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ASMS 2019 Sees Slew of New Releases as Vendors Highlight Throughput, Ion Mobility Options

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NEW YORK (GenomeWeb) – The American Society for Mass Spectrometry annual meeting held here this week saw a slew of new instrument releases as a number of vendors updated or expanded their existing product lines.

In terms of technologies, data-independent acquisition (DIA) mass spec and ion mobility received significant attention with Bruker highlighting a recently developed workflow for its timsTOF pro instrument, diaPASEF, that combines the two. Bruker also launched its timsTOF flex instrument, which includes a MALDI source to enable imaging applications on the platform.

Waters launched its Select Series Cyclic IMS mass spec featuring its newly developed cyclic ion mobility technology, which allows for multiple IMS passes to boost instrument resolution.

Sciex introduced an updated version of its popular SWATH DIA method for use on its new TripleTOF 6600+ instrument.

Thermo Fisher Scientific, meanwhile, refreshed its high-end Orbitrap portfolio, launching its Thermo Scientific Orbitrap Exploris 480 instrument, essentially the latest in the company's line of Q Exactive instruments, as well as its Thermo Scientific Orbitrap Eclipse Tribrid mass spec, the new flagship in its Orbitrap Tribrid line.

Competing on throughput

Proteomics research has shifted in recent years from an emphasis on identifying and quantifying as many proteins in a samples as possible to experiments focused on achieving the throughput needed to obtain meaningful statistics about the clinical validity of potential protein biomarkers.

This year's ASMS meeting saw vendors likewise place an emphasis on throughput with a number of mass spec firms touting the speed of their new instruments and their ability to easily run large numbers of samples while still retaining sufficient depth of analysis.

This has been a major selling point for Bruker's timsTOF Pro instrument since it was introduced it in 2017, and the company further emphasized this capability this week, highlighting the recent presentation of its diaPASEF workflow in a bioRxiv preprint published last week.

Developed by a team including the Max Planck Institute's Matthias Mann and the Swiss Federal Institute of Technology Zurich's Ruedi Aebersold, the diaPASEF technique takes advantage of the timsTOF Pro's trapped ion mobility spectrometry component to sample a higher proportion of peptide precursor ions, thus improving assay performance. In the bioRxiv preprint the researchers demonstrated that the approach could identify 7,565 proteins in a 200-nanogram HeLa cell digest run over two hours.

During Bruker's ASMS presentation, President and CEO Frank Laukien said he believed the technique would prove an important step towards the goal of proteomics "by mass spectrometry at large scale, at high reproducibility, and with high sensitivity."

Also during the Bruker presentation, Vicki Wysocki, professor of chemistry and biochemistry, detailed her lab's use of the timsTOF pro, noting that with the instrument they were able to obtain the same number of protein identifications from an unfractionated 200-nanogram sample run over two hours of instrument time as they had previously obtained analyzing 12 micrograms of fractionated sample over 12 hours of instrument time.

Thermo Fisher likewise highlighted the potential of its new platforms to enable higher throughput proteomic experiments. Ken Miller, vice president of marketing, life sciences mass spectrometry, cited experiments on the Orbitrap Exploris 480 identifying roughly 6,000 proteins from 1 microgram of HeLa cell digest using a one-hour analysis as well as a 21-minute experiment in which the instrument identified around 3,000 proteins from a 500-nanogram HeLa digest. The instrument was also able to identify around 3,000 proteins from the same sample in a five-minute DIA experiment.

In an interview prior to the meeting, Miller also said the Exploris had been engineered for robustness and ease of maintenance, which he acknowledged have been issues for some Q Exactive customers.

"Maintenance and keeping the [Q Exactive] systems up and operating in a high-throughput environment has been a challenge for some labs," he said. "This system was specifically designed to address a lot of those issues."

Sciex was arguably the forerunner, at least among vendors, of the shift towards emphasizing throughput with its move several years ago to develop what it called "industrialized" proteomics, as exemplified by its work with the Australian Cancer Research Foundation International Centre for the Proteome of Cancer (ProCan) to generate proteomic profiles of roughly 70,000 tumor samples, as well as work at the University of Manchester's Stoller Biomarker Discovery Centre running thousands of samples to discover biomarkers for diseases ranging from lung cancer to lupus.

Aiming to keep pace with competitors, the company introduced at this year's meeting its TripleTOF 6600+ and a new DIA method, Scanning SWATH, which uses a sliding quadrupole window as opposed to stepped isolation windows, which boosts performance by improving ion accumulation and providing additional information for matching of precursor and fragment ions.

