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Nuevas fronteras en
Investigación con el
nuevo ICP-MS/MS
Agilent 8800
Transformando la
tecnología en ICP-MS
1 March 20, 2014
Rubén García Especialista de Producto, Agilent Technologies
New 8800 ICP-MS/MS - Outline
1. Introduction to the new 8800 ICP Triple Quad
2. Key technology in the 8800
3. Unique modes of operation with MS/MS
4. 8800 performance in some key applications
2 March 20, 2014
Agilent 8800 ICP-MS/MS
World’s first Triple Quadrupole ICP-MS (tandem MS)
New modes of operation and performance not possible with quadrupole ICP-MS
Joins the Agilent 7700, Agilent’s high performance quadrupole ICP-MS system
Unique capabilities, based on proven technology (shared sample introduction, HMI,
many consumables, robustness, key hardware components and software platform)
Agilent 7700
Single-quad
(ICP-QMS)
New Agilent 8800
ICP-MS/MS
3
Why ICP-MS/MS?
March 20, 2014
New Agilent 7900
Single-quad (ICP-
QMS)
Interference Removal in Quadrupole ICP-MS
7700 Series with He mode is well-known for accurate multi-element analysis of
unknown, variable and high-matrix samples (enviro, food, clinical, pharma…)
He mode on 7700 is effective for ALL polyatomic interferences at low- and sub-ppb levels
BUT He mode can’t remove/avoid isobaric overlaps (e.g. 40Ar on 40Ca) or doubly-
charged interferences (e.g. 150Sm++ and 150Nd++ on 75As+). Reaction mode can…
Also, reactive gases can give more complete removal of interferences when ppt
level detection is needed (H2 and NH3 commonly used in semicon applications)
4
Complex matrix in no gas (above) and
He mode (right, with standard inset)
7700 removes ALL polyatomics
7700 - He mode for Polyatomic Interferences
No gas mode (left) and He mode (below)
March 20, 2014
Reaction Gases for ICP-QMS and ICP-MS/MS
Limitations of reactive cell gases in quadrupole ICP-MS are well-
documented:
All ions enter the cell, affecting reaction processes. Gives variable results when
sample type/matrix or co-existing analytes change
Product ions from matrix or other elements can create new overlaps on analytes
Analyte product ions can be overlapped by other analytes/matrix elements
Tandem MS configuration eliminates the variability caused by co-existing
elements and changing matrix components, as Q1 rejects all masses
except the target analyte and on-mass interferences
Results are consistent and reliable
5
Agilent 8800 ICP-MS/MS matches 7700
performance in He mode, but also
offers controlled and consistent MS/MS
operation in reaction mode.
March 20, 2014
8800 ICP-QQQ Key Product Hardware
6 March 20, 2014
Low flow
sample
introduction
system
High matrix
introduction
(HMI)
technology
Fast, frequency-
matching 27MHz
RF generator Efficient twin-turbo
vacuum system
Dual conical Extraction and
Omega lens focuses ions
across the mass range
9 orders
dynamic range
electron
multiplier (EM)
detector
Analyzer quad Q2:
High frequency
hyperbolic quadrupole
– selects ions that
pass to detector
High-transmission,
matrix tolerant interface
First quad Q1: High frequency
hyperbolic quadrupole mass filter –
selects ions that enter the cell
3rd generation collision/
reaction cell (ORS3)
with 4 cell gas lines
Peltier-
cooled
spray
chamber
Robust, high-temperature
plasma ion source
Introduction to INORGANIC MS/MS
This is the very first and only instrument to make MS/MS
technology available to inorganic analytical chemistry
Completely novel
Allows the determination of elements that would otherwise be
“difficult” for quadrupole (and SF) ICP-MS
Elements such as Sulphur and Phosphorus become “laughably”
easy!
Uniquely, Isotopic information is retained when using reaction
mode
March 20, 2014 7
QQQ in Organic MS
170 210 250 290
210
222
268 280 165
Quad Mass Filter (Q3) Quad Mass Filter (Q1)
Collision Cell
Spectrum with
background
ions (from ESI)
Q1 lets only
target ion 210
pass through
190 210
210
Collision cell
breaks ion 210
apart
150 170 190 210
210 158
191
Q3 monitors only
characteristic
fragments 158
and 191 from ion
210 for quant and
qual.
160
158
190
191
no chemical background
QQQ in Inorganic
Unlike Organic QQQ we do not split the parent ion into product
ions
Not trying to split the atom!
