Mass spectrometry solutions

1. 1
The world leader in serving science
Tuomo Lukkari
2019
Advanced detection with mass spectrometry

2. 2 Proprietary & Confidential
Thermo Scientific Portfolio of Mass Spectrometry
For the
scientific
rigor you
demand
Applied
Markets
Research
Markets
Orbitrap
HRAM
MS, MSn
Non-targeted analysis
Targeted analysis
QualitativeQuantitative
• Biomarker Discovery
• Proteomics
• Metabolomics
• Lipidomics
• Metabolism
• Metabolomics
• Proteomics
• Lipidomics
• Bioanalysis
• Clinical Research/
Precision Medicine
• Food Safety
• Environmental
• Clinical Research/
Forensic Toxicology
• PTM Analysis
• Proteomics
• Forensic Toxicology

3. The world leader in serving science
Tomorrow’s Quantitation with Triple Quadrupole MS

4. 4
VALUE
PERFORMANCE
TSQ Altis MS
• Mass Range m/z 5 – 2000
• Max Resolution 0.2 FWHM
• Max 30,000transitions per run
• Polarity Switching < 20 msec
• Dynamic interscantime
• 600 SRM/sec
• TNG software
• Chromeleonsupport
• 500,000:1S/N
TSQ Quantis MS
• Mass Range m/z 5 – 3000
• Max Resolution 0.4 FWHM
• Max 30,000transitions per run
• Polarity Switching < 20 msec
• Dynamic interscantime
• 600 SRM/sec
• TNG software
• Chromeleonsupport
• 150,000:1S/N
TSQ Fortis MS
• Mass Range m/z 5 – 3000
• Max Resolution 0.4 FWHM
• Max 30,000transitions per run
• Polarity Switching < 20 msec
• Dynamic interscantime
• 600 SRM/sec
• TNG software
• Chromeleonsupport
• 50,000:1S/N
Food Safety
Pharma
Clinical Research
Forensic Toxicology
Environmental and Food Safety
Clinical Research
Pharma QA/QC
Pharma/Biopharma
Environmental and Food Safety
Omics
Thermo Scientific™ TSQ Fortis™ Triple Quadrupole MS Thermo Scientific™ TSQ Quantis™ Triple Quadrupole MS Thermo Scientific™ TSQ Altis™ Triple Quadrupole MS

5. 5
TSQ Fortis Triple Quadrupole MS: Affordable Productivity, For Everyone
Segmented Quadrupoles with hyperbolic surfaces
for enhanced performance with both SRM and H-SRM (0.4 FWHM)
Enhanced dual-mode electron multiplier detector
Ensures excellent linearity and dynamic range
Matrix Separator Ion Guide (MSIG)
Ensures robustness while efficiently
transmitting the ion beam
Ion beam guide with neutral blocker
Reduces chemical background
Active collision cell with axial DC field
Facilitates more SRMs/sec
Active Ion Management Plus (AIM+) - The next step in precision design
delivers the ultimate in ion management, inception to detection, from the Thermo Scientific™
OptaMaxTM NG ion source to the enhanced electron multiplier. Incorporates segmented
quadrupoles with hyperbolic surfaces and enhanced RF Electronics to further optimize ion
management precision, reliability, speed, and reproducibility.
OptaMaxTM NG
APCI ready
NEW!
NEW!
NEW!
NEW!

6. 6
TSQ Quantis Triple Quadrupole MS: Confidence, Day After Day
Segmented Quadrupoles
with hyperbolic surfaces for enhanced performance with
both SRM and H-SRM (0.4 FWHM)
Enhanced dual-mode electron multiplier
detector
Ensures excellent linearity and dynamic range
Stacked ring ion guide (SRIG)
Increases ion flux
Ion beam guide with neutral blocker
Reduces chemical background
Active collision cell with axial DC field
Facilitates more SRMs/sec
Active Ion Management Plus (AIM+) - The next step in precision design delivers the ultimate in
ion management, inception to detection, from the OptaMax NG ion source to the enhanced electron multiplier.
Incorporates segmented quadrupoles with hyperbolic surfaces and enhanced RF Electronics to further
optimize ion management precision, reliability, speed, and reproducibility.
OptaMax NG
APCI ready
NEW!
NEW!
NEW!

