special report
Inductively Coupled Plasma Mass
Spectrometry
Steven Woeste, PhD
Submissions Editor, Laboratory Medicine
DOI: 10.1309/UKMHB2TD8BKFUYVW
One technique used in clinical laboratories for trace element detection is inductively coupled plasma mass spectrometry, or ICP-MS. Introduced commercially in 1983,1 the basic
design is still the same today. It is well-suited to detecting
very small amounts of material, in the parts per billion (ppb)
to the parts per trillion (ppt) range.2 Samples for ICP-MS can
be either liquid or solid, though liquid samples are more common. Besides detecting very small amounts of substances,
ICP-MS is good at separating isotopes of the same element.1
To understand ICP-MS, a short list of its components
and an explanation of how they work is essential. The components shown in F1, from right to left, are the nebulizer and
spray chamber, ICP torch, radio power supply, MS interface,
mechanical pump, ion optics, turbomolecular pumps, mass
separator, and ion detector.3
The explanation of how the components work starts with
the nebulizer. Nebulizer is a fancy term for something that
takes a liquid sample and converts it to tiny droplets. The
nebulizer is also part of the spectrometer that brings the sample into the sample introduction area. Usually, a peristaltic
pump brings the liquid sample in at about 1 mL per minute3;
this type of pump also keeps the flow rate the same between
different kinds of samples. The nebulizer in F1 is 2 small
tubes that meet at a right angle to each other; 1 tube has the
sample pumped through it, while the other tube has argon
gas flowing through it and out to meet the sample. Where
MS interface
Ion detector
ICP torch
Ion optics
Spray
chamber
Mass analyzer
Nebulizer
Radio frequency
power supply
Turbomolecular
pump
[F1] ICP-MS system diagram.
Turbomolecular
pump
Mechanical
pump
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Plasma Auxilliary
gas
gas
Interface
RF coil
Outer
tube
Middle
tube
Nebulizer
gas
Sample
injector
RF power
[F2] Detailed view of a plasma torch and RF coil relative to the ICPMS interface.
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they meet is where the sample liquid is broken into small
droplets (an aerosol) by the argon. The droplets, though
small, need to be separated by size, with droplets over 10
micrometers in diameter removed from the aerosol, and
smaller droplets, 5 to 10 micrometers in diameter, passed
through to the next part of the machine. F1 shows a crossflow nebulizer; there are other types. The crossflow design
does not make small aerosol droplets as efficiently as other
nebulizer types,3 so there is some loss of precision and sensitivity. However, the crossflow nebulizer does not clog as easily as other types,3 so it is good for samples that have
undissolved material.
The separation of the aerosol droplets occurs in the spray
chamber, where the smaller droplets make it through without
striking the chamber’s walls, and the larger droplets settle out
from gravity, striking the chamber walls, coalescing, and running out the drain. The spray chamber also has another function, which is to even out the pulses of aerosol droplets from
the peristaltic pump that brings the sample to the spray chamber. The aerosol that leaves the spray chamber for the next
part of the spectrometer has a much more uniform distribution
of droplets than the pulses that entered the chamber. Once
formed, the small aerosol droplets enter the plasma torch.
In the plasma torch, the sample is converted to a stream
of ions for analysis and other key events occur. The nebulizer
gas containing the sample aerosol droplets enters, and the
sample is first desolvated (made a solid), vaporized (made a
gas), atomized (made into atoms), and then ionized.4 In F2,
the major parts of the plasma torch are shown (the portion
labeled “interface” is not part of the torch).4 The 3 tubes
(outer, middle, and sample) are usually quartz. Each of the 3
tubes has gas flowing through them; the plasma gas (usually
argon) flows through the outer tube, the auxiliary gas (usually argon) flows through the middle tube, which changes the
position of the base of the plasma, and the nebulizer gas
(usually argon) flows through the sample tube.
Creation of the inductively coupled plasma occurs in the
plasma torch. In F2, an RF (radio frequency) coil (usually
copper) is around the end of the torch where the gases exit,
and connected to a radio frequency generator. The coil (also
called the load coil) conducts an oscillating alternating current, which makes an electromagnetic field around the torch.
With argon flowing from the tip of the torch, a high-voltage
spark is released, removing electrons from some of the argon
atoms. The magnetic field from the coil accelerates the electrons, and they collide with unionized argon atoms, removing
their electrons; more and more of the argon atoms are converted to positively charged ions, with more electrons
released. Thus, the ICP portion of the technique, or the “inductively coupled plasma” aspect, continues to supply radio
frequency energy to the argon gas, forming more ions, and
making more plasma.4 The “seeding” of the argon gas with
the initial spark is from a Tesla unit (like a spark plug), but
the electric spark is not required to maintain the plasma;
there will be a constant supply of it as long as the radio frequency energy, and a flow of argon gas, is present.
Ions from the analyte then move to the interface region,
which is 2 metallic cones, each with a very small opening. The
first, or sampler cone, has a larger orifice inside diameter, about
1.0 mm, than the second, or skimmer cone, with an inside
diameter about 0.4 to 0.8 mm.5 The cones are usually made of
nickel. Assuming a neutral plasma, the analyte ions in it have
about the same velocity, though different kinetic energies, depending on their mass-to-charge ratio. However, the problem
with analyzing the sample ions is not their velocity, but their
abundance, relative to the matrix (argon, as described here)
ions. The analyte ions are fewer than the matrix ions. Anything
that can be done to change the balance in favor of increasing
the analyte ions number compared to the matrix ions increases
the sensitivity of the ICP-MS. That is done by the ion optics.
