Bruker and Evosep Announce Major Progress in Unbiased, Quantitative True Single-cell Proteomics
January 05 2021 - 7:00AM
Business Wire
- Breakthrough new paper by Mann-group demonstrates that
unbiased, quantitative true single-cell proteomics can address
important questions in cell biology and single-cell
pathobiology
- Measured single-cell protein and RNA levels are very
different, which implies distinct RNA and protein abundance
regulation mechanisms. Protein measurements thus yield
complementary quantitative biology information.
- Results also imply stable cellular core proteomes with
sufficient protein copy numbers to make quantitative single-cell
proteomics meaningful, compared to sparsely populated single-cell
transcriptomes.
Bruker Corporation (Nasdaq: BRKR) and Evosep today announced
major progress in high-sensitivity, quantitative true single-cell
proteomics, using a modified timsTOF Pro mass spectrometer
connected to an Evosep One low-flow chromatography system.
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Figure 1: Evosep One LC and timsTOF Pro
MS (Photo: Business Wire)
These advances have been demonstrated by the Mann-group in a
paper by A. Brunner et al., which is now available on Bioarchive at
https://www.biorxiv.org/content/10.1101/2020.12.22.423933v1. Key
results include the first untargeted and unbiased analysis of true
single cells achieving an identification depth of up to 1,500
protein groups from single FACS-sorted and individually digested
HeLa cells. This remarkable sensitivity was achieved by the
combined Evosep–timsTOF platform using crucial innovations.
Two new ultra low-flow methods on an otherwise unmodified Evosep
One system offer 100 nL/min gradients that lead to approximately 10
times higher sensitivity than gradients at 1 µL/min, confirming
theoretical expectations. These new nano-flow methods, using the
Whisper™ flow technology, have the same low overhead as the other
established Evosep One methods, and offer a throughput of either 20
or 40 samples per day. They make single-cell analysis robust, as
shown by the analysis of 420 single cells that were analyzed on the
same column. The workflow retrieved known and unexpected proteins
changing abundance upon chemically arresting the cell cycle at
discrete points.
Also crucial for achieving ultra-high true single-cell
sensitivity was a new modified timsTOF mass spectrometer that
included a new, brighter ion source with associated modified ion
optics. These precommercial innovations on the timsTOF platform
were combined with the newly developed dia-PASEF® 1 scan mode,
wherein a large percentage of all peptides are sampled in an
unbiased manner. The study provided further evidence of the
advantages of data-independent analysis (DIA) for short LC
gradients or extremely low abundance samples, such as single cells.
Even for these single cells, the quantitative reproducibility was
high in this novel Evosep–timsTOF workflow.
The authors performed an in-depth comparison to cells analyzed
by single-cell RNA sequencing by two different technologies,
allowing them to distinguish technical vs. fundamental biological
differences between the proteomes and transcriptomes. This revealed
that single cells have stable core proteomes with sufficient
protein copy numbers to permit meaningful quantitation, whereas the
transcriptome appears to behave more randomly, presumably because
of low copy numbers of many mRNA transcripts per cell.
The principal investigator behind the Bioarchive article,
Professor Matthias Mann at the Max-Planck Institute of
Biochemistry, stated: “The sensitivity and robustness to truly
analyze single cell proteomes is becoming a practical reality. We
are now able to routinely measure cohorts of single cells, and
quantitatively assess single-cell states to reveal new cell
biological information. The Evosep One and timsTOF Pro have been
pivotal to enable and scale these true single cell measurements,
making it also a suitable platform for single-cell proteomic
biomarker discovery and quantitation work.”
Bruker’s Vice President of Proteomics, Dr. Gary Kruppa, noted:
“I am very excited about the new quantitative, true single cell
study. This is another great example of what the timsTOF platform
can achieve, and a further cell biology breakthrough facilitated by
the dia-PASEF method. We anticipate providing the new ultra-high
sensitivity timsTOF technologies to early-access collaborators in
the second half of 2021 on dedicated single-cell proteomics
systems, and we plan for full commercialization in 2022.”
Dr. Nicolai Bache, a co-author on the study and Head of
Applications at Evosep, concluded: “This type of robust single cell
analysis is an important step towards enabling proteome analysis
and digital pathology in everyday clinical diagnostics. We are very
happy that the Evosep One stands to make a significant contribution
to this promising new area.”
1. ‘diaPASEF: parallel accumulation-serial fragmentation
combined with data-independent acquisition’, Meier F, Brunner AD,
Frank M, Ha A, Bludau I, Voytik E, Kaspar-Schoenefeld S, Lubeck M,
Raether O, Bache N, Aebersold R, Collins BC, R�st HL, Mann M,
Nat Methods. 2020 Dec;17(12):1229-1236. doi:
10.1038/s41592-020-00998-0.
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 research, in applied and pharma applications, in
microscopy and nanoanalysis, and in industrial applications, as
well as in cell biology, preclinical imaging, clinical phenomics
and proteomics research and clinical microbiology. For more
information: www.bruker.com.
About Evosep Evosep aims to improve quality of life and
patient care by radically innovating protein based clinical
diagnostics, initially through collaborations with world-leading
scientists about developing new technologies and solutions to make
sample separation 100 times more robust and 10 times faster than
today’s alternatives. This calls for fast sample processing and
because clinical samples, in the form of blood or biopsies, are
much more crude, very robust protocols and consumables are also
required. Read more about Evosep One and the two new nano-flow
methods on www.evosep.com.
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Bruker Media Contact: Petra Scheffer Bruker Daltonics
Marketing Communications T: +49 (421) 2205-2843 E:
petra.scheffer@bruker.com
Bruker Investor Contact: Miroslava Minkova Director of
Investor Relations & Corporate Development T: +1 (978)
663-3660, ext. 1479 E: Investor.Relations@bruker.com
Evosep Media Contact: Christian Ravnsborg, CEO T: +45 26
33 20 21 E: cr@evosep.com
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