March 20, 2014 9
ICP-MS/MS: How Does it Work?
ICP (plasma) and Interface: Forms and
extracts ions from the sample (just like the
7700 or 7900)
EM (detector): Measures the
ions that are scanned by Q2
(just like the 7700)
10
Q1 – controls ions
that enter the cell
• Consistent reactions
even if sample
composition changes
ORS3 – collision/
reaction gas added
• Ions react and are
neutralized or moved
• Product ions are formed
Q2 – selects the
target analyte mass
• Interference-free analyte
ions passed to EM
March 20, 2014
Q1 – controls ions
that enter the cell
• Consistent reactions
even if sample
composition changes
ORS3 – collision/
reaction gas added
• Ions react and are
neutralized or moved
• Product ions are formed
Q2 – selects the
target analyte mass
• Interference-free analyte
ions passed to EM
ICP-MS/MS: How Does it Work?
ICP (plasma) and Interface:
Forms and extracts ions from
the sample (just like the 7700)
EM (detector): Measures the
ions that are scanned by Q2
(just like the 7700)
Unique aspect of 8800 is MS/MS Mode
• Q1 controls the ions that enter the cell
With MS/MS, reaction processes in the cell
are consistent and predictable, even if
sample composition is complex or variable
• Consistent cell conditions means reaction
mode method development is much
easier than on single quad (same method
can be used for different samples)
11 March 20, 2014
Operational Modes
• Q1 opens allowing all ions into ORS3
Single Quad
• Q1 allows a range of m/ƶ into ORS3 Single Quad with Band Pass Filter
• Both Q1 and Q2 set to same mass MS/MS – On
Mass
• Q1 and Q2 set to different masses MS/MS – Mass
Shift
Unique to the 8800
Quad Cell m/z
Ions
Reaction Gas
M0
Single Quad Configuration Analyte (unreactive) Interference (reactive)
M1
If the ions of mass M1 react with the gas to form ions of mass M0, they act as new
interference.
ICP-QQQ-MS Operating Principles
Q2 Cell
Ions
Q1
(set to M0)
Reaction Gas
m/z of Q2
M0
QQQ Configuration
M0
M1
Analyte (unreactive) Interference (reactive)
ICP-QQQ-MS Operating Principles
Quad Cell
Ions
Reaction Gas
M0
Single Quad Configuration
-Mass Shift Method- Analyte (reactive) Interference
M2
If there are unreactive ions of M2, the mass shift method does not work.
ICP-QQQ-MS Operating Principles
M0
QQQ Configuration
-Mass Shift Method- Analyte (reactive) Interference
M2
Q2 Cell
Ions
Q1
(set to M0)
Reaction Gas
M0
m/z of Q2
ICP-QQQ-MS Operating Principles
Which Applications Need ICP-MS/MS?
Applications that may benefit from ICP-MS/MS with Agilent 8800.
• Environmental: As and Se analysis in presence of REE. REE++ overlap As+ & Se+.
• High purity chemical: Ti and Zn analysis in semiconductor grade H2SO4 / H3PO4. S and P
polyatomic ions such as SO+, PO+ and SO2+ overlap Ti+ and Zn+.
• Material: P in Si matrix. SiH+ and SiH2+ overlap on P+.
• Material: As in Co matrix. Fe and Ni in Ca matrix. MoO+/MoOH+ interference on Cd.
• Geology: REE analysis. BaO and REE-O ion overlap other REE.
• Food: Sulfur Isotope Ratio analysis.
• Clinical: Ti and Cr analysis in blood and serum. S , P and C matrix.
• Nuclear: 129Iodine analysis. 129Xe atomic isobar interference.
• Nuclear: Long lived radio nuclide analysis. 93Zr, 99Tc, 135Cs and so on.
• Life Science: Trace Sulfur for protein/peptide quantification.
