Interferences between Communications and Computations in ...
Handling Interferences in the Modern Lab with...
Transcript of Handling Interferences in the Modern Lab with...
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Shona McSheehy Ducos
Handling Interferences in the Modern Laboratory with Advanced Triple Quadrupole ICP-MS Technology
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What are you trying to accomplish?
• Quantification of elemental impurities to validate purity of final product
• QA/QC to monitor quality, flag contaminated reagents, measure reaction efficiency/completeness
Elemental Analysis
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A Complete Elemental Analysis Portfolio
AAS
ICP-OES
Single Quadrupole
ICP-MS
SF-ICP-MS
Features include:
• Single- or multi-element analysis
• Measurement at concentrations from parts
per trillion to percent
• Low-cost, high-throughput systems
• Space-saving ergonomic design with low
gas consumption
OEA
Triple Quadrupole
ICP-MS
Measure elemental impurities:
• Any sample matrix
• Any concentration
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• Many elemental analysis techniques are suitable for measuring:
• Toxic metals (e.g. As, Cd, Hg, Pb)
• Impurities (e.g. S, Al, Ni)
• Essential elements (e.g. Fe, Se)
• Elemental species or nanoparticles
• ICP-MS is advantageous:
• Matrix tolerance – robust interface and sample handling systems can significantly increase analysis times
between operator intervention
• Interference removal – advances in collision/reaction cell technology providing way to analyze more
accurately at lower levels
• High sensitivity – higher detection power enables lower limits of detection
• More than 9 orders dynamic range – enables the analysis of both minors and majors in one analytical run
• Sensitive enough to determine high precision isotope ratios, speciation concentrations and particle numbers
Why Use an ICP-MS?
Are there any challenges?
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Interferences
Spectral Interferences – ICP-MS
• 2 most common types: isobaric and polyatomic
• Isobaric Interferences
• Produced when isotopes from different elements have the same m/z ratio (58Fe on 58Ni, 204Hg on 204Pb)
Isotopic pattern for Ni
64Ni (1% abundant)
Isotopic pattern for Zn
64Zn (49% abundant)
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Interferences – Spectral
Spectral Interferences – ICP-MS
• 2 most common types: isobaric and polyatomic
• Polyatomic Interferences
• Produced when 2 or more isotopes combine to form a species with the same m/z as that of the analyte ion
Ar, Air (O, N, C)
H2O, Ca, Na, K, Mg, Cl
ArAr, ArO, ArN, ArC,
ArH, ArCa, ArNa, ArK,
ArMg, ArCl, ClO, NO,
CO, CaO, NaO, etc
Reactants Reaction Products
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• Some typical interferences in ICP-MS:
Handling Interferences – What Options are Available?
• Alternative sample introduction techniques
• E.g. aerosol desolvation to minimize the population of
the precursor (parent) ions in the ICP ion source
• Cold Plasma:
• Reduce plasma power to reduce amount of Ar
ionization
• Mathematical Correction Equations:
• Measure the isotope of interest, an un-interfered
isotope, a polyatomic isotope and mathematically de-
convolute to return an interference free value
Mass Interferences Precursors
51V 35Cl16O, 37Cl14N, 34S16OH
H, N, O, S, Cl
56Fe 40Ar16O, 40Ca16O O, Ar, Ca
63Cu 40Ar23Na, 12C16O35Cl, 31P32S
C, N, O, Na,
P, S, Cl, Ar
75As 40Ar35Cl, 40Ca35Cl, 40Ar34SH, 37Cl2H
H, S, Cl, Ca,
Ar
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• Some typical interferences in ICP-MS:
Handling Interferences – What Options are Available?
