mass spectrometry

or mass spectroscopy

Analytic technique by which chemical substances are identified by sorting gaseous ions by mass using electric and magnetic fields.

A mass spectrometer uses electrical means to detect the sorted ions, while a mass spectrograph uses photographic or other nonelectrical means; either device is a mass spectroscope. The process is widely used to measure masses and relative abundances of different isotopes, to analyze products of a separation by liquid or gas chromatography, to test vacuum integrity in high-vacuum equipment, and to measure the geological age of minerals.

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Introduction

also called  mass spectroscopy,  

      analytic technique by which chemical substances are identified by the sorting of gaseous ions (ion) in electric and magnetic fields according to their mass-to-charge ratios. The instruments (instrumentation) used in such studies are called mass spectrometers and mass spectrographs, and they operate on the principle that moving ions may be deflected by electric and magnetic fields. The two instruments differ only in the way in which the sorted charged particles are detected. In the mass spectrometer they are detected electrically, in the mass spectrograph by photographic or other nonelectrical means; the term mass spectroscope is used to include both kinds of devices. Since electrical detectors are now most commonly used, the field is typically referred to as mass spectrometry.

      Mass spectroscopes consist of five basic parts: a high vacuum system; a sample handling system, through which the sample to be investigated can be introduced; an ion source, in which a beam of charged particles characteristic of the sample can be produced; an analyzer, in which the beam can be separated into its components; and a detector or receiver by means of which the separated ion beams can be observed or collected.

      Many investigations have been conducted with the help of mass spectrometry. These include the identification of the isotopes of the chemical elements and determination of their precise masses and relative abundances, the dating of geologic samples, the analysis of inorganic and organic chemicals especially for small amounts of impurities, structural formula determination of complex organic substances, the strengths of chemical bonds and energies necessary to produce particular ions, the identification of products of ion decomposition, and the analysis of unknown materials, such as lunar samples, for their chemical and isotopic constituents. Mass spectroscopes also are employed to separate isotopes and to measure the abundance of concentrated isotopes when used as tracers in chemistry, biology, and medicine.

History

      The foundation of mass spectroscopy was laid in 1898, when Wilhelm Wien, a German physicist, discovered that beams of charged particles could be deflected by a magnetic field. In more refined experiments carried out between 1907 and 1913, the British physicist J.J. Thomson (Thomson, Sir J.J.), who had already discovered the electron and observed its deflection by an electric field, passed a beam of positively charged ions through a combined electrostatic and magnetic field. The two fields in Thomson's tube were situated so that the ions were deflected through small angles in two perpendicular directions. The net result was that the ions produced a series of parabolic curves on a photographic plate placed in their paths. Each parabola corresponded to ions of a particular mass-to-charge ratio with the specific position of each ion dependent on its velocity; the lengths of the parabolic curves provided a measure of the range of ion energies contained in the beam. Later, in an attempt to estimate the relative abundances of the various ion species present, Thomson replaced the photographic plate with a metal sheet in which was cut a parabolic slit. By varying the magnetic field, he was able to scan through a mass spectrum and measure a current corresponding to each separated ion species. Thus he may be credited with the construction of the first mass spectrograph and the first mass spectrometer.

      The most noteworthy observation made with the parabola spectrography was the spectrum of rare gases present in the atmosphere. In addition to lines due to helium (mass 4), neon (mass 20), and argon (mass 40), there was a line corresponding to an ion of mass 22 that could not be attributed to any known gas. The existence of forms of the same element with different masses had been suspected since it had been found that many pairs of radioactive materials could not be separated by chemical means. The name isotope (from the Greek for “same place”) was suggested by the British chemist Frederick Soddy (Soddy, Frederick) in 1913 for these different radioactive forms of the same chemical species, because they could be classified in the same place in the periodic table of the elements. The ion of mass 22 was, in fact, a stable heavy isotope of neon.

Focusing spectroscopes

      The spectroscopes discussed so far are analogous to the pinhole camera in optics, because no focusing of the ion beams is involved. The introduction of focusing types of mass spectroscopes came in the years 1918–19 and was due to the British chemist and physicist Francis W. Aston (Aston, Francis William) and to the American physicist Arthur J. Dempster (Dempster, Arthur Jeffrey).

      In Aston's version, successive electric and magnetic fields were arranged in such a way that all perfectly collimated ions of one mass were brought to a focus independent of their velocity, thus giving rise to what is known as velocity focusing. Aston's design was the basis of his later instruments with which he systematically and accurately measured the masses of the isotopes of many of the elements. He chose ¹⁶O (the isotope of oxygen of mass 16) as his standard of mass.

      Dempster's spectrometer utilized only a magnetic field, which deflected the ion beam through an arc of 180°. In Dempster's machine, an ion beam homogeneous in mass and energy but diverging from a slit could be brought to a direction focus. This spectrometer was employed by Dempster to make accurate determinations of the abundances of the isotopes of magnesium, lithium, potassium, calcium, and zinc, laying the foundation for similar measurements of the isotopes of all the elements.

      The resolving power, or resolution, of a mass spectroscope is a measure of its ability to separate adjacent masses that are displayed as peaks on the detector. If two peaks due to mass m and (m + Δm) can just be separated, the resolving power is m/Δm. The early machines had resolving powers of only a few hundred. In 1935 and 1936, Dempster, Kenneth T. Bainbridge, both working in the United States, and Josef Mattauch, in Germany, independently developed instruments with electric and magnetic fields arranged in tandem in such a way that ion beams that emerged from the source slits in divergent directions and with different velocities were refocused. Such focusing is termed double focusing. It was thus possible to achieve a resolving power of about 60,000.

Ion-velocity spectrometers

      The energy of an ion is proportional to the square of its velocity, so ions of constant energy can be separated through the use of fields that vary with time. In the United States William R. Smythe first proposed such a device in 1926 based on electrodes to which radio-frequency voltages are applied and which are arranged so that ions of a given velocity pass undeflected. He built a working model a few years later in collaboration with Mattauch. The method did not prove to be particularly useful and did not see further development. Following World War II the techniques of manipulating very short electrical pulses allowed the construction of the time-of-flight mass spectrometer, in which a short emission of ions is released from the source and their arrival times recorded after having traversed a distance sufficiently long to sort out the different speeds.

