- Email: [email protected]
Inductively Coupled Plasma Mass Spectrometry Methods
Inductively Coupled Plasma Mass Spectrometry Methods D Beauchemin, Queen’s University, Kingston, ON, Canada ã 2017 Elsevier Ltd. All rights reserved.
Inductively coupled plasma mass spectrometry (ICP-MS) combines an ICP with a mass spectrometer. It features a multielemental capability, good precision, a long linear dynamic range, simple spectra, low detection limits, and the ability to do rapid isotopic analysis. With such advantages, ICP-MS has found wide application to the analysis of a variety of samples, including water and food, as well as geochemical, environmental, and biological samples. However, it has a number of limitations, such as matrix effects, which can be important, and the need to keep the concentration of dissolved solids low to avoid clogging problems. These complicate the analysis by requiring sample pretreatment and/or more involved calibration strategies. Nonetheless, with the appropriate method development and/or optional accessories, these limitations can be largely circumvented, thereby allowing ICP-MS to be applied to the analysis of virtually any type of sample.
Description of a Basic ICP-MS Instrument Figure 1 shows a block diagram of a typical ICP-MS instrument. A 1–2.5 kW Ar ICP is the typical ion source for MS. The ICP is a high-temperature (5000–10 000 K, depending on operating conditions and location in the plasma) electrodeless discharge that is sustained in argon flowing within a torch. It is partially ionized Ar (with typically less than 1% of the Ar being ionized).1 The plasma is generated and sustained by the plasma gas that tangentially flows in the outer tube of a quartz torch and also isolates it from the walls of the torch. An auxiliary gas is used during ignition to carry the seed electrons generated by a spark from a Tesla coil to the magnetic field produced by the radio-frequency (RF) current supplied by a generator through a water-cooled Cu coil (called load coil). These electrons move in circular orbits around the magnetic field until they collide with some Ar atoms and cause them to become ionized, generating electrons that also get caught in this self-perpetuating process, which continues as long as there are an RF current and plasma gas. The auxiliary gas is also used to position the plasma so as to prevent melting of the inner tubes. In general, the ICP uses samples in solution, which presents the advantages of good control over homogeneity and ease of calibration. A sample solution is delivered to a nebulizer using a peristaltic pump to minimize physical interferences (from, for instance, changes in viscosity). The nebulizer converts this solution into an aerosol that is then carried by the nebulizer gas (also called aerosol carrier gas) through a spray chamber where large droplets drain out. This aerosol filtering is required to prevent plasma extinction by solvent overloading. The Diane Beauchemin, Inductively Coupled Plasma Mass Spectrometry, Methods, In Encyclopedia of Spectroscopy and Spectrometry (Second Edition), edited by John C. Lindon, Academic Press, Oxford, 1999, Pages 1005–1010.
236
resulting fine aerosol, which typically constitutes 2–5% of the sample (the rest going down the drain), is injected into the heart of the plasma and undergoes several processes sequentially, as it moves deeper into the plasma: desolvation, vaporization, atomization, and finally ionization, as illustrated in Figure 2. These processes take energy from the plasma, resulting in a cooler central region, called the central channel (Figure 1). In an Ar ICP, the degree of ionization of 52 elements is expected to be 90%.2 Only three elements (He, F, and Ne) that possess a first ionization potential greater than that of Ar would not be significantly ionized and could therefore not be determined by ICP-MS with an Ar ICP. Similarly, the highest degree of double ionization is 10% and occurs only for a few elements.2 The ICP is therefore an efficient elemental ion source for MS since the majority of elements in the periodic table are singly ionized. A portion of the plasma (which is typically three sampler orifice diameters wide and two sampler orifice diameters deep)3 is sampled from the central channel of the plasma and extracted through a differentially pumped interface (through two water-cooled metal cones with orifice diameter 1 mm, the sampler and the skimmer (see Figure 1)), which is maintained at approximately 1 Torr using a mechanical roughing pump and whose main purpose is to evacuate most of the argon gas. Because of the expansion taking place in the interface, only the centerline flow of the sampler, which is slightly smaller than the sampler orifice diameter, actually passes the skimmer.3 The ion optic then separates electrons from analyte ions, resulting in a positive ion beam that is then transmitted into the mass spectrometer where ions are separated according to their mass-to-charge ratios (m/z) (in Daltons) and then counted. The detector is usually installed off-axis (i.e., not in line with the ion source) to minimize the background noise that can be generated by photons. Different mass spectrometers are used in the current commercially available ICP-MS instruments. The most compact ones use a quadrupole to achieve ion separation based on a dynamic arrangement of electromagnetic fields through which only ions of a certain mass will have a stable path and reach the detector (Figure 3). As a result, ions of different m/z are separated sequentially. An alternative is a time-of-flight (TOF) tube. With TOFMS, packets of ions, which must first have been accelerated to the same kinetic energy, are admitted into the flight tube, where they each acquire a velocity that is inversely proportional to mass and thus have a travel time that is proportional to mass (Figure 4). Because this separation can be done very quickly over the atomic mass range, i.e., 10 000–50 000 mass spectra can be acquired per second,4 TOFMS allows the quasi-simultaneous detection of elements over the whole mass range. However, it is the least utilized approach in ICP-MS because of its low duty cycle. Indeed, because all ions of a given m/z arrive at the detector within
Encyclopedia of Spectroscopy and Spectrometry, Third Edition
http://dx.doi.org/10.1016/B978-0-12-409547-2.11222-3
Inductively Coupled Plasma Mass Spectrometry Methods
237
Figure 1 Block diagram of a typical ICP-MS instrument along with the function of its main components.
Figure 2
Main processes involved in the generation of ions in ICP-MS.
Figure 3 Operating principles of a quadrupole mass analyzer.
1–10 ns, only a single ion of a given m/z can be counted in each mass spectrum with ion counting detectors.4 Furthermore, ions generated while a given packet of ions is undergoing separation are not measured at all. Double-focusing instruments use a magnetic sector analyzer, for momentum focusing, and an electrostatic analyzer, for energy focusing, in series.4 Different geometries are available, depending on the vendor, which are illustrated in Figure 5. Single-collector (shown in Figure 5) and multicollector versions of instruments with the Matsuda (a) or
Nier–Johnson (b) geometry are available. In the latter case, several detectors are used to simultaneously detect ions over a narrow mass range. Only the Mattauch–Herzog geometry (c) allows simultaneous detection over the whole mass range. Despite being significantly more expensive than quadrupole-based instruments, double-focusing instruments are nonetheless relatively popular because of distinctive features. For instance, instruments with geometry a or b can be operated at low (R ¼ 300–500), medium (R ¼ 4000), or high (R ¼ 10 000–15 000) resolving power, R (defined as m/Dm at 5% height),4 increasing R being simply attained by narrowing the slit widths. Nonetheless, this allows the resolution of several spectroscopic interferences occurring when a polyatomic ion has the same nominal mass as the analyte ions (such as 40 16 þ Ar O vs 56Feþ) that plague quadrupole-based instruments. The low resolving power setting is equivalent to that achieved with quadrupole-based instruments as well as with TOF instruments with axial geometry (where the ion beam and flight axis are coaxial). Double-focusing instruments with geometry c and TOF instruments with orthogonal geometry (where the ion beam and flight axis are at right angle from each other) currently offer better R than low resolving power instruments but usually less than 4000. Another distinctive feature of double-focusing instruments is the negligible background across the mass range. This results from the curved path that the ion beam must follow, which efficiently prevents photons from reaching the detector, as well as from the operating pressure that is considerably lower than that of quadrupole and TOF instruments, thereby minimizing collisional processes in the ion beam. However, like the quadrupole-based instruments, double-focusing instruments with geometry a or b allow a sequential multielement measurement. Quasi-simultaneous multielement detection is done by ICP-TOFMS. Only the double-focusing instrument with geometry c allows truly simultaneous detection over the entire mass range. To get around the problem of spectroscopic interferences, most quadrupole instruments can come with a collision/ reaction cell or interface option, where collisions or reactions with a gas can be used to either break the interfering
238
Inductively Coupled Plasma Mass Spectrometry Methods
Figure 4 Operating principles of a TOF mass analyzer.
Figure 6 Example of the operation of a tandem mass spectrometer. The analyte ion (orange) is separated from ions of different m/z by quadrupole one. A gas is added to the collision/reaction cell to break up the interfering polyatomic ion (blue), and the second quadrupole is finally used to isolate analyte ions.
cell to systematically bring back ions to the center of the rods, even if they were deflected by a collision. Different types of cells are used (quadrupole, octopole, etc.), depending on the vendor. In the collision/reaction interface, the gas is simply added through the tip of a hollow skimmer or sampler. A tandem mass spectrometer (Figure 6) can also be used for even better resolution of interferences.
