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Bruker Unveils the timsTOF Ultra Mass Spectrometer: Unparalleled Sensitivity, 300 Hz PASEF MS/MS, and VistaScan™ for Advanced dia-PASEF® 4D-Proteomics™

Tuesday, June 06, 2023

Bruker Corporation (Nasdaq: BRKR) has unveiled the timsTOF Ultra mass spectrometer, introducing transformative sensitivity to their 4D-Proteomics timsTOF platform. The new instrument incorporates several advanced features, including the Captive Spray Ionization (CSI) Ultra ion source with an optimized vortex gas flow and larger capillary, a 4th-generation TIMS XR cell, and a 14-bit digitizer.

The timsTOF Ultra sets a new benchmark by achieving unparalleled sensitivity and quantitation performance. It can identify over 55,000 peptides mapping into 5,000 protein groups at a single-cell level with just 0.125 ng protein loading, maintaining a 1% false discovery rate (FDR). Additionally, it quantifies more than 4,800 protein groups at coefficients of variation (CVs) below 20%, even at protein load levels below 1 ng.

The remarkable sensitivity of the timsTOF Ultra, combined with its improved PASEF duty cycle of up to 300 Hz for MS/MS, offers significant performance improvements for applications involving ultra-low sample amounts. These include unbiased single-cell proteomics, single-cell lipidomics, unbiased spatial proteomics, immunopeptidomics, phosphoproteomics, PTM analysis, and protein-protein interaction (PPI) studies.

Bruker's timsTOF Ultra mass spectrometer pushes the boundaries of analytical performance, providing researchers with exceptional sensitivity and robustness, even when working with minimal sample quantities.

Dr. Fabian Coscia, the Group Leader for Spatial Proteomics at the Max Delbruck Center in Berlin, Germany, has expressed his enthusiasm for the timsTOF Ultra and its impact on their low-input tissue proteomics research. By utilizing a 20-minute nanoflow LC gradient and Bruker's optimized dia-PASEF (3x8 window) method, they have achieved remarkable results. Specifically, they can reliably quantify 1,500-2,000 proteins from laser micro-dissected mouse liver FFPE tissue samples as small as 1,500 µm2, which corresponds to approximately 1-2 hepatocytes.

The timsTOF Ultra offers these advancements in sensitivity without compromising its robustness for high-throughput proteomics. It can handle up to 50 samples per day (SPD) or even up to 398 SPD while maintaining exceptional identification confidence, with peptide and protein false discovery rates (FDRs) below 1%. Notably, this eliminates the cross-reactivity issues often encountered with targeted immune-recognition methods.

Professor Dr. Karl Mechtler, the Proteomics Head at the Innovation Hub of the Research Institute for Molecular Pathology (IMP), Gregor Mendel Institute (GMI), and the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), expressed the importance of differentiating between various cell types to gain a comprehensive understanding of cellular mechanisms and diseases. While single-cell analysis has been a transformative approach, there have been challenges in maximizing its throughput and expanding the scope of protein groups that can be analyzed. Dr. Mechtler emphasized the biological significance of detecting 6,000 or more proteins in a single-cell experiment.

The timsTOF Ultra has effectively overcome these obstacles, allowing researchers to explore the proteome of individual cells with exceptional speed and sensitivity. This breakthrough has elevated single-cell analysis to new levels, opening up exciting opportunities for future research.

Furthermore, Bruker has introduced VistaScan software, which enables the synchronization of TIMS ramp with the quadrupole scan. This integration enhances the utilization of ion mobility information on a larger scale. The software supports the innovative midia-PASEF mode, initially introduced by Stefan Tenzer (doi.org/10.1101/2023.01.30.526204).