      In 1953 the West German physicists Wolfgang Paul (Paul, Wolfgang) and Helmut Steinwedel described the development of a quadrupole mass spectrometer. The application of superimposed radio frequency and constant potentials between four parallel rods can be shown to act as a mass separator in which only ions within a particular mass range will perform oscillations of constant amplitude and be collected at the far end of the analyzer. This device has the advantage of high transmission.

General principles

      The evolution of mass spectrometry has been marked by an ever-increasing number of applications in science and technology. New applications and new developments have gone hand in hand to create a complex array of instruments, but all may be understood by tracing the ions through three basic elements: an ion source, a method of analyzing the ion beams according to their mass-to-charge ratio, and detectors capable of measuring or recording the currents of the beams. These elements exist in many forms and are combined to produce spectrometers with specialized characteristics. The needs of users vary, as do the chemical form and the amount of sample available for analysis, which may be in submicrogram quantities. The result is a great variety of design.

Ion sources

Direct-current arc

      Historically this was the first way of producing a beam of ions and came quite naturally out of the 19th-century experiments for observing the passage of electricity in gases at low pressure. Two planar electrodes (electrode) oriented perpendicular to the axis of the electric field can, with a few hundred-volt potential difference, form a plasma discharge. (Plasma refers to an ionized gas containing an approximately equal number of positive ions (cation) and electrons.) Electrons attracted to the anode collide with molecules of the gas to form ions and free more electrons; the positive ions contribute in turn to further ionization by their collisions. A hole in the cathode allows positive ions to emerge collimated into a beam. Such sources are found with many electrode configurations, including electron-emitting filaments, and operate with wide ranges of pressures and voltages. Sources with magnetic fields parallel to the electric fields can yield beams greater than one milliampere. Direct-current sources were widely used during the first decades of mass spectrography. They served well for gases and liquids introduced as vapours and for many solids as well, because these could be transformed into gaseous atoms and incorporated into the plasma through impact by the ions, a process called sputtering. One disadvantage of this kind of ionization is the wide band of energies attained by the ions, ranging from the maximum electrode potential to almost zero. Such a distribution of energies was the cause of Thomson's parabolas, but accurate work requires a narrow energy range, which in this case must be achieved in the analyzer section of the instrument.

Electron bombardment

 Electrons extracted from a glowing filament may be used to ionize gases. This is the basis for the electron bombardment ion source (see Figure 1—>). A satisfactory electrode arrangement enables the production of a beam of ions much more nearly homogeneous in energy than with the arc, greatly simplifying the ensuing analyzing method. Electron impact has remained the most widely used method of ionization in mass spectrometry. It is subject to problems common to the arc: an almost total lack of selectivity as to the chemical element ionized and, to a lesser extent, the production of ions with degrees of ionization greater than one. Electron impact is utilized extensively in fields of study in which the sample is gaseous or prepared in gaseous form. Isotopic studies of carbon, nitrogen, oxygen, sulfur, and the noble gases make up a large field of endeavour. Electron impact is useful for studying organic compounds (organic compound). Organic molecules are ionized not only as ions of the whole molecule but in a range of fragments as well. This property, which may at first seem disadvantageous, is actually quite valuable in organic identifications because the resulting mass spectrum allows the identification of the source molecule as uniquely as fingerprints are used in human identification. This forms the basis of a powerful method of organic analysis. If the fragmentation of the molecule is harmful to the objectives of the experiment, another method of ionization can be employed that produces few fragments. In this technique a reagent such as methane (CH₄) is mixed with the sample gas and subjected to electron bombardment. The ionized methane (CH⁴/₊) reacts to form CH⁵/₊, which in turn reacts to ionize the sample gas by proton or charge transfer. This process is called chemical ionization (ionization), and in some cases it increases the mass of the ion formed by one unit.

Thermal ionization

      Atoms with low ionization potentials can be ionized by contact with the heated surface of a metal, generally a filament, having a high work function (the energy required to remove an electron from its surface) in a process called thermal, or surface, ionization. This can be a highly efficient method and has the experimental advantage of producing ions with a small energy spread characteristic of the filament temperature, typically a few tenths of an electron volt, as compared with beam energies of thousands of electron volts. The filaments, generally made of platinum, rhenium, tungsten, or tantalum, are heated by current. Surface ionization requires a nearby source of atoms, often another filament operating at lower temperatures. Samples can also be loaded directly on the filament, a widely used and successful technique and one that has resulted in many interesting chemical treatments of the sample when it is deposited on the filament. One such application changed lead from a difficult to an easy element to analyze, enabling important geochronological and environmental measurements. A disadvantage of thermal ionization is the possible change in isotopic composition during the measurement. This effect is caused by Rayleigh distillation, wherein light isotopes evaporate faster than heavy ones. Studies done on isotopes that come from radioactive decay, such as those used in determining the ages of rocks, encounter this problem, but it is correctable using the measured values of the isotopes that are not radiogenic. With few exceptions the use of a thermal source requires the chemical separation of the sample. Useful data are commonly obtained on extremely small (e.g., nanogram) samples.

Spark discharge

      In the vacuum spark source, a pulsed, high-frequency potential of about 50 kilovolts is built up between two electrodes until electrical breakdown occurs. Hot spots appear on the electrodes, and electrode material is evaporated and partially ionized by bombardment from electrons present between the electrodes. The principal merit of the vacuum spark source is its ability to produce copious quantities of ions of all elements present in the electrodes.

Secondary-ion emission

      Direct analysis of solids can be accomplished by bombarding the surface with an ion beam, the impact of which creates additional ions from the solid surface. The bombarding ions transfer substantial momentum to the target atoms, knocking them loose from the crystal lattice of the solid. The process is, generally speaking, not selective, although there are significant differences by element in the efficiency of ionization. The bombarding ions can be given a fine focus, with beam diameters of a few micrometres attainable. This allows the observer to select specific regions of the solid surface for analysis through the use of an auxiliary microscope and micrometre values for sample motion. Ion bombardment eats away the surface with time, allowing the solid to be analyzed for depth as well. This method is the basis for the ion microprobe.

