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ABSTRACT
Inductively coupled plasma mass spectrometry (ICP-MS) is a type of mass spectroscopy that is
highly sensitive and capable of the determination of a range of metals and several non-metals at
concentrations below one part in 1012 (part per trillion). Inductively coupled plasma mass
spectrometry is a method used for separating and detecting the ions. In trace elemental analysis,
the method has advantages of high speed, precision and sensitivity compared to atomic
absorption technique1. It is an analytical technique used for elemental determinations. This
technique is superior to detection capability of ICP-AES with the same sample throughput and
the ability to obtain isotopic information.
INTRODUCTION
An inductively coupled plasma (ICP) is a type and soil science, mining/metallurgy, food
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of plasma source in which the energy is sciences .
supplied by electric currents which are The most important things to remember about
1
produced by electromagnetic induction, that is, the argon ICP plasma are
1
by time-varying magnetic fields .There are two 1. The argon discharge with a
types of ICP geometries: planar and temperature of around 6000-10000°K is an
cylindrical. In planar geometry, the electrode is excellent ion source.
a coil of flat metal wound like a spiral. In 2. The ions formed by the ICP discharge
+ +
cylindrical geometry, it is like a helical spring. are typically positive ions, M or M ², therefore,
Inductively Coupled Plasma Mass elements that prefer to form negative ions
Spectrometry was commercially introduced in such as Cl, I, F, etc., are very difficult to
1983 and has gained general acceptance in determine via ICP-MS.
many types of laboratories. Inductively 3. The detection capabilities of the
Coupled Plasma Mass Spectrometry is an technique can vary with the sample
analytical technique used for elemental introduction technique which allows differing
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determinations . The resulting instrument is amounts of sample to reach the ICP plasma.
capable of identifying trace multielement 4. Detection capabilities will vary with the
analysis, often at the part per trillion levels. sample matrix, which may affect the degree of
ICP-MS has been used widely over the years, ionization that will occur in the plasma or allow
finding applications in a number of different the formation of species that may interfere with
fields including drinking water, wastewater, the analyte determination.
natural water systems/hydrogeology, geology
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where the ions arrive at the detector electrons. The released electron is in turn
sequentially or a simultaneous process where accelerated by the rapidly changing magnetic
the ions are sampled at the same time. field. The process continues until the rate of
In the final process, an ion detector converts release of new electrons in collisions is
the ions into an electrical signal. The most balanced by the rate of recombination of
common design used today is a discrete electrons with argon ions (atoms that have lost
dynode detector, which contains a series of an electron). This produces a ‘fireball’ that
metal dynodes along the length of the detector consists mostly of argon atoms with a rather
[4]
. In this design, when the ions emerge from small fraction of free electrons and argon ions.
the mass filter, they impinge on the first The temperature of the plasma is very high, of
5
dynode and are converted into electrons. As the order of 10,000 K .
the electrons are attracted to the next dynode, The ICP can be retained in the quartz torch
electron multiplication takes place, resulting in because the flow of gas between the two
a very high stream of electrons emerging from outermost tubes keeps the plasma away from
the final dynode. This electronic signal is then the walls of the torch. A second flow of argon
processed by the data handling system in the (around 1 liter per minute) is usually
conventional way and converted into analyte introduced between the central tube and the
concentration using ICP-MS calibration intermediate tube to keep the plasma away
standards. Most detection systems used can from the end of the central tube. A third flow
handle up to eight orders of dynamic range, (again usually around 1 liter per minute) of gas
which means they can be used to analyze is introduced into the central tube of the torch.
samples from low parts-per-trillion (ppt) levels, This gas flow passes through the center of the
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up to hundreds of parts-per-million (ppm) . plasma, where it forms a channel that is cooler
Most commercial ICP mass spectrometers, than the surrounding plasma but still much
particularly the quadrupole models, use just hotter than a chemical flame. Samples to be
one detector. However, specialized magnetic- analyzed are introduced into this central
sector ICP-MS instrumentation with multiple channel, usually as a mist of liquid formed by
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detectors is available for isotopic ratio passing the liquid sample into a nebulizer .
