timsTOF Ultra Further Advances Quantitative
Spatial and Single-cell 4D-Proteomics and 4D-Lipidomics™,
Immunopeptidomics, PTM and Protein-Protein Interactions Analysis -
with Speed and Robustness
- timsTOF Ultra mass spectrometer enables ID of >5000
protein groups and >55k peptides at single-cell sensitivity
(0.125 ng) with highest confidence at <1% False Discovery
Rate
- New CSI Ultra ion source with vortex flow enhances ion
formation across nanoLC (50 nL-5000 nL/min) gradients, leading to
dramatic sensitivity increases
- VistaScan software supports novel midia-PASEF scan for
dda-like MS/MS traceability with dia-sensitivity for ‘high
fidelity’ 4D-Proteomics
- timsTOF Ultra PASEF scan speed increased to 300 Hz for
ultra-fast MS/MS
- New microFlow emitters for capillary and analytical flow
4D-Proteomics using unique VIP-HESI ion source for high method
robustness and sensitivity
- ProteoScape™ software now with real-time QC mode using
Biognosys iRT kit
- SCiLS™ Lab 2024 mass spec imaging software integrates MALDI
lipid and HiPlex-IHC protein expression for MALDI-guided spatial
tissue biology
At the 71st ASMS meeting, Bruker Corporation (Nasdaq: BRKR)
announced transformative sensitivity on the 4D-Proteomics timsTOF
platform with the launch of the new timsTOF Ultra mass
spectrometer. It incorporates a new Captive Spray Ionization
(CSI) Ultra ion source with larger capillary and optimized vortex
gas flow, a novel 4th-generation TIMS (trapped ion mobility
separation) XR cell and 14bit digitizer. The timsTOF Ultra
can identify over 55K peptides that map into 5000 protein groups at
the single-cell level of 0.125 ng protein loading, at 1% FDR, and
over 4800 protein groups quantified at CVs of <20%. This
breakthrough sensitivity and quantitation performance below the 1
ng protein load level sets a new benchmark. Unparalleled
sensitivity, with the proven robustness of the timsTOF platform,
and with PASEF duty cycle now up to 300 Hz for MS/MS, offers
significant further performance improvements for ultra-low sample
amounts, including unbiased single-cell proteomics and single-cell
lipidomics, unbiased spatial proteomics, immunopeptidomics,
phosphoproteomics, PTM analysis, and protein-protein interaction
(PPI) studies.
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Dr. Fabian Coscia, Group Leader for Spatial Proteomics at
the Max Delbruck Center, Berlin, Germany, said: “The single-cell
sensitivity dia-PASEF workflow on the timsTOF Ultra has brought our
low-input tissue proteomics research to a new level. Using a 20-min
nanoflow LC gradient combined with Bruker’s optimized dia-PASEF
(3x8 window) method, we can now reproducibly quantify 1,500 – 2,000
proteins from laser micro-dissected mouse liver FFPE tissue of only
1,500 µm2, regions corresponding to approximately 1-2
hepatocytes.”
These timsTOF Ultra advances have been achieved without
compromising the excellent robustness for high-throughput
proteomics, e.g., at 50 samples per day (SPD), or even up to 398
SPD, nor the highest identification confidence of <1% peptide
and <1% protein FDRs (false discovery rates), avoiding the
cross-reactivity seen with targeted immune-recognition methods.
Professor Dr. Karl Mechtler, 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),
added: “To truly understand cellular mechanisms and diseases, it's
crucial to differentiate between the various cell types. While
single-cell analysis has been game-changing, we face obstacles in
maximizing its potential for throughput and proteins groups that
can be analyzed. It would make biological sense to detect 6000 or
more proteins in a single-cell experiment. The timsTOF Ultra has
overcome these barriers, allowing us to explore the proteome of
individual cells at speed and unparalleled sensitivity. Thanks to
the timsTOF Ultra, single-cell analysis has reached new heights,
and I'm excited to see where this breakthrough will lead us
next.”