Field ionization

      Intense fields, of the order of 10⁸ volts per centimetre, can be generated in the neighbourhood of sharp points and edges of electrodes, and these have been used as field ionization, or field emission, sources. This source is becoming popular in the study of organic compounds, which can be introduced as vapours and ionized in the intense fields. The ions are formed with very little excitation energy, so that there is little fragmentation of the molecular ions, making molecular formulas easier to determine.

High-frequency-produced plasma

      An oscillator can create an electrodeless discharge in gas at low pressure within a glass tube. The plasma so produced is now a commonly used source for mass spectrometers but was first used in plasma-emission spectrometry (optical and near optical). Samples are introduced by means of a carrier gas, typically argon, and ions result as from the direct-current arc but with very few molecular ions and with the absence of impurities introduced by source electrodes. Such discharges are generally coupled by a coil to an oscillator having a frequency of about 20 megahertz and are called inductively coupled. Discharges can also be produced for specialized experiments in a device called a waveguide that is connected to a cavity magnetron, which has a frequency more than 100 times higher and significantly greater power. This is the basis for the inductively coupled mass spectrometer.

Photoionization (photo-ionization)

      Instead of electrons, photons (photon) in the far ultraviolet region may be used, as they have sufficient energy to produce positive ions in a sample gas or vapour to be analyzed. A discharge in a capillary tube through which is passed a suitable gas, such as helium, is a good source for such radiation. Photoionization sources usually produce fewer ions than electron-bombardment sources but have advantages when the ionization chamber must be held at low temperature.

Resonance photoionization

      All of the methods of ionization described above suffer from a lack of selectivity as to which element is ionized and depend either on the mass spectrometer for differentiation or on careful sample chemistry. A technique that achieves higher elemental selectivity is resonance ionization. In this scheme, a laser with adjustable wavelength irradiates the volume of gas from which the ions are to be extracted, exciting a transition from an atom's ground state to one of its excited (high-energy) states. This strong excitation enables an equilibrium to be established between the two states, while at the same time other radiation—or sometimes the same radiation—takes atoms from the well-populated excited state to ionization. A slight change in the irradiating wavelength stops the equilibration and leaves the excited state unpopulated, which cuts off the ionization. The intense levels of radiation required are produced by pulsed lasers with very short duty cycles, however, making efficient sample use difficult. (The duty cycle is the ratio of the number of atoms irradiated in a given volume to the total number of atoms entering that volume.) For further discussion, see spectroscopy: Resonance-ionization spectroscopy (spectroscopy).

Negative ions (anion)

      Discussions of the above methods have assumed that the ionization process removes one or more electrons from the atom or molecule to produce a positive ion. Negative ions are formed by many of these same methods as well and can be useful in mass spectrometry. The accelerating voltages of the source and the direction of analyzing fields must be reversed, but the detectors respond equally well, with the exception of the Daly detector (see below Ion beam detection: Daly detector (mass spectrometry)). Arc discharges and electron impact produce negative ions, although at rates varying widely according to the construction and mode of operation. Negative ions can be formed in a two-stage process wherein positive ions are accelerated into a gas from which they capture two electrons, a technique infrequently used in mass spectrometry. Negative ions can result from thermal ionization, with those of the halogens easily formed. The elements rhenium, iridium, platinum, and gold are efficiently ionized as molecular negative ions for important applications in geochemistry. The cesium sputter source produces copious quantities of negative ions and is used exclusively for accelerator mass spectrometry. In this source the low ionization potential of cesium is utilized in two ways: (1) surface ionization provides a beam of positive cesium ions that bombard a sample having a thin layer of cesium condensed on it; and (2) the atoms or molecules dislodged by the bombarding beam capture an electron from this layer. In addition to providing beams for accelerator mass spectrometry, this source completely changed the manner in which tandem Van de Graaff accelerators are employed in nuclear physics (see below Accelerator mass spectrometry (mass spectrometry)). Roy Middleton of the United States invented and developed the cesium sputter source.

Sample introduction

      The wide use of mass spectrometers as analytical instruments is accompanied by a correspondingly wide range of forms that the sample can take. Gases (gas) for which electron impact is a suitable ionization method are introduced into the vacuum of the source through a fine valve from the sample reservoir, although in some cases the gas may be devolved from a solid by heating in the source. Liquids (liquid) invariably have vapour pressures high enough for them to be handled as gases. Organic chemistry often furnishes mixtures of gas and liquid in need of analysis. As mentioned above, electron bombardment not only ionizes these molecules but fragments them as well with distributions by which they can be identified. By comparison with a catalog of mass spectra, one can even identify limited mixtures. In 1952 the invention of the gas chromatograph (gas chromatography) by A.T. James and A.J.P. Martin provided chemists with a method of separating mixtures of volatile substances into their component fractions. In this technique the substance to be analyzed is introduced into a stream of gas, usually helium or nitrogen, and carried by it through a capillary containing or coated with an absorbing substance. The various fractions move with different speeds, and the arrival of each at the end of the column is signaled by a suitable detector. In 1957 a mass spectrometer was first employed as the detector, and an important instrument for organic analysis found its place in the modern laboratory, the gas chromatograph–mass spectrometer. The chromatograph causes the fractions of the sample mixture to arrive at the ion source in succession. Mass analyses of the fractions then allow determinations of high reliability. Liquid chromatography may be combined with mass spectrometry as well (see chromatography: Methods of detection (chromatography)).

Ion-beam analysis

General objectives

      The separation of ions according to their mass is accomplished with static magnetic fields, time-varying electric fields, or methods that clock the speeds of ions having the same energies—the time-of-flight method. Static electric fields cannot separate ions by their mass but do separate them by their energy and so provide an important design element by functioning as an energy filter; they are described here along with magnetic fields (magnetic field).

Magnetic field analysis

      Ions of mass m and charge z moving in vacuo with a velocity v in a direction perpendicular to a magnetic field B will follow a circular path with radius r given by

      .

