Advances in Clinical Mass Spectrometry: Proteomics and Phenomics

Recent developments have added strength to the overall trend of mass spec in the clinical laboratory. The past year has witnessed the advent of several Class 1 medical device MS platforms, as well as the first FDA-approved MS-based test for Vitamin D, among other noted achievements. The expansion of MS into the clinical realm will continue to gain momentum with the release of novel technologies for new applications. Several developments thus far this year have fit that profile.

Clinical Phenomics and Proteomics

Proteomics is the large-scale study of proteins within a system. The emerging field of phenomics aims to understand and characterize the phenome, or the set of physical and biochemical traits associated with a given system at the whole organism level.

Bruker has announced a newly established application for their IVDr-by-NMR solution for phenomics research. The platform, unveiled at Pittcon 2018, is targeted towards analysis of samples with increased quality and integrity using rigorous standard operating procedures (SOPs). The novel application has demonstrated the ability to provide quantitative data for 150 metabolic biomarkers in urine in a single experiment. Added strengths include full automation, high-throughput processing, and low cost per sample.

Biobanking quality control of clinical samples has traditionally been an underdeveloped area, despite the importance in advanced MS analysis and other techniques. Advanced biomarker research and high resolution analytical technologies have necessitated new solutions towards the complex workflows of sample collection, storage, and traceability. Biochemical concerns including the prevention of oxidation, thermal lability, and other problems, add greater complexity to the issue.

The IVDr-by-NMR is meant to stratify samples kept under quality standards (SOPs) with the objectives to couple with MS analysis platforms and others for better precision and diagnostic power. The technology achieves this by utilizing a standard spectral database where results are compared among others in the network. The results are accessible to all those involved in order to strengthen SOPs and validate data generation procedures. The overarching goal is the translation to higher accuracy and precision for diagnostic methods such as high-resolution MS, whether for personalized medicine or population-wide studies on phenotypes and metabolic risk factors.

High-throughput Clinical Proteomics

Bruker’s previously launched timsTOF Pro MS system for high sensitivity proteomics can now be coupled with the Evosep One separations device. The details of this new high-throughput clinical proteomics platform were showcased at Pittcon 2018.

The timsTOF MS platform is based on ion mobility analysis and is designed as an open platform to facilitate adoption of ion mobility MS across research applications. The timsTOF Pro instrument allows for ions to be accumulated in the front section, while ions in the rear section are simultaneously released depending on their ion mobility. The rapidly synchronized process is termed Parallel Accumulation Serial Fragmentation (PASF).

Evosep One is an advanced chromatography system designed for larger cohort proteomics. This technology achieves >200 sample/day throughput and enables >90% MS utilization. The LC peak widths of 2 seconds for 5-minute gradients have been combined with the PASEF method on the timsTOF Pro with MS/MS rates of >150 Hz. The combination results in excellent sensitivity and high-throughput, with label free quantitation (LFQ) of ~1200 proteins in ~ 5 minutes. The total system enables large sample cohort analysis for biomarker research and validation. An impressive milestone in advanced clinical proteomics.

Growing Trends in Clinical Proteomics

These are just two developments which exemplify a growing trend in clinical proteomics and biomarker research – the synergistic power of combined technologies. Advanced biobanking quality control SOPs necessitate analytical approaches to validate samples for downstream analysis by MS. The IVDr-by-NMR is designed to enable high-throughput high-quality sample analysis with the ultimate goal of increased diagnostic power and precision. The timsTOF Pro Evosep combines simplified upstream separations with high-throughput ion-mobility MS analysis – with the goal to screen large sample cohorts and characterize (putative) biomarkers.

Mass Spec instrumentation can now achieve unprecedented sensitivity, resolution, and speed, this is a fact. Beyond instrument horsepower however, enabling solutions are needed more than ever to ensure quality and efficiency of the upstream workflows. A continuing trend will undoubtedly be the combination of technologies such as those described and those yet to come.


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