• …
17
Mercury Interference on Lead
18
Pb measurement - Mercury Reaction with Ammonia Detailed version presented at Goldschmidt Conference
Mercury undergoes a charge-transfer reaction:
Hg+ + NH3 Hg0 + NH3+
(NH3+ + NH3 NH4
+ + “NH2”)
This reaction is very rapid and essentially 100% efficient
This means that 204Hg could be eliminated as an overlap on 204Pb if Pb does not react in the same way
This is an important measurement in geochronological
measurements or isotope tracer studies (e.g. spike a specific
isotope and trace protein interaction)
Pb, Tl at 1ppb in presence of 10ppb Hg
21
No Cell Gas
Hg
interference
on 204Pb
isotope
Pb Isotopes
do not match
theoretical
template
Impossible to
measure the
natural Pb
contribution
204Pb Clearly overlapped by 204Hg
Pb, Tl at 1ppb in presence of 10ppb Hg + 100ppb REE’s
25
NH3 Cell
Gas NOT
USING
MS/MS
All isotope
patterns a
complete
mess from
REE cluster
ions
Mass Cluster
204 (Pb) Eu(NH3)3
Yb(NH3)2
Ce(NH3)4
205 (Tl) Yb(NH3)2
Gd(NH3)3
206 (Pb) Yb(NH3)2
Lu(NH2)2
La(NH3)4
Ce(NH3)4
Gd(NH3)3
207 (Pb) La(NH3)4
Yb(NH3)2
Gd(NH3)3
208 (Pb) Ce(NH3)4
GdNH(NH3)2
TbNH(NH3)2
Yb(NH3)2
Gd(NH3)3
Pb, Tl at 1ppb in presence of 10ppb Hg + 100ppb REE’s
26
MS/MS NH3
Cell Gas
All isotope
patterns
match theory
again.
MS/MS
controls the
reaction
chemistry
Pb, Tl at 1ppb in presence of 10ppb Hg + 100ppb REE’s
27
MS/MS NH3
Cell Gas
All isotope
patterns
match theory
again.
MS/MS
controls the
reaction
chemistry
As 204Hg isotope is more abundant than 204Pb; “real” interference is ~5x higher
MS/MS – On Mass Measurement - Pb
All none on mass interferences rejected by Q1
Mercury-based interferences react with ammonia through charge transfer and are neutralised. The neutral atom is pumped to “waste” in vacuum chamber
28
< 204 >Hg+
< 204 >Pb+
All REE’s+
204Hg+
204Pb+
< 204 >Hg+
< 204 >Pb+
All REE’s+
204Hg0
204Pb+
Reaction gas
NH3
1st Quad (Q1) Rejects ALL masses except
analyte (204Pb) and on-mass
interferences (204Hg+
ORS3 Cell Converts Hg+
to Hg0
Product
2nd Quad (Q2) Set at Q1
Rejects all cell
formed ions and
neutral species from m/z 204
Tungsten Interference on Mercury
29
MS/MS – On Mass Measurement - Hg
All none on mass Hg and W-based interferences rejected by Q1
Tungsten-based interferences react with oxygen and are mass shifted away from selected Hg isotopes
30
195 196 197 198 199 200 201 202 203 204
195 196 197 198 199 200 201 202 203 204
MS/MS for Hg with O2 Cell Gas
MS/MS On-Mass Mode – separation of Hg+ from WO+ overlap
Spectrum of 2ppb Hg (top) and 5ppm
W (bottom) on the same scale.
WO+/WOH+ overlap is reduced to
<10cps at 201Hg
31
Molybdenum Interference on Cadmium
32
Molybdenum Oxide Interference
Molybdenum is a fairly prevalent element within the environment
• The 54th most abundant element in the Earth's crust and the 25th most abundant element in the oceans
It is an alloying agent in many steels
It is an important cofactor and constituent of over 50 enzymes
• An important micronutrient
Cadmium is toxic and (usually) present at low concentration
It is important to be able to reliably measure Cd at low concentrations in the presence of Mo
Mo has several isotopes, all forming interferences on Cd
SF ICP-MS requires resolution of >32,000
MoO Interference
34
No Cell Gas
1mg/Kg Mo
MoO
interference
on all
available Cd
isotopes
MoO Interference
35
No Cell Gas
1mg/Kg Mo
+ 1ug/Kg Cd
MoO
interference
on all
available Cd
isotopes
Peak pattern
does not fit
MoO Interference
36
MS/MS NH3
Cell Gas
1mg/Kg Mo
+ 1ug/Kg Cd
MoO
interference
completely
removed
Excellent fit
for all Cd
isotopes
1,028
1,119
1,565
2,075
1,097
0,991 0,992 1,003 0,99
0,0005 0
0,5
1
1,5
2
2,5
20ppb Mo + 1ppb Cd 100ppb Mo + 1ppb Cd 500ppb Mo + 1ppb Cd 1000ppb Mo + 1ppb Cd 1000ppb Mo
No Gas
MS/MS NH3
Cadmium: Recovery in Variable Mo Matrix
37
Special Alloy Test, Trace Mg with Ti
38
Ti++ Interference on Mg in Specialist Alloy
Special Ti-based alloy – Ti concentration ~0.5g l-1 in Aqua
Regia; Mg very low (<1ppb in solution) but Ti++ biases data
39
No Cell Gas Ammonia Cell Gas
Isobaric interference removal: I-129
Rest of ions
including I-127 Removal of Xe
O2 as reaction gas and MS/MS- on mass
Reaction
gas (O2)
Xe129
I129
I+
Xe
Isobaric interference removal: I-129
O2 completely removes
the Xe and now the I-129
can be detected at
ultratrace levels
Without interference removal
, the isotopic pattern of Xe
interferres I-219 (and I-127)
Isobaric interference removal: I-129
Detection limit obtained using the calibration curve:
0.025ppt.