Capabilities of ICP-MS Figure 5 Operating principles of different double-focusing mass analyzers.
polyatomic ion (as illustrated in the collision cell of Figure 6) or transform the analyte into a polyatomic ion of heavier mass than the interfering one, hence allowing its detection in an interference-free region of the mass spectrum.5 With these instruments, even some isobaric interferences can be resolved, which is not possible with double-focusing instruments even at high resolving power. The only requirement is that either the interfering ion or the analyte ion (but not both) reacts with the reaction gas. In all cases, the collision/reaction cell precedes the quadrupole (i.e., essentially Figure 6 without the first quadrupole). An RF-only field can be used in the collision
Table 1 summarizes key features of ICP-MS, which also offers the advantages of working with samples in solution and providing good precision. Even with sequential instruments, the multielement capability of ICP-MS allows the determination of, for instance, 70 elements in less than 2 min, using less than 2 ml of solution at an uptake rate of 1 ml min1. Detection limits are 1 ng l1 for many elements with quadrupole instruments and even lower with double-focusing instruments operated in low mass resolving power mode. This difference arises from the lower background obtained on the latter instruments, as well as the higher reliability in peak hopping, as flattop peaks are generated. With the exception of ICPTOFMS, which is inherently limited by a lower duty cycle, sensitivity (i.e., the slope of a calibration curve) is similar on
Inductively Coupled Plasma Mass Spectrometry Methods
Table 1
239
Major features of ICP-MS
Feature
Advantage
Implications
Linear dynamic range
At least nine orders of magnitude
Detection limit (based on three standard deviations of the blank signal) Mass spectrum
Down to sub ng l1, depending on the element Simple: only 1–10 lines per element
Major, minor, trace, and ultratrace levels of elements may all be determined at once Enables ultratrace analysis
Isotope information
Isotope ratio measurement
Multielement capability
Determination of all elements but He, F, Ne, and Ar
Table 2
Less spectroscopic interferences than in ICP optical emission spectrometry But few or no alternative in case of interference Enables the most accurate calibration strategy: isotope dilution analysis High sample throughput
Examples of applications of ICP-MS
General category
Sample types
Sample pretreatment
Reference
Water
Seawater, industrial wastewater, pore water, river water, freshwater, rain, groundwater, lake water, spring water, snow, tap water, high-purity water
6
Environmental and geochemical
Soil, dust, leaves, sediments, sewage, industrial effluents, paint, atmospheric aerosols, suspended particulate matter, tobacco smoke condensate, domestic sludge, glass, spent nuclear fuel, leachates of high-activity waste, rocks, metals, ores, alloys, ceramic materials Seafood, flours, vegetables, wine, beef kidney, milk, etc. Fecal material, urine, human serum, plasma, red blood cells, whole blood, cerebrospinal fluids Ultrapure water, high-purity HF, H2O2, NH4OH, HCl, H2SO4, 2-propanol, photoresist, Si wafer; high-purity gases (N2, O2, H2, arsine, silane, phosphine) Crude oil, gasoline
Filtration and any of the following: acidification and dilution, ion exchange separation to remove interferents and/or preconcentrate analytes, preconcentration by evaporation Crushing or grinding and either digestion with highpurity acids or fusion and dissolution, followed by dilution
Food Biological Semiconductor
Organic
all instruments in low mass resolving power. It is degraded by increasing mass resolving power because the width of the entrance and exit slits on double-focusing instruments are then decreased, which leads to a reduction in ion transmission. In any case, isotope ratios can readily be measured. For applications requiring high-precision isotope ratios, simultaneous detection of the different isotopes is required, which is best achieved using double-focusing instruments with geometry c (see Figure 5) over the entire mass range or with multicollectors for a few elements over a narrow mass range. In any case, all instruments enable the most accurate calibration using isotope dilution analysis, which essentially involves internal standardization with an enriched isotope of the analyte. All these features explain why even the basic ICP-MS instrument is being applied to analyses in a variety of areas. For instance, Table 2 shows that ICP-MS is widely used for environmental, clinical, and geochemical studies, with appropriate sample preparation procedures. These are required not only to put solid samples in solution but also to avoid or circumvent limitations of ICP-MS by, for instance, removing sources of interference.
Digestion with high-purity acids followed by dilution Dilution or drying, ashing, and/or digestion with highpurity acids followed by dilution or extraction Dilution of aqueous samples, digestion, vapor phase decomposition of Si, impinger method for gases Extraction into aqueous acidic solution
6–8
9 10 11
12,13
Limitations of ICP-MS Whatever the mass resolving power, detection limits (and more realistically determination limits in a given matrix) vary with the element being determined by ICP-MS. There are, indeed, several factors affecting them. The degree of ionization of the analyte, the natural abundance of the isotope that is used for the determination of a particular element, spectroscopic interferences from the background and/or the sample matrix, and mass bias are the most notorious sources of degradation. Obviously, if an element is only 50% ionized in the plasma, then its detection limit will be reduced by a factor of 2 compared to an element that is completely ionized. Similarly, if only one isotope of a multi-isotope element is detected, the resulting detection limit will be less than that of a monoisotopic element. Furthermore, the sample introduction system is the Achilles heel of all ICP-based instruments. Indeed, only about 2–5% of the sample solution actually reaches the plasma with a conventional system (composed of a pneumatic nebulizer and spray chamber, as shown in Figure 1), most of it going down
240
Inductively Coupled Plasma Mass Spectrometry Methods
the drain. This means, therefore, that only a small fraction of the total possible signal is measured. As mentioned earlier, because the mass spectrum is simple, the likelihood of spectroscopic interferences is reduced, particularly with high mass resolving power instruments. However, when they occur, the number of alternative lines is small (there are indeed a number of monoisotopic elements). One example of an isobaric interference that cannot be resolved even at high mass resolving power is that of 40Arþ on 40Caþ, the major isotope of Ca. Other severe interferences arise from Arcontaining polyatomic ions as well as oxides of matrix elements. Several of these can be resolved at higher resolution but with a concurrent sacrifice in sensitivity and detection limits. On low mass resolving power instruments, a ‘cold plasma,’ where the ICP is operated at lower power and higher nebulizer gas flow rate, can be used to reduce important interferences from the background, but, again, a lower sensitivity concurrently results across the mass range. Collision/reaction cells are very useful to reduce interferences from polyatomic ions and do so with a much smaller sacrifice in sensitivity than a cold plasma. Because repulsion of like charges or space-charge effects can occur in the ion beam on its way to the mass spectrometer and that the extent of such repulsion depends on total ion current, the response of the instrument is not constant across the mass range, as illustrated in Figure 7. The shape of this curve depends on the instrument and operating conditions and can change in the presence of a given matrix, especially if the latter significantly increases the total ion current. Nonetheless, in general, the transmission of light ions is reduced compared with heavier ions, as they are more easily repelled, which is why this effect is referred to as mass bias. The worst suppression is observed for a light analyte in the presence of a matrix of heavy element. Another parameter that may also affect the detection capability of ICP-MS is the plasma sampling position, which may not be optimal for all the analytes being determined simultaneously.14 This position is indeed important to
maximize the density of analyte ions extracted from the ICP. Even the chemical form (i.e., speciation) of an element in solution may influence where it undergoes the various processes (desolvation, vaporization, etc.) in the plasma, ultimately determining where the maximum ion density will be. The sampling process itself is the source of another limitation: because part of the plasma passes through a small orifice, this orifice can become clogged by dissolved solids. The maximum concentration of dissolved solids that can be tolerated on a continuous basis is 0.2%. Finally, even if this level is kept reasonably low, nonspectroscopic interferences (also called matrix effects) can occur, whereby the analyte signal is either suppressed or enhanced by the presence of other elements. For example, a heavy matrix element will in general induce a more important suppression than a light matrix element because of space–charge effects. The signal of elements that are not completely ionized in the ICP may be enhanced by carboncontaining matrices as a result of an additional ionization mechanism involving charge transfer with carbon ions.15 However, the extent of matrix effects is still largely unpredictable, which complicates the calibration process for samples that do not possess a relatively simple matrix. Whenever possible, a simple dilution of the sample is recommended to minimize such nonspectroscopic interferences, as they depend on the absolute amount of concomitant element. The various calibration strategies available with ICP-MS are summarized in Table 3, along with implications of the aforementioned limitations. (More elaborate chemometric calibration procedures have also been developed by a few groups.) In general, unless the sample matrix is simple, internal standardization (or frequent calibration through sample-standard bracketing) will be required for quantitative analysis using external calibration with a series of standard solutions. The choice of the internal standard(s) depends on the instrument, the sample, etc. For the best results, an element with properties similar to that of the analyte (so that it will behave similarly in ICP-MS) is needed. Similarity in mass is thus a prerequisite as well as similarity in first ionization potential for elements that
Figure 7 Example of the response from an ICP-MS instrument, corrected for the varying degree of ionization of elements.
