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Landmarks in the last 50 years of British Mass SpectrometryMass Spectrometry
Mike Morris
MS Research Department, Waters Corporation, Wilmslow
Department of Surgery and Cancer, Imperial College, London
©2014 Waters Corporation 1
BMSS Annual MeetingAlderley Park, April 2014
AcknowledgementsAcknowledgements
Martin Elliott
Gareth Brenton
F k P ll Frank Pullen
Alison Ashcroft
John Monaghan
…..and the surviving Aston Medal recipients……
©2014 Waters Corporation 2
OverviewOverview
Origins of BMSS
A reflection of landmarks through the Aston Medal winners
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Commercial DriversCommercial Drivers
©2014 Waters Corporation 5
Journal PublishersJournal Publishers
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Origins of BMSS
Institute of Petroleum
Origins of BMSS
MS Discussion Group
Mass Spectroscopy Group13th M 1964— 13th May 1964
— Maccoll & Elliott
British Mass Spectroscopy Group— 1974
BMSS— 1981
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1981
Meetings aren't what they used to beMeetings aren t what they used to be….
AEI MS Users Meeting - 1967?
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IMSC 1985 SwanseaIMSC 1985 - Swansea
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F W AstonF W Aston
University of Birmingham— Studies of discharge tubes
C di h L b t Cavendish Laboratory— Worked with Thomson— Sector instrumentationSector instrumentation
o Momentum AND Energy Focusing— Accurate masses of natural isotopes
o Whole number rule
Nobel Prize for Chemistry 1922 Nobel Prize for Chemistry 1922
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Citation for the Aston MedalCitation for the Aston Medal
…..to be given to individuals deserving special recognition …..to be given to individuals deserving special recognition
by reason of their outstanding contributions to knowledge
i th bi l i l h i l i i th ti l in the biological, chemical, engineering, mathematical,
medical, or physical sciences relating directly to mass
spectrometry.
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Aston Medal WinnersAston Medal Winners
Alan Maccoll 18th Annual Conference, Nottingham 1989John Beynon 19th Annual Conference, UCL, 1990Brian Green 22nd Annual Conference, Swansea 1996Keith Jennings 23rd Annual Conference, Warwick 1998Dai Games LC-MS Meeting, Cambridge 2000C li Pilli IMSC Edi b h 2003Colin Pillinger IMSC, Edinburgh 2003Tom Preston 28th Annual Conference, York 2005John Todd IMSC Prague 2006John Todd IMSC, Prague 2006Robert Bateman 30th Annual Conference, York 2008Richard Evershed 31st Annual Conference, Cardiff 2010Richard Evershed 31 Annual Conference, Cardiff 2010Carol Robinson 32nd Annual Conference, Cardiff 2011Tony Stace 34th Annual Conference, Eastbourne 2013
©2014 Waters Corporation 13
y ,
1989 Allan Maccoll1989 - Allan Maccoll
University College, London— Lecturer (1947)— Reader (1953)
P f (1963)— Professor (1963)— Emeritus Professor (1981)
Founding Editor - Organic Mass Spectrometry
Founding Editor - European Mass S t tSpectrometry
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Organic Mass SpectrometryOrganic Mass Spectrometry
Founded 1968
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European Journal of Mass SpectrometryEuropean Journal of Mass Spectrometry
Founded 1995
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1990 John Beynon1990 - John Beynon
ICI Blackley— MS8 (Robert Craig)
Purdue UniversityPurdue University— RMH2— MS9
Royal Society Research Unit, Swansea— ZAB
Founding Editor - Rapid Communications in Mass Spectrometryin Mass Spectrometry
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IMSF Thomson Medal 1985
Molecular Formula DeterminationMolecular Formula Determination
'(mass spectrometers) can also be used for qualitative analysis of unknown substances'
'Since the mass spectrometer can Since the mass spectrometer can handle milligram quantities of material…'
'from an analytical point of view 'from an analytical point of view, the molecular weight is perhaps the most useful single item of
f b bl binformation obtainable by mass spectrometry…'
'…if the mass of any ion is …if the mass of any ion is measured with sufficient precision, its elemental composition can immediately be deduced '
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immediately be deduced…
Ion Kinetic Energy SpectroscopyIon Kinetic Energy Spectroscopy
Metastable peak from loss of CO Metastable peak from loss of CO from phenol molecular ion
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Rapid Communications in Mass SpectrometryRapid Communications in Mass Spectrometry
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1996 Brian Green1996 - Brian Green
Metropolitan Vickers / AEI (1958)— MS9
o First unit - Shell AmsterdamMaccollo Maccoll
o Yale
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SabbaticalSabbatical…..