analysis. As a droplet of nebulized sample enters the
central channel of the ICP, it evaporates and
COMPONENTS any solids that were dissolved in the liquid
Inductively coupled plasma vaporize and then break down into atoms. At
Inductively coupled plasma is plasma that the temperatures prevailing in the plasma a
contains a sufficient concentration of ions and significant proportion of the atoms of many
electrons to make the gas electrically chemical elements are ionized, each atom
conductive. The plasmas used in losing its most loosely bound electron to form
spectrochemical analysis are essentially a singly charged ion.
electrically neutral, with each positive charge
on an ion balanced by a free electron. In these Mass spectrometry
plasmas the positive ions are almost all singly For coupling to mass spectrometry, the ions
charged and there are few negative ions, so from the plasma are extracted through a series
there are nearly equal amounts of ions and of cones into a mass spectrometer, usually a
electrons in each unit volume of plasma. quadrupole. The ions are separated on the
Inductively coupled plasma (ICP) for basis of their mass-to-charge ratio and a
spectrometry is sustained in a torch that detector receives an ion signal proportional to
consists of three concentric tubes, usually the concentration.
made of quartz. The end of this torch is placed The concentration of a sample can be
inside an induction coil supplied with a radio- determined through calibration with certified
[5]
frequency electric current . A flow of argon reference material such as single or multi-
gas (usually 14 to 18 liters per minute) is element reference standards. ICP-MS also
introduced between the two outermost tubes lends itself to quantitative determinations
of the torch and an electric spark is applied for through Isotope Dilution, a single point method
a short time to introduce free electrons into the based on an isotopically enriched standard.
gas stream. These electrons interact with the Other mass analyzers coupled to ICP systems
radio-frequency magnetic field of the induction include double focusing magnetic-electrostatic
coil and are accelerated first in one direction, sector systems with single and multiple
then the other, as the field changes at high collector, as well as time of flight systems
frequency. The accelerated electrons collide (both axial and orthogonal accelerators have
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with argon atoms, and sometimes a collision been used .
causes an argon atom to part with one of its
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INSTRUMENT DESCRIPTION AND THEORY used to transmit radio frequency to the heated
ICP technology was built upon the same argon gas, producing an argon plasma "flame"
principles used in atomic emission located at the torch.The hot plasma removes
spectrometry. Samples are decomposed to any remaining solvent and causes sample
neutral elements in high temperature argon atomization followed by ionization. In addition
plasma and analyzed based on their mass to to being ionized, sample atoms are excited in
charge ratios (fig 1). the hot plasma, a phenomenon which is used
in ICP-atomic emission spectroscopy. Shown
Sample Introduction to the right is an ICP torch. The aerosol moves
The first step in analysis is the introduction of into the bottom of the torch body. The green
the sample. This has been achieved in ICP- ports on the right side of the body are where
MS through a variety of means. ICP-MS more argon is introduced to the flow. At the top
spectrometers can accept solid as well as are two high quality quartz tubes and an inner
liquid samples. Solid samples are introduced alumina injector tube (fig 3).
into the ICP by way of a laser ablation system
which can usually be purchased as an ICP-MS Interface
accessory. Aqueous samples are introduced Because atomization/ionization occurs at
by way of a nebulizer which aspirates the atmospheric pressure, the interface between
sample with high velocity argon, forming a fine the ICP and MS components becomes crucial
mist. The aerosol then passes into a spray in creating a vacuum environment for the MS
chamber where larger droplets are removed system. Ions flow through a small orifice,
via a drain (fig 2). approximately 1 millimeter in diameter, into a
The most common method is the use of a pumped vacuum system. Here a supersonic
nebulizer. This is a device which converts jet forms and the sample ions are passed into
liquids into an aerosol, and that aerosol can the MS system at high speeds, expanding in
then be swept into the plasma to create the the vacuum system. The entire mass
ions. Nebulizers work best with simple liquid spectrometer must be kept in a vacuum so
samples (i.e. solutions). However, there have that the ions are free to move without
been instances of their use with more complex collisions with air molecules. Since the ICP is
materials like slurry. Many varieties of maintained at atmospheric pressure, a
nebulizers have been coupled to ICP-MS, pumping system is needed to continuously pull
which includes pneumatic, cross-flow, a vacuum inside the spectrometer. In order to
Babington, ultrasonic, and desolating types. most efficiently reduce the pressure several
The aerosol generated is often treated to limit pumps are typically used to gradually reduce
-5
it to only smallest droplets, commonly by pressure to 10 mbar before the ion stream
means of a double pass or cyclonic spray reaches the quadruple. If only one pump were
chamber. Use of auto samplers makes this used, its size would be excessive to reduce
easier and faster. the pressure immediately upon entering the
Less commonly, the laser ablation has been mass spectrometer.
