These include BiopharmaLynx™ 1.2, which confirms peptide assignment using fragment ion information and UPLC/MS data, MetaboLynx™ XS and MarkerLynx™ XS for metabolite identification and profiling on Waters MS systems, and ProteinLynx Global Server™ 2.4 to improve management of large proteomic data sets for nanoAcquity 2-D UPLC/MSE applications.

Thermo Scientific launched the LTQ Velos™ linear ion trap MS and the LTQ Orbitrap Velos at the ASMS meeting. The LTQ Velos features a dual-pressure trap that allows decoupling of ion manipulation and detection and optimization of pressure levels.

The LTQ Orbitrap Velos combines the Velos technology with Thermo’s Orbitrap mass analyzer and a new higher-energy collisional dissociation cell, which improves quantitation of isobarically labeled peptides, for example, in experiments that require tandem mass tags, according to the company. It also features electron transfer dissociation to enable post-translational modification analysis and de novo sequencing.

Agilent Technologies showcased its new Ultra-High-Def (UHD) Q-TOF LC/MS and new Triple Quad LC/MS systems. The Agilent 6540 benchtop UHD Accurate-Mass Q-TOF MS incorporates the company’s ion beam compression technology and enhanced mirror technology to enhance its resolution and mass accuracy. The Agilent 6430 Triple Quadrupole LC/MS improves on the 6410 instrument, providing higher sensitivity and faster ion monitoring and polarity switching. Agilent also launched a Web portal at ASMS, which tracks trends and advances in metabolomics.

“We have achieved huge gains in mass accuracy and resolution while maintaining the instrument’s sensitivity and dynamic range,” says Ken Miller, senior global marketing director for LC/MS at Agilent. “This is an ideal system for state-of-the-art qualitative analysis in support of proteomic or metabolomic studies.”

Bruker Daltonics introduced three MS platforms at ASMS 2009 together with applied proteomics solutions for MALDI-MS. The new product launches included the ultrafleXtreme™ MALDI-TOF/TOF system, with the company’s smartbeam™-II laser technology that enables 1 KHz image-acquisition speed, a new Flash Detector™, and a 4 GHz digitizer. Bruker credits its PAN™ panoramic technology for the instrument’s resolving power of up to 40,000 FWHM in both MS and MS/MS modes. The system offers 1 ppm mass accuracy.

Bruker also introduced the amaZon™ ion trap mass spectrometer, featuring dual-ion funnel transfer technology and a data acquisition speed of 52,000 µ/sec at

The solariX™ from Bruker is a hybrid Qq-FTMS platform with broad-band mass resolving power >1,000,000 at 7 Tesla, according to the company. Bruker’s Ion Charge Control (ICC™) method maintains sub-ppm mass accuracy throughout the LC-MS analysis. At ASMS, Bruker also introduced its Edmass™ top-down protein-sequencing solution with MALDI-TOF MS, which can sequence up to 70 residues from the N-terminus and up to 50 residues from the C-terminus of an intact protein on a single MS spectrum.

From Shimadzu comes the new AXIMA Resonance™ MALDI QIT TOF mass spectrometer designed for structural characterization and sequencing of biomolecules. The instrument combines a quadrupole ion trap and reflectron TOF analyzer, uses argon gas to excite selected precursor ions for controlled collision-induced dissociation, and utilizes the company’s Hypercool™ technology to cool the ions and prevent fragmenting.

The Resonance offers high-resolution precursor ion selection at up to 1,000 FWHM, and it is compatible with Shimadzu’s newly released PTM Finder™ and SeqLab de novo sequencing software. Shimadzu also introduced the LCMS-2020 single quadrupole mass spec designed for use with Ultra-Fast LC. It features rapid scanning at 15,000 AMU/ sec and fast polarity switching for simultaneous detection of positive and negative ions.