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1996 Brian Green1996 - Brian Green
Metropolitan Vickers / AEI (1958)— MS9
o First unit - Shell AmsterdamMaccollo Maccoll
o Yale
VG Micromass (1972)— First scanning accurate mass
dmeasurements into data systems.— Laminated magnets— Dioxin methodologiesDioxin methodologies— ESI of haemoglobins
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Laminated MagnetsLaminated Magnets
Higher mass range— Less saturation
L h t i Lower hysteresis— 4x less than solid core— Faster scanningFaster scanning— No degradation in mass
resolution
Lower stray fields— 8x less than solid core— 8x less than solid core— Less interference
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HaemoglobinopathiesHaemoglobinopathies
Determination of amino acid sequence in variant haemoglobins.
Over 1 000 reported variants e g Over 1,000 reported variants e.g. Sickle (6 GluVal, m-30Da)
Of the 4,550 samples analysed, 321 different variants have been analysed (151 -chain, 162 -chain, analysed (151 chain, 162 chain, 1 -chain, 2G chain, 5 hybrids
3 l i h b 73 novel mutations have been discovered since 1988 (44 -chain, 29 -chain).
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1998 Keith Jennings1998 - Keith Jennings
NRC Ottawa
University of SheffieldMetastable studies— Metastable studies
— Collision-induced dissociation
University of Warwick— CID
Metastable studies— Metastable studies— MS/MS
ACS Field & Franklin Award ASMS Distinguished Contributions
IMSF Th M d l 1985
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IMSF Thomson Medal 1985
Fragmentation and Metastable Ion StudiesFragmentation and Metastable Ion Studies
Studies of fragmentation - AEI MS10 & MS9 (early 1960s)— Metastable fragmentation — m* = m2
2/m1
Increase fragmentation through introduction of gas— Increase fragmentation through introduction of gas
CID & SID - Four sector instruments (1980s)CID & SID Four sector instruments (1980s)
Application of mass spectrometry in Life Sciences (from 1994)
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An unlikely collection of charactersAn unlikely collection of characters……
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2000 Dai Games2000 - Dai Games
King's College. London
McMaster University, Hamilton
University of Wales, Cardiff
Swansea University Swansea University
Edit i Chi f Bi di l d Editor-in-Chief - Biomedical and Environmental Mass Spectrometry
IMSF Thomson Medal 1997
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Field Desorption & Field IonisationField Desorption & Field Ionisation
Low-energy ionisation techniques
Promote molecular ion formation
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Hyphentaed MSHyphentaed MS
Coupling of chromatography and mass spectrometry— LC— SFC
CEC— CEC— HSCC
Finnigan moving belt interface (Bill McFadden)— EI— Library-searchable spectra
BMSS LC MS courses BMSS LC-MS courses
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Biomedical & Environmental Mass SpectrometrySpectrometry
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Proudest acheivement??Proudest acheivement??
The students!
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2003 Colin Pillinger2003 - Colin Pillinger
University of Bristol
University of Cambridge
Open University
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Martian MeteoritesMartian Meteorites
Studies of astronomical samples
C fi ti f th Confirmation of the presence of martian meteorites on earth— SensitivitySensitivity— Isotope ratio measurements
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Beagle 2Beagle 2
Consortium Leader & Lead Scientist
Communication lost - Christmas D 2003Day 2003
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RosettaRosetta
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2005 Tom Preston2005 - Tom Preston
Stable Isotope Biochemistry Laboratory SUERCLaboratory, SUERC
Professor of Stable Isotope Biochemistry University of GlasgowBiochemistry, University of Glasgow
Adjunct Professor, St John’s Research Institute Bangalore IndiaInstitute, Bangalore, India
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EA-IRMS : the first CF-IRMS instrument
Aquatic biogeochemistryTerrestrial productivityAgriculture/soils
Nick Owens and Tom Preston about to hoist the
Agriculture/soilsEcologyForensicsFisheries Management Nick Owens and Tom Preston about to hoist the
first commercial EA-IRMS (Europa Scientific) onto the RRS Challenger, Troon, July 1987.
