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Technical
Note: 40719
Biomedical sample analysis using the
XSERIES 2 ICP-MS
Introduction
Key Words
• Ari Mist
Nebulizer
• Biomedical
Analysis
• 3rd Generation
CCTED
• Xt Interface
Trace element measurement in clinical samples is a
challenging task. The complex sample matrices that need
to be analyzed, such as serum and whole blood, together
with the often low analyte concentrations present in these
samples, both increase the difficulty of the measurements.
Highly sensitive and robust instruments, capable of rapid
and reliable analysis are required to accurately and
precisely detect and quantify the analytes of interest,
which has led biomedical analysts to invest in ICP-MS
technology. The development in recent years of collision
and reaction cell interference reduction technology for
ICP-MS has provided an enhancement in data quality for
key elements of biomedical interest that suffer from
interference problems (for example 40Ar2+ on 80Se, 40Ar
35Cl+ on 75As+ and 40Ar12C+ on 52Cr+), thereby increasing
the appeal of the technique to the biomedical community.
This technical note describes the sample introduction
apparatus and hardware features of the Thermo Scientific
XSERIES 2 ICP-MS developed by Thermo Fisher Scientific
to provide optimum performance for routine biomedical
sample analysis.
after dilution, less than 2 ml of sample is available. In
these circumstances a low-flow nebulizer coupled with
reduced sample uptake rates is required.
In order to meet these requirements, a standard, robust
sample introduction system for analysis of liquid biological
specimens has been developed for the XSERIES 2 ICP-MS.
This system incorporates the low-flow, blockage resistant
Burgener Ari Mist nebulizer (Figure 1) and the highly
matrix tolerant Xt interface (see XSERIES 2 ICP-MS
Technical Note 40705) (Figure 2).
Sample Introduction Requirements for Biomedical
ICP-MS Analysis
Several sample introduction characteristics are required to
meet the demands of elemental analysis in biomedical
samples. The elements of interest range from nmol/L levels
of non-nutritional elements, such as Cd, in whole blood,
through the µmol/L range, for Cu and Zn in serum, to
mmol/L concentrations, for Na and K in all biomedical
sample types, so a wide dynamic detection range is
essential. The varying sample matrix composition, from
blood, serum and urine, to hair, tissue, tooth and bone
digests means that a robust sample introduction system,
capable of handling these matrices without blocking or
becoming unstable, is required. The complex sample
composition also means that the interface cones of the
ICP-MS must be sufficiently matrix tolerant to minimize
the signal drift caused by sample deposition around the
cone tips (particularly the skimmer cone tip). In addition
to the sample matrix demands on the ICP-MS,
occasionally the volume of sample provided for analysis
may also be an issue. Since biological samples cannot be
readily analyzed directly, because of their matrix ion
concentration and viscosity, they normally require dilution
(typically 10 or 20-fold) prior to analysis, which
conveniently reduces the required amount of starting
material required. However, there are cases when even
Figure 1. The Burgener Ari Mist nebulizer
Figure 2. The Xt interface.
The Burgener Ari Mist nebulizer utilizes a parallel path
design, in which the sample and nebulizer gas channels run
alongside each other until meeting at the nebulizer tip. This
design, which requires that samples be pumped through it (it
does not free-aspirate, whereas concentric devices can),
prevents particulates and other detritus in the sample
blocking the nebulizer capillary or tip, a problem often
encountered during biological sample analysis using
standard concentric nebulizers. In addition, the parallel path
design offers improved nebulization robustness and
reproducibility with changes in sample matrix compared to
concentric nebulizers. This offers particular performance
improvements during urine analysis, where large variations
in sample composition are frequently encountered.
The Xt interface is composed of a Ni sample cone and
exchangeable copper-cored Ni skimmer cone tip inserted
into a metal adapter. The choice of adapter material,
resulting from extensive investigations of different
candidate metals, optimizes heat dissipation from the
skimmer tip so that while the instrument is operating, the
skimmer runs at a high enough temperature to prevent
sample matrix from coalescing around the cone orifice.