  Therefore, all ions with the same charge and momentum entering the magnetic field from a common point will move in the same radius r and will come to a first-order focus after 180°, as shown in Figure 2—>, regardless of their masses. Hence, the mass spectrometer used by Dempster can be referred to as a “momentum spectrometer.” If all ions of charge z enter the magnetic field with an identical kinetic energy zV, owing to their acceleration through a voltage drop V, a definite velocity v will be associated with each mass, and the radius will depend on the mass. Since zV = ¹/₂mv², substitution in the previous equation will give m/z = B²r²/2V. This formula shows that the radius of curvature r for ions in this spectrometer depends only on the ratio of the ions' mass to charge, as long as their kinetic energy is the same. Thus, a magnetic field can be used to separate a monoenergetic ion beam into its various mass components. A magnetic field will also exert a focusing action on a monoenergetic beam of ions of mass m as is shown in Figure 2—>. In this figure an ion beam emerges from a point A with a spread in direction 2α and comes to an approximate focus at B after traversing 180°. When a molecular ion of mass m₁ carries a single positive charge, it may decompose in front of the magnetic sector to form a fragment ion of mass m₂ and a neutral fragment. If there is no kinetic energy of separation of the fragments, the ion m₂, and also the neutral fragment, will continue along the direction of motion of m₁ with unchanged velocity. The equation of motion for the ion m₂ entering the magnetic sector can now be written from a previous relationship, r = m₂v/Bz. In this equation v is the initial velocity appropriate to m₁ and given by √2zV/m₁. Multiplying both sides of the equation v = √2zV/m₁ by m₂, one obtains m₂v = √2zV (m ²/₂/m₁). Since the general momentum equation for any mass m can be written mv = √2zVm, it is apparent from the former equation that the momentum m₂v is appropriate to an ion of mass m ²/₂/m₁. Thus, the decomposition of the metastable (metastable state) ion will give rise to a peak at an apparent mass m* = m ²/₂/m₁, not necessarily an integral number. This peak is known as a metastable peak. Generally, metastable peaks occur at nonintegral mass numbers, and, because there usually is a kinetic energy of separation during fragmentation of the polyatomic ion, they tend to be more diffuse than the normal mass peaks and thus are recognized easily. For any value of m* a pair of integers m₁ and m₂ can be found such that m* = m ²/₂/m₁. Thus, the action of the magnetic field on the charged metastable-ion decomposition product can be used to give information on the individual fragmentation processes taking place in a mass spectrometer.

Electrostatic field (electric field) analysis

 An electrostatic field that attracts ions toward a common centre—i.e., a radial field—will also exert a focusing action on a divergent beam of ions as shown in Figure 3—>. The radial force on the ions due to the electrostatic field will be Ez, the product of the field E and the ionic charge z, and is equal to the centripetal force mv²r, of mass m moving with velocity v about a radius r. Thus, one may write the equation

      .

      The radius of the arc traversed by the ions will be proportional to their kinetic energy, and an electric sector will thus produce an energy spectrum of the ions passing through it. Alternatively, if narrow collimating slits are placed at either end of the sector, a monoenergetic beam of ions can be selected.

Combined electric and magnetic field analysis

      Use of an electric wedge or sector to obtain a monoenergetic beam of ions, which is then separated for mass analysis by a magnetic sector, is another possible technique. General equations for combined electric and magnetic sectors have been developed; they show that a suitable combination of fields will give direction focusing for an ion beam of given mass-to-charge ratio, even though the beam may be heterogeneous in energy. The term double focusing is used for those combinations in which the angular and velocity aberrations effectively cancel.

 Two of the best examples of double-focusing mass spectroscopes, both of which have been used in a variety of commercial instruments, were built by Mattauch and Richard Herzog in West Germany and by the American physicist Alfred O. Nier and his collaborators. The Mattauch-Herzog geometry is shown in Figure 4—>. Ions of all masses focus along a line that coincides with the second magnetic field boundary. Many versions of this design have been used when high resolution (up to 10⁵) is desired for accurate mass and abundance measurements and general analytical work. It can give good spectra, even for a spread of 5 percent in energy of the ion beam, and can be used with virtually any ion source. The resolved ion beams can be recorded electrically or with a photographic plate.

 Nier's design is illustrated in Figure 5—>. In this instrument, Nier was able to achieve high sensitivity as well as high resolution. Using an electron-bombardment ion source, a resolving power of 2 × 10⁵ has been attained in a commercial instrument. The design has yielded mass measurements of the highest precision for a very large number of the isotopes, and it has also been the most popular design for high-resolution work in organic chemistry.

z-axis focusing

      The form of focusing in the analyzers described above has assumed that the forces acting upon an ion lie entirely in the same plane, generally referred to as the x-y plane, with the y axis defining the direction of the beam. This is adequate for most applications in magnetic sector machines where the beam is ribbon-shaped and where slight deviations in velocity in the z direction, which is perpendicular to the principal plane, cause negligible beam loss. At the entrance and exit of a trajectory passing through a field produced by a magnet, the field is not parallel but rather is bowed out. As a consequence, an ion encounters a small, but not negligible, field component parallel to the x-y plane, which generates a correspondingly small force in the z direction. Magnets have been constructed that take advantage of such forces to focus the beam in the z direction. It is possible to make the x focus and z focus coincident. Focusing in the z direction is often accomplished electrostatically by a suitably arranged pair of electrodes in the ion source.

Time of flight

      The simplest form of mass analysis that does not use magnetic fields depends on the differing speeds of ions with the same energy but different masses. The ion source is generally of the electron-impact type and has one or more electrodes modulated so as to extract ions for a time that is brief compared with the time it takes them to reach the detector. The ion velocities, as given above by v = √2zV/m, and the distance between source and detector allow the mass to be calculated directly. In practice, the response of the detector is displayed on a cathode-ray oscillograph and recorded by a computer. This method has two advantages: it is fast and, if desired, can display the entire mass spectrum. Its deficiencies are poor resolution, poor accuracy of signal, and poor efficiency, due to the short period during which ions are extracted from the source.