Inductively Coupled Plasma Mass Spectrometry Methods
Table 3
Calibration strategies in ICP-MS
Method
Requirements
Quality of results
External calibration
One isotope free of spectroscopic interference per analyte Matrix matching and/or correction for drift (using internal standardization or frequent calibration) One isotope free of spectroscopic interference per analyte May require a correction for drift (using internal standardization) Two isotopes free of spectroscopic interference per analyte Good equilibrium between isotopic spike and sample
Good accuracy and precision
Standard additions Isotope dilution
are not completely ionized. So, several internal standards may be required for a multielemental analysis spanning the entire mass range. The method of standard additions efficiently compensates for matrix effects but not for drift. If the latter is also present (for instance, because of gradual clogging), internal standardization may also be required. The best method to compensate for both matrix effects and drift is isotope dilution analysis. However, it is only applicable to elements with at least two isotopes (stable and/or long-lived radioactive) free of spectroscopic interferences. However, this normally standardless technique requires a prior determination of mass bias using standards of known isotopic composition in order to correct the measured isotope ratios for the nonuniform instrument response.
Accessories Available to Expand the Capabilities of ICP-MS Several more or less expensive accessories can be readily interfaced to ICP-MS to circumvent one or more of the aforementioned limitations. The most frequently used are summarized in Table 4. The sample introduction system can simply be replaced by a high-efficiency one, such as an ultrasonic nebulizer coupled to a desolvation system, which provides up to 30% analyte transport efficiencies.16 Other high-performance nebulization systems include a direct injection nebulizer, which introduces 100% of the sample directly into the plasma (i.e., no spray chamber is needed), or a high-efficiency nebulizer; but they are prone to blockage, so they are best used with relatively clean matrices. This in contrast to the so-called highsolids nebulizers (such as parallel-path and V-groove nebulizers) that can handle high concentrations of dissolved solids.16 The characteristics of the plasma can also be modified by adding another gas to argon. For instance, an addition of O2 to the plasma is widely done for the analysis of organic solutions as it prevents the deposition of soot on the interface. The amount of O2 must however be adjusted so as to minimize soot deposition without unduly decreasing the lifetime of the sampler and skimmer cones. Several ICP-MS instruments include an additional gas line for such purpose, which allows the addition of O2 to the aerosol carrier gas using a tee or a sheathing device. The addition of gases with a higher thermal conductivity than argon (such as N2 and H2) can be used to reduce and/or eliminate some spectroscopic as well as nonspectroscopic interferences and reduce mass bias, which can be advantageous for the analysis of samples with complex
241
Good accuracy and precision High accuracy and precision
matrices using a simple external calibration if a small sacrifice in sensitivity can be afforded. For instance, a little bit of N2 in the plasma not only increased robustness to the extent that accurate analysis of seawater could be performed with an external calibration using aqueous standard solutions, without matrix matching or internal standardization.17 This small change also has the side effect of reducing oxide formation to a negligible level, thereby eliminating an important source of spectroscopic interference.17 Table 2 demonstrates that various approaches can be used with a basic ICP-MS instrument to overcome spectroscopic interferences. Many of these approaches consist in separating the problematic element(s) from the analyte during sample preparation (by extraction, chelation, selective precipitation, etc.). Although they can be quite effective at reducing both spectroscopic and nonspectroscopic interferences (if the source of the latter is also removed during sample processing), they are nonetheless time-consuming and increase the likelihood of contamination. Most of these separations can be carried out online with ICP-MS using flow injection, sequential injection, or lab-onvalve technologies.16 The most established of these technologies is flow injection, which involves the injection of a discrete volume of sample into an unsegmented carrier flow, which can also double as reactant, diluent, etc. A big advantage of this approach is that all the chemistry is done in a closed system, often on a reduced scale, thereby reducing sources of contamination, as well as sample and reagent consumption. The two most widely used types of manifold are illustrated in Figure 8. The simplest manifold (a) simply involves the insertion of a sample injection valve between the peristaltic pump (which is standard on all ICP-MS instruments) and the nebulizer. This simple approach can be used to effectively prevent solid deposition problems on the MS interface, as residual matrix is immediately washed away by the carrier solution following each sample injection.18 The second manifold (b), or variants of it, is used whenever analytes must be separated from the matrix or when preconcentration must be carried out to allow their detection. The sample is carried through a minicolumn of sorbent that selectively retains analytes while the matrix is pumped to waste. The valve is then switched to allow the eluent to pass through the minicolumn, where it releases analytes and carries them to the nebulizer. To minimize back-pressure problems, sample loading and analyte elution are usually done through the opposite ends of the minicolumn. Chemical vaporization approaches can also be used to selectively transform the analyte into a volatile species, thereby
242
Table 4
Inductively Coupled Plasma Mass Spectrometry Methods
Options widely used to enhance the capabilities of ICP-MS
Method
Advantages
Disadvantages
Examples of applications
Ultrasonic nebulization with desolvation
High sample introduction efficiency Reduction of oxides through solvent removal Reduced spectroscopic interferences Reduced matrix effects Reduced soot deposition Reduced memory effects Increased sample throughput Reduced matrix effects Enhanced sensitivity Online pretreatment chemistry Speciation analysis of aqueous and gaseous samples Separation of analyte from matrix Selective separation of analyte from matrix Up to 100% sample introduction efficiency Improved detection limit Small sample volume Direct solid analysis In situ pretreatment of sample Up to 100% sample introduction efficiency Selective vaporization of analyte Separation of isobars Eliminates digestion and fusion steps Calibration with aqueous standards Direct solid analysis In situ analysis of fluid inclusions Microscopic profiling of solid samples
Prone to memory effects, cone blockage, and matrix effects from concentrated matrix
Analysis of river water, lake water, rain, and other samples with simple matrix
Higher incidence of torch melting Sacrifice in sensitivity
Analysis of fuel oil, vegetable oil, seawater, urine, slurries, or digests of geochemical samples
System must be modified and optimized for each type of application
Analysis of samples with high level of dissolved solids (seawater, brines, urine, etc.), concentrated acids, volumelimited samples Online analyte preconcentration and/or separation prior to analysis
Different interfaces required for different techniques Separation efficiency dependent on interface to ICP
Determination of toxic and nontoxic species in biological materials, food, environmental samples
Different chemistries and/or conditions required for different analytes Not applicable to all elements
Determination of hydride-forming elements and/or species in a variety of samples
Matrix modifiers often required to prevent loss of analyte Limited multielement capability with sequential ICP-MS instruments Degraded precision (typically 5–10%) vs nebulization (1%)
Analysis of waters, biological materials, food, volume-limited samples, airborne particulate matter, fuel, diesel, biodiesel, fluorocarbon polymer, Ni chips, ceramic material
No available sample blanks Efficiency of calibration dependent on particle size and sample type Limited number of reference materials available for calibration No available sample blanks Elemental fractionation may occur
Analysis of rocks, soils, hard-to-dissolve samples (such as coal)
Mixed-gas plasmas
Flow injection analysis
Chromatographic and electrophoretic techniques Chemical vapor generation
Electrothermal vaporization
Slurry nebulization
Laser ablation
Analysis of geologic samples, ceramic materials, glass, forensics samples, and archeology artifacts Mapping of biological tissues
Inductively Coupled Plasma Mass Spectrometry Methods
243
Figure 8 Examples of flow injection manifold widely used with ICP-MS.
separating it from the matrix, in either continuous or flow injection mode.19 Hydride generation is the most widely used process, which is not applicable to all elements. A prereduction of certain elements (such as As and Se) is required, as the most oxidized form does not readily form a hydride. However, if hydride generation is quantitative and all the hydride is introduced into the ICP, then up to two orders of improvement can be achieved in detection limit. Indeed, not only is there 100% sample introduction efficiency (vs 2–5% with conventional nebulization), but also the introduction of the analyte in gaseous form requires less energy from the plasma, as no desolvation and vaporization steps are needed, resulting in a further improvement in detection limit. The hydrogen by-product of hydride generation also increases the transfer of energy from the bulk of the plasma to the central channel, which further helps. A commercially available unit, called multimode sample introduction system (MSIS), can be used for conventional nebulization, hydride generation, or both simultaneously. In hydride generation mode (Figure 9), the reductant and sample solution are mixed in the unconfined gap between two facing inlets while the nebulizer is only used to introduce Ar to carry hydrides as they are formed into the ICP. The small contact surface and time between the sample and reductant effectively minimize interfering reactions that occur more slowly than hydride generation of analytes. Alternatively, various species of the analyte can be determined by coupling gas, liquid or supercritical fluid chromatography, or capillary electrophoresis to ICP-MS.20 Because the toxicity of an element and its mobility in the environment often depends on its chemical form, speciation analysis is increasingly required by government agencies worldwide. As a result, these techniques are used for the speciation analysis of several elements in body fluids and biological tissues,21 of metal-based pharmaceuticals,22 as well as to trace pollutants in the environment, which requires detection by multicollector ICP-MS or other simultaneous sensitive ICP-MS instruments.23 Because the concentrations of the different species of an element can be much smaller than the total concentration of that element, further hyphenations may be necessary, such as liquid chromatography and hydride generation, in order to obtain sufficient detection limit.24 As mentioned earlier, solid samples must first be put in solution for analysis by conventional ICP-MS, which
Figure 9 Operating principle of the MSIS in hydride generation mode.