used as a means of sample introduction. In
this method, a laser is focused on the sample Plasma torch
and creates a plume of ablated material which The plasma used in an ICP-MS is made by
+ −
can be swept into the plasma. This is partially ionizing argon gas (Ar → Ar + e ).
particularly useful for solid samples, though The energy required for this reaction is
can be difficult to create standards for leading obtained by pulsing an electrical current in
the challenges in quantitative analysis. wires that surround the argon gas.
Other methods of sample introduction are also After the sample is injected, the plasma's
utilized. Electro thermal vaporization (ETV) extreme temperature causes the sample to
and in torch vaporization (ITV) hot surfaces separate into individual atoms (atomization).
(graphite or metal, generally) are used to Next, the plasma ionizes these atoms (M →
+ −
vaporize samples for introduction. These can M + e ) so that they can be detected by the
use very small amounts of liquids, solids, or mass spectrometer (fig 4).
slurries. Other methods like vapor generation Inductively coupled plasma (ICP) for
are also known. spectrometry is sustained in a torch that
consists of three concentric tubes, usually
Argon Plasma/Sample Ionization made of quartz. The end of this torch is placed
Once the sample passes through the inside an induction coil supplied with a radio-
nebulizer and is partially de solvated, the frequency electric current. A flow of argon gas
aerosol moves into the torch body and is (usually 14 to 18 liters per minute) is
mixed with more argon gas. A coupling coil is introduced between the two outermost tubes
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of the torch and an electrical spark is applied ion will have a specific m/z ratio. Many
for a short time to introduce free electrons into combinations of voltages are chosen which
the gas stream. These electrons interact with allows an array of different m/z ratio ions to be
the radio-frequency magnetic field of the detected.
induction coil and are accelerated first in one Shown below is animation of this process.
direction, then the other, as the field changes Three mass fragments enter into the
at high frequency (usually 27.12 MHz). The quadrupole vacuum chamber. The voltage of
accelerated electrons collide with argon the rods is set so that only the pink mass
atoms, and sometimes a collision causes an fragment passes completely through the
argon atom to part fraction of free electrons quadrupole rod array and into the detector.
and argon ions. The green and blue fragments are unstable at
An ICP-MS combines a high-temperature ICP this voltage combination and their path
(Inductively Coupled Plasma) source with a eventually brings them into contact with the
mass spectrometer. The ICP source converts rods so that they never reach the detector (fig
the atoms of the elements in the sample to 6).
ions. These ions are then separated and Quadrupole rods require periodic maintenance
detected by the mass spectrometer. and cleaning due to the buildup of ions which
Figure 5 shows a schematic representation of are removed during the mass discrimination
an ICP source in an ICP-MS. Argon gas flows process. These ions form a film which
inside the concentric channels of the ICP eventually builds up and dulls the metallic
torch. The RF load coil is connected to a radio- surface. To remove this film the vacuum
frequency (RF) generator. As power is chamber must be repressurized and
supplied to the load coil from the generator, disassembled. This process can be time
oscillating electric and magnetic fields are consuming and very delicate but is essential to
established at the end of the torch (fig 5). keep a mass spectrometer performing well (fig
The sample is typically introduced into the ICP 7).