Very low Blank Equivalent Concentration: 0.25ppt
due to the complete removal of the Xe-129
Calibration
curve using the
I-129 standard
Ejemplo de MS/MS en modo “on-mass” con N2O en la celda
45 March 20, 2014
Eliminación de interferencias isobáricas y poliatómicas en Selenio
Se+ + N2O apenas reacciona
Br+ + N2O BrO+ (totalmente)
Q1 – elimina todas las
masas excepto la del analito
(Se+ y su interferencia Br+)
ORS3 – se forma el BrO+
Q2 – Elimina todos los iones
formados en la celda distintos al
ion analito Se+, dejando a este
libre de solapamientos
Gas de Reaccion (N2O en He)
79Se
79Br
Se+
BrO+
Adicionalmente las interferencias ArAr, BrH son eliminadas por efecto colisional con
Helio
Determinación de Se en modo reacción con N2O
March 20, 2014
Confidentiality Label
46
1 ppb Se: Sin interfererencia ArAr o BrH
Desplazamiento 79Br y 91Br a masas
95 y 97
Datos cortesía ISC-Science y
Universidad de Oviedo
Operational Modes
• Q1 opens allowing all ions into ORS3
Single Quad
• Q1 allows a range of m/ƶ into ORS3 Single Quad with Band Pass Filter
• Both Q1 and Q2 set to same mass MS/MS – On
Mass
• Q1 and Q2 set to different masses MS/MS – Mass
Shift
Operational Modes
• Q1 opens allowing all ions into ORS3
Single Quad
• Q1 allows a range of m/ƶ into ORS3 Single Quad with Band Pass Filter
• Both Q1 and Q2 set to same mass MS/MS – On
Mass
• Q1 and Q2 set to different masses MS/MS – Mass
Shift
48
High Purity Materials.
Trace elements in HCl
Ti and V in 10% H2SO4
P and Ti in 2000ppm Si
49
Ge and As Measured as GeO+ and AsO+ in 20% HCl DLs 1.5ppt for Ge and 2.6ppt for As
MS/MS – Removal/avoidance of Cl-based interferences on 74Ge and 75As
In 20% HCl, Ge and As are key interfered elements (Cl2+, ArCl+).
• Both analytes react quickly with O2 cell gas and can be measured at low levels as
their oxide product ions.
50 March 20, 2014
V and Ti Measured in 9.8% H2SO4 (1:10 dilution)
In 10x diluted (9.8%) H2SO4, V and Ti are key interfered elements (SO+, SOH+).
• V reacts slowly with NH3 cell gas, so 51V+ can be measured on-mass.
• Ti reacts quickly with NH3, so 63TiNH+ (and other) product ions can be measured.
MS/MS on-mass and mass-shift can be combined in the same acquisition method.
DLs and BECs for both elements are single-ppt or sub-ppt
51V measured on-mass 48Ti measured as 63TiNH+
51 March 20, 2014
P Measured as PH3+
in 2000ppm Si/HF
H2 cell gas mode - DL 170ppt
C-flow 50 nebulizer P is a critical
contaminant in solar Si
(for PV cells)
Difficult to measure at
low levels in high silicon
matrix due to
interference from 30SiH
8800 with MS/MS allows
controlled reaction mode
with H2 cell gas to
measure P at low levels
as its reaction product
ion PH3+ at mass 34
52 March 20, 2014
48Ti Measured as TiNH+ in 2000ppm Si/HF
NH3 cell gas mode - DL 6.2ppt
C-flow 50 nebulizer Ti is very difficult to
measure at low levels in
high Si matrix (29Si19F
and 28Si19FH overlaps
on the major Ti isotope
at mass 48)
8800 MS/MS in NH3 cell
gas mode moves Ti
away from matrix-based
overlaps and allows low
ppt level measurement
of Ti as TiNH+ product
ion at m/z 63
53 March 20, 2014
Sulphur, Arsenic and Selenium
54
Sulphur is difficult!