introduces potential sources of contamination. Slurry nebulization, which simply consists in grinding the sample and suspending it in a suitable dispersing agent, can significantly reduce these contaminations.25 However, it is not widely used because a number of conditions must be satisfied for this approach to be effective. Various techniques that allow direct solid analysis have thus been coupled to ICP-MS. The most widely used, which are commercially available, are electrothermal vaporization16 (Figure 10) and laser ablation (Figure 11).26 These techniques are particularly valuable for samples that are difficult to dissolve. Electrothermal vaporization involves placing 1–5 mg of sample in a graphite furnace where it is heated in steps to desolvate it, ash the matrix, and vaporize the analyte, the resulting vapor and/or particles then being carried into the ICP by a carrier gas. To facilitate the determination of elements that are in refractory forms or that form refractory carbides, a reactant gas (a fluorinated or chlorinated gaseous compound) can be added to the carrier gas to help transform refractory compounds into volatile chlorides or fluorides. In fact, if the analyte is completely separated from the matrix, then external calibration with aqueous standard solutions can be carried out. Electrothermal vaporization can also readily be used for the analysis of solutions and slurries.16 Furthermore, if different species of an element have different vaporization temperatures (such as inorganic Hg and methylmercury), speciation analysis can be performed in situ.16 However, because of the small sample mass involved and gradual aging of the graphite tube,
244
Inductively Coupled Plasma Mass Spectrometry Methods
Figure 10 Operating principles of solid-sampling electrothermal vaporization.
single method can be used for the direct analysis of every sample. Some method development is thus usually required for each new sample type, whether ICP-MS is used with or without one or more of the available options.
Figure 11 Schematic representation of laser ablation.
the precision that can be achieved is significantly poorer than with conventional nebulization. For heterogeneous samples, like soil, the relative standard deviation for replicate analysis can be as high as 20%. By far the most widely used technique for direct solid analysis is laser ablation, which involves focusing a laser onto the surface of a sample to eject particles that are then transported into the plasma by a carrier gas. The ablation process depends, among other things, on the wavelength of the laser. An ultraviolet laser beam acts directly on the sample surface, and the particles that are ejected form a microplasma. In contrast, an infrared laser interacts with the carrier gas, and the resulting microplasma erodes the sample surface.27 Several parameters must be optimized for each sample matrix. Nonetheless, different types of analysis can be conducted. Bulk analysis involves numerous laser shots while translating or rotating the sample. In contrast, microanalysis requires a few high-resolution laser shots on one position to create a single crater. Depth profiling and mapping of a sample can also be performed. While qualitative and semiquantitative analyses can readily be carried out, quantitative analysis is not as straightforward because of elemental fractionation (when the elemental composition of the ablated particles is different than that in the sample itself) and the lack of a large number of suitable standards. All of the aforementioned approaches enhance the capabilities of ICP-MS, although the optimization process may be complicated in some cases (such as slurry nebulization). Furthermore, realizing the full potential (in terms of the number of elements that can be determined simultaneously) of some of them (such as laser ablation in microanalysis mode, electrothermal vaporization, etc.), which generate short transient signals, requires an instrument allowing simultaneous multielement detection (such as TOF or the double-focusing instrument with Mattauch–Herzog geometry). In any case, no
See also: Biometallics/Metallomics Techniques and Applications; Forensic Science, Applications of Mass Spectrometry; Glow Discharge Mass Spectrometry; Inductively Coupled Plasma Mass Spectrometry Applications; Ion Trap Mass Spectrometers; Ion–Molecule Reactions in Mass Spectrometry; Isotope Ratio Studies Using Mass Spectrometry; Laser Ablation Inductively Coupled Plasma Mass Spectrometry; Proton Microprobe (Method and Background); Quadrupoles, Use of in Mass Spectrometry; Sector Mass Spectrometers; Time of Flight Mass Spectrometers.
References 1. 2. 3. 4.
5. 6. 7.
8.
9. 10.
11.
12. 13. 14. 15. 16.
17.
Olesik JW (1991) Anal. Chem. 63: 12A–21A. Houk RS (1986) Anal. Chem. 58: 97A–105A. Douglas DJ and French JB (1988) J. Anal. At. Spectrom. 3: 743–747. Ray SJ (2010) Mass Analyzers in Plasma Ionization. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry, vol. 5, pp. 111–122. Oxford: Elsevier Chapter 1.12. Tanner SD, Baranov VI, and Bandura DR (2002) Spectrochim. Acta B 57: 1361–1452. Beauchemin D (2010) Mass Spectrometry Reviews 29: 560–592. Field MP (2010) Applications of ICP-MS for Elemental Analysis of Geochemical Samples. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry, vol. 5, pp. 173–191. Oxford: Elsevier Chapter 1.17. Becker JS (2010) Applications: Determination of Long-Lived Radionuclides. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry, vol. 5, pp. 200–211. Oxford: Elsevier Chapter 1.19. Pizzolon J-C and Hoenig M (2005) Can. J. Anal. Sci. Spectrosc. 50(5): 221–227. Morton J and Nelms SM (2010) Biomedical Applications of ICP-MS. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry, vol. 5, pp. 212–221. Oxford: Elsevier Chapter 1.20. Kishi Y (2010) Applications of ICP-MS for Semiconductors. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry, vol. 5, pp. 191–199. Oxford: Elsevier Chapter 1.18. Botto RI (2002) Can. J. Anal. Sci. Spectros. 47(1): 1–13. Smith S, Bolchi M, and Magarini R (2010) At. Spectrosc. 31(5): 170–174. Holliday AE and Beauchemin D (2004) Spectrochim. Acta B 59: 291–311. Agatemor C and Beauchemin D (2011) Anal. Chim. Acta 706: 66–83. Todoli JL and Vanhaecke F (2005) Liquid Sample Introduction and Electrothermal Vaporisation for ICP-MS: Fundamentals and Applications. In: Nelms SM (ed.) ICP Mass Spectrometry Handbook, pp. 182–227. Oxford: Blackwell Publishing. Agatemor C and Beauchemin D (2011) Spectrochim. Acta B 66: 1–11.
Inductively Coupled Plasma Mass Spectrometry Methods
18. Beauchemin D (2000) Flow Injection Techniques. In: Barcelo D (ed.) Comprehensive Analytical Chemistry, vol. XXXIV, pp. 213–346. Amsterdam: Elsevier Chapter 2. 19. Gao Y, Liu R, and Yang L (2013) Chin. Sci. Bull. 58(17): 1980–1991. 20. Wrobel K, Wrobel K, and Caruso JA (2010) Elemental Speciation in Small Molecules by ICP-MS. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry. Vol. 5pp. 222–233. Oxford: Elsevier Chapter 1.21. 21. Dressler VL, Antes FG, Moreira CM, Pozebon D, and Duarte FA (2011) Int. J. Mass Spectrom. 307(1–3): 149–162. 22. Meermann B and Sperling M (2012) Anal. Bioanal. Chem. 403(6): 1501–1522.
245
23. Negrel P, Blessing M, Millot R, Petelet-Giraud E, and Innocent C (2012) Trends Anal. Chem. 38: 143–153. 24. Maher W, Krikowa F, Ellwood M, Foster S, Jagtap R, and Raber G (2012) Microchem. J. 105: 15–31. 25. Ferreira SLC, Miro M, da Silva Paranhos, Matos GD, Reis PSanches dos, Brandao GC, Santos WNLopes dos, Duarte AT, Vale MGR, and Araujo RGO (2010) Appl. Spectros. Rev. 45(1): 44–62. 26. Koch J and Gunther D (2011) Appl. Spectrosc. 65(5): 155A–162A. 27. Gu¨nther D and Mermet J-M (2000) Laser Ablation for Inductively Coupled Plasma-Mass Spectrometry. In: Barcelo D (ed.) Comprehensive Analytical Chemistry, vol. XXXIV, pp. 445–501. Amsterdam: Elsevier Chapter 4.