7. 7
TSQ Altis Triple Quadrupole MS: Sensitivity with Robustness, No Compromises
Segmented quadrupoles
with hyperbolic surface for enhanced performance with both
SRM and H-SRM (0.2 FWHM)
Enhanced dual-mode electron multiplier detector
Ensures excellent linearity and dynamic range
Electrodynamic ion funnel (EDIF)
Increases ion flux
High capacity Ion transfer tube (HCTT)
Increases ion flux
Ion beam guide with neutral blocker
Reduces chemical background
Active collision cell with axial DC field
Facilitates more SRMs/sec
OptaMax NG
APCI ready
Active Ion Management Plus (AIM+) - The next step in precision design delivers the
ultimate in ion management, inception to detection, from the OptaMax NG ion source to the
enhanced electron multiplier. Incorporates segmented quadrupoles with hyperbolic surface and
enhanced RF Electronics to further optimize ion management precision, reliability, speed, and
reproducibility.
NEW! NEW!
NEW!

8. 9
TargetedQuantitaton
Workflows
TEXT
Sensitivity
Superior sensitivity for all molecule types
regardless of matrix complexity
Speed
Enables higher throughput, faster analysis of
complex mixtures
Robustness
Consistency in day-to-day performance,
sample-to-sample results, and user-to-user
productivity
Resolution
Unusual for QqQs, however, significant
benefits for complex mixtures, large
molecules in complex matrices
Features that Enable Every Analytical Laboratory

9. 11
TSQ Quantis MS: Demonstration of Robustness – Food Safety
125000
225000
325000
425000
525000
625000
0 50 100 150 200 250 300 350 400
AreaCounts
Number of Matrix Injections
Atrazine (QC 10μg/Kg) monitored in Leek
+20%
-20%
4.5% RSD
Atrazine QC monitored in leek for more than 400 injections with 4.5% RSD . Red lines
represent ± 20% response at 10 μg/Kg. Yellow lines show the time the system was placed in
standby mode for 12h to demonstrate consistent performance after standby period
Application Note 64971

10. 12
• Active Collision Cell with axial DC
field
• 90°cell design for noise reduction
• New main RF/DC electronics
• Analyze more compounds in the same time
window or better quantitation results with
better ion statistics (more scans across your
chromatographic peak)
• Up to 600 SRM/sec
Factors Contributing Towards Enhanced Speed
Speed
Critical feature when targeting more analytes in
the same method or when increasing throughput
by reducing the analysis time.

11. 15
TSQ Altis MS: Sensitivity, Precision and Dynamic Range
Superior Sensitivity and
Reproducibility - Fluticasone
Propionate in matrix!
25 fg on column with 4.2% CV!
UHPLC : Thermo ScientificTM VanquishTM Flex Binary UHPL System
Flow rate: 0.75 mL/min
Solvent : 75% MeOH:25%H2O with 0.01% NH4OH
MS: TSQ Altis Triple Quadrupole MS
Software: TraceFinder Software 4.1
Experimental Details
UHPLC : Thermo ScientificTM VanquishTM Flex Binary UPLC System
Flow rate: 0.4 mL/min
Solvent A: 0.5 mM NH4F in Water
Solvent B: MeOH
MS: TSQ Altis Triple Quadrupole MS
Software: TraceFinder Software 4.1
Experimental Details
Superior Sensitivity and
Reproducibility – Testosterone in
human plasma
5 fg on column with 3% CV!
For Research Use Only. Not for use in diagnostic procedures.

12. 16
TSQ Altis MS: Confident Quantitation of Challenging Analytes in Environmental Matrices
10.0 11.0 12.0 13.0 14.0
Time (min)
50
100
RelativeAbundance
AA 7310
IC-MS/MS Analysis of Glyphosate at 5 ng/L
3 % RSD for 3 replicate injections
Y = -1218.79+1766.21*X R^2 = 0.9958 W: 1/X
0 200 400 600 800 1000
Concentration of Glyphosate (ng/L)
0
500000
1000000
1500000
Area
IC-MS/MS solutions for environmental analysis
Quantitation of Glyphosate at 5 ng/L, 3% RSD
ICS 5000+
Flow rate: 0.3 mL/min
Eluent Source: Eluent Generator
Mobile Phase: KOH
MS: TSQ Altis MS
Software: Thermo Scientific™ TraceFinder™ Software 4.1
Experimental Details