In early work with the method, Sciex researchers have achieved a 30 percent boost in peptide identifications compared to conventional SWATH approaches, said Christie Hunter, director of applications at Sciex, adding that she expected this would further improve with more method development and optimization of the approach.

"There are obviously more levels we can pull in terms of improved algorithms and acquisition strategies and things like that," she said. "But that's kind of where we're at today for the preliminary data."

The TripleTOF 6600+ is currently available only to early adopters with a broad commercial launch planned down the road, Hunter said.

A moment for ion mobility

In addition to throughput concerns, ion mobility technology proved a touchpoint for the meeting, with Waters' Select Series Cyclic IMS instrument a particularly notable release in this regard.

The Cyclic IMS instrument features an IMS device with a circular path which both reduces the instrument's footprint while also allowing researchers to cycle ions of interest through the IMS device multiple times to achieve higher resolution separations.

The device is conceptually similar to ion mobility technology developed at the Pacific Northwest National Laboratory and licensed by Exton, Pennsylvania-based Mobilion Systems, which aims to launch a beta product in 2020. That technology uses structures for lossless ion manipulations (SLIM) technology to extend ion mobility path lengths beyond that allowed by conventional IMS systems and to direct ions through a system multiple times. The company is working with several major life sciences mass spec vendors to integrate its IMS technology with their platforms.

James Langridge, director of advanced MS technologies at Waters, acknowledged that Waters and Mobilion were pursuing somewhat similar approaches in terms of offering multi-pass IMS technologies but suggested that the Cyclic IMS instrument offered more flexibility in manipulating populations of ions within the IMS to allow for isolation and separation of specific analytes of interest.

Langridge said that thus far the company has received interest in the instrument from high-end academic centers as well as from industries like pharma and biopharma. With regard to protein analysis, he said he didn't expect the instrument would prove most beneficial for typical shotgun proteomic workflows but rather for more challenging analyses looking at difficult-to-separate species.

"I think the benefit of this type of platform is with things where there are, for example, isobaric modifications," he said. "People looking at protein structure, protein function, trying to look at things like histone modifications where you've got a lot of interplay between different isobaric populations and modifications — really challenging types of experiments where you need the benefit of enhanced resolution."

In a note covering the ASMS releases, SVB Leering analysts Puneet Souda and David Delahunt wrote that adoption of the Cyclic IMS instrument "will still largely depend on the robustness and readiness of the software that translates raw IMS data to meaningful experimental data for the labs," and added that "ion mobility remains a niche application."

Langridge said that it was with this issue in mind that Waters chose to put the Cyclic IMS instrument's operating system on its MassLynx software system, which he noted uses file formats compatible with "a lot of open source, academic tool sets."

He added that he believes the development and implementation of ion mobility technologies by other mass spec vendors would help drive adoption of Waters instruments.

"I think in general a wider appreciation of the benefits of ion mobility is good for us as a company," he said.

Rohan Thakur, managing director and executive VP, life sciences at Bruker, noted that the collisional cross section (CCS) data provided by the timsTOF Pro's IMS system provided an additional dimension of information that could enable more reproducible and sensitive analyses — something Waters has been highlighting regarding its own IMS systems for years.

Thermo Fisher's recently released High Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS) technology does not make CCS measurements, but the company highlighted during the meeting the compatibility of the Orbitrap Exploris 480 and the Orbitrap Eclipse Tribrid with its FAIMS device, the FAIMS Pro.

Other introductions of note

In addition to the TripleTOF 6600+, Sciex released its Triple Quad 5500+ - QTRAP Ready, a new triple quad that can be upgraded to a QTRAP via a field-upgradable license. The company also introduced its Acoustic Ejection Mass Spectrometry technology, which it developed in collaboration with its fellow Danaher firm Labcyte and uses acoustic sample handling to enable mass spec experiments running as many as three samples per second.

The system, which Sciex is targeting to the pharma industry, is similar to a platform developed by AstraZeneca in collaboration with Labcyte and Waters that the drugmaker described in an Analytical Chemistry paper published earlier this year.

Meanwhile, Waters launched a new version of its Synapt line, the Synapyt XS, which is aimed at the research market; Shimadzu launched the MALDImini-1, a benchtop MALDI digital ion trap instrument with the footprint of a piece of paper; andAgilent launched its 6495C Triple Quadrupole system and InfinityLab LC/MSD iQ System and highlighted the recently released 6546 LC/QTOF instrument.

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