Precision mass analyzers

The previous discussion has centered on how to obtain as much molecular mass and chemical structure information as possible from a given sample. However, there are many uses of mass spectrometry where precise isotope ratios are needed and total molecular mass information is unimportant. For accurate measurement of isotope ratio, the sample can be vaporized and then directed into a plasma torch. The sample can be a gas or a solution that is vaporized to form an aerosol, or it can be a solid that is vaporized to an aerosol by laser ablation. Whatever method is used to vaporize the sample, it is then swept into the flame of a plasma torch. Operating at temperatures of about 5000 K and containing large numbers of gas ions and electrons, the plasma completely fragments all substances into ionized atoms within a few milliseconds. The ionized atoms are then passed into a mass analyzer for measurement of their atomic mass and abundance of isotopes. Even intractable substances such as glass, ceramics, rock, and bone can be examined directly by this technique. 

Fourier transform mass spectrometry is made possible by the measurement of an AC current produced from the movement of ions within a magnetic field under ultra-high vacuum, commonly referred to as ion cyclotron motion.21 Ion motion, or the frequency of each ion, is recorded to the precision of one thousandth of a Hertz and may last for several seconds, depending on the vacuum conditions. Waveform motion recorded by the mass analyzer is subjected to a Fourier transform to extract ion frequencies that yield the corresponding mass to charge ratios. To a first approximation, motion of a single ion in a magnetic field can be defined by the equation... 

For high-throughput analysis, it is important to increase the specihcity of each bioanalytical method. The enhancement of chromatographic resolution presents various limitations. Better selectivity can be obtained with TOF mass analyzers that routinely provide more than 5000 resolution (full width at half-mass or FWHM). The enhanced selectivity of a TOF MS is very attractive for problems such as matrix suppression and metabolite interference. In one report of quantitative analysis using SRM, TOF appeared less sensitive than triple quadrupole methods but exhibited comparable dynamic range with acceptable precision and accuracy.102... 

Ion detection is carried out using image current detection with subsequent Fourier transform of the time-domain signal in the same way as for the Fourier transform ion cyclotron resonance (FTICR) analyzer (see Section 2.2.6). Because frequency can be measured very precisely, high m/z separation can be attained. Here, the axial frequency is measured, since it is independent to the first order on energy and spatial spread of the ions. Since the orbitrap, contrary to the other mass analyzers described, is a recent invention, not many variations of the instrument exist. Apart from Thermo Fischer Scientific s commercial instrument, there is the earlier setup described in References 245 to 247. 

Mass spectrometry is a sensitive analytical technique which is able to quantify known analytes and to identify unknown molecules at the picomoles or femto-moles level. A fundamental requirement is that atoms or molecules are ionized and analyzed as gas phase ions which are characterized by their mass (m) and charge (z). A mass spectrometer is an instrument which measures precisely the abundance of molecules which have been converted to ions. In a mass spectrum m/z is used as the dimensionless quantity that is an independent variable. There is still some ambiguity how the x-axis of the mass spectrum should be defined. Mass to charge ratio should not lo longer be used because the quantity measured is not the quotient of the ion s mass to its electric charge. Also, the use of the Thomson unit (Th) is considered obsolete [15, 16]. Typically, a mass spectrometer is formed by the following components (i) a sample introduction device (direct probe inlet, liquid interface), (ii) a source to produce ions, (iii) one or several mass analyzers, (iv) a detector to measure the abundance of ions, (v) a computerized system for data treatment (Fig. 1.1). 

For this experiment Bainbridge used the high-precision mass spectrograph he had developed by combining a Wien filter with a 180° magnetic analyzer.13... 

An easy calibration strategy is possible in ICP-MS (in analogy to optical emission spectroscopy with an inductively coupled plasma source, ICP-OES) because aqueous standard solutions with well known analyte concentrations can be measured in a short time with good precision. Normally, internal standardization is applied in this calibration procedure, where an internal standard element of the same concentration is added to the standard solutions, the samples and the blank solution. The analytical procedure can then be optimized using the internal standard element. The internal standard element is commonly applied in ICP-MS and LA-ICP-MS to account for plasma instabilities, changes in sample transport, short and long term drifts of separation fields of the mass analyzer and other aspects which would lead to errors during mass spectrometric measurements. 