Interferences from Oxygen, Nitrogen and Hydrogen polyatomics:
32S: 16O16O; 14N18O; 15N16O1H
33S: 32S1H; 16O16O1H; 16O17O; 15N18O; 14N18O1H
34S: 33S1H; 33S1H2; 16O18O
…and more!
55
Sulphur Measurement
With conventional Collision-Reaction Cell (CRC) ICP-MS interferences can be reduced but not necessarily to a level that is useful or for all isotopes of interest.
Due to the intensity of the interferences a mass-shift (neutral gain) methodology is often employed.
• S measured as SO at +16amu
– If another isotope resides at the +16 mass (e.g. 48Ca & 48Ti on32S16O) analysis will be impaired
– All S isotopes react with all O2 isotopes causing low mass S isotopes to interfere with higher mass isotopes
• 32S17O+ interference on 33S16O+
• 32S18O+ & 33S17O+ interference on 34S16O+
56
Sulphur (O2 Mode) - Summary
Most S isotopes can be measured using 16O mass
shift:
• 32S – SO+ @ 48
• 33S – SO+ @ 49
• 34S – SO+ @ 50
Limiting factor for the analysis of S is now the
background signal due to contamination.
S is commonly present as a contaminant in reagents,
plastic-ware (e.g. phthalates)
57
Oxygen Mass Shift for 34S – with MS/MS
58
50Cr+/50V+/50Ti+
38Ar12C+
13C37Cl+
34S+
17O2+
16O18O+
O2 reaction gas
34S16O+
Q1
MS/MS
34amu
Q2
50amu
The mass difference between Q1 and Q2 is fixed (16) therefore a single
transition is observed – the other oxygen isotopes are eliminated so the
original isotopic pattern is preserved!
59
ICP-MS/MS: Mass Shift with O2 Cell Gas
32S16O+
33S16O+
34S16O+
34S/32S ratios
Blank 0.0484 ± 0.0017
100 ppb standard 0.0487 ± 0.0012
Theoretical 0.0447 ± 0.0025
0
10.000
20.000
30.000
40.000
50.000
60.000
47 48 49 50 51 52 53
ion
co
un
ts [
cp
s]
m/z of Q2
32S16O
33S16O
34S16O
36S16O 36Ar16O
0
2.000
4.000
6.000
8.000
10.000
47 48 49 50 51 52 53
ion
co
un
ts [
cp
s]
m/z of Q2
Sulphur in DIW and AcN – limit is contamination
0
1.000
2.000
3.000
4.000
5.000
47 48 49 50 51 52 53
ion
co
un
ts [c
ps
] m/z of Q2
5ppb S in UPW UPW only AcN
60 March 20, 2014
Publication on Sulphur by Isotope Dilution
61
REE++ Interferences on As and Se
M++ interferences are not polyatomic, so not removed by He cell gas
In He mode, REE++ interferences can actually appear to be higher due to
transmission efficiency of heavier (and slightly smaller) 2+ ions
• Nd & Sm have isotopes at m/z 150, so the 2+ ions appear at m/z 75 (As)
• Eu has an isotope at m/z 151, so the 2+ ion appears at m/z 75.5 (As)
• Gd has an isotope at m/z 156, so the 2+ ion appears at m/z 78 (Se)
Sample 75 [ No Gas ] 75 [ He ] 78 [ No Gas ] 78 [ He ] 75 -> 91 [ O2 ] 78 -> 94 [ O2 ] La 500ppb 0.000 0.000 0.000 0.559 0.000 0.004
Ce 0.000 0.000 0.000 0.109 0.000 0.001
Nd 0.730 5.890 0.000 0.000 0.000 0.000
Sm 0.634 8.916 0.000 0.000 0.002 0.001
Eu 1.761 16.321 0.000 0.000 0.000 0.001
Gd 0.000 0.000 34.728 290.035 0.000 0.007
Tb 0.000 0.000 0.000 0.000 0.000 0.000
Dy 0.000 0.000 0.000 0.423 0.000 0.000
62 March 20, 2014
O2 cell gas moves As and Se to AsO+ & SeO+ product ions, so avoiding the REE++
overlaps
Some Solutions in Clinical Sample Analysis
63
Gd++ Interference on Selenium
Gd used as a contrasting
agent for MRI
Concentration in patient can be at the high ppb to
ppm level
This causes problems with
obtaining accurate Se
measurements for those patients
Using oxygen to shift Se mass
+16amu effectively
removes bias
No Gas Oxygen
Serum 93.64 91.42
Serum + Gd 250 µg l-1
99.87 91.38
Serum + Gd 500 µg l-1
112.12 91.70
Serum + Gd 1000 µg l-1
121.07 91.78
64 March 20, 2014
Titanium in clinical samples
Clinical samples are a complex mix of matrix elements. Of the range of
reaction gases that can be used, NH3 gives good performance for several
key elements in clinical samples, such as Ti (metal-on-metal joints).
