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Mass spectrometry: Bringing Precision and Clarity to Precision Medicine

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Mass spec systems are helping biomedical researchers gain deeper insight into the mechanisms of disease progression and therapeutic intervention, but the sheer volume and complexity of samples are challenging instrument makers to innovate. According to speakers at the American Society of Mass Spectrometry (ASMS), held June 4-8 in Indianapolis, for researchers in OMICs, accuracy, and throughput is king.

"Like any other industry, healthcare and life science research is being disrupted by step changes in science and technology,” says Mark Cafazzo, Director, Global Academic & Applied Markets Business at SCIEX. Worldwide adoption of the concept of precision medicine is causing basic researchers to get closer and closer to clinical partners in hospitals and healthcare networks around the world. “The lines between those labs are blurring more and more every year,” Cafazzo adds.  

LC/MS-based Omics is trying to link the phenotype that is more measurable by MS to the genotype that is addressed by next-generation sequencing, Cafazzo says. “We need solutions that are scalable, can provide answers in very reproducible form, and are very precise and accurate. So in developing products, we are building in more robustness. We're building in more capabilities for higher throughput to fit the applications that our customers are addressing, and we look for automation anywhere we can to minimize the opportunity for human error and improve laboratory efficiency overall.”

To make meaningful progress in proteomics, researchers need tools that identify and quantify proteins, peptides, lipids, glycans and small molecules accurately and in less time. Thermo Fisher Scientific’s customers were looking for solutions with more sensitivity—to look “deeper” into the proteome—and the ability to analyze more samples. To this end, Thermo introduced the HF-X Hybrid Quadrupole Orbitrap mass spectrometer to its Q Exactive family of products. The Q Exactive HF-X uses a high-capacity transfer tube for maximum ion loading, an electrodynamic ion funnel that accommodates and transmits ions over a broader mass range, and a high-field Orbitrap mass analyzer.  Dr. Jesper V. Olsen, professor and vice director of the Novo Nordisk Foundation and Center for Protein Research at the University of Copenhagen, says his team identified 1,100 unique peptides per minute using Q Exactive HF-X Hybrid spectrometer—a new world record.

Thermo also introduced three enhancements for its Orbitrap Fusion Lumos MS for scientists performing top-down proteomics, small molecule characterization, lipidomics and biopharma research. Integrated Ultraviolet Photodissociation (UVPD), a complementary fragmentation technology, allows researchers to perform large and small molecule structure determination on an LC time scale. The Advanced Peak Determination (APD) algorithm is designed to improve the performance of most proteomic workflows with high peptide and protein identification rates in data-dependent experiments, while the 1M resolution feature is geared toward researchers who need ultra-high resolution to measure fine isotope structures or separate isobaric compounds.

Iain Mylchreest, vice president of R&D at Thermo’s analytical instruments group says metabolomics needs to be fully understood to grasp the mechanisms of disease progression or therapeutic intervention, but the metabolome is as complex or even more so than the proteome.  "One of the biggest challenges for metabolomics is the chemical diversity. Unlike peptides and proteins, which are based around the same building blocks, that's not true of metabolites. So we have to use very different separation technology if we want to do a full proteome map,” he adds. These solutions include UHPLC, HILIC, ion chromatography, and GC—all capabilities within Thermo’s portfolio.

"Comprehensive solutions for metabolomics really requires a whole system and workflow," Mylchreest adds. A new partnership with BIOCRATES Life Sciences will help Thermo build out workflows. The AbsoluteIDQ p400 HR kit is the industry’s first, comprehensive kit for targeted metabolomics analysis and takes advantage of the HRAM capabilities of Thermo's Orbitrap mass spectrometry and BIOCRATES’ metabolic phenotyping technologies.

Sciex also announced that it is introducing metabolomics on its X500R platform. “We're expanding the value of SWATH Acquisition with the advent of X500r and the Sciex OS software that drive it,” Caffazo says. “This combination makes it possible to take the power of an advanced metabolomics workflow and make it very streamlined, push-bottom, to take you all the way from your raw samples to final answers.”