Bruker also introduces VistaScan software for
synchronizing TIMS ramp with the quadrupole scan to further benefit
from ion mobility information at scale. This sophisticated dynamic
linked-ramp supports the novel midia-PASEF mode, introduced
by Stefan Tenzer (doi.org/10.1101/2023.01.30.526204).
Dr. Stefan Tenzer, Professor for Quantitative Proteomics
and Head of MS Core Facility, Johannes Gutenberg University Mainz,
commented: “Our laboratory focuses on methods for quantitative
proteomics that require highest sensitivity and highest information
extraction. Together with Bruker, we have developed the novel
maximum information dia (midia) PASEF scanning acquisition mode
which offers sensitivity of data-independent acquisition (dia),
while transforming data into data-dependent acquisition (dda)-like
spectra. The midia-PASEF potential for immunopeptidomics and
phosphoproteomics is particularly exciting.”
Bruker has exclusively licensed midia-PASEF from Johannes
Gutenberg University Mainz and plans to release midia-PASEF
as a product in 2023. The timsTOF Ultra is equipped with the
required VistaScan acquisition capabilities.
In addition, the timsTOF Ultra features a further improved
dda-PASEF acquisition mode, increasing the speed to 300 Hz for up
to 18,000 collision cross-section (CCS)-enabled MS/MS spectra per
minute to enable in-depth 4D-Proteomics and 4D-Lipidomics /
4D-Metabolomics with very short LC gradients of just minutes.
Captive Spray Ionization (CSI) Ultra
Bruker’s CSI Ultra ion source, pivotal for highest nanoflow
sensitivity, has been further optimized for the timsTOF Ultra by
focussing the vortex gas at the nanospray tip to improve ion
transmission. The vortex ensures ionization across gradients for
flowrates of 50-5000 nL/min.
Dr. Christof Lenz, Head of the Core Facility Proteomics
at Universitätsmedizin G�ttingen, commented: “Installation of the
new CSI source has become even simpler, and we can now literally
exchange columns and emitters in a minute, at the same or better
performance. In addition, the novel screw-on design provides
emitter positioning and alignment without the need for manual
adjustment. I like it, and importantly, the technicians in my lab
do!”
microFlow Emitter for Higher-Flow 4D-Proteomics
Bruker’s successful VIP-HESI ion source is now equipped with new
microFlow emitter capabilities. This enables efficient ionization
at microflow and analytical LC flowrates, taking advantage of the
ultra-high sensitivity, robustness, and speed of the timsTOF
platform.
Dr. Johanna Tüshaus from the Küster lab at Technical
University Munich said: “Planning a large-scale brain proteomics
project, we needed a fast, sensitive, and robust LC-MS/MS setup.
Coupling our well-established micro-flow LC technology via the
VIP-HESI source to the timsTOF HT turned out to be a powerful
combination. It enables deep proteome coverage using short
gradients, thereby linking speed with sensitivity. The development
of the 50 µm ESI emitter was key to boost the sensitivity of our
micro-flow LC timsTOF setup.”
Dr. Mukul Midha, Ph.D., Research Scientist at the Moritz
Lab, Institute for Systems Biology, Seattle, added: “To conduct
large-scale quantitative proteomics, it is essential to have highly
stable electrospray conditions. The Bruker VIP-HESI source delivers
the reproducibility for complex plasma samples. The source
connections are straightforward, the parameters easy to optimize,
and the spray stability is superb. These improvements increase
sample throughput, achieve 100% uptime, and stable, precise protein
quantification.”
Real-Time QC Capability in Bruker ProteoScape Software with
Biognosys iRT kit
Bruker introduces 4D-Proteomics ProteoScape software for
GPU-powered real-time analysis with new capabilities for quality
control (QC) using Biognosys iRT kit. The kit contains eleven
non-naturally occurring synthetic peptides, designed for stability,
sensitivity, retention time spacing, and CCS-enablement to ensure
optimal system performance monitoring in real-time.