Inductively coupled plasma mass spectrometry (ICP-MS) combines an ICP with a mass spectrometer. It features a multielemental capability, good precision, a long linear dynamic range, simple spectra, low detection limits, and the ability to do rapid isotopic analysis. With such advantages, ICP-MS has found wide application to the analysis of a variety of samples, including water and food, as well as geochemical, environmental, and biological samples. However, it has a number of limitations, such as matrix effects, which can be important, and the need to keep the concentration of dissolved solids low to avoid clogging problems. These complicate the analysis by requiring sample pretreatment and/or more involved calibration strategies. Nonetheless, with the appropriate method development and/or optional accessories, these limitations can be largely circumvented, thereby allowing ICP-MS to be applied to the analysis of virtually any type of sample.
Description of a Basic ICP-MS Instrument Figure 1 shows a block diagram of a typical ICP-MS instrument. A 1–2.5 kW Ar ICP is the typical ion source for MS. The ICP is a high-temperature (5000–10 000 K, depending on operating conditions and location in the plasma) electrodeless discharge that is sustained in argon flowing within a torch. It is partially ionized Ar (with typically less than 1% of the Ar being ionized).1 The plasma is generated and sustained by the plasma gas that tangentially flows in the outer tube of a quartz torch and also isolates it from the walls of the torch. An auxiliary gas is used during ignition to carry the seed electrons generated by a spark from a Tesla coil to the magnetic field produced by the radio-frequency (RF) current supplied by a generator through a water-cooled Cu coil (called load coil). These electrons move in circular orbits around the magnetic field until they collide with some Ar atoms and cause them to become ionized, generating electrons that also get caught in this self-perpetuating process, which continues as long as there are an RF current and plasma gas. The auxiliary gas is also used to position the plasma so as to prevent melting of the inner tubes. In general, the ICP uses samples in solution, which presents the advantages of good control over homogeneity and ease of calibration. A sample solution is delivered to a nebulizer using a peristaltic pump to minimize physical interferences (from, for instance, changes in viscosity). The nebulizer converts this solution into an aerosol that is then carried by the nebulizer gas (also called aerosol carrier gas) through a spray chamber where large droplets drain out. This aerosol filtering is required to prevent plasma extinction by solvent overloading. The Diane Beauchemin, Inductively Coupled Plasma Mass Spectrometry, Methods, In Encyclopedia of Spectroscopy and Spectrometry (Second Edition), edited by John C. Lindon, Academic Press, Oxford, 1999, Pages 1005–1010.
236
resulting fine aerosol, which typically constitutes 2–5% of the sample (the rest going down the drain), is injected into the heart of the plasma and undergoes several processes sequentially, as it moves deeper into the plasma: desolvation, vaporization, atomization, and finally ionization, as illustrated in Figure 2. These processes take energy from the plasma, resulting in a cooler central region, called the central channel (Figure 1). In an Ar ICP, the degree of ionization of 52 elements is expected to be 90%.2 Only three elements (He, F, and Ne) that possess a first ionization potential greater than that of Ar would not be significantly ionized and could therefore not be determined by ICP-MS with an Ar ICP. Similarly, the highest degree of double ionization is 10% and occurs only for a few elements.2 The ICP is therefore an efficient elemental ion source for MS since the majority of elements in the periodic table are singly ionized. A portion of the plasma (which is typically three sampler orifice diameters wide and two sampler orifice diameters deep)3 is sampled from the central channel of the plasma and extracted through a differentially pumped interface (through two water-cooled metal cones with orifice diameter 1 mm, the sampler and the skimmer (see Figure 1)), which is maintained at approximately 1 Torr using a mechanical roughing pump and whose main purpose is to evacuate most of the argon gas. Because of the expansion taking place in the interface, only the centerline flow of the sampler, which is slightly smaller than the sampler orifice diameter, actually passes the skimmer.3 The ion optic then separates electrons from analyte ions, resulting in a positive ion beam that is then transmitted into the mass spectrometer where ions are separated according to their mass-to-charge ratios (m/z) (in Daltons) and then counted. The detector is usually installed off-axis (i.e., not in line with the ion source) to minimize the background noise that can be generated by photons. Different mass spectrometers are used in the current commercially available ICP-MS instruments. The most compact ones use a quadrupole to achieve ion separation based on a dynamic arrangement of electromagnetic fields through which only ions of a certain mass will have a stable path and reach the detector (Figure 3). As a result, ions of different m/z are separated sequentially. An alternative is a time-of-flight (TOF) tube. With TOFMS, packets of ions, which must first have been accelerated to the same kinetic energy, are admitted into the flight tube, where they each acquire a velocity that is inversely proportional to mass and thus have a travel time that is proportional to mass (Figure 4). Because this separation can be done very quickly over the atomic mass range, i.e., 10 000–50 000 mass spectra can be acquired per second,4 TOFMS allows the quasi-simultaneous detection of elements over the whole mass range. However, it is the least utilized approach in ICP-MS because of its low duty cycle. Indeed, because all ions of a given m/z arrive at the detector within
Encyclopedia of Spectroscopy and Spectrometry, Third Edition
http://dx.doi.org/10.1016/B978-0-12-409547-2.11222-3
Inductively Coupled Plasma Mass Spectrometry Methods
237
Figure 1 Block diagram of a typical ICP-MS instrument along with the function of its main components.
Figure 2
Main processes involved in the generation of ions in ICP-MS.
Figure 3 Operating principles of a quadrupole mass analyzer.
1–10 ns, only a single ion of a given m/z can be counted in each mass spectrum with ion counting detectors.4 Furthermore, ions generated while a given packet of ions is undergoing separation are not measured at all. Double-focusing instruments use a magnetic sector analyzer, for momentum focusing, and an electrostatic analyzer, for energy focusing, in series.4 Different geometries are available, depending on the vendor, which are illustrated in Figure 5. Single-collector (shown in Figure 5) and multicollector versions of instruments with the Matsuda (a) or
Nier–Johnson (b) geometry are available. In the latter case, several detectors are used to simultaneously detect ions over a narrow mass range. Only the Mattauch–Herzog geometry (c) allows simultaneous detection over the whole mass range. Despite being significantly more expensive than quadrupole-based instruments, double-focusing instruments are nonetheless relatively popular because of distinctive features. For instance, instruments with geometry a or b can be operated at low (R ¼ 300–500), medium (R ¼ 4000), or high (R ¼ 10 000–15 000) resolving power, R (defined as m/Dm at 5% height),4 increasing R being simply attained by narrowing the slit widths. Nonetheless, this allows the resolution of several spectroscopic interferences occurring when a polyatomic ion has the same nominal mass as the analyte ions (such as 40 16 þ Ar O vs 56Feþ) that plague quadrupole-based instruments. The low resolving power setting is equivalent to that achieved with quadrupole-based instruments as well as with TOF instruments with axial geometry (where the ion beam and flight axis are coaxial). Double-focusing instruments with geometry c and TOF instruments with orthogonal geometry (where the ion beam and flight axis are at right angle from each other) currently offer better R than low resolving power instruments but usually less than 4000. Another distinctive feature of double-focusing instruments is the negligible background across the mass range. This results from the curved path that the ion beam must follow, which efficiently prevents photons from reaching the detector, as well as from the operating pressure that is considerably lower than that of quadrupole and TOF instruments, thereby minimizing collisional processes in the ion beam. However, like the quadrupole-based instruments, double-focusing instruments with geometry a or b allow a sequential multielement measurement. Quasi-simultaneous multielement detection is done by ICP-TOFMS. Only the double-focusing instrument with geometry c allows truly simultaneous detection over the entire mass range. To get around the problem of spectroscopic interferences, most quadrupole instruments can come with a collision/ reaction cell or interface option, where collisions or reactions with a gas can be used to either break the interfering
238
Inductively Coupled Plasma Mass Spectrometry Methods
Figure 4 Operating principles of a TOF mass analyzer.
Figure 6 Example of the operation of a tandem mass spectrometer. The analyte ion (orange) is separated from ions of different m/z by quadrupole one. A gas is added to the collision/reaction cell to break up the interfering polyatomic ion (blue), and the second quadrupole is finally used to isolate analyte ions.
cell to systematically bring back ions to the center of the rods, even if they were deflected by a collision. Different types of cells are used (quadrupole, octopole, etc.), depending on the vendor. In the collision/reaction interface, the gas is simply added through the tip of a hollow skimmer or sampler. A tandem mass spectrometer (Figure 6) can also be used for even better resolution of interferences.