• Alternative sample introduction techniques
• E.g. aerosol desolvation to minimize the population of
the precursor (parent) ions in the ICP ion source
• NOT A UNIVERSAL SOLUTION
• Cold Plasma:
• Reduce plasma power to reduce amount of Ar
ionization
• NOT A UNIVERSAL SOLUTION
• Mathematical Correction Equations:
• Measure the isotope of interest, an un-interferred
isotope, a polyatomic isotope and mathematically de-
convolute to return an interference free value
• AMPLIFIES ERRORS, DOESN’T ACCOUNT
FOR UNKNOWN INTERFERENCES
Mass Interferences Precursors
51V 35Cl16O, 37Cl14N, 34S16OH
H, N, O, S, Cl
56Fe 40Ar16O, 40Ca16O O, Ar, Ca
63Cu 40Ar23Na, 12C16O35Cl, 31P32S
C, N, O, Na,
P, S, Cl, Ar
75As 40Ar35Cl, 40Ca35Cl, 40Ar34SH, 37Cl2H
H, S, Cl, Ca,
Ar
The ultimate solution: Thermo Scientific™ iCAP™ QCell Technology
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• Interference Removal in SQ-ICP-MS
Target
Analyte 75As+
Quadrupole set to filter out
exact mass of target analyte
QCell in collision mode with pure
He uses energy discrimination
ArCl+, Ca(OH)2H+
Quadrupole
isolates ions
required for
measurement
He KED filters out
unwanted polyatomic
interferences, based on
difference in cross-
sectional size of the
analyte and polyatomic
Complex
Sample
Matrix
Comprehensive
interference
removal is
achieved
Handling Interferences with Collision Reaction Cell Technology
Kinetic Energy Discrimination (KED)…
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• Interference Removal in SQ-ICP-MS
Quadrupole
isolates ions
required for
measurement
Complex
Sample
Matrix
Comprehensive
interference
removal is
achieved
Handling Interferences with Collision Reaction Cell Technology
Target
Analyte 75As+
40Ar+, 40Ca+, 35Cl+, 16O+, 1H+
Low mass cut off
filters out unwanted
precursor ions; ions are
then unable to
recombine later in the
QCell and backgrounds
are reduced further
than He KED alone
Quadrupole set to filter out
exact mass of target analyte
QCell in collision mode with pure
He uses energy discrimination
… and Low Mass Cut-Off
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• Eliminates lower mass ions that contribute to interferences from travelling through the QCell...
…and reduces BECs even further than He KED alone
Handling Interferences – Low Mass Cut Off
Mass Interferences Precursors
51V 35Cl16O, 37Cl14N,
34S16OH H, N, O, S, Cl
56Fe 40Ar16O, 40Ca16O O, Ar, Ca
63Cu 40Ar23Na,
12C16O35Cl, 31P32S
C, N, O, Na, P, S,
Cl, Ar
75As 40Ar35Cl, 40Ca35Cl,
40Ar34SH, 37Cl2H H, S, Cl, Ca, Ar
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• Eliminates lower mass ions that contribute to interferences from travelling through the QCell...
…and reduces BECs even further than He KED alone
Handling Interferences – Low Mass Cut Off
Mass Interferences Precursors
51V 35Cl16O, 37Cl14N,
34S16OH H, N, O, S, Cl
56Fe 40Ar16O, 40Ca16O O, Ar, Ca
63Cu 40Ar23Na,
12C16O35Cl, 31P32S
C, N, O, Na, P, S,
Cl, Ar
75As 40Ar35Cl, 40Ca35Cl,
40Ar34SH, 37Cl2H H, S, Cl, Ca, Ar
Universal interference removal for polyatomic interferences
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There is No Application That Cannot be Tackled...Right?
Pb in blood
Cr speciation in toys
Trace elements in NaCl
Trace elements in food
Elemental impurities in
drug products
Drinking water contaminants
Air monitoring
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• Measuring Se in a matrix containing
high levels of Mo or Zr
• Use oxygen reaction gas in the
collision cell:
• Shift mass of Se away from Ar dimer
• Measure Se at the shifted mass
• Problem: how to remove the matrix
ions with m/z = 96 that do not react
with oxygen?
An Application Challenge for a Single Quadrupole ICP-MS
Complex
Sample
Matrix
40Ar40Ar+, 80Se+, 96Zr+, 96Mo+
80Se16O+, 96Zr+, 96Mo+
Introduce O2
reaction gas
Mass filter –
restrict to m/z = 96
40Ar40Ar+
80Se+ 80Se16O+
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Interference removal with an additional quadrupole:
• Filter all ions to allow passage of only ions with a
mass-to-charge ratio of 80
• Use reaction gas to shift the mass of the analyte ion
• Filter remaining ions to allow passage of ions with a
mass-to-charge ratio of 96
• Remove all interference effects from ions such as:
• 40Ar40Ar+
• 96Zr+
• 96Mo+
• 96Ru+
• 160Gd++
• 160Dy++
The Interference Removal Power of a Triple Quadrupole ICP-MS
Complex
Sample
Matrix
40Ar40Ar+, 80Se+, 96Zr+, 96Mo+
Introduce O2
reaction gas
Mass filter –
restrict to m/z = 80
Mass filter –
restrict to m/z = 96
80Se16O+
96Zr+, 96Mo+
40Ar40Ar+
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Thermo Scientific iCAP Qnova Series ICP-MS
Thermo Scientific™ iCAP™ RQ ICP-MS (launched at Pittcon 2016)
Simplicity, productivity and robustness for routine labs
The iCAP RQ ICP-MS delivers the reliability,
analytical performance and ease of use needed to
meet the demands of the highest throughput labs.