Fisheries ManagementPlant water use efficiency
etc…
Non-invasive 13C breath tests
Urea Breath testGastric emptyingLiver functionLiver functionOro-caecal transitSmall bowel overgrowthFat digestionFat digestionStarch digestion etc
Raw Data and Seigel Curve FitRaw Data and Seigel Curve Fit
50 060.070.080.0
R 20.025.0
30.0
-1
CumulativeS i l Fit
0.010.020.030.040.050.0
cPD
R
0.05.0
10.015.0
PDR
h Seigel FitRaw DataCurve Fit
0.0 2.0 4.0 6.0
Time (h)
AP2003 13C breath test IRMS, Analytical Precision, UK
GC-combustion-IRMS: low enrichment, low concentration
GC-C-IRMS of short chain fatty acid production fromfatty acid production from
dietary fibreVolatiles in a helium carrier are
t d b GC d b t dseparated by GC and combusted on line to CO2
13C-labelled cereals
GC-C-IRMS analysis of VFA
1.20E-09
1.40E-09
1 30E 02
1.35E-02
1.40E-02
A t t3-methylvalerate
6.00E-10
8.00E-10
1.00E-09
Maj
or B
eam
1.15E-02
1.20E-02
1.25E-02
1.30E-02
45:4
4 ra
tio
Acetate
PropionateButyrate Valerate
0.00E+00
2.00E-10
4.00E-10
580 680 780 880 980 1080 1180
Time (s)
1.00E-02
1.05E-02
1.10E-02
e (s)
In-house GC-combustion interface, 20-20 IRMS, SerCon, Crewe, UK
Body composition and total energy expenditure
Obesity and type II diabetes
Thermo Fisher Delta V Advantage, IAEA Collaborating Centre for Nutrition, St John’s Research Institute, Bangalore
2006 John Todd2006 - John Todd
Leeds University
Yale University
University of Kent at Canterbury
IMSF Thomson Medal 1997
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Ion TrapsIon Traps
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RosettaRosetta
Conceived 1994
Launched 02-Mar-2004— Dormant for 2.5 years— Woke up in January 2014— Now switching on instrumentsNow switching on instruments
Scheduled comet landing November 2014
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MODULUS Ptolemy Experiment— Methods of Determining and
Understanding Light elements from Unequivocal Stable from Unequivocal Stable isotope compositions
— Accurate isotope measurement 12 250Thmeasurement 12-250Th
— 250x330x110mm— 4.5kg— <10W power consumption
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2008 Bob Bateman2008 - Bob Bateman
Cambridge University
AEI (1969)
VG Micromass (1973)
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VG 7070KVG 7070K
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VG ZAB 2FVG ZAB 2F
Reverse geometry - collision cell for ion activation
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VG 70-70 & 70E VG 70-70 & 70E
Non-normal entry into same magnet— Half angle, double radius, increase mass range 4x
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VG AutospecVG Autospec
Tri-sector EBEconfiguration
16 bit ADC at400 kHz sampling rate
(16 bit ADC at500 kHz sampling rate)500 kHz sampling rate)
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Autospec 6FAutospec 6F
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oaTOFoaTOF
SensitivitySpeedSize
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SizeSimplicityAutoSpec-TOF
Q-ToFQ-ToF
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Synapt HDMSIMS MSIMS-MS
NAF_03.raw : 1
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2010 Richard Evershed2010 - Richard Evershed
Ph.D. Keele
University of Bristol (1981)
University of Liverpool (1984)
University of Bristol (1993)— Chair of Biogeochemistry— Chair of Biogeochemistry
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2010 Richard Evershed2010 - Richard Evershed
Ph.D. Keele
University of Bristol (1981)
University of Liverpool (1984)
University of Bristol (1993)— Chair of Biogeochemistry— Chair of Biogeochemistry
“Pioneered the development and papplication of molecular and isotopic techniques to study environments of the past and present”
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past and present
Analytical chemistry of molecules past and present