Unlike glass or quartz lenses in a light microscope, the
ion optics in ICP-MS are metal structures which conduct electricity. Two primary functions of the ion optics are a) to get
the maximum number of analyte ions to the next part of the
unit (the mass analyzer) and to reject as many matrix ions as
possible; and b) to keep particulate and neutral material from
getting to the mass analyzer (causing unstable signals and
background noise).6 Once the plasma passes through the
skimmer cone, the plasma is in a high vacuum environment;
the smaller particles in the plasma, the electrons, diffuse further from the center of the plasma beam than the larger particles, the positive ions. Since positive ions will repel each
other, those with larger masses will tend to concentrate in the
center of the plasma beam, and force the smaller positive ions
to the periphery.6 At this point, the different metal lenses of
the ion optics, each with different voltages, work together to
select only analyte ions for admission to the mass analyzer;
thus, the analyte ions, if they have moved to the periphery of
the plasma beam, are brought back to the center. An
additional feature to “refine” the plasma beam for the mass
analyzer is to have the analyzer off axis to the ion beam; undesired entities strike a metal plate, while analyte ions are deflected by the ion optics to the mass analyzer.
The mass analyzer, or mass separation device, separates
ions by their mass to charge ratio (m/z). Though there are
different kinds of mass analyzers, the most common type is
the quadropole mass filter,7 made of 4 metal rods of the same
length (approximately 15 to 20 cm long and 1 cm wide),
often of stainless steel or molybdenum. One pair of rods conducts direct current and the other carries a radio frequency
field. Between the 2, only ions of interest can move into and
through the space bordered by the 4 rods until exiting the
quadrupole, and striking the detector to register for detection.
Individual elements are scanned in each sample; depending
on which elements are of interest, scans can cover a range up
to 300 atomic mass units, though even scans of 25 elements
could be done in a few minutes.7 Of course, distinguishing
different elements, or even different isotopes of the same element, from each other demands sufficient resolution from the
mass analyzer. Quadrupole mass analyzers usually have a
working resolution of approximately 1 atomic mass unit.
Last, the detector in the ICP-MS counts the ions emerging
from the mass analyzer and converts their impact to electrical
impulses that are measured. Modern ICP-MS employs something called dual-stage discrete dynode detector technology,
which allows both low and high concentrations of analytes to
be measured in the same scan.8 The basic design measures low
ion concentrations with a pulse signal, while high ion concentrations are measured as an analog signal (either in units of
counts per second). A total range of counts per second between
pulse and analog measures is from 0 to 1,000,000,000; that corresponds to analyte concentrations of 0.1 parts per trillion to
100 parts per million, linear over that range.8
ICP-MS is a prime example of the union of chemistry,
physics, and biology in the modern laboratory for measuring
elements of clinical interest at even vanishingly small concentrations. Like any mature technology, ICP-MS is the result of decades of work and constant refinement; even the
current ability to measure accurately in the parts per trillion
will be superseded by future developments.
1. Thomas R. A beginner’s guide to ICP-MS part I. Spectroscopy. Available
at: http://www.spectroscopymag.com/spectroscopy/data/articlestandard/
spectroscopy/452001/1062/article.pdf. Accessed on December 19, 2003.
2. Highlights of the technique (in “welcome to the ICP-MS laboratory
(homepage)). Available at http://www.gso.uri.edu/icpms/highlights.htm.
Accessed on December 19, 2003.
3. Thomas R. A beginner’s guide to ICP-MS part II: The sample-introduction
system. Spectroscopy. Available at http://www.spectroscopymag.com/
spectroscopy/data/articlestandard/spectroscopy/452001/1066/article.pdf.
Accessed on December 19, 2003.
4. Thomas R. A beginner’s guide to ICP-MS part III: The plasma source.
Spectroscopy. Available at http://www.spectroscopymag.com/
spectroscopy/data/articlestandard/spectroscopy/452001/1096/article.pdf.
Accessed on December 19, 2003.
5. Thomas R. A beginner’s guide to ICP-MS part IV: the interface region.
Spectroscopy. Available at http://www.spectroscopymag.com/
spectroscopy/data/articlestandard/spectroscopy/452001/1097/article.pdf.
Accessed on December 19, 2003.
6. Thomas R. A beginner’s guide to ICP-MS part V: The ion focusing region.
Spectroscopy. Available at http://www.spectroscopymag.com/
spectroscopy/data/articlestandard/spectroscopy/452001/1098/article.pdf.
Accessed on December 19, 2003.
7. Thomas R. A beginner’s guide to ICP-MS part VI: The mass analyzer.
Spectroscopy. Available at http://www.spectroscopymag.com/
spectroscopy/data/articlestandard/spectroscopy/452001/1099/article.pdf.
Accessed on December 19, 2003.
8. Thomas R. A beginner’s guide to ICP-MS part X - detectors. Spectroscopy.
Available at http://www.spectroscopymag.com/spectroscopy/data/
articlestandard/spectroscopy/152002/15304/article.pdf. Accessed on
December 19, 2003.
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