Compared NH3 to no gas, He, O2 mode NH3 is a
highly
reactive cell
gas. 48Ti
forms
several
cluster ions
with NH3 cell
gas,
including
TiNH2(NH3)4
TiNH2(NH3)4+
m/z=114
65 March 20, 2014
Q1 set to let in only m/ƶ 46, 47, 48, 49, 50 INDIVIDUALLY
Q2 set to transition masses:
Q1 +84amu [TiNH2(NH3)4]
Q1 +102amu [Ti(NH3)6]
Therefore transitions used:
46 130 46 148
47 131 47 149
48 132 48 150
49 133 49 151
50 134 50 152
MS/MS Neutral Gain Scan – Titanium with
Ammonia Adducts at Two Mass Transitions
66
Q2 set to Q1 +84amu [TiNH2(NH3)4] & +102amu [Ti(NH3)6]
Serum and Urine Check
Based upon results from this HNO3 standard the system was run using basic
preparation for clinical samples (dilution into NH4OH, EDTA, Triton-X, BuOH)
• Standards were prepared in the basic preparation medium
• Standard addition NOT used
• Both diluted serum and urine (10x) run within same batch against same
calibration
• Data compared to no cell gas and other gas modes
Titanium – No Gas, He, O2, NH3
Target 47 -> 131 Ti [ NH3 ] 48 -> 132 Ti [ NH3 ] 49 -> 133 Ti [ NH3 ] 50 -> 134 Ti [ NH3 ]
Sample Name Conc. [ ug/l ] Conc. [ ug/l ] Conc. [ ug/l ] Conc. [ ug/l ]
Urine Blank 4.6 (2.2-7.0) 2.80 2.79 2.92 2.49
Urine Blank 4.6 (2.2-7.0) 3.50 2.93 3.33 2.66
Urine Trace Elements 14.81 15.27 14.42 15.13
Urine Trace Elements 14.99 15.49 15.50 15.05
Serum L1 1.28 (0.86-1.80) 1.21 1.15 1.14 0.80
Serum L1 1.28 (0.86-1.80) 1.27 1.18 1.09 0.89
Serum L2 1.76 1.92 1.61 1.13
Serum L2 1.82 1.64 1.76 1.22
Target 47 Ti [ No Gas ] 47 Ti [ He ] 48 -> 64 Ti [ O2 ]
Sample Name Conc. [ ug/l ] Conc. [ ug/l ] Conc. [ ug/l ]
Urine Blank 4.6 (2.2-7.0) 1989.79 41.44 15.48
Urine Blank 4.6 (2.2-7.0) 2004.91 44.30 15.76
Urine Trace Elements 1789.92 51.41 26.30
Urine Trace Elements 1749.13 52.58 27.08
Serum L1 1.28 (0.86-1.80) 144.18 3.79 7.33
Serum L1 1.28 (0.86-1.80) 128.97 2.95 7.37
Serum L2 100.16 3.95 9.20
Serum L2 95.65 3.02 9.00
“Conventional” Modes (no gas, He, O2)
Ammonia Cell Gas using the +84 transition - TiNH2(NH3)4
NH3 mode gives very consistent recovery for 4 Ti isotopes (47, 48, 49, 50). All results within range of “target”
values, but reference range (all from HR-ICP-MS) is very wide. 8800 ICP-QQQ results on low side of range
67 March 20, 2014
Practical Benefits of Improved Abundance
Sensitivity of ICP-MS/MS
Mn in Fe matrix
Mn in whole blood
B in organics
68
Abundance Sensitivity
69
Abundance
Sensitivity Q1 Q2
Low 5x10-7 5x10-7
High 1x10-7 1x10-7
8800 Abundance Sensitivity in Single-Quad Mode
Trace 55Mn is overlapped by 56Fe in 1000ppm Fe
Abundance Sensitivity (AS) is
the degree of peak “tailing” – the
contribution a peak makes to the
adjacent (-1 and +1amu) masses
7700 specification is 5 x 10-7 on the
low mass side
Note: log intensity scale
70 March 20, 2014
MS/MS Abundance Sensitivity is
the product of Q1 AS x Q2 AS,
so overlaps to adjacent peaks
are virtually eliminated
8800 AS is almost too good to
measure (<10-9)
8800 Abundance Sensitivity in MS/MS Mode 55Mn is free from overlap by 56Fe in 1000ppm Fe