Thermo Scientific™ iCAP™ TQ ICP-MS (launched at WPC Feb 2017)
Redefining triple quadrupole technology with unique ease of use
The first, future proof triple quadrupole ICP-MS solution
delivering enhanced performance and uncompromised
ease of use for demanding routine analysis and
challenging research applications.
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Same Hardware Platform – Familiar Look and Feel
If you know how to use our single quadrupole, you already know how to use our triple quadrupole!
iCAP RQ ICP-MS iCAP TQ ICP-MS Innovative collision
cell
Bench-level easy-
access interface
Compact footprint
Intuitive user-friendly
software
Simplified power
connections
Robust RF
generator
Quick connect and push-
fit sample intro
components
Reaction Finder
Software
4 mass flow controllers:
He, O2, H2, NH3
Built-in safety for
handling reactive
gases
Additional quadrupole
for superior interference
removal
Analysis with SQ and
TQ in a single
sample run
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Thermo Scientific iCAP TQ ICP-MS – How it Works
• More specific interference
removal through reactive
chemistry inside the CRC
• Removal of unwanted ions in
Q1 allows eliminates
interferences on product ion
mass and unwanted side
reactions
Q1 rejects unwanted ions and
preselects the analyte. This first
stage of mass filtration rejects
precursors and ions with the same
m/z ratio as the product ion.
Optimal reaction conditions in Q2
are achieved through the selection
of the appropriate measurement
mode in Reaction Finder
Q3 isolates the product ion of the
analyte and removes any
remaining interferences through a
second stage of mass filtration
75As+
59Co+, 91Zr+
Q1 set to analyte
mass (m/z 75)
Q3 set to product ion
mass (m/z 91)
Q2 filled with reactive
gas (O2)
91[AsO]+
75As+ 91[AsO]+
59Co16O+, 150Sm++
Result: - Better detection limits, even in
challenging sample matrices
- Get more accuracy in unknown or
varying sample matrices
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• Elemental impurities in Ni alloys
• Ti, Cr in high purity sulfuric acid
• As in Vitamin B12 (high Co matrix)
• Cd in the presence of high Mo concentrations
• As, Se in samples containing rare earth elements
• P, Ti in high Si matrix
• Ti in human serum
• As, Cr, V in high purity hydrochloric acid
• S, P in steel and high concentrations of iron
• Measure nanoparticles at ever decreasing diameters
The Power of Triple Quadrupole Technology
The possibilities are endless!
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• Problem: the possibilities are endless!
• Collision cell operation:
• Standard mode, collision (KED) mode, reaction
mode, or a combination?
• If reaction mode, which reaction gas/es?
• Collision mode: what gas flow rate?
• Reaction mode: what gas flow rate/s?
• Collision cell voltage setting?
• Do you measure the analyte on mass or on mass-
shift?
• Quadrupole 1: • Voltage setting?
• Quadrupole 3: • Voltage setting?
• Sample intro settings (RF power, plasma gases,
spray chamber temperature)
The Power of Triple Quadrupole Technology
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Kick Interference to the Curb
Product ion
M+
Gas
Analyte
Result
Reaction Finder – eliminate the complexity of
triple quadrupole ICP-MS analysis
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• Reaction Finder for Thermo Scientific™ Qtegra™ Intelligent Scientific Data Solution™ Software
Eliminate the Complexity of Triple Quadrupole ICP-MS
Redefining triple quadrupole technology with unique ease of use
• Reaction Finder proposes the most
appropriate gas/scan settings
• Settings for both single quad mode and triple
quad mode are suggested, for reference
Step 1: Select your element/s or isotope/s
Step 2: You’re done!
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Simplest Method Development Using Reaction Finder
Without Reaction Finder
With Reaction Finder
Select • Select the Analytes to be measured
Select • Select the internal standard element
Decide
• Are the suggested settings ok? If not, update them
Analyze
• Enter sample names and positions or import from LIMS and start the LabBook
Select • Select the Analytes to be measured
Select • For each analyte, select the isotopes to be measured
Select • Select the internal standard element
Select • Select the Q1 Analyte
Select • Select the CRC gas (None, He, H2, O2, NH3)
Select • Select the mode (KED, Single Quad Mode, Triple Quad Mode)
Select • Select the Q3 Mass (On-mass/mass shift product ion)
Decide • Are the suggested settings ok? If not, update them
Analyze
• Enter sample names and positions or import from LIMS and start the LabBook
Less than 20 Minutes until a method is
set up and the samples are ready to run!