Dr. Stefan Tenzer, a professor for Quantitative Proteomics and Head of the MS Core Facility at Johannes Gutenberg University Mainz, has expressed enthusiasm for the laboratory's focus on developing methods for quantitative proteomics that prioritize sensitivity and information extraction. One notable achievement of their collaboration with Bruker is the creation of the maximum information dia (midia) PASEF scanning acquisition mode. This innovative mode combines the sensitivity of data-independent acquisition (DIA) with the spectrum quality of data-dependent acquisition (DDA), resulting in spectra that resemble DDA spectra while maintaining high sensitivity. Dr. Tenzer has specifically highlighted the potential of midia-PASEF for immunopeptidomics and phosphoproteomics.

Bruker has obtained an exclusive license for midia-PASEF from Johannes Gutenberg University Mainz, with plans to release it as a product in 2023. The timsTOF Ultra, equipped with VistaScan acquisition capabilities, will support this acquisition mode.

Additionally, the timsTOF Ultra introduces an improved DDA-PASEF acquisition mode, enabling a speed of 300 Hz for acquiring up to 18,000 collision cross-section (CCS)-enabled MS/MS spectra per minute. This enhancement allows for in-depth 4D-Proteomics and 4D-Lipidomics/4D-Metabolomics analyses with significantly shorter LC gradients, lasting only a few minutes. The faster data acquisition, combined with the shortened LC gradients, empowers researchers in conducting comprehensive studies in these areas.

In summary, the timsTOF Ultra, developed by Bruker in collaboration with Johannes Gutenberg University Mainz, brings about notable advancements in acquisition modes and speed for quantitative proteomics, immunopeptidomics, phosphoproteomics, and lipidomics/metabolomics research.

Bruker has developed the CSI Ultra ion source specifically for use with the timsTOF Ultra instrument. This ion source is designed to achieve high sensitivity in nanoflow liquid chromatography-mass spectrometry (LC-MS) experiments.

The CSI Ultra ion source has been further improved for optimal performance on the timsTOF Ultra system. One of the key enhancements is the focused delivery of vortex gas at the nanospray tip, which enhances ion transmission efficiency. This ensures that a greater number of ions generated during ionization are effectively transmitted into the mass spectrometer for analysis.

The vortex gas is directed towards the nanospray tip, enabling ionization across a range of flow rates from 50 to 5000 nanoliters per minute (nL/min). This wide flow rate range allows for flexibility in different applications and experimental setups, ensuring consistent ionization performance.

The optimized CSI Ultra ion source, when used with the timsTOF Ultra instrument, offers improved nanoflow sensitivity. This improvement leads to enhanced detection limits and greater accuracy in analyzing low-abundance analytes in complex samples.

Dr. Christof Lenz, the Head of the Core Facility Proteomics at Universitätsmedizin Göttingen, has provided positive feedback on the new CSI source. He mentioned that the installation process has become simpler, allowing for quick exchange of columns and emitters without compromising performance. The screw-on design of the CSI source eliminates the need for manual adjustment, providing precise emitter positioning and alignment. Dr. Lenz expressed his satisfaction with the new design, and his lab technicians also appreciate its benefits.

In addition to the CSI Ultra ion source, Bruker has enhanced its VIP-HESI ion source by incorporating microFlow emitter capabilities. This advancement enables efficient ionization at both microflow and analytical LC flow rates. By leveraging the high sensitivity, robustness, and speed of the timsTOF platform, the microFlow emitter enhances performance in 4D-proteomics experiments. It offers improved flexibility in flow rate options and optimizes ionization for different experimental setups.

In reference to a large-scale brain proteomics project, Dr. Johanna Tüshaus from the Küster lab at Technical University Munich mentioned the requirement for a fast, sensitive, and robust LC-MS/MS setup. They successfully combined their established micro-flow LC technology with the VIP-HESI source on the timsTOF HT instrument. This combination proved to be powerful as it allowed for deep proteome coverage using short gradients, thereby achieving a balance between speed and sensitivity. The introduction of the 50 µm ESI emitter was instrumental in enhancing the sensitivity of their micro-flow LC timsTOF setup.