Ion-trap methods

      It is possible to configure electric and magnetic fields so that ions can be held in stable orbits for a period of time long enough to perform useful measurements on them. Two forms of mass spectrometers are derived from this idea, the omegatron and the Fourier-transform spectrometer. Both make use of the cyclotron principle (see particle accelerator: Cyclotrons (particle accelerator)), in which positive ions produced by a beam of electrons flowing along the axis of a uniform magnetic field follow circular trajectories with a radius proportional to momentum, r = mv/zB, and a frequency of rotation inversely proportional to mass, ω = v/r = zB/m. In the omegatron the frequency of an oscillator is varied so as to bring ions of various masses in tune and by so doing increase their momenta until they reach a radius at which a detector is located. Mass can be directly calculated from frequency. Resolution can be remarkably high if a sufficient magnetic field is provided, but this analyzer is most frequently operated with less than ideal resolution as a device for analyzing the residual gas of a vacuum, information that can be extremely valuable in diagnosing the problems that often befall such systems.

      In the Fourier-transform method, the frequency of the oscillator is swept through the range corresponding to the mass range of interest. Each ion is placed into a circular orbit of approximately constant radius but well-defined frequency. The oscillator is turned off, and an electrode picks up radio-frequency radiation from the moving ions. The amplified output can be recorded either directly or after having been mixed with the frequency of a local oscillator, a standard radio technique. This yields a complex time-varying signal that follows the amplitude of the various ion radiators. The signal is converted to digital form and stored in a computer memory. The computer converts this periodic signal to its frequency spectrum by the mathematical technique known as the Fourier transform, with mass being inversely proportional to frequency. The process is repeated many times in order to enhance accuracy. These devices are capable of resolutions exceeding one million. In order to have orbital radii of convenient size, very high magnetic fields are required, generally provided by superconductors.

Tandem spectrometry

      The combination of two analytical techniques, such as resulted in the gas chromatograph–mass spectrometer, has been followed by the combination of two mass spectrometers, which has proved helpful in determining the structure of complicated molecules. A beam from the first spectrometer is passed into a gas cell (maintained in the vacuum system by differential pumping), where it is dissociated by collisions, and these fragments are passed on to a second mass analyzer, which generally discloses a more easily identified spectrum.

Quadrupole spectrometer

 Positive ions (cation) incident along an axis parallel to four cylindrical electrodes, as shown in Figure 6—>, experience for the static potentials indicated a focusing force along the x axis and a defocusing one in the z direction. If one superimposes a radio frequency voltage onto the static voltage, oscillatory ion trajectories can be found that allow ions of a given mass to pass through the quadrupole with other masses being defocused and lost from the beam. A knowledge of the potentials and frequency specifies the mass. This device is widely used where speed of data acquisition and high transmission are important. It is compact and lightweight and can trade off sensitivity for resolution by simple adjustment of electrical parameters. It is the common analyzing element of gas chromatograph–mass spectrometers.

Ion beam detection

Photographic plates

 Especially sensitive photographic plates are employed to compensate for the low penetrating power of the ions. It has proved possible with these to detect an element over a sensitivity range of one part in one billion. In addition to the sensitivity, a major advantage of the photographic plate arises when it is used in a double-focusing mass spectroscope in which the whole or a major part of the mass spectrum is focused in a plane (see the design of Mattauch and Herzog shown in Figure 4—> and described above). In this case, one can make use of the integrating action of the plate and compare the densities of lines due to different elements.

Faraday cup

      The direct measurement of ion currents collected by a shielded electrode, called a Faraday cup, became possible in the 1930s with the introduction of electrometer tubes capable of measuring currents below a nanoampere, although sensitive galvanometers had been used for larger currents. The introduction of feedback led to greater stability and accuracy and faster response time, but it was the introduction of the vibrating-reed electrometer that allowed isotopic ratios to be routinely measured to a few parts in a hundred thousand. For more than three decades, these electrometers functioned unsurpassed as laboratory workhorses and were only slightly modified in design. They can now be equaled and in some respects surpassed in performance by the feedback electrometer, which uses a metal-oxide silicon field-effect transistor instead of a tube to measure extremely small currents.

Electron multipliers

      The development of electronic techniques for television during the 1930s yielded a device of extraordinary sensitivity for measuring small electron beams—namely, the secondary electron multiplier. Although originally invented for the amplification of the tiny currents from a photocathode, it soon proved to be an excellent detector for ion beams with a sensitivity sufficient to record the arrival of single ions. The fundamental principle of the multiplier is, as the name suggests, a multiplication of the number of electrons emerging from an electrode as compared with the number incident upon it. Electrodes, called dynodes, are so arranged that each succeeding generation of electrons is attracted to the next dynode. For example, if 4 electrons are released at the first dynode, then 16 will emerge from the second and so forth. Gains of as much as one million are easily attained; the noise is limited to the currents originating from the few electrons leaving the first dynode as a result of thermal electron emission. Multipliers were originally constructed with discrete dynodes, a form still in wide use. Continuous dynode multipliers, which use a semiconducting glass to provide the distribution of electrostatic potential, are smaller and perform equally well in most applications. A multiplier can be employed in an analog mode, in which the output current is measured with an electrometer as is any small current, or in a pulse-counting mode, in which individual ions are counted.

 The mass spectrum of osmium (Os), obtained using an electron multiplier detector, is shown in Figure 7—>. It is a recorder trace of the electrometer output from an electron multiplier detecting OsO₃⁻ taken as the field of the analyzing magnet was steadily increased. Owing to their small sizes, the leftmost and two rightmost peaks were recorded with an electrometer gain 100 times what was used for the other peaks; the change in gain is marked by a change in the position of the baseline. The osmium isotopes observed, from left to right, are 184, 186, 187, 188, 189, 190, and 192. The oxygen (O) in the ions results in very small satellite peaks caused by the low abundance isotopes ¹⁷O and ¹⁸O; the satellite peaks of ¹⁹²Os are at the right. This trace is typical of machines used in geochronology, where flat-topped peaks are desired rather than high resolution. The irregular signal of the three weak isotopes results from the low rate at which these ions are detected.