plasma as an aerosol, either by aspirating a Once the ions enter the mass spectrometer,
liquid or dissolved solid sample into a they are separated by their mass-to-charge
nebulizer or using a laser to directly convert ratio. The most commonly used type of mass
solid samples into an aerosol. Once the spectrometer is the quadrupole mass filter. In
sample aerosol is introduced into the ICP this type, 4 rods (approximately 1 cm in
torch, it is completely desolvated and the diameter and 15-20 cm long) are arranged as
elements in the aerosol are converted first into in (Fig 8).
gaseous atoms and then ionized towards the In a quadrupole mass filter, alternating AC and
end of the plasma. DC voltages are applied to opposite pairs of
the rods. These voltages are then rapidly
Mass Spectrometer switched along with an RF-field. The result is
In the first stage of the mass spectrometer that an electrostatic filter is established that
ions are removed from the plasma by a only allows ions of a single mass-to-charge
pumped extraction system. An ion beam is ratio (m/e) pass through the rods to the
produced and focused further into the actual detector at a given instant in time. So, the
unit. There are several different types of mass quadrupole mass filter is really a sequential
analyzers which can be employed to separate filter, with the settings being change for each
isotopes based on their mass to charge ratio. specific m/e at a time. However, the voltages
Quadrupole analyzers are compact and easy on the rods can be switched at a very rapid
to use but offer lower resolution when dealing rate. The result is that the quadrupole mass
with ions of the same mass to charge (m/z) filter can separate up to 2400 amu (atomic
ratio. Double focusing sector analyzers offer mass units) per second.
better resolution but are larger and have
higher capital cost. Detector
The quadrupole mass filter is made up of four The most common type of ion detector found
metal rods aligned in a parallel diamond in an ICP-MS system is the channeltron
pattern. A combined DC and AC electrical electron multiplier. This cone or horn shaped
potential is applied to the rods with opposite tube has a high voltage applied to it opposite
rods having a net negative or positive in charge to that of the ions being detected.
potential. Ions enter into the path between all Ions leaving the quadrupole are attracted to
of the rods. When the DC and AC voltages are the interior cone surface. When they strike the
set to certain values only one particular ion is surface additional secondary electrons are
able to continue on a path between the rods emitted which move farther into the tube
and the others are forced out of this path. This emitting additional secondary electrons (fig 9).
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As the process continues even more electrons the users can further this by diluting
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are formed, resulting in as many as 10 samples with known high concentration
electrons at the other end of the tube after one values or choosing a less abundant
ion strikes at the entrance of the cone. The isotope for their analysis.
drawing below is an illustration of electron 3. They are expensive. A new detector will
multiplying and the photograph is an actual cost on the order of $1500-2500
electron multiplier removed from a mass depending on the specific type. Care
spectrometer for cleaning. Importance of should be taken to protect it.
cleaning is similar to that of the quadrupole 4. They are light sensitive. Most detectors
rods (fig 10). are as sensitive to photons as they are to
ions. Care should be taken to store spare
A few things to remember about the ICP-MS detectors in the dark and never expose a
detector detector to the light while the high voltage
1. It is a consumable item. As ions hit the power supply to it is on.
surface of the detector and are converted
to electrons, the active film coating will be Detection Limits
consumed. Depending on usage, a typical One of the great advantages to ICP-MS is
discrete dynode detector will last 6-18 extremely low detection limits for a wide
months in a quadrupole ICP-MS. variety of elements. Some elements can be
2. It should be protected from high signal measured down to part per quadrillion range
count rates. Most manufacturers' design while most can be detected at part per trillion
the detector circuitry to protect it from levels. The table below shows some common
potentially fatal ion count rates. However, detection limits by element.
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argon in the sample. Other blocked regions to blockages as some of the ions reunite
may include mass 80 (due to the argon dimer), after leaving the torch and build up around
and mass 56 (due to ArO), the latter of which the orifice of the skimmer cone. This can
greatly hinders Fe analysis unless the be avoided by diluting samples whenever
instrumentation is fitted with a reaction high salt concentrations are suspected,
chamber. though at a cost to detection limits.