Capabilities of ICP-MS Figure 5 Operating principles of different double-focusing mass analyzers.
polyatomic ion (as illustrated in the collision cell of Figure 6) or transform the analyte into a polyatomic ion of heavier mass than the interfering one, hence allowing its detection in an interference-free region of the mass spectrum.5 With these instruments, even some isobaric interferences can be resolved, which is not possible with double-focusing instruments even at high resolving power. The only requirement is that either the interfering ion or the analyte ion (but not both) reacts with the reaction gas. In all cases, the collision/reaction cell precedes the quadrupole (i.e., essentially Figure 6 without the first quadrupole). An RF-only field can be used in the collision
Table 1 summarizes key features of ICP-MS, which also offers the advantages of working with samples in solution and providing good precision. Even with sequential instruments, the multielement capability of ICP-MS allows the determination of, for instance, 70 elements in less than 2 min, using less than 2 ml of solution at an uptake rate of 1 ml min1. Detection limits are 1 ng l1 for many elements with quadrupole instruments and even lower with double-focusing instruments operated in low mass resolving power mode. This difference arises from the lower background obtained on the latter instruments, as well as the higher reliability in peak hopping, as flattop peaks are generated. With the exception of ICPTOFMS, which is inherently limited by a lower duty cycle, sensitivity (i.e., the slope of a calibration curve) is similar on
Inductively Coupled Plasma Mass Spectrometry Methods
Table 1
239
Major features of ICP-MS
Feature
Advantage
Implications
Linear dynamic range
At least nine orders of magnitude
Detection limit (based on three standard deviations of the blank signal) Mass spectrum
Down to sub ng l1, depending on the element Simple: only 1–10 lines per element
Major, minor, trace, and ultratrace levels of elements may all be determined at once Enables ultratrace analysis
Isotope information
Isotope ratio measurement
Multielement capability
Determination of all elements but He, F, Ne, and Ar
Table 2
Less spectroscopic interferences than in ICP optical emission spectrometry But few or no alternative in case of interference Enables the most accurate calibration strategy: isotope dilution analysis High sample throughput
Examples of applications of ICP-MS
General category
Sample types
Sample pretreatment
Reference
Water
Seawater, industrial wastewater, pore water, river water, freshwater, rain, groundwater, lake water, spring water, snow, tap water, high-purity water
6
Environmental and geochemical
Soil, dust, leaves, sediments, sewage, industrial effluents, paint, atmospheric aerosols, suspended particulate matter, tobacco smoke condensate, domestic sludge, glass, spent nuclear fuel, leachates of high-activity waste, rocks, metals, ores, alloys, ceramic materials Seafood, flours, vegetables, wine, beef kidney, milk, etc. Fecal material, urine, human serum, plasma, red blood cells, whole blood, cerebrospinal fluids Ultrapure water, high-purity HF, H2O2, NH4OH, HCl, H2SO4, 2-propanol, photoresist, Si wafer; high-purity gases (N2, O2, H2, arsine, silane, phosphine) Crude oil, gasoline
Filtration and any of the following: acidification and dilution, ion exchange separation to remove interferents and/or preconcentrate analytes, preconcentration by evaporation Crushing or grinding and either digestion with highpurity acids or fusion and dissolution, followed by dilution
Food Biological Semiconductor
Organic
all instruments in low mass resolving power. It is degraded by increasing mass resolving power because the width of the entrance and exit slits on double-focusing instruments are then decreased, which leads to a reduction in ion transmission. In any case, isotope ratios can readily be measured. For applications requiring high-precision isotope ratios, simultaneous detection of the different isotopes is required, which is best achieved using double-focusing instruments with geometry c (see Figure 5) over the entire mass range or with multicollectors for a few elements over a narrow mass range. In any case, all instruments enable the most accurate calibration using isotope dilution analysis, which essentially involves internal standardization with an enriched isotope of the analyte. All these features explain why even the basic ICP-MS instrument is being applied to analyses in a variety of areas. For instance, Table 2 shows that ICP-MS is widely used for environmental, clinical, and geochemical studies, with appropriate sample preparation procedures. These are required not only to put solid samples in solution but also to avoid or circumvent limitations of ICP-MS by, for instance, removing sources of interference.
Digestion with high-purity acids followed by dilution Dilution or drying, ashing, and/or digestion with highpurity acids followed by dilution or extraction Dilution of aqueous samples, digestion, vapor phase decomposition of Si, impinger method for gases Extraction into aqueous acidic solution
6–8
9 10 11
12,13
Limitations of ICP-MS Whatever the mass resolving power, detection limits (and more realistically determination limits in a given matrix) vary with the element being determined by ICP-MS. There are, indeed, several factors affecting them. The degree of ionization of the analyte, the natural abundance of the isotope that is used for the determination of a particular element, spectroscopic interferences from the background and/or the sample matrix, and mass bias are the most notorious sources of degradation. Obviously, if an element is only 50% ionized in the plasma, then its detection limit will be reduced by a factor of 2 compared to an element that is completely ionized. Similarly, if only one isotope of a multi-isotope element is detected, the resulting detection limit will be less than that of a monoisotopic element. Furthermore, the sample introduction system is the Achilles heel of all ICP-based instruments. Indeed, only about 2–5% of the sample solution actually reaches the plasma with a conventional system (composed of a pneumatic nebulizer and spray chamber, as shown in Figure 1), most of it going down
240
Inductively Coupled Plasma Mass Spectrometry Methods
the drain. This means, therefore, that only a small fraction of the total possible signal is measured. As mentioned earlier, because the mass spectrum is simple, the likelihood of spectroscopic interferences is reduced, particularly with high mass resolving power instruments. However, when they occur, the number of alternative lines is small (there are indeed a number of monoisotopic elements). One example of an isobaric interference that cannot be resolved even at high mass resolving power is that of 40Arþ on 40Caþ, the major isotope of Ca. Other severe interferences arise from Arcontaining polyatomic ions as well as oxides of matrix elements. Several of these can be resolved at higher resolution but with a concurrent sacrifice in sensitivity and detection limits. On low mass resolving power instruments, a ‘cold plasma,’ where the ICP is operated at lower power and higher nebulizer gas flow rate, can be used to reduce important interferences from the background, but, again, a lower sensitivity concurrently results across the mass range. Collision/reaction cells are very useful to reduce interferences from polyatomic ions and do so with a much smaller sacrifice in sensitivity than a cold plasma. Because repulsion of like charges or space-charge effects can occur in the ion beam on its way to the mass spectrometer and that the extent of such repulsion depends on total ion current, the response of the instrument is not constant across the mass range, as illustrated in Figure 7. The shape of this curve depends on the instrument and operating conditions and can change in the presence of a given matrix, especially if the latter significantly increases the total ion current. Nonetheless, in general, the transmission of light ions is reduced compared with heavier ions, as they are more easily repelled, which is why this effect is referred to as mass bias. The worst suppression is observed for a light analyte in the presence of a matrix of heavy element. Another parameter that may also affect the detection capability of ICP-MS is the plasma sampling position, which may not be optimal for all the analytes being determined simultaneously.14 This position is indeed important to
maximize the density of analyte ions extracted from the ICP. Even the chemical form (i.e., speciation) of an element in solution may influence where it undergoes the various processes (desolvation, vaporization, etc.) in the plasma, ultimately determining where the maximum ion density will be. The sampling process itself is the source of another limitation: because part of the plasma passes through a small orifice, this orifice can become clogged by dissolved solids. The maximum concentration of dissolved solids that can be tolerated on a continuous basis is 0.2%. Finally, even if this level is kept reasonably low, nonspectroscopic interferences (also called matrix effects) can occur, whereby the analyte signal is either suppressed or enhanced by the presence of other elements. For example, a heavy matrix element will in general induce a more important suppression than a light matrix element because of space–charge effects. The signal of elements that are not completely ionized in the ICP may be enhanced by carboncontaining matrices as a result of an additional ionization mechanism involving charge transfer with carbon ions.15 However, the extent of matrix effects is still largely unpredictable, which complicates the calibration process for samples that do not possess a relatively simple matrix. Whenever possible, a simple dilution of the sample is recommended to minimize such nonspectroscopic interferences, as they depend on the absolute amount of concomitant element. The various calibration strategies available with ICP-MS are summarized in Table 3, along with implications of the aforementioned limitations. (More elaborate chemometric calibration procedures have also been developed by a few groups.) In general, unless the sample matrix is simple, internal standardization (or frequent calibration through sample-standard bracketing) will be required for quantitative analysis using external calibration with a series of standard solutions. The choice of the internal standard(s) depends on the instrument, the sample, etc. For the best results, an element with properties similar to that of the analyte (so that it will behave similarly in ICP-MS) is needed. Similarity in mass is thus a prerequisite as well as similarity in first ionization potential for elements that
Figure 7 Example of the response from an ICP-MS instrument, corrected for the varying degree of ionization of elements.
