Technological developments in mass spectrometry

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Our laboratory has a long history of developing state-of-the-art mass spectrometry (MS) technology. In close collaboration with leading vendors, we advance MS technology for proteomics on both the Orbitrap (Thermo Fisher Scientific) and TIMS time-of-flight (Bruker Daltonik) MS platforms.

Tackling the  dynamic range challenges in proteomics, we recently developed a data acquisition method termed ‘BoxCar’ (Meier et al., Nat. Methods, 2018), which dramatically boosts the proteome coverage in samples with a large abundance range of proteins, such as plasma or tissue samples (Geyer et al., Cell Syst., 2018, Doll et al., Nat Commun., 2017) .

Our multiplexing technology ‘EASI-tag’ (Virreira Winter et al., Nat. Methods, 2018) enables us to measure proteomes with accurate ratios, avoiding many pitfalls of alternative isobaric labeling strategies. 

To make our developments readily available for the large community of Orbitrap users, we developed MaxQuant.Live, which compiles our advanced data acquisition strategies in a user-friendly instrument control software (www.maxquant.live).

This also includes a novel strategy for targeted proteomics, termed global targeting, where tens of thousands of peptides can be targeted for MS2 fragmentation while mass, retention time and intensity are calibrated in real-time. This allows for the reproducible analysis of identical peptides across many samples or the in-depth characterization of large classes individual peptides of interest.

A recent focus of our work is the application of trapped ion mobility spectrometry (TIMS) to proteomics. Ion mobility spectrometry separates ions in the gas phase based on their shape and size, and thus adds another dimension of separation to the established liquid chromatography – MS workflows. In 2015, we introduced Parallel Accumulation – Serial Fragmentation, which multiplies the sequencing speed of TIMS-QTOF mass spectrometers without any loss in sensitivity. The Bruker timsTOF Pro implements this scan mode commercially and achieves sequencing rates exceeding 100 Hz, allowing very rapid proteome analyses, while achieving a very high sensitivity for minute sample amounts. (PASEF) (Meier et al., MCP, 2018)

In addition to MS method developments, our group established the widely used in-StageTip (Kulak et al., Nat. Methods, 2014) and EasyPhos (Humphrey et al., Nat. Biotechnol., 2015, 2015, Humphrey et al., Nat. Protoc., 2018) sample preparation workflows enabling deep, fast and reproducible proteomic and phosphoproteomic analyses. We also developed bioinformatics tools, most prominently MaxQuant  and Perseus to analyze the large MS-based proteomics datasets.

 
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