Daly detector

      In 1960 N.R. Daly introduced a form of detector with properties superior to the electron multipliers described above. In this design the incident ions are attracted to a rounded electrode of a few centimetres in dimension that is held at 10,000 to 20,000 volts negative. The ions strike the “door knob” and release a few secondary electrons for each incident ion; these electrons are then accelerated from the high negative potential to a scintillation crystal mounted on a photomultiplier (photomultiplier tube) at ground potential. The electrons generate a light signal in the scintillation crystal that is amplified by the photomultiplier. The output is then treated just as the output of an electron multiplier. The advantage of this more complicated device is an almost complete independence of the signal size with the position of the ion beam in the defining slit that precedes the detector. This is an important property for accurate measurement of isotopic ratios because the invariable instability of the analyzing magnet and the ion-source voltage cause the beam to drift within the limits set by the slit, and so a nonuniform response gives rise to errors in the measured ratios. Electron multipliers require various adjustments, not always satisfactory, to produce a signal size independent of beam position. The Daly detector cannot be used with negative ions.

Multiple detectors

      In instances in which the ratio of two or more isotopes is the experimental goal with a magnetic sector analyzer, there are advantages in measuring the currents of the beams simultaneously in multiple detectors rather than switching the magnetic field. This is relatively simple for light elements that have widely spaced beams at the detector location and is often employed in such cases. For heavy elements the small spacing necessitates more difficult techniques that came into routine use only in the 1980s.

Important technical adjuncts

Vacuum (vacuum technology)

      In the devices heretofore described, the presence of a good vacuum system has been assumed. Mass spectroscopy originated at about the time that high vacuum was first attained in the laboratory. High vacuum refers to a pressure low enough that the mean free path (the distance traveled between collisions) of molecules in the residual gas is greater than the dimensions of the vacuum vessel. Mass spectroscopists invariably seek conditions of improved vacuum. The properties that render low pressures desirable include a reduction in the scattering of the beam in the analyzer, which causes interfering background effects and a reduction in the production of spurious beams out of the residual gases, particularly from the organic compounds that are present. The history of vacuum techniques is varied and great and has provided present mass spectrometrists with pressures that are routinely four to five orders of magnitude lower than those first used by Thomson, Aston, and Dempster. The invention of the diffusion pump by the German physicist Wolfgang Gaede in 1915, with important improvements by the American chemist Irving Langmuir (Langmuir, Irving) shortly thereafter, freed mass spectroscopy from the severe limitations of poor vacuum. During the 1960s diffusion pumps began to be replaced by ion-getter pumps, with turbomolecular pumps becoming common in the 1980s.

Electronics

      The operation of a mass spectrometer depends on elaborate electronic equipment: ion sources require extremely stable power supplies, magnets need instruments for measuring the magnetic field and controlling the current supply for the coils, detectors use a variety of power supplies and amplifiers, and general operation requires electronic auxiliary equipment. The rapid increase in the use of mass spectrometers following World War II can likely be attributed in part to the large number of physicists who had gained electronic training during the war, many of whom had utilized mass spectroscopy during that conflict to monitor uranium isotope separation and to analyze aviation gasoline.

Computers (computer)

      The introduction of small computers for laboratory work during the 1960s altered entirely the manner in which mass spectrometry was performed and widened its applications to an extraordinary degree. Computers were interfaced with spectrometers, making it possible to repeat a measurement schedule on a steady basis and record the data acquired. In organic analysis the computer was programmed to store the spectra of thousands of compounds, allowing rapid identification of the substance under study. Users soon devised ways by which the answers to their questions came within minutes after the conclusion of the analysis.

Applications

Atomic (atom)

Atomic masses (atomic mass)

      The discovery of isotopes (isotope) with the first mass spectrograph answered the question about the integer value of atoms only to a crude level of accuracy and made all too clear the need for more accurate mass determinations. These were first undertaken by Aston and repeated with increasing precision by succeeding generations. The first data showed slight deviations from an integer law but also showed a quasi-systematic variation as a function of atomic number. In the early 1930s these data explained the energies of nuclear reactions then being observed through the mass-energy relation that had been given two decades earlier by the special theory of relativity. Since that time mass spectroscopy and nuclear physics have combined to determine isotopic masses to a high degree of accuracy. The mass unit now used is defined so that the mass of the carbon-12 isotope is exactly 12 atomic mass units (amu). Nuclear theory is continually tested in its ability to reproduce the observed values. Indeed, these masses provide an early and critical test of nuclear models. Mass spectrometry has been closely associated with nuclear physics since its beginning. A mass spectrometer is frequently found in some form as a part of nuclear experiments to identify reaction products. Large mass spectrometers are employed as isotope separators and are capable of producing weighable amounts of selected stable isotopes that have valuable analytical applications. They are used for labeling compounds so that they can be traced through various chemical, physical, and environmental processes without the problems created by radioisotope tracers. Analysis is, of course, performed by mass spectrometer. In addition, nuclear reactions often produce extremely small amounts of radioactive products, which cannot easily be manipulated by normal chemical procedures. In such cases, stable isotopes of the product are added to the radioactive element, thereby increasing the concentration so that it falls within the range of the analytical method. These enriched isotopes are indispensable for research in nuclear physics.

geochronology and geochemistry

      The early studies of the radioactive decay (radioactivity) of uranium and thorium into lead caused the British physicist Ernest Rutherford to suggest that this process could be used to determine the age of rocks and consequently of the Earth by observing the amount of helium retained by a rock relative to its uranium and thorium contents. Mass spectrometers capable of measuring isotopic ratios allow the composition of elements to be determined in which one or more isotopes result from radioactive decay. The age of the rock from which the element has been obtained can be determined if the amount of the parent element can be measured and certain requirements on the environmental history of the rock are met (see dating: Absolute dating (dating)).