Inductively Coupled Plasma Mass Spectrometry Methods
Table 3
Calibration strategies in ICP-MS
Method
Requirements
Quality of results
External calibration
One isotope free of spectroscopic interference per analyte Matrix matching and/or correction for drift (using internal standardization or frequent calibration) One isotope free of spectroscopic interference per analyte May require a correction for drift (using internal standardization) Two isotopes free of spectroscopic interference per analyte Good equilibrium between isotopic spike and sample
Good accuracy and precision
Standard additions Isotope dilution
are not completely ionized. So, several internal standards may be required for a multielemental analysis spanning the entire mass range. The method of standard additions efficiently compensates for matrix effects but not for drift. If the latter is also present (for instance, because of gradual clogging), internal standardization may also be required. The best method to compensate for both matrix effects and drift is isotope dilution analysis. However, it is only applicable to elements with at least two isotopes (stable and/or long-lived radioactive) free of spectroscopic interferences. However, this normally standardless technique requires a prior determination of mass bias using standards of known isotopic composition in order to correct the measured isotope ratios for the nonuniform instrument response.
Accessories Available to Expand the Capabilities of ICP-MS Several more or less expensive accessories can be readily interfaced to ICP-MS to circumvent one or more of the aforementioned limitations. The most frequently used are summarized in Table 4. The sample introduction system can simply be replaced by a high-efficiency one, such as an ultrasonic nebulizer coupled to a desolvation system, which provides up to 30% analyte transport efficiencies.16 Other high-performance nebulization systems include a direct injection nebulizer, which introduces 100% of the sample directly into the plasma (i.e., no spray chamber is needed), or a high-efficiency nebulizer; but they are prone to blockage, so they are best used with relatively clean matrices. This in contrast to the so-called highsolids nebulizers (such as parallel-path and V-groove nebulizers) that can handle high concentrations of dissolved solids.16 The characteristics of the plasma can also be modified by adding another gas to argon. For instance, an addition of O2 to the plasma is widely done for the analysis of organic solutions as it prevents the deposition of soot on the interface. The amount of O2 must however be adjusted so as to minimize soot deposition without unduly decreasing the lifetime of the sampler and skimmer cones. Several ICP-MS instruments include an additional gas line for such purpose, which allows the addition of O2 to the aerosol carrier gas using a tee or a sheathing device. The addition of gases with a higher thermal conductivity than argon (such as N2 and H2) can be used to reduce and/or eliminate some spectroscopic as well as nonspectroscopic interferences and reduce mass bias, which can be advantageous for the analysis of samples with complex
241
Good accuracy and precision High accuracy and precision
matrices using a simple external calibration if a small sacrifice in sensitivity can be afforded. For instance, a little bit of N2 in the plasma not only increased robustness to the extent that accurate analysis of seawater could be performed with an external calibration using aqueous standard solutions, without matrix matching or internal standardization.17 This small change also has the side effect of reducing oxide formation to a negligible level, thereby eliminating an important source of spectroscopic interference.17 Table 2 demonstrates that various approaches can be used with a basic ICP-MS instrument to overcome spectroscopic interferences. Many of these approaches consist in separating the problematic element(s) from the analyte during sample preparation (by extraction, chelation, selective precipitation, etc.). Although they can be quite effective at reducing both spectroscopic and nonspectroscopic interferences (if the source of the latter is also removed during sample processing), they are nonetheless time-consuming and increase the likelihood of contamination. Most of these separations can be carried out online with ICP-MS using flow injection, sequential injection, or lab-onvalve technologies.16 The most established of these technologies is flow injection, which involves the injection of a discrete volume of sample into an unsegmented carrier flow, which can also double as reactant, diluent, etc. A big advantage of this approach is that all the chemistry is done in a closed system, often on a reduced scale, thereby reducing sources of contamination, as well as sample and reagent consumption. The two most widely used types of manifold are illustrated in Figure 8. The simplest manifold (a) simply involves the insertion of a sample injection valve between the peristaltic pump (which is standard on all ICP-MS instruments) and the nebulizer. This simple approach can be used to effectively prevent solid deposition problems on the MS interface, as residual matrix is immediately washed away by the carrier solution following each sample injection.18 The second manifold (b), or variants of it, is used whenever analytes must be separated from the matrix or when preconcentration must be carried out to allow their detection. The sample is carried through a minicolumn of sorbent that selectively retains analytes while the matrix is pumped to waste. The valve is then switched to allow the eluent to pass through the minicolumn, where it releases analytes and carries them to the nebulizer. To minimize back-pressure problems, sample loading and analyte elution are usually done through the opposite ends of the minicolumn. Chemical vaporization approaches can also be used to selectively transform the analyte into a volatile species, thereby
242
Table 4
Inductively Coupled Plasma Mass Spectrometry Methods
Options widely used to enhance the capabilities of ICP-MS
Method
Advantages
Disadvantages
Examples of applications
Ultrasonic nebulization with desolvation
High sample introduction efficiency Reduction of oxides through solvent removal Reduced spectroscopic interferences Reduced matrix effects Reduced soot deposition Reduced memory effects Increased sample throughput Reduced matrix effects Enhanced sensitivity Online pretreatment chemistry Speciation analysis of aqueous and gaseous samples Separation of analyte from matrix Selective separation of analyte from matrix Up to 100% sample introduction efficiency Improved detection limit Small sample volume Direct solid analysis In situ pretreatment of sample Up to 100% sample introduction efficiency Selective vaporization of analyte Separation of isobars Eliminates digestion and fusion steps Calibration with aqueous standards Direct solid analysis In situ analysis of fluid inclusions Microscopic profiling of solid samples
Prone to memory effects, cone blockage, and matrix effects from concentrated matrix
Analysis of river water, lake water, rain, and other samples with simple matrix
Higher incidence of torch melting Sacrifice in sensitivity
Analysis of fuel oil, vegetable oil, seawater, urine, slurries, or digests of geochemical samples
System must be modified and optimized for each type of application
Analysis of samples with high level of dissolved solids (seawater, brines, urine, etc.), concentrated acids, volumelimited samples Online analyte preconcentration and/or separation prior to analysis
Different interfaces required for different techniques Separation efficiency dependent on interface to ICP
Determination of toxic and nontoxic species in biological materials, food, environmental samples
Different chemistries and/or conditions required for different analytes Not applicable to all elements
Determination of hydride-forming elements and/or species in a variety of samples
Matrix modifiers often required to prevent loss of analyte Limited multielement capability with sequential ICP-MS instruments Degraded precision (typically 5–10%) vs nebulization (1%)
Analysis of waters, biological materials, food, volume-limited samples, airborne particulate matter, fuel, diesel, biodiesel, fluorocarbon polymer, Ni chips, ceramic material
No available sample blanks Efficiency of calibration dependent on particle size and sample type Limited number of reference materials available for calibration No available sample blanks Elemental fractionation may occur
Analysis of rocks, soils, hard-to-dissolve samples (such as coal)
Mixed-gas plasmas
Flow injection analysis
Chromatographic and electrophoretic techniques Chemical vapor generation
Electrothermal vaporization
Slurry nebulization
Laser ablation
Analysis of geologic samples, ceramic materials, glass, forensics samples, and archeology artifacts Mapping of biological tissues
Inductively Coupled Plasma Mass Spectrometry Methods
243
Figure 8 Examples of flow injection manifold widely used with ICP-MS.
separating it from the matrix, in either continuous or flow injection mode.19 Hydride generation is the most widely used process, which is not applicable to all elements. A prereduction of certain elements (such as As and Se) is required, as the most oxidized form does not readily form a hydride. However, if hydride generation is quantitative and all the hydride is introduced into the ICP, then up to two orders of improvement can be achieved in detection limit. Indeed, not only is there 100% sample introduction efficiency (vs 2–5% with conventional nebulization), but also the introduction of the analyte in gaseous form requires less energy from the plasma, as no desolvation and vaporization steps are needed, resulting in a further improvement in detection limit. The hydrogen by-product of hydride generation also increases the transfer of energy from the bulk of the plasma to the central channel, which further helps. A commercially available unit, called multimode sample introduction system (MSIS), can be used for conventional nebulization, hydride generation, or both simultaneously. In hydride generation mode (Figure 9), the reductant and sample solution are mixed in the unconfined gap between two facing inlets while the nebulizer is only used to introduce Ar to carry hydrides as they are formed into the ICP. The small contact surface and time between the sample and reductant effectively minimize interfering reactions that occur more slowly than hydride generation of analytes. Alternatively, various species of the analyte can be determined by coupling gas, liquid or supercritical fluid chromatography, or capillary electrophoresis to ICP-MS.20 Because the toxicity of an element and its mobility in the environment often depends on its chemical form, speciation analysis is increasingly required by government agencies worldwide. As a result, these techniques are used for the speciation analysis of several elements in body fluids and biological tissues,21 of metal-based pharmaceuticals,22 as well as to trace pollutants in the environment, which requires detection by multicollector ICP-MS or other simultaneous sensitive ICP-MS instruments.23 Because the concentrations of the different species of an element can be much smaller than the total concentration of that element, further hyphenations may be necessary, such as liquid chromatography and hydride generation, in order to obtain sufficient detection limit.24 As mentioned earlier, solid samples must first be put in solution for analysis by conventional ICP-MS, which
Figure 9 Operating principle of the MSIS in hydride generation mode.