Dr. Eduardo Chicano-Gálvez, Head of IMIBIC Mass
Spectrometry and Molecular Imaging Unit, Reina Sofia Hospital,
University of Cordoba, Spain, said: “The Quality Control (QC)
module monitors in real time, ensuring that our platform is running
smoothly, and precious clinical samples are not lost. We are now
able to go from sample to results on large-cohort clinical
proteomics projects in a short time, maintaining sensitivity,
robustness, traceability and analytical quality.”
The Bruker ProteoScape software also integrates third-party
tools, including the BPS Novor package for fast, precise,
and accurate de novo sequencing for immunopeptidomics and
meta-proteomics, where typical specific enzymatic cleavage
information is not available. All existing Bruker PaSER software
users will be offered upgrades to Bruker ProteoScape.
SCiLS Lab Integrates MetaboScape® Annotation for Multiomics
Spatial Biology
SCiLS Lab 2024 now includes metabolite and lipid annotation
utilizing MetaboScape annotation, as well as improvements in
CCS-enabled 4D feature finding to accelerate multiomics spatial
tissue biology. SCiLS Lab 2024 offers an integrated multiomics
workflow, combining MALDI HiPLEX-IHC protein analysis with lipid,
metabolite and glycan analysis from the same tissue, including
auto-segmentation and statistical profiling.
Dr. Erin H. Seeley, Ph.D., Mass Spectrometry Imaging
Facility Director, Department of Chemistry, University of Texas at
Austin, said: “The novel 4D feature finding in SCiLS Lab focuses on
the relevant information in our CCS-enabled MALDI Imaging studies.
This greatly accelerates our MS imaging workflows and allows to
efficiently evaluate tissue samples. The integration into SCiLS Lab
makes it easier than ever to get the most out of our timsTOF
fleX.”
MetaboScape 2024 now also supports semi-quantitative analysis
utilizing stable isotopically labeled lipid standards and
integration of the Mass Spec Query Language (MassQL), a
domain-specific language driven by the metabolomics community.
OligoQuest™ 2.0 Software adds Capability for Custom
Oligonucleotide Modifications
The new release of OligoQuest 2.0 offers enhanced RNA and
oligonucleotide characterization enabling sequence confirmation of
full-length products (FLP) as well as side products by intact mass
and MS/MS analysis. Further, the OligoQuest solution confirms
modified RNA sequences and base exchanges in isomeric
oligonucleotides. Customers can customize their oligonucleotide
“alphabet” for denoting standard or customized modifications.
Dr. Fritz Schweikart, Pharmaceutical
Development/AstraZeneca, Gothenburg, commented: “With OligoQuest we
finally got a long, long waited evaluation tool in hands, that
tremendously simplifies, if not even enables us to analyze MS/MS
data in depth from our pharmaceutical Antisense oligonucleotides
(ASOs). Chemical degradation now can be analyzed at ease and manual
investigation of MS/MS data is history. The user interaction with
the tested beta version is remarkably easy and straightforward with
respect to the complex mass matching algorithms happening in the
background.”
About Bruker Corporation (Nasdaq: BRKR)
Bruker is enabling scientists to make breakthrough discoveries
and develop new applications that improve the quality of human
life. Bruker’s high performance scientific instruments and high
value analytical and diagnostic solutions enable scientists to
explore life and materials at molecular, cellular and microscopic
levels. In close cooperation with our customers, Bruker is enabling
innovation, improved productivity and customer success in life
science molecular and cell biology research, in applied and pharma
applications, in microscopy and nanoanalysis, as well as in
industrial applications. Bruker offers differentiated, high-value
life science and diagnostics systems and solutions in preclinical
imaging, clinical phenomics research, proteomics and multiomics,
spatial and single-cell biology, functional structural and
condensate biology, as well as in clinical microbiology and
molecular diagnostics. Please visit www.bruker.com.
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