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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

The world leader in serving science

Application Examples

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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

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Serving Your Science

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Thank You

Please join me in the

Trace Elemental

section of our booth where I’ll

address comments and questions.