introduces potential sources of contamination. Slurry nebulization, which simply consists in grinding the sample and suspending it in a suitable dispersing agent, can significantly reduce these contaminations.25 However, it is not widely used because a number of conditions must be satisfied for this approach to be effective. Various techniques that allow direct solid analysis have thus been coupled to ICP-MS. The most widely used, which are commercially available, are electrothermal vaporization16 (Figure 10) and laser ablation (Figure 11).26 These techniques are particularly valuable for samples that are difficult to dissolve. Electrothermal vaporization involves placing 1–5 mg of sample in a graphite furnace where it is heated in steps to desolvate it, ash the matrix, and vaporize the analyte, the resulting vapor and/or particles then being carried into the ICP by a carrier gas. To facilitate the determination of elements that are in refractory forms or that form refractory carbides, a reactant gas (a fluorinated or chlorinated gaseous compound) can be added to the carrier gas to help transform refractory compounds into volatile chlorides or fluorides. In fact, if the analyte is completely separated from the matrix, then external calibration with aqueous standard solutions can be carried out. Electrothermal vaporization can also readily be used for the analysis of solutions and slurries.16 Furthermore, if different species of an element have different vaporization temperatures (such as inorganic Hg and methylmercury), speciation analysis can be performed in situ.16 However, because of the small sample mass involved and gradual aging of the graphite tube,
244
Inductively Coupled Plasma Mass Spectrometry Methods
Figure 10 Operating principles of solid-sampling electrothermal vaporization.
single method can be used for the direct analysis of every sample. Some method development is thus usually required for each new sample type, whether ICP-MS is used with or without one or more of the available options.
Figure 11 Schematic representation of laser ablation.
the precision that can be achieved is significantly poorer than with conventional nebulization. For heterogeneous samples, like soil, the relative standard deviation for replicate analysis can be as high as 20%. By far the most widely used technique for direct solid analysis is laser ablation, which involves focusing a laser onto the surface of a sample to eject particles that are then transported into the plasma by a carrier gas. The ablation process depends, among other things, on the wavelength of the laser. An ultraviolet laser beam acts directly on the sample surface, and the particles that are ejected form a microplasma. In contrast, an infrared laser interacts with the carrier gas, and the resulting microplasma erodes the sample surface.27 Several parameters must be optimized for each sample matrix. Nonetheless, different types of analysis can be conducted. Bulk analysis involves numerous laser shots while translating or rotating the sample. In contrast, microanalysis requires a few high-resolution laser shots on one position to create a single crater. Depth profiling and mapping of a sample can also be performed. While qualitative and semiquantitative analyses can readily be carried out, quantitative analysis is not as straightforward because of elemental fractionation (when the elemental composition of the ablated particles is different than that in the sample itself) and the lack of a large number of suitable standards. All of the aforementioned approaches enhance the capabilities of ICP-MS, although the optimization process may be complicated in some cases (such as slurry nebulization). Furthermore, realizing the full potential (in terms of the number of elements that can be determined simultaneously) of some of them (such as laser ablation in microanalysis mode, electrothermal vaporization, etc.), which generate short transient signals, requires an instrument allowing simultaneous multielement detection (such as TOF or the double-focusing instrument with Mattauch–Herzog geometry). In any case, no
See also: Biometallics/Metallomics Techniques and Applications; Forensic Science, Applications of Mass Spectrometry; Glow Discharge Mass Spectrometry; Inductively Coupled Plasma Mass Spectrometry Applications; Ion Trap Mass Spectrometers; Ion–Molecule Reactions in Mass Spectrometry; Isotope Ratio Studies Using Mass Spectrometry; Laser Ablation Inductively Coupled Plasma Mass Spectrometry; Proton Microprobe (Method and Background); Quadrupoles, Use of in Mass Spectrometry; Sector Mass Spectrometers; Time of Flight Mass Spectrometers.
References 1. 2. 3. 4.
5. 6. 7.
8.
9. 10.
11.
12. 13. 14. 15. 16.
17.
Olesik JW (1991) Anal. Chem. 63: 12A–21A. Houk RS (1986) Anal. Chem. 58: 97A–105A. Douglas DJ and French JB (1988) J. Anal. At. Spectrom. 3: 743–747. Ray SJ (2010) Mass Analyzers in Plasma Ionization. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry, vol. 5, pp. 111–122. Oxford: Elsevier Chapter 1.12. Tanner SD, Baranov VI, and Bandura DR (2002) Spectrochim. Acta B 57: 1361–1452. Beauchemin D (2010) Mass Spectrometry Reviews 29: 560–592. Field MP (2010) Applications of ICP-MS for Elemental Analysis of Geochemical Samples. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry, vol. 5, pp. 173–191. Oxford: Elsevier Chapter 1.17. Becker JS (2010) Applications: Determination of Long-Lived Radionuclides. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry, vol. 5, pp. 200–211. Oxford: Elsevier Chapter 1.19. Pizzolon J-C and Hoenig M (2005) Can. J. Anal. Sci. Spectrosc. 50(5): 221–227. Morton J and Nelms SM (2010) Biomedical Applications of ICP-MS. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry, vol. 5, pp. 212–221. Oxford: Elsevier Chapter 1.20. Kishi Y (2010) Applications of ICP-MS for Semiconductors. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry, vol. 5, pp. 191–199. Oxford: Elsevier Chapter 1.18. Botto RI (2002) Can. J. Anal. Sci. Spectros. 47(1): 1–13. Smith S, Bolchi M, and Magarini R (2010) At. Spectrosc. 31(5): 170–174. Holliday AE and Beauchemin D (2004) Spectrochim. Acta B 59: 291–311. Agatemor C and Beauchemin D (2011) Anal. Chim. Acta 706: 66–83. Todoli JL and Vanhaecke F (2005) Liquid Sample Introduction and Electrothermal Vaporisation for ICP-MS: Fundamentals and Applications. In: Nelms SM (ed.) ICP Mass Spectrometry Handbook, pp. 182–227. Oxford: Blackwell Publishing. Agatemor C and Beauchemin D (2011) Spectrochim. Acta B 66: 1–11.
Inductively Coupled Plasma Mass Spectrometry Methods
18. Beauchemin D (2000) Flow Injection Techniques. In: Barcelo D (ed.) Comprehensive Analytical Chemistry, vol. XXXIV, pp. 213–346. Amsterdam: Elsevier Chapter 2. 19. Gao Y, Liu R, and Yang L (2013) Chin. Sci. Bull. 58(17): 1980–1991. 20. Wrobel K, Wrobel K, and Caruso JA (2010) Elemental Speciation in Small Molecules by ICP-MS. In: Beauchemin D and Matthews DE (eds.) The Encyclopedia of Mass Spectrometry, Elemental and Isotope Ratio Mass Spectrometry. Vol. 5pp. 222–233. Oxford: Elsevier Chapter 1.21. 21. Dressler VL, Antes FG, Moreira CM, Pozebon D, and Duarte FA (2011) Int. J. Mass Spectrom. 307(1–3): 149–162. 22. Meermann B and Sperling M (2012) Anal. Bioanal. Chem. 403(6): 1501–1522.
245
23. Negrel P, Blessing M, Millot R, Petelet-Giraud E, and Innocent C (2012) Trends Anal. Chem. 38: 143–153. 24. Maher W, Krikowa F, Ellwood M, Foster S, Jagtap R, and Raber G (2012) Microchem. J. 105: 15–31. 25. Ferreira SLC, Miro M, da Silva Paranhos, Matos GD, Reis PSanches dos, Brandao GC, Santos WNLopes dos, Duarte AT, Vale MGR, and Araujo RGO (2010) Appl. Spectros. Rev. 45(1): 44–62. 26. Koch J and Gunther D (2011) Appl. Spectrosc. 65(5): 155A–162A. 27. Gu¨nther D and Mermet J-M (2000) Laser Ablation for Inductively Coupled Plasma-Mass Spectrometry. In: Barcelo D (ed.) Comprehensive Analytical Chemistry, vol. XXXIV, pp. 445–501. Amsterdam: Elsevier Chapter 4.