BIOGEOCHEMISTRY
Role of microbes and invertebrates in soil
i tt liorganic matter cycling
CHROMATOGRAPHYORGANIC
GEOCHEMISTRYBIOMOLECULAR
PALAEONTOLOGY CHROMATOGRAPHYMASS SPECTROMETRY
Molecular and stable isotopic compositions
Reconstructing past climate and
environments (peat bogs and lakes)
Fossilisation processes and
palaeoenvironmentalinformation isotopic compositions (peat bogs and lakes)information
BIOMOLECULAR ARCHAEOLOGY
Reconstructing human activity in the past
Organic Chemistry Archaeology
O
CO2H H
OH
CH2OH
OH CO2H
CO2H
Pistacia resin FrankincenseCO2H
Birch bark products Heated resin product2
Coniferous resin
HOHOH
HOH
Widely occurring sterol Manure indicators in soils Petroleum bitumenWidely occurring sterol Manure indicators in soils
Plant epicuticular waxes
O
O
OOH
Petroleum bitumen
Common fatty acid
O
Beeswax O
OHIsoprenoid fatty acid Natural dyesyp y
Oxidised fatty acid
y
Macromolecule building blocks: collagen, aDNA, carbohydrates, etc.Thermally altered fatty acids
ge s
oil Resins, tars,
pitches and bitumensm
etic
og b
ody
Bro
nze
A
oman
cos Bo
B Ro
ents Plant remains
MummiesMummies
ic p
igm
e
ody O
rgan
Bog
bo
ryArt objects
hic
potte
rj
Skeletal remainsMary Rose Neo
lith
Synergies in structures and isotopic compositions
O
OH
Fatty acid
CH3 Compound-specific isotopes and biomolecular
HCO2H
archaeology12C, 13C (metabolism/biochemical pathways)***** 14C (radiocarbon dating)*
Amino acid
NH214C (radiocarbon dating)1H, 2H (temperature/precipitation)*16O, 18O (temperature/precipitation)14N, 15N (trophic interactions/metabolism)*
University Research Centre & NERC Facility for molecular and light stable isotope MS analysesa d g t stab e sotope S a a yses3 x GC/MS 6 x GC-C-IRMSLC/MS/MS LC-IRMSLC/MS/MS LC-IRMSHRMS
New accelerator mass spectrometer for UK science for 2015
2011 Carol Robinson2011 - Carol Robinson
M.Sc. Swansea (Beynon)
Ph.D. Cambridge (Williams)
Oxford University (1991)
Cambridge University (2001)
Oxford University (2009)
Biemann Medal (2003) DBE (2013)
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( 0 3)
2012 Carol Robinson2012 - Carol Robinson
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Pfizer
I t t G EL iIntact GroEL 14-mer survives
AA Rostom, CV Robinson. J. Am. Chem. Soc. 121:4718‐4719, 1999.
t = 5 ms
t =15 mst =15 ms
t=30 ms
Ruotolo, Science 2005
First mass spectrum of a membrane complex
Barrera et al Science 2008, 321: 243
Mass spectrum of intact ATPase from Thermus thermophilusThermus thermophilus
Zhou et al 334,380 Science 2011
2013 Tony Stace2013 - Tony Stace
Ph.D. Essex
Sussex University (1974)
Southampton University (1977)
Sussex University (1983)
Nottingham University (2004)
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Cluster studiesCluster studies
Cluster fragmentation patterns— Solvation of protons in solvent— Formation of proton hydrates in ionosphere
Metal multi-cation complexes in the gas phase
Coulomb fission from multiple-charged cations— Applications in cloud formation to nebuliser delivery
©2014 Waters Corporation 71
Spectroscopy of clusersSpectroscopy of clusers
Cold trap techniques — Visible / UV laser spectroscopy metal dication complexes
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Most newcomers to mass spectrometry in the last 10 Most newcomers to mass spectrometry in the last 10
years will have little concept of the difficulties faced
in obtaining the mass spectra of four solid samples
during a working day……g g y
Keith Jennings, 2012
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Concluding thoughtsConcluding thoughts
Mass spectrometry has changed enormously in the last half century
N i ti t hi t f d il li Now in routine use, touching many aspects of our daily lives
Where will we be 50 years from now? Where will we be 50 years from now?
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