The result is enhanced stability and reduced signal drift
during long term analysis of biological materials. The
skimmer cone geometry matches that of the field-proven
Xi interface, allowing the Xt interface to retain the
benefits of this interface. These benefits, all of which are
relevant for elemental analysis in biological samples, are:
• Reduced polyatomic species and lower blank equivalent
concentrations (BEC's) for easily ionized elements, such
as Li, and cone derived ions, such as Ni
Sampling and Sample Monitoring Requirements
The varying and complex sample matrices that are
introduced to the ICP-MS during biological analysis also
mean that rapid washout is required to maximise sample
throughput and minimise cross contamination from one
sample to the next. The XSERIES 2 ICP-MS meets these
requirements by offering several sample uptake and wash
options with the combination of its versatile PlasmaLab™
software and the Cetac range of autosamplers (Figure 3).
The options available include:
• Fast uptake and wash, whereby the sample flow rate can
be increased during the uptake and rinse cycles. This
reduces analysis time, increases sample throughput and
reduces analysis costs.
• Monitored uptake / wash, where the uptake and wash
times can be optimized sample-by-sample by intelligent
monitoring of selected elements. This facility avoids
carry-over problems from one sample to the next, by
ensuring that the target signals have returned to baseline
before the next measurement is started. It also ensures
that sample uptake times are optimized, leading to
increased productivity.
• Autosampler probe-to-wash-early functionality, where
the sample uptake probe can be sent to the wash after a
predetermined time of taking up the sample. This allows
the rinse cycle to start before the sample analysis has
finished, thereby reducing rinse times to a minimum. It
is a beneficial facility for analyses where only one or
two, rapidly rinsed out analytes are required in a large
number of samples (e.g. Pb in whole blood). Using this
approach, sample throughput of > 50 samples per hour
is achievable.
• Low off-peak instrumental background of <0.5 cps,
leading to industry leading detection limit capabilities
for non-interfered isotopes
• Attenuated signal at low masses, allowing major
elements to be quantified together with minor and trace
analytes in a single run without the need for further
sample dilution
Figure 3. XSERIES 2 ICP-MS and Cetac autosampler.
Interferences in Biomedical ICP-MS Analysis
Spectroscopic interferences in ICP-MS, arising from
interaction of the sample matrix components and the
plasma gas, have been extensively studied and
characterized ever since the initial development of the
technique in the early 1980's. For biomedical analysis, the
most important spectroscopic interferences to be
considered are given in Table 1 below.
ISOTOPE
Al
V
35
C
40
Cr
40
Mn
40
Fe
40
Co
40
Ni
44
Cu
40
As
40
Se
38
Se
40
51
52
53
55
INTERFERENCE
12 14
27
56
59
60
63
75
78
80
Cd
111
C N1H+, 12C15N+
Cl16O+
Ar12C+, 36Ar16O+ and 35Cl16O1H+
Ar13C+, 36Ar16O1H+ and 37Cl16O+
Ar14N1H+, 40Ar15N+ and 54Fe1H+
Ar16O+
Ar18O1H+ and 40Ca18O1H+
Ca16O+
Ar23Na+
Ca16OH(H2O)+
Ar40Ar+
methane, oxygen or mixtures of these gases) inside the
collision cell of the instrument. The target analyte ions
undergo less interaction with the gas as they transit the
cell and are detected, free of interference, downstream of
it. The performance of the XSERIES 2 collision cell for the
measurement of Se is illustrated by the calibration shown
in Figure 4. With the XSERIES 2 ICP-MS the collision cell
forms part of the standard ion focusing optics and as such
can be easily switched on and off within a sample analysis
to allow optimum data to be obtained for interfered and
non-interfered analytes. All that is required is a short
delay (typically 30 seconds) after switching the cell on or
off to allow the ion beam to stabilize (further information
about the XSERIES 2 ICP-MS collision cell technology
can be found in the product note 40346_E). Using this
technology, high accuracy results at low concentrations
can be achieved for those elements of biomedical interest
in biological specimens that are interfered in the absence
of the cell (see Table 1).