      The Earth's crust is generally richer in oxygen-18 (¹⁸O) than is the mantle, as a result of the reaction of these upper-layer rocks with the hydrosphere and atmosphere. This fact allows oxygen-18 to be used to assess the degree to which ascending magmas have incorporated crustal rocks as they rise to the surface. The use of isotopes has proved especially valuable in understanding the origin and nature of the solar system. A great body of evidence now suggests that meteorites (meteorite) are objects that solidified very early in the history of the solar system. Extinct radioactivities of elements with various half-lives have been identified that set limits on the time between the synthesis of the elements and their condensation. (Extinct radioactivities are nuclides that have nearly completely decayed into their daughter elements.) An example is the excess of magnesium-26 (²⁶Mg) found in primitive meteorites that resulted from the decay of aluminum-26 (²⁶Al), which has a 720,000-year half-life.

hydrogen, carbon, nitrogen, oxygen, and sulfur in nature

      These elements, each of which has two or more stable isotopes, are vital to life. All show measurable variation in isotope composition as a result of natural and, in particular, metabolic processes. It was observed as early as 1939 that living matter preferentially incorporates the light isotope of carbon at rates differing according to species and environment. Knowledge of this is valuable in understanding the early biochemical evolution of the Earth. The evaporation of seawater causes a lower ratio of ¹⁸O to ¹⁶O in fresh water during times of high average temperature than in times of low temperatures. Examination of the oxygen preserved in polar ice and calcareous fossil shells has revealed the climatic evolution of the recent geologic past.

trace element analysis

      Mass spectrometry may be used to measure with high sensitivity trace amounts of an element through the technique of isotope dilution. A small, measured amount of an isotopically enriched sample, called a spike, is added to the original material, thoroughly mixed with it, and extracted with that element. The mass spectrum of this mixture will be a combination of the natural spectrum of the element plus the unnatural one of the spike. By knowing the amount of the spike added, one may calculate the amount of the unknown. Rigorous measures must be undertaken to ensure that the reagents and vessels used do not themselves supply the element, but this is easily controlled by chemically processing a known amount of the spike alone and determining the amount of the element picked up.

Molecular

Ion- molecule reactions

      Owing to the poor vacuums available prior to the contributions of Gaede and Langmuir (see above), this subject was forced on the attention of early experimenters. They observed masses of 3 and 19, which could not have been produced by simple ionization and which arise from the following reactions, respectively:

      These “problems” disappeared with improved vacuum. Ion-molecule reactions are important in understanding the chemistry of flames, of electrical discharges, of the upper atmosphere, and of samples subject to radiation. The mass spectrometer is the instrument of choice for such investigations.

Organic chemistry

      Mass spectrometry has a critical role in organic chemistry. Its utility in chemical analysis was discussed earlier when describing appropriate experimental techniques. The same techniques can be used in determining the structure of complicated molecules, but perhaps of even greater value for such work are high-resolution measurements.

      With a high-resolution mass spectrometer it is possible to carry out mass measurements on the molecular ion (or any other ion in the spectrum) to an accuracy of approximately one part in one million. This mass provides the best index for determining ionic formulas. The accurate masses of the ions C₆H₁₂⁺ and C₄H₄O₂⁺ are, for example, 84.0939 and 84.0211, respectively, and these ions can easily be distinguished solely on the basis of their masses. Once the molecular formula is known it is possible to deduce the total of rings and double bonds making up the molecular structure and to begin to speculate on possible structural formulas. In order to deduce structural formulas from molecular formulas, it is essential to study the fragment ions in the mass spectrum. It is still not possible to predict definitively the fragmentation patterns for organic molecules, but many semi-empirical rules of fragmentation are known, and it is usually possible to pick out peaks in the spectrum that are characteristic of particular chemical groups. The technique is valuable in that it is generally not necessary to know any details of the composition of the unknown compound in order to deduce a complete or partial structure. Only a small quantity of compound, a hundred micrograms or less, is necessary for an analysis.

      Using a computer coupled to a high-resolution mass spectrometer, about 1,000 mass peaks per minute can be plotted at a resolving power of up to 20,000, accurate measurements can be made on each peak, and peak heights and ion compositions can be printed out in the form of an “element map” to aid in the interpretation of the spectrum. It is also possible for the computer to carry out many of the logical steps in reducing the data that lead to structural elucidation.

      Continuous sampling of the materials contained in a reaction vessel, followed by analysis with a mass spectrometer, has been used to identify and measure the quantity of intermediate species formed during a reaction as a function of time. This kind of analysis is important, both in suggesting the mechanism by which the overall reaction takes place and in enabling the detailed kinetics of reactions to be resolved.

      Isotopic labeling (isotopic tracer) is widely used in such studies. It can indicate which particular atoms are involved in the reaction; in rearrangement reactions it can show whether an intramolecular or intermolecular process is involved; in exchange reactions it can show that particular atoms of, for example, hydrogen are exchanging between the reacting species. Labeling is also widely used in mass-spectrometric research to give information about the fragmentation reactions occurring in the mass spectrometer.

      Fields of investigation that employ mass spectrometry include studies of protein structure, drug metabolism, flavour and smell, petroleum and petrochemicals, organic fossils, inherited metabolic diseases, atmospheres and respiratory gases, and many other highly specialized subjects.

Space probes

      Future space exploration, addressing the question of whether life exists elsewhere in the solar system, will rely on the mass spectrometer to produce spectra of those molecules characteristic of life. An unmanned spacecraft equipped with a mass spectrometer has already revealed much about the surface and atmosphere of Mars and set limits on the amount of organic matter present.

Leak detection

      A widely used commercial device designed to locate leaks in vacuum (vacuum technology) systems consists of a small mass spectrometer with an electron-bombardment ion source that is connected to the troubled system. The mass spectrometer is set to detect helium, and the gas is played onto suspected parts through a capillary. A signal develops when the helium enters through the leak, and the exact location can be determined by adept manipulation of the capillary.