13. 17
Specificity
The ability to filter the m/z of interest and obtain a better
signal to noise ratio in complex matrices.
Resolution
TSQ Altis MS – 0.2 Da FWHM
TSQ Quantis MS – 0.4 Da FWHM
TSQ Fortis MS – 0.4 Da FWHM
New segmented quadrupoles
with hyperbolic surfaces

14. 18
Superior Sensitivity with H-SRM (0.2 Da FWHM) – GPSVFPLAPSSK
%CV = 1.3
AA: 621
SN: 21
%CV = 11.3
AA: 2689
SN: 5
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Time (min)
GPS
SRM
Q1 0.7 Da FWHM
GPS
H-SRM
Q1 0.2 Da FWHM
H-SRM
LOQ = 25 ng
SRM
LOQ = 100 ng
Internal Standard
SRM
Q1 0.7 Da FWHM
%CV = 3.2
AA: 63810
GPSVFPLAPSSK - Peptide from monoclonal antibody hinge region
LC : Ultimate NCS-3500RS
Flow rate: 25µL/min
Solvent A: 2% ACN in H2O w/0.1% FA
Solvent B: 5% H20 in ACN w/0.1% FA
Experimental Details
25 ng GPSVFPLAPSSK and IS

15. 19
Q Exactive

16. 20 Proprietary & Confidential
Thermo Scientific™ Exactive™ Series Portfolio
Q Exactive
• Orbitrapanalyzer
• MassRange
m/z50 -6000
• MassAccuracy<1ppm
• Max. MassResolution
>140,000
• Scanspeed up to
12Hz MS and MS/MS
• Polarityswitching
• Hyperbolic quadrupole:
MS, ddHCD, AIF,SIM,
PRM, DIA
• SpectralMultiplexing
Q Exactive HF
• UltraHigh FieldOrbitrap
analyzer
• MassRange
m/z50 -6000
• MassAccuracy<1ppm
• Max. MassResolution
>240,000
• Scanspeed up to
18Hz MS and MS/MS
• Advanced Quadrupole
Technology (AQT)
• Advanced ActiveBeam
Guide (AABG)
• Polarityswitching
• Segmentedquadrupole:
MS, ddHCD, AIF,SIM,
PRM, DIA
• SpectralMultiplexing
• PRMdynamicRT
correction
• Opt. IntactProteinMode
• OptionalBioPharmaMode
massrange up to 8000
Exactive Plus (EMR)
• Orbitrapanalyzer
• MassRange
m/z50 -6000
• MassRange EMR:
300 -20,000
• MassAccuracy:<1ppm
• MassResolution
>140,000
• ScanSpeed up to12 Hz
• Octapoletransferfor MS
and AIF
Q Exactive Focus
• Orbitrapanalyzer
• MassRange
m/z50 -3000
• MassAccuracy<1ppm
• Max. MassResolution
>70,000
• Scanspeed up to
12Hz MS and MS/MS
• Polarityswitching
• Hyperbolic quadrupole:
MS, ddHCD, AIF,SIM,
PRM, vDIA
• Multiplexing SIMonly
• Refined workflows for
applied markets
Q Exactive HF-X
• UltraHigh FieldOrbitrap
analyzer
• MassRange
m/z50 -6000
• MassAccuracy<1ppm
• Max. MassResolution
>240,000
• Scanspeed up to
40Hz MS and MS/MS
• Highcapacitytransfertube
• Electrodynamicionfunnel
• Advanced Quadrupole
Technology (AQT)
• Advanced ActiveBeam
Guide (AABG)
• Polarityswitching
• Segmentedquadrupole:
MS, ddHCD, AIF,SIM,
PRM, DIA
• SpectralMultiplexing
• PRMdynamicRTcorrection
• Advanced ddHCD algorithm
• Optional BioPharmaMode
massrange up to 8000
with IntactProteinsettings
Q Exactive Plus
• Orbitrapanalyzer
• MassRange
m/z50 -6000
• MassAccuracy<1ppm
• Max. MassResolution
>140,000
• Scanspeed up to
12Hz MS and MS/MS
• Advanced Quadrupole
Technology (AQT)
• Advanced ActiveBeam
Guide (AABG)
• Polarityswitching
• Segmentedquadrupole:
MS, ddHCD, AIF,SIM,
PRM, DIA
• SpectralMultiplexing
• PRMdyn-RTcorrection
• Opt. IntactProteinMode
• Opt. Enh Res.Mode(280k)
• OptionalBioPharmaMode
massrange up to 8000
VALUE
PERFORMANCE