The performance of the collision cell for biological
sample analysis is illustrated in the XSERIES 2 ICP-MS
application notes AN_E0604 (Determination of Cu, Zn
and Se in serum), AN_E0601 (Measurement of As and Cr
in urine) and AN_E0649 (Trace element quantification in
blood and serum in a single run).
Ar40Ar+ and 79Br1H+
94
Mo16O1H+, 95Mo16O+
Table 1. Interferences of most importance for biomedical analysis using
ICP-MS
In some cases, such as the 40Ar23Na+ interference on
63Cu, an alternative analyte isotope is available (65Cu, in
this example). In others, mathematical interference
correction, using another mass of the interfering species to
determine the signal intensity of the parent interference,
can be applied. For example, to correct for the 40Ar35Cl+
interference on 75As, the 40Ar37Cl+ signal at mass 77
(which itself must be corrected for 77Se) can be used. For
interferences such as 40Ca16O+ on 60Ni, it is often effective
to use empirically determined interference formation
factors (i.e. formation rates) for the interfering species and
then applying these correction factors in the software.
Both these mathematical correction approaches are
effective when the analyte signal is relatively large
compared to the interference, but when the analyte signal
is small with respect to the interference, mathematical
corrections become less accurate. For this reason, an
alternative approach is required to achieve accurate results
at low analyte concentrations. This approach is the
application of collision cell technology.
3rd Generation Collision Cell Interference
Elimination Technology (CCTED)
This technology, which has now been commercially
available in ICP-MS instruments for more than 5 years,
works by removing interferences through a combination
of chemical and physical interaction of the ion beam with
a collision gas (typically hydrogen, helium, ammonia,
Figure 4. Se calibration using CCTED
Conclusions
With its standard liquid biomedical sample introduction
system, versatile productivity-enhancing sample
uptake/wash handling and advanced 3rd generation
collision cell technology, the Thermo Scientific XSERIES 2
ICP-MS offers unrivalled performance for biomedical
elemental analysis. The combination of the Burgener Ari
Mist nebulizer and matrix tolerant Xt interface provides
optimum robustness for routine, high throughout analysis
of blood, urine and serum materials, following simple
dilution of the samples. The high sensitivity and low
background of the instrument yields exceptional detection
limit capability, providing high quality data even at low
analyte concentrations. These features, coupled with the
effective interference elimination capabilities of the
collision cell option, ensure that the XSERIES 2 ICP-MS is
a powerful and effective tool for elemental analysis in
biomedical analysis laboratories.
Plasma Capabilities from Thermo Fisher Scientific
In addition to these
offices, Thermo Fisher
Scientific maintains
The use of an Inductively Coupled Plasma
source (ICP) is the accepted and most
powerful technique for the analysis and
quantification of trace elements in both solid
and liquid samples. Its applications range
from routine environmental analyses to the
materials industry, geological applications to
clinical research and from the food industry
to the semiconductor industry.
Thermo Fisher Scientific is the only
instrument manufacturer to offer the full
range of Inductively Coupled Plasma
Spectrometers (ICP, Quadrupole and Sector
ICP-MS) to satisfy every aspect of plasma
spectrometry from routine to highly
demanding research applications.
Develop your lab from the easy-to-use
iCAP ICP to the high performance XSERIES 2
Quadrupole ICP-MS and up to the ultrasophisticated ELEMENT2 and NEPTUNE
Sector ICP-MS instruments. Each
instrument combines leading-edge
technology, fit for purpose and affordability
with a tradition of quality, longevity,
accuracy and ease of use.
Thermo Scientific
iCAP ICP
Thermo Scientific
XSERIES 2 ICP-MS
Thermo Scientific
ELEMENT2 HR-ICP-MS
Thermo Scientific
NEPTUNE Multi-collector ICP-MS
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