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Proteomics Vendors Focus More on Implementation Than New Instrumentation at ASMS 2016


SAN ANTONIO (GenomeWeb) – From a vendor perspective, the American Society for Mass Spectrometry annual meeting this week in San Antonio was a quiet one — for proteomics, at least — with relatively few major releases targeting the field.

Most companies did use the conference to launch new mass spec instrumentation, but the larger focus was on sample prep and informatics workflows surrounding mass spec analysis and on implementation of existing technologies.

Perhaps the most significant release in terms of an actual mass spec instrument was Bruker's timsTOF machine, which couples trapped ion mobility spectrometry (TIMS) to a high-end QTOF system.

Broadly speaking, ion mobility is based on the notion of running ions through gas under the influence of an electric field, which serves to separate them based on their differing likelihoods of colliding with the gas molecules. The method is employed by a number of mass spec vendors, most prominently Waters and Sciex, as an additional separation step between the LC and mass spec analysis.

TIMS differs from IMS techniques currently in use in that it uses an electric field to trap ions in the device, allowing them to accumulate in parallel. They are then released into the mass spec on the basis of their collisional cross section, which is a function of their size.

The system's design allows for high-resolution separations in a very compact device. For instance, according to Christian Bleiholder, a Florida State University researcher and Bruker collaborator specializing in TIMS who spoke at the company's presentation this week, a conventional drift tube would have to be several meters long to achieve the resolution the company's TIMS device manages in a matter of inches.

Bleiholder's work focuses on studying the native structure of intact proteins and of protein-ligand binding events, and he noted this week that the high resolution of the TIMS system could prove highly useful for such work.

The system also has great potential for conventional proteomics research, Bruker President and CEO Frank Laukien said during the company's presentation, highlighting in particular work from the lab of Max Planck Institute of Biochemistry researcher Matthias Mann that used the Bruker TIMS system for a new shotgun mass spec workflow, Parallel Accumulation-Serial Fragmentation (PASEF), that combines collection of ions via TIMS with rapid quadrupole switching on a QTOF instrument to enable the fragmentation of multiple simultaneously eluting precursor ions.

Detailed in a paper published last year in the Journal of Proteome Research, the method could allow researchers to fragment significantly more precursors than in current shotgun proteomic experiments, upping the technique's coverage while retaining its selectivity.

At the time of the JPR study, the method was still at the proof-of-principle stage with broader implementation requiring modifications by Bruker to its instrument controls and software. Speaking to GenomeWeb this week, Dietrich Hauffe, executive vice president for life sciences mass spectrometry at Bruker, said that work on fully implementing the PASEF technique was ongoing.

In addition to the timsTOF, Bruker also highlighted its RapifleX MALDI-TOF/TOF mass spectrometer, which it first introduced at last year's Human Proteome Organization annual meeting.

Shimadzu, Waters, and Sciex also introduced new instruments, aimed primarily at targeted quantitation work. Shimadzu released its LCMS-8045 Triple Quad, a mid-range instrument intended mostly for routine analyses.

Waters released its Xevo TQ-XS, the latest and most sensitive of its tandem quadrupole systems. The instrument features a newly designed Stepwave XS ion guide, which the company said provided improved robustness and between a two- and 10-fold increase in signal to noise compared to the previous Stepwave system.

Sciex introduced its QTRAP 6500+, which the company said brings enhanced selectivity to targeted quantitation by employing the company's SelexIon ion mobility technology as well as MS3 level analysis.

More than new instrumentation, though, Sciex's presentation focused on implementation, with significant emphasis given to its efforts in what it has named "industrial proteomics," the company's term for automated, large-scale proteomics workflows.

The centerpiece of Sciex's "industrial proteomics" initiative is the Australian Cancer Research Foundation International Centre for the Proteome of Cancer (ProCan), which is using Sciex instrumentation to pursue the goal of profiling the proteomes of roughly 70,000 tumor samples over the next seven years.

Using $10 million in seed money from the Australian Cancer Research Foundation, the Sydney-based center, which is scheduled to open in the next several weeks, purchased six Sciex TripleTOF 6600 mass specs that it plans to use for Swath-based analysis of the tumors. 

Speaking at Sciex's presentation this week, Phil Robinson, co-head of the center, said the researchers hope to generate massive amounts of proteomic data that would allow them to better type and subtype cancers as well as identify relevant biomarkers and drug targets and suggest potential treatments on an individual patient basis.

To facilitate this, the center is embedding pathologists with the hope of collaborating with them on analyses and ultimately winning their support for use of such proteomic tools as adjuncts to conventional pathology techniques, Robinson said.

"We believe in precision medicine," said Sciex President Jean-Paul Mangeolle, noting that projects like the ProCan initiative provide the company a proving ground to test its implementation of ideas like "industrial proteomics."

Establishing a large-scale, automated proteomics facility like ProCan "will require that you SOP [standard operating procedure] the heck out of the instruments," he said. "If we succeed and ten years down the road [such facilities become commonplace], it is a big win for us. So that is why it is worth the effort."

Thermo Fisher likewise emphasized the shift toward large-scale, high-throughput proteomics, with Ken Miller, the company's vice president of marketing, life sciences mass spectrometry, noting its customers' desire to go "from sample to digital proteome read out in a day."

Miller also announced that Bruno Domon, currently the head of the Luxembourg Clinical Proteomics Center, will be taking over as the director of Thermo Fisher's Biomarker Research Initiatives in Mass Spectrometry (BRIMS) Center. In recent years, Domon has been particularly active in using the company's Q Exactive instrument to develop high-resolution targeted quantitation assays for purposes like protein biomarker development and validation.

Thermo Fisher and Sciex also both highlighted their cloud computing systems, the Thermo Fisher Cloud and OneOmics, respectively, which the companies' cited as key to their larger efforts in developing systems for large-scale proteomics projects.

Bearing this out, ProCan's Robinson said that Sciex's OneOmics cloud platform, which it runs in collaboration with Illumina, was an important consideration in he and his colleagues' decision to partner with Sciex on the facility.

"Having OneOmics operating already was one of the deciding factors for us to go this route," he said, noting that handling the vast amounts of data the center expects to generate would be impossible outside a cloud environment.

Waters, meanwhile, introduced its Symphony Data Pipeline software, which, though not a cloud-based tool, is similarly aimed at helping researchers deal with large quantities of data. The package automates the movement and processing of mass spec data.

Waters also released version 3.0 of its Progenesis QI software for proteomics, which supports label-free proteomic experiments ranging from traditional data-dependent analysis to Waters MSE and HDMSE data-independent analyses. The new version reports charge-deconvoluted peptide quantification results, making it easier to review quantitative data at the peptide level.

Agilent presented an addition to its AssayMap automated protein sample prep line.