Accelerator mass spectrometry

Development

      The particle accelerators used in nuclear physics can be viewed as mass spectrometers of rather distorted forms, but the three principal elements—the ion source, analyzer, and detector—are always present. L.W. Alvarez (Alvarez, Luis W.) and Robert Cornog of the United States first used an accelerator as a mass spectrometer in 1939 when they employed a cyclotron to demonstrate that helium-3 (³He) was stable rather than hydrogen-3 (³H), an important question in nuclear physics at the time. They also showed that helium-3 was a constituent of natural helium. Their method was the same as that described above for the omegatron except that a full-sized cyclotron was used, and it easily distinguished the two isotopes. The method was not employed again for nearly 40 years; however, it has found application in measuring cosmogenic isotopes, the radioisotopes produced by cosmic rays incident on the Earth or planetary objects. These isotopes are exceedingly rare, having abundances on the order of one million millionth of the corresponding terrestrial element, which is an isotopic ratio far beyond the capabilities of normal mass spectrometers. If the half-life of a cosmogenic isotope is relatively short, such as beryllium-7 (⁷Be; 53 days) or carbon-14 (¹⁴C; 5,730 years), its concentration in a sample can be determined by radioactive counting; but if the half-life is long, such as beryllium-10 (¹⁰Be; 1.5 million years) or chlorine-36 (³⁶Cl; 0.3 million years), such a course is ineffective. The advantage of the large, high-energy accelerator mass spectrometer is the great detector selectivity that results from ions having 1,000 times more energy than any previously available machine could provide. Conventional mass spectrometers have difficulty measuring abundances less than one hundred-thousandth of the reference isotope, because interfering ions are scattered into the analyzer location where the low-abundance isotope is to be sought. Extremes of high vacuum and antiscattering precautions can improve this by a factor of 10 but not the factor of 100 million that is required. An accelerator suffers from this defect to an even greater degree, and large quantities of “trash” ions are found at the expected analyzer location of the cosmogenic isotope. The ability of certain kinds of nuclear particle detectors to identify the relevant ion unambiguously enables the accelerator mass spectrometer to overcome this shortcoming and function as a powerful analytical tool.

Operation of the tandem electrostatic accelerator

 The tandem electrostatic accelerator (see particle accelerator: Van de Graaff generators (particle accelerator)) quickly displaced all other machines for this purpose, primarily because its ion source, the cesium sputter source described above, is located near ground potential and is easily accessible for changing samples. The ions must be negative, but this does not prove to be a handicap as they are easily and efficiently produced. Before entering the high-voltage tube, the ions are mass-analyzed so that only the beam emerging at the mass location of the cosmogenic isotope enters the accelerator; the intense reference isotope beam is often measured at this location without entering the accelerator at all. The cosmogenic isotope beam is attracted to the high-voltage terminal of the machine where collisions with gas or a thin carbon foil or both strip various numbers of electrons (electron), thereby leaving the subject isotope with a distribution of multiple positive charge states that are repelled by the positively charged terminal. All molecular ions are broken up. The emerging beam then passes through analyzing fields of which a high dispersion magnet is the principal part. Upon leaving the analyzer, the beam enters the detector. Each ion is examined individually in a manner that allows its identity to be established. The most common way of doing this is by using a combination of two particle detectors: one detector measures the rate at which the particle loses energy when passing a given length of matter, while the other simultaneously measures the total energy of the particle. The counts are stored in the bins of a two-dimensional computer array, the coordinates of which are given by the amplitudes of the signals from the two detectors. The numerous “trash” ions take on values from the two detectors that fill regions of the data array but generally do not overlap the well-defined region occupied by the subject ion. Each kind of isotope requires a specially designed detector system with various additional analyzing fields and, in some cases, even the use of time-of-flight techniques. A schematic diagram of an accelerator mass spectrometer is shown in Figure 8—>.

Applications

      The accelerator method has opened lines of investigation that had previously been inaccessible. A strong motivation for the inventors was the improvement of radiocarbon dating (carbon-14 dating). Scientists are now able to make age determinations from much smaller samples and to make them much more rapidly than by radioactive counting, but carbon-14 proved to be a considerably more difficult problem for instrumental development than the other cosmogenic isotopes. The method was applied almost immediately to analyses involving beryllium-10 and chlorine-36, with aluminum-26 (²⁶Al), calcium-41 (⁴¹Ca), and iodine-129 (¹²⁹I) following soon after; notable achievements resulted from all five. Cosmic rays striking the atmosphere are a strong source of beryllium-10, carbon-14, and chlorine-36, which are deposited in rain and snow, whence their migration may be followed. A question concerning the origin of the lavas of island-arc volcanoes, which had been disputed since the general acceptance of the plate tectonic theory of the Earth's structure, was settled from the observation of beryllium-10 in these lavas. The presence of beryllium-10 proved that deep-ocean sediment, rich in the isotope, had been subducted (i.e., carried on the surface of a descending tectonic plate beneath another such plate) and some of the sediment incorporated into the magma. The first application of chlorine-36 was the study of the migration of ancient groundwater. Later improvements in instrumental techniques added iodine-129 as a needed tracer for this challenging problem. Nuclear bomb tests at oceanic sites produced huge amounts of chlorine-36 that were injected into the atmosphere. For a few years rain contained this isotope at a level up to 1,000 times higher than the cosmogenic level. This yielded a tracer with a well-defined time of origin that will be useful long into the future for following the course of such water in soils and aquifers (water-bearing layers of rock). The four lightest of these isotopes have proved useful in determining the ages and irradiation histories of meteorites and lunar samples. There have been extensive studies of beryllium-10 in cores of polar ice and ocean sediments that give unique information about the intensity of cosmic rays over the past few million years.

John Herbert Beynon Louis Brown

Additional Reading

F.W. Aston, Mass-spectra and Isotopes, 2nd ed. (1942), is a comprehensive account of the early work that laid the foundations of accurate mass and isotopic abundance measurements. H.E. Duckworth, R.C. Barber, and V.S. Venkatasubramanian, Mass Spectroscopy, 2nd ed. (1986), provides good general coverage of techniques and applications. Ian Howe, Dudley H. Williams, and Richard D. Bowen, Mass Spectrometry: Principles and Applications, 2nd ed. (1981), emphasizes applications to molecular reactions. F. Adams, R. Gijbels, and R. van Grieken (eds.), Inorganic Mass Spectrometry (1988), surveys the most recent experimental developments. J.R. Chapman, Practical Organic Mass Spectrometry (1985), is a simple, up-to-date text. Gordon M. Message, Practical Aspects of Gas Chromatography/Mass Spectrometry (1984), contains a general treatment of practice and application. Peter H. Dawson (ed.), Quadrupole Mass Spectrometry and Its Applications (1976), gives an extensive treatment of theory. Alan G. Marshall and Francis R. Verdun, Fourier Transforms in NMR, Optical, and Mass Spectrometry (1990), very lucidly explains this technique. David Elmore and Fred M. Phillips, “Accelerator Mass Spectrometry for Measurement of Long-lived Radioisotopes,” Science, 236(4801):543–550 (May 1, 1987), surveys this method.Louis Brown

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