17. 21 Proprietary & Confidential
LC Orbitrap | Exactive Series Portfolio
Small to Large Molecule
Exactive Plus Q Exactive Focus Q Exactive Q Exactive Plus Q Exactive HF Q Exactive HF-X Exactive Plus EMR
Analyses MS only
Qual/Quan Screening
MS and MS/MS
Qual/Quan
Screening & Confirmation
MS only
Qual/Quan
Scan Functions Full scan
AIF scan Full Scan, AIF, SIM, PRM, vDIA
Full scan
AIF scan
Minimum Resolution
(FWHM @ m/z 200)
140,000 70,000 140,000 140,000
(280,000 with Enhanced
Resolution Option )
240,000 240,000 140,000
Mass Accuracy Internal Calibration
<1 ppm
External Calibration
< 3 ppm
Internal Calibration
<1 ppm
External Calibration
< 3 ppm
Internal Calibration
<1 ppm
External Calibration
< 3 ppm
Internal Calibration
<1 ppm
External Calibration
< 3 ppm
Internal Calibration
<1 ppm
External Calibration
< 3 ppm
Internal Calibration
<1 ppm
External Calibration
< 3 ppm
Internal Calibration
<1 ppm
External Calibration
< 3 ppm
Mass Range 50 – 6,000 50 - 3,000 50 - 6,000 50 – 6,000 50 – 6,000 50 – 6,000 300 - 20,000
Scan Speed Up to 12 Hz Up to 12 Hz Up to 12 Hz Up to 12 Hz Up to 18 Hz Up to 40 Hz Up to 12 Hz
Dynamic Range Up to 5 orders Up to 5 orders Up to 5 orders Up to 5 orders Up to 5 orders Up to 5 orders Up to 5 orders
Polarity Switching (1
full cycle under one
second)
Yes Yes Yes Yes Yes Yes Yes
Top N N/A 3 10 10 20 40 N/A
Spectra Multiplexing N/A SIM SIM & PRM SIM & PRM SIM & PRM SIM & PRM N/A
Protein Mode N/A N/A N/A Optional Optional BioPharma Standard

18. 22 Proprietary & Confidential
Q Exactive: Orbitrap
C-Trap
HV Lens Stack
Split Lens
Orbitrap
S-Lens
Capillary
RF lens (MP0)
Lens 0
Collision cell (MP3)
Flatapole
(MP1)
Transfer
Octapole (MP2)
Quad Exit Lens
Quadropole
TK Lens
Electrometer
Lens 6

19. 23 Proprietary & Confidential
The Orbitrap

20. 25 Proprietary & Confidential
zm
k
/

• Frequency of axial
oscillations of each ring
induces an image current on
split outer electrodes
• Multiple ions in the Orbitrap
generate a complex signal
whose frequencies are
determined using a Fourier
Transformation
• Lighter ions enter Orbitrap earlier therefore they are squeezed closer to the central electrode than
heavier ions
• An image current transient of these oscillations is converted to a frequency spectrum
using a Fourier transform similar to the approach used in FTICR
• eFT: enhanced FT transformation algorithm for high resolution at the same transient time
& Higher Resolution in shorter detection time
Detection of ions in the Orbitrap

21. 26 Proprietary & Confidential
RelativeAbundance
222.0 222.1 222.2 222.3
m/z
0
10
20
30
40
50
60
70
80
90
100
222.1263
Resolution 17.500 is not enough to
distinguish between
Carbofuran 62.1ppm
Formetanate 11.7ppm
Name
Molecular
Formula
[M+H]+
Carbofuran C12H15NO3 222.1125
Formetanate C11H15N3O2 222.1237
RESOLUTION 17.500
High Resolution Means Specificity

22. 27 Proprietary & Confidential
RelativeAbundance
222.0 222.1 222.2 222.3
m/z
0
10
20
30
40
50
60
70
80
90
100
222.1238
222.1124
With resolution of 35.000 the two
compounds are partially separated
Carbofuran 0.45ppm
Formetanate 0.45ppm
Name
Molecular
Formula
[M+H]+
Carbofuran C12H15NO3 222.1125
Formetanate C11H15N3O2 222.1237
RESOLUTION 35.000
High Resolution Means Specificity