71 March 20, 2014
Other Sample Types – Manganese in Whole Blood
Mn is difficult to measure by ICP-
QMS at natural (sub-ppb) levels in
whole blood, due to “tail” of 56Fe
(and 54Fe) peak across 55Mn
8800 MS/MS ensures 55Mn is
completely separated from 54/56Fe
Overlaid spectra show blank whole
blood (10x dil) & 500ppt Mn spike
72 March 20, 2014
Abundance Sensitivity Test - 1ppm Fe, MS/MS
Mode
73
In a 1ppm Fe standard,
Abundance Sensitivity
is almost too good to
measure, so we
decided to test it
further…
Boron is difficult to measure by ICP-
QMS at trace (low-/sub-ppb) levels
in organic solvents, due to “tail” of 12C peak across major 11B isotope
8800 MS/MS ensures 11B is
completely separated from 12C
Overlaid spectra show blank
kerosene and 5.8ppb B spike (12C is
over-range and skipped)
Practical Applications of Better AS – Boron in
Organics (kerosene)
74 March 20, 2014
Boron in Kerosene BEC & DL Improvement in MS/MS Mode
BEC and DL greatly improved, especially for 11B due to no
contribution from 12C – 11B BEC 140ppt; DL 28ppt
No gas single quad mode No gas MS/MS mode
75 March 20, 2014
ICP-QQQ-MS in the “-omics”
76
ICP-MS as element-specific detector for the life
science applications - Metallomics
•Very sensitive - 1000 times or better than organic mass.
•High ionisation efficiency - good for P, S, Se compounds.
•Compound independent calibration - easy and quick quantification.
•Multi-element capabilities > 30 elements simultaneously
•Wide dynamic range = ppm~ppb~ppt simultaneously
•Isotope ratio measurement - Isotope Dilution, Metal tracer.
•Easily interfaced to multiple separation techniques - On-line detector.
It is recognized that metals play an important roles in proteomics processes as such:
- About 30% of all proteins may bind metal ions.
- There are many proteins known to bind Ca, Mg, Fe, Zn or Ni ions or chromogenic groups like heme or chlorophyll which bind metal ions.
77
Analytical strategy in Metallomics
Separation HPLC, CE
Sample Result
ES-MS/MS MALDI-TOF
Molecular information &
Identification/structure
information
Metal binding information &
Absolute quantification
without specific standards
Extraction/
Purification/
Concentration
Metalloprotein
Sequence
2-D Separation
ICP-MS
79
Absolute Quantitative Proteomics by the ICP-QQQ
The first result from the collaboration with Dr Jorge Ruiz Encinar of Oviedo
University, Spain on the quantitative proteomics by ICP-QQQ has been
obtained and is published in Analytical Chemistry.
80
0
10
20
30
40
50
60
70
80
0
50
100
150
200
250
300
350
400
3,2 3,3 3,4 3,5 3,6
x103
Coun
tsx1
03
Time (min) 34S/32S ratios measured
Injected (Methionine) 0.0489 ± 0.0017
Infusion (sulphate) 0.0487 ± 0.0012
Isotope ratios measured in transient
signal as peak area ratios
32S as 32S16O+
34S as 34S16O+
Mass discrimination factors again
ranging from -4.0 to -4.3%
ICP-QQQ for S isotope ratio analysis
81
Applications Handbook (Publication number 5991-
2802EN)
82
Application Notes
March 20, 2014
83
84 March 20, 2014