A typical ICP-MS will be able to detect in the 6. Quantification of proteins and bio
region of Nano grams per liter to 10 or 100 molecules by icp-ms: There is an
milligrams per liter or around 8 orders of increasing trend of using ICP-MS as a tool
magnitude of concentration units. in speciation analysis normally involves a
front end chromatograph separation and
PHARMACEUTICAL APPLICATIONS an elemental selective detector such as
1. One of the largest volume uses for ICP- AAS and ICP-MS. For example, ICP-MS
MS is in the medical and forensic field, may be combined with size exclusion
specifically, toxicology. A physician may chromatography and quantitative
order a metal assay for a number of preparative native continuous
reasons, such as suspicion of heavy metal polyacrylamide gel electrophoresis for
poisoning, metabolic concerns, and even identifying and quantifying native metal in
hepatological issues. Depending on the bio fluids. Also the phosphorylation status
specific parameters unique to each of proteins can be analyzed.
patient's diagnostic plan, samples 7. A new type of protein tagging reagents
collected for analysis can range from called metal coded affinity tags (Me CAT)
whole blood, urine, plasma, serum, to were introduced to label proteins
even packed red blood cells. quantitatively with metals, especially
2. Another primary use for this instrument lanthanides. The Me CAT labeling allows
lies in the environmental field. Such relative and absolute quantification of all
applications include water testing for kind of proteins or other biomolecules like
municipalities or private individuals all the peptides. Me CAT comprises a site-
way to soil, water and other material specific biomolecule tagging group with at
analysis for industrial purposes. least a strong chelate group which binds
3. This technique is also widely used the field metals.
of radiometric dating, in which it is used to 8. The Me CAT labeled proteins can be
analyze relative abundance of different accurately quantified by ICP-MS down to
isotopes. ICP-MS is more suitable for this low attomol amount of analyte which is at
application than the previously used least 2–3 orders of magnitude more
Thermal Ionization Mass Spectrometry, as sensitive than other mass spectrometry
species with high ionization energy such based quantification methods.
as Osmium (Os) and Tungsten (Hf-W) can 9. By introducing several Me CAT labels to a
be easily ionized. biomolecule and further optimization of
4. In the field of flow cytometry, a new LC-ICP-MS detection limits in the
technique uses ICP-MS to replace the zeptomol range are within the realms of
traditional fluorochromes. Briefly, instead possibility. By using different lanthanides
of labeling antibodies (or other biological Me CAT multiplexing can be used for
probes) with fluorochromes, each antibody pharmacokinetics of proteins and peptides
is labeled with a distinct combination of or the analysis of the differential
lanthanides. expression of proteins e.g. in biological
5. Regardless of the sample type, blood, fluids.
water, etc., it is important that it be free of
clots or other particulate matter, as even CONCULSION
the smallest clot can disrupt sample flow It is here by concluded that this technique is
and block or clog the sample tips within superior to other technique giving the result’s
the spray chamber. Very high up to a level of one part in trillion by using
concentrations of salts, e.g. sodium same sample.
chloride in sea water, can eventually lead
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ABBREVATIONS
ICP-MS: - Inductively coupled plasma mass
spectrometry.
LA ICP-MS: - Laser Ablation Inductively
Coupled Plasma Mass Spectrometry.
Fig. 7: Photo of quadrupole rods from AC: - Alternating Current.
mass spectrometer DC: -Direct Current.
ETV:-Electro thermal Vaporization
ITV: - In Torch Vaporization.
AMU:-Atomic Mass Unit
RF:-Radio Frequency.
M/z: - Mass to charge ratio.
Me CAT:-Metal coded affinity tags.
REFERENCES
1. Montaser.A and Golightly DW.
Inductively Coupled Plasmas in
Analytical Atomic Spectrometry, VCH
Publishers, Inc., New York, 1992.
2. B'Hymer , Clayton, Judith A Brisbin,
Karen L Sutton and Joseph A. Caruso.
Fig. 8: Schematic of quadrupole mass filter "New approaches for elemental
speciation using plasma mass
spectrometry." American Laboratory.
2000;32(3):17-32.
3. Jarvis KE, AL Gray and RS Houk.
Handbook of Inductively Coupled
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680