23. 28 Proprietary & Confidential
RelativeAbundance
222.0 222.1 222.2 222.3
m/z
0
10
20
30
40
50
60
70
80
90
100
222.1238
222.1129
Name
Molecular
Formula
[M+H]+
Carbofuran C12H15NO3 222.1125
Formetanate C11H15N3O2 222.1237
At 70.000 the two compounds are
completely separated
RESOLUTION 70.000
High Resolution Means Specificity

24. 29 Proprietary & Confidential
Resolution: QE HF, QE and State-of-Art QToFs
0
50000
100000
150000
200000
250000
300000
350000
100 200 300 400 500 600 700 800 900 1000
Resolution(FWHM)
Q Exactive HF Q Exactive
Q Exactive Focus AB Sciex Triple Tof 5600
Agilent 6540 Bruker Maxis
Waters Synapt G2
m/z
Much higher resolution at
low m/z range

25. 31 Proprietary & Confidential
Peak intensity (area) variation during 900 injections (blue) with according mass
accuracy (peak apex scan, red)
RSD = 11.9%

26. 34 Proprietary & Confidential
Summary: HRAM and QQQ – A Comparison
HRAM QQQ Comment
Sensitivity + + QQQ can be more sensitive
Selectivity + +
HRAM can use intact mass or accurate mass also on
fragment
Targeted Analysis <10
compounds + + QQQ and HRAM are good to use
Targeted Analysis <100
compounds + + QQQ and HRAM are good to use
Targeted Analysis >100
compounds
+ + QQQ better choice depending on matrix and Scan mode in
HRAM*
Ease of use + + QQQ requires optimization for each compound
HRAM requires calibration each week (easy and fast)
Retrospective Analysis + - Only possible with HRAM - untargeted analysis
Unknown Screening + - Only possible with HRAM - untargeted analysis
* For SIM mode, which is supposedly the most sensitive mode > 100 targets is
too many for good data quality

27. 36 Proprietary & Confidential
ORBITRAP FUSION MS
ORBITRAP FUSION LUMOS
MS
Hybrid/Tribrid Portfolio - 2018
ORBITRAP ELITE MS
PRICE
PERFORMANCE,VERSATILITY,USABILITY
ADVANCED HYBRID
Scan Rate: 8-10 Hz
Dissociations: CID, HCD, ETD
MSn
240,000 FWHM
THE ORIGINAL TRIBRID
Scan Rate: 30-40 Hz
Dissociations: CID, HCD, ETD,
EThcD
MSn
500,000 FWHM
SPS
IC
PREMIUM TRIBRID
HCTT and EDIF
AQT
Advance Vacuum Technology
APD
Scan Rate: 30-40 Hz
Dissociations: CID, HCD, ETD HD,
EThcD HD, UVPD
MSn
500,000, 1M FWHM
SPS
IC
Better
Best
Good

28. 37 Proprietary & Confidential
Orbitrap Fusion Lumos Tribrid Mass Spectrometer (Fusion Features)
Increases ion
flux into the mass
spectrometer
Focuses ions after HCTT;
Broad tuning curves
Segmented design improves
transmission at higher
resolution; symmetric transmission
across the window
Enables parallel
analysis; performs HCD
at any MSn stage
Improved dynamic range and
detection limit of ETD event
Based on Townsend
discharge; reliable and
easy to use
Offers resolution >500K FWH
and scan rates up to 20Hz at
15K FWHM
MSn and sensitive mass analysis of four
fragmentation types: CID, HCD, ETD
and EThcD
Reduces pressure in UHV
region, improving transmission
to the Orbitrap analyzer
Electrodynamic
Ion Funnel
High Capacity
Transfer Tube
Advanced Vacuum
Technology
ETD HD
Prevents neutrals and
high velocity clusters
from entering mass resolving
quadrupole
Advanced Active Ion
Beam Guide
Advanced Quadrupole
Technology
EASY ETD Source
Ultra-High Field Orbitrap
Analyzer
Dual-Pressure
Linear Ion Trap
Ion Routing
Multipole
Original Ion
transfer tube
ETD
15 Hz @ 15k
D30