Additionally, Dr. Mukul Midha, a Research Scientist at the Moritz Lab, Institute for Systems Biology in Seattle, highlighted the significance of highly stable electrospray conditions for conducting large-scale quantitative proteomics. Dr. Midha acknowledged that the Bruker VIP-HESI source delivers the required reproducibility for complex plasma samples. The source connections are straightforward, parameter optimization is easy, and the spray stability is excellent. These advancements contribute to increased sample throughput, ensure 100% uptime, and enable stable and precise protein quantification in their research.

Bruker ProteoScape software has introduced a new feature for real-time analysis with GPU-powered capabilities and integrated quality control (QC) using the Biognosys iRT kit. The iRT kit consists of eleven synthetic peptides designed to optimize system performance monitoring by ensuring stability, sensitivity, retention time spacing, and CCS-enablement.

Dr. Eduardo Chicano-Gálvez, Head of IMIBIC Mass Spectrometry and Molecular Imaging Unit at Reina Sofia Hospital, University of Cordoba, Spain, praised the real-time QC module, stating that it ensures smooth operation and prevents the loss of valuable clinical samples. The ProteoScape software allows for efficient sample-to-results turnaround on large-scale clinical proteomics projects while maintaining sensitivity, robustness, traceability, and analytical quality.

ProteoScape software also incorporates third-party tools, such as the BPS Novor package, which enables fast, accurate de novo sequencing for immunopeptidomics and meta-proteomics applications where specific enzymatic cleavage information is unavailable. Existing users of Bruker PaSER software will have the opportunity to upgrade to Bruker ProteoScape and take advantage of its enhanced features and capabilities.

SCiLS Lab 2024 has introduced new features and improvements to enhance its capabilities in multiomics spatial tissue biology. The software now includes metabolite and lipid annotation using MetaboScape annotation, allowing for comprehensive analysis of these molecular components. Additionally, there are advancements in CCS-enabled 4D feature finding, which accelerates mass spectrometry imaging workflows.

SCiLS Lab 2024 offers an integrated multiomics workflow, enabling the analysis of proteins, lipids, metabolites, and glycans from the same tissue sample. It provides auto-segmentation and statistical profiling features to streamline data analysis processes.

Dr. Erin H. Seeley, the Mass Spectrometry Imaging Facility Director at the University of Texas at Austin, expressed the benefits of the novel 4D feature finding in SCiLS Lab. This feature focuses on relevant information in CCS-enabled MALDI imaging studies, leading to faster evaluation of tissue samples and improved efficiency in MS imaging workflows. The integration of this feature into SCiLS Lab simplifies the optimization of data obtained from the timsTOF fleX instrument.

MetaboScape 2024 has also been enhanced to support semi-quantitative analysis using stable isotopically labeled lipid standards. Additionally, it incorporates the Mass Spec Query Language (MassQL), which is a domain-specific language developed by the metabolomics community, facilitating advanced data analysis and interpretation.

The OligoQuest 2.0 Software has recently been released, introducing new features that allow for custom oligonucleotide modifications. This updated version offers enhanced RNA and oligonucleotide characterization, enabling users to confirm the sequence of full-length products (FLP) and side products through intact mass and MS/MS analysis. It also provides the capability to identify modified RNA sequences and base exchanges in isomeric oligonucleotides. One notable aspect is the ability for customers to customize their oligonucleotide "alphabet" to denote standard or customized modifications.

Dr. Fritz Schweikart, a member of the Pharmaceutical Development team at AstraZeneca in Gothenburg, expressed excitement about the OligoQuest software. He described it as a highly anticipated evaluation tool that greatly simplifies the analysis of MS/MS data for pharmaceutical Antisense oligonucleotides (ASOs). The software streamlines the analysis of chemical degradation and eliminates the need for manual investigation of MS/MS data. Dr. Schweikart praised the user-friendly and intuitive interface, which conceals the complexity of the mass matching algorithms running in the background.

In summary, the OligoQuest 2.0 Software offers advanced capabilities for the analysis and customization of oligonucleotides, enabling the characterization of RNA sequences and modifications. It aims to simplify the analysis process and enhance the user experience, particularly in the field of pharmaceutical development.

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