New from Applied Biosystems (ABI) is the AB SCIEX QTRAP® 5500 LC/MS/MS system, optimized for protein and peptide quantitation for biomarker discovery and validation. It contains ABI’s new fast eQ™ electronics and the new Linear Accelerator™ ion trap. The new AB SCIEX Triple Quad™ 5500 MS was designed for performing DMPK and ADMET studies.

Also newly introduced is the AB SCIEX TOF/TOF™ 5800 system for protein identification and relative quantitation as part of a biomarker discovery platform. The 5800 features low attomole sensitivity. As part of an LC-MALDI workflow, the instrument can uncover more and different proteins in a complex sample compared to an electrospray strategy, according to the company.

“Mass spectrometry continues to evolve with more scientists using this technique for a growing number of new applications,” says Laura Lauman, president of Life Technologies’ mass spectrometry division. “These systems incorporate intuitive software and comprehensive support to take performance to a new level.”

Water’s Synapt G2 MS is a high-resolution exact mass MS/MS platform designed for metabolite profiling, proteomics, biomarker discovery, biopharmaceuticals, and screening applications.

Posters Highlight Advanced Methods

Many of the posters presented at the ASMS meeting described studies utilizing innovative MS methods such as multiple reaction monitoring (MRM)-MS, differential MS (dMS), and label-free quantitative LC/MS-based analysis. These techniques are expanding the capabilities and market opportunities for MS technology, but they also create new challenges for sample preparation, fractionation, and high-abundance protein depletion upstream of MS.

In the poster “MRM for Oral Cancer Biomarker Validation in Saliva: Inherent Challenges, Solutions and Methods Development,” Ebbing de Jong and colleagues from the University of Minnesota describe efforts to simplify sample prep for MRM validation studies of protein biomarkers in saliva through amylase depletion.

The researchers loaded saliva samples onto starch columns to remove much of the amylase component, and then eluted the remaining protein fractions. These were run on Western blots or digested and analyzed by 1-D LC-MS on a Thermo Scientific LTQ Orbitrap. A comparison of the amylase-depleted sample versus whole saliva showed that amylase depletion revealed new protein bands and allowed for enhanced detection of low-abundance peptides such as kallikrein-1 on MRM chromatograms.

A.K. Yocum and colleagues from the University of Michigan described the development and optimization of an assay to discriminate between benign and cancerous prostate cell lines using multiplexed stable isotope dilution MRM-MS/MS.

They presented the results of a study to measure absolute concentrations of eight peptide biomarkers for prostate cancer in whole cell protein extracts. The protein extracts from six benign and cancerous prostate cell lines were separated by 1-D SDS-PAGE and digested, and the peptides were analyzed using LC-MRM-MS/MS on the 1200 Series HPLC-CHiP and 6410 Triple Quadrupole from Agilent Technologies.

Based on the results, the authors concluded that the multiplexed MRM-MS/MS assay will provide greater discriminatory power for the identification of tissue samples positive for prostate cancer, reducing the frequency of false positive findings and unnecessary biopsies.

Researchers from Pacific Northwest Laboratory and Oregon Health Sciences University presented the poster, “Application of Label-Free Quantitative LC-MS-based Proteomics for Biomarker Identification in Salmonella typhimurium,” in which they identified a set of proteins coordinately upregulated on infection of host macrophages.

The study involved a comparison of the proteomes of knock-out mutants of Salmonella, in which proteins associated with regulating virulence are not expressed, with the proteomes of wild-type Salmonella, to identify specific proteins involved in infection that could serve as novel targets for drug discovery.

Samples were fractionated and analyzed by LC-MS/MS on a Thermo Scientific LTQ Orbitrap, and candidate protein biomarkers were selected based on the following inclusion criteria: must exhibit > twofold reduction in expression in mutant compared to wild-type; must be coordinately regulated in a minimum of seven of twelve  regulator mutants; and must be identified by > three peptides. Five LC-MS discovered biomarkers were validated via Western blot, which demonstrated upregulated expression on Salmonella infection of host macrophage cells.

The AXIMA Resonance features high mass resolution and mass accuracy across MS and MSn analyses

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