Operator skills required
Product Ion
M+
Gas
Analyte
Result
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Background
• Joint replacements more frequently consist of metal-on-metal joints over ceramic or polymer
• Wear and tear on joints can release metal ions into the body – accumulates in serum, blood and
can pass into the urine
• Ti in these bodily fluids can indicate premature joint failure and infection
Application challenge:
• Concentrations of Ti are extremely low (less than 1 ng·mL-1)
• Main Ti isotope (48Ti) has an isobaric interference from Ca, SO, PO
• Low concentrations (less than 1 ng·mL-1)
• Isobaric interference of main isotope 48Ti through 48Ca
Analysis of Ti in Serum
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Analytical method needs to be:
• Robust to cope with sample matrix
• Sensitive to enable detection of low levels
• Specific to address Ti accurately despite interferences
Analysis of Ti:
• Use Q1 to allow passage of only ions with m/z = 48
• Use NH3 to react with Ti and shift its mass to 114
• Use Q3 to allow passage of only ions with m/z = 114
Analysis of Ti in Serum
ICP-MS using triple quadrupole technology – iCAP TQ ICP-MS
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• Excellent agreement between measured and
certified values
• Sensitivity achieved allowed trace concentrations
of Ti to be measured in the prepared sample
Results for Ti in Serum
SQ mode produces false positive
results – unresolved isobaric 48Ca
interference!
Only by using triple quad
technology can accurate
results for Ti be obtained! Background signal on 48Ti14N4H10 for a solution
containing 10 mg·L-1 of Cd
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• Excellent agreement between
measured and certified/reported
values was achieved for all elements
• Full multi-elemental analysis together
with dedicated interference removal
for difficult analytes in one sample run
Results – All Other Elements
Detection Limits as low as 20 ppq
Elements accurately measured from 0.005 – 10,806 ppb
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Background
• Ni is used to produce a variety of alloys: stainless steels, copper-nickel alloys, nickel-chromium
alloys
• Electronics, high temperature machine parts, hard-wearing coatings
• Presence of metal impurities (such as Se) can affect the properties of the material (corrosion
resistance, high temperature strength, thermal expansion properties
Application challenge:
• Se is challenging to ionize in a high Ni matrix (elevated 1st ionization potential)
• Argon-based ions interfere with most abundant isotopes of Se
• Ni interferes with all isotopes of Se
• Additional interferences are generated in the presence of Br
Analysis of Se in Nickel Alloys
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• Let’s use O2 and measure Se as SeO with a single quadrupole ICP-MS!
Analysis of Se in Nickel Alloys
Ion Mass
76Se
77Se
78Se
80Se
82Se
Shifted Mass
76Se16O+ (m/z = 92)
77Se16O+ (m/z = 93)
78Se16O+ (m/z = 94)
80Se16O+ (m/z = 96)
82Se16O+ (m/z = 98)
Interferences
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• With the iCAP TQ ICP-MS, prevent precursor
ions from entering into the collision cell, prior to
reaction with O2
• Use Reaction Finder to automatically select the
most appropriate mode, reaction gas and flow
settings
Analysis of Se:
• Use Q1 to allow passage of only ions with
m/z = 80
• Use O2 to react with Se and shift its most
abundant isotope to mass to m/z = 96
• Use Q3 to allow passage of only ions with
m/z = 96
Analysis of Se in Nickel Alloys
80Se+
H2O+, H3O
+, Ni+, 96Zr+, 96Mo+
96[SeO]+
80Se+ 80Se16O+
64Ni16O+, 79Br1H+,
40Ar40Ar+
Q3 set to product ion mass m/z
96
Q2 filled with reactive gas
O2
Q1 set to m/z 80
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• A triple quadrupole instrument built on our original, innovative
single quadrupole platform
• Triple quadrupole with smallest footprint on the market
• Easy-access sample introduction area
• Bench-level, pop-out interface
• Low maintenance and argon consumption requirements
• Intuitive set-up and operation
• Powerful interference removal for maximum sensitivity and accuracy
• Streamlined method development with Reaction Finder
• Automated, unattended analysis and intelligent dilution
• Common software with ICP-OES for reduced training and operator
flexibility
Summary
The power of a triple quadrupole with the ease of use of a single quadrupole
Find out more:
thermofisher.com/iCAPTQ
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Additional Resources – analyteguru.com
• Educational • Fun • Engaging
Keyword: Elemental Analysis