The complications just described can be minimized if there is greater selectivity in the ionization process, as is sometime possible when photoionization is used as the excitation mechanism. Because the ionization energy can be more precisely controlled, it is possible in selected cases to produce only the desired reactant-ion species, or at least to minimize production of other ions. As already noted in the earlier section on formation of excited ions, it is also possible to populate specific internal-energy states of some reactant ions by using a photoionization source. One of the earliest photoionization mass spectrometers used to study interaction of internally excited ions with neutrals was that constructed by Chupka et al.91 Such apparatuses typically incorporate a photon source (either a line or a continuum source) and an optical monochromator, which are coupled to the reaction chamber. Various types of mass analyzer, including sector type, time-of-flight (TOF), and quadrupole mass filters, have been used with these apparatuses. Chupka has described the basic instrumental configuration in some detail.854 Photoionization mass spectrometers employed to study interactions of excited ions with neutral species have also been constructed in several other laboratories.80,1144,142,143 The apparatus recently developed by LeBreton et al.80 is illustrated schematically in Fig. 7 and is typical of such instrumentation. 

Finally, one concept that must be included in assessing quantitation by HRMS is the effective scan rate of the system. Quadrupole and time of flight mass analyzer are capable of rapid scan rates for SRM-type quantitation, with individual dwell times (quad) or scans (TOF) at 10-50 milliseconds possible. This permits acquisition of numerous data points across a chromatographic peak, which is critical for accurate and precise quantitation. Mass resolution is unaffected by changes in dwell time/scan... 

In a quadrupole device, not as accurate and precise as double-focusing instruments but fast, a quadrupolar electrical field comprising radio-frequency (RF) and direct-current components is used to separate ions. Quadrupole instruments as mass analyzers are used together with ESI as the ion source the configuration employing a three-dimensional quadrupolar RF electric field (Wolfgang Paul, University of Bonn, 1989 Nobel prize for physics) is referred to as an ion trap analyzer (see below). 

Laser microprobe mass analyzers permit mass spectrometric analysis of very small volumes (0.01-1 pm3) of thin Sections. The method is based on laser induced ion production from a microvolume and analysis of the evaporated ions in a time-of-flight mass-spectrometer. The technique allows detection of all elements and isotopes with a sensitivity approaching the ppm range and an extremely low limit of detection 10 15 to 10-20 g. Transmission type instruments such as the LAMMA 500 are designed for the analysis of particles of 3 pm in diam. The lateral resolution is about 0.5-1 pm. Because the area to be analyzed is selected by an optical microscope, distribution of chemical constituents can be precisely correlated with morphologic structures (Hillenkamp et al., 1982 39), Simons, 198440), Kaufmann, 1984)41 >. 

Elemental mass spectrometry has undergone a major expansion in the past 15-20 years. Many new a, elopments in sample introduction systems, ionization sources, and mass analyzers have been realized. A vast array of hybrid combinations of these has resulted from specific analytical needs such as improved detection limits, precision, accuracy, elemental coverage, ease of use, throughput, and sample size. As can be seen from most of the other chapters in this volume, however, the mass analyzers used to date have primarily been magnetic sector and quadrupole mass spectrometers. Ion trapping devices, be they quadrupole ion (Paul) [1] traps or Fourier transform ion cyclotron resonance (Penning) traps, have been used quite sparingly and most work to date has concentrated on proof of principal experiments rather that actual applications. 

A method based on ICP-MS using an SF mass analyzer with multicollector unit was employed for the precise determination of 87Sr-86Sr in 11 wines [96]. To avoid the 87Sr-87Rb isobaric interference, Sr was separated from Rb and the Sr-rich fraction was introduced into the plasma. Precision values of 0.002-0.003 percent were routinely obtained. To check the accuracy, a CRM namely, the NIST SRM 987, was analyzed, measurements being within +0.02 percent of the target value. 

Mass spectrometry can be used to determine the precise mass of a protein. Because of their large size and low volatility, proteins require specialized mass spectral techniques, such as electrospray ionization spraying a charged, heated stream of droplets into the evacuated source chamber. The solvent evaporates to leave ions of the compound to be analyzed. 

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