Ion Trap Mass Spectrometry Philip S.H. Wong The operating principles of linear quadrupoles and quadrupole ion traps Bioanalytical Systems West Lafayette, IN are described, and the performance characteristics of triple quadrupoles 47906-1382 and ion trap instruments are compared. The theoretical basis for mass R. Graham Cooks* analysis using quadrupole fields is also described. The high Department of Chemistry performance of quadrupole ion traps is illustrated by introducing some Purdue University West Lafayette, IN new developments, including mass range extension, high resolution 47907 experiments, MSn experiments, selective ion manipulation techniques, *Corresponding author and non-destructive ion detection. E-mail: [email protected] Mass spectrometry, the science and particles with electric and/ or mag- Quadrupoles and Ion Traps technology of gaseous ions (1), has netic fields. T1 summarizes the as its basis the measurement of most common mass analyzers and With the above background on mass-to-charge ratios (m/z) of ions. lists some analytical performance ionization and mass analysis, we All atomic and molecular ions are, characteristics by which they can can now introduce a family of mass in principle, accessible by mass be compared (6). As with the vari- analyzers whose operation is based spectrometry, making it a universal ous ionization methods, there is no on ion motion in rf electric fields. method for chemical analysis. Its single right choice — the nature of The quadrupole mass filter (8), or implementation requires suitable the problem and the resources of linear quadrupole, consists of a lin- methods of ion generation, ion the laboratory will dictate which ear array of four symmetrically ar- analysis, and ion detection. We treat mass analyzer is most appropriate. ranged rods (F1) to which rf and dc each of these processes in turn and Most uses of mass spectrome- voltages are supplied. Forces are show below that there are multiple try are made in combination with exerted in a plane normal to the di- methods of accomplishing each. chromatographic separation, princi- rection (z-direction) in which the The first step in recording a pally in the form of the GC/MS or ions drift through the array in their mass spectrum is to convert analyte LC/MS technique. These combina- journey from the ion source to the molecules (or atoms) into gas phase tions have been used, for example, detector. The rf potential gives rise ions. In biological applications, the in organic analysis in the environ- to a field which alternatively rein- most common ionization tech- mental sciences and in charac- forces and then dominates the dc niques are electrospray ionization terization of biological compounds, field, also applied by coupling op- (ES) (2), atmospheric pressure including molecular weight (MW) posite sets of rods. Ions oscillate in chemical ionization (APCI) (3,4), determinations, and sequence the x,y-plane with frequencies and matrix-assisted laser desorption analyses of biopolymers (7). In- which depend on their m/z values ionization (MALDI) (5). These are creasingly important applications and with excursions which depend soft ionization methods in the sense have been found in drug metabo- on the amplitudes of the applied that at least some analyte molecules lism and protein sequencing due to potentials and their initial positions. are converted, intact, into corre- the high sensitivity and chemical If the oscillations of an ion in this sponding ions. Solution phase sam- specificity of mass spectrometry. plane are stable, the ion will con- ples are examined with ES and These advantages apply even when tinue to drift down the rod assem- APCI while MALDI is particularly the samples are presented to the bly and reach the detector. Stable appropriate for solid phase samples. mass spectrometer as mixtures oscillations are only achieved by Having successfully generated gas since the two-stage tandem mass ions of given m/z values for a given phase ions, they must then be mass spectrometry (MS/MS) experiment rod assembly, oscillation frequency, analyzed. There are several differ- serves as a method of separation as rf voltages, and dc voltage. The ent types of mass analyzers, all well as characterization of the sepa- range of values of m/z which corre- based on the interactions of charged rated components. spond to stable motion can be made T1 Quantity Mass/charge Resolution at Dynamic Characteristics of Differ- Method Measured (m/z) range m/z = 1,000 Range ent Mass Analyzers. (Adapted from 4 5 7 reference 6.) Sector Magnet momentum/charge 10 10 10 Time of Flight flight time 106 103 -104 104 Ion Cyclotron cyclotron Resonance frequency 105 106 104 Ion Trap frequency 104 104 104 Quadrupole filters mass filter for m/z 103 -104 103 -104 105 very large (wide band pass) or it F1 Quadrupole Mass Filter can be a single m/z value (narrow Schematic diagram showing the operation band pass). In practice, ions of a of the quadrupole mass particular m/z value are often se- filter. Note that as ions drift through the array lected, and mass scanning is usually of rods they are sub- Ion Source Detector achieved by sweeping the dc and rf jected to forces which cause oscillation in the voltages, keeping their ratio and the x,y-plane (shaded). oscillator frequency constant. The quadrupole ion trap, X (9,10), the subject of this article, is the three dimensional analogue of the linear quadrupole mass filter. In this device too, ions are subjected to Z forces applied by an rf field but the Y forces occur in all three, instead of F2 just two, dimensions. Stable motion The ion trap consists of of ions in the linear quadrupole al- three electrodes with hy- perbolic surfaces, the lowed ions freedom of motion in central ring electrode, one dimension (z-direction); in the and two adjacent end- cap electrodes. The ion trap, stable motion allows no schematic of the assem- degrees of freedom. Hence, ions are bly shows how the elec- trodes are aligned and trapped within the system of three isolated using ceramic Ions in Zo Ions out electrodes-a ring electrode and two spacers and posts. The Ion Source Detector device is radially sym- ro end-cap electrodes of hyperbolic metrical, and ro and zo cross-section (F2). The principal represent its size. advantages of the quadrupole ion trap in chemical analysis can be summarized as follows: (i) high sensitivity, (ii) compactness and mechanical simplicity in a device which is Endcap Ring Endcap nevertheless capable of high Ceramic post performance, and spacer (iii) tandem mass spectrometry ex- periments are available by per- forming sequential mass analy- sis measurements, (iv) ion/molecule reactions can be studied for mass-selected ions, (v) high resolution (>106 at m/z >1000) is accessible through slow scans, but mass measure- ment accuracy is relatively poor, Endcap Ring Endcap F3 Φ formance characteristics, one im- Potential and field mediately notes that a unique fea- strength in a hypothetical one-dimensional quadru- ture of an ion trap is that MS/MS pole field. The slope of experiments are possible. Even the plot of potential (Φ) against position (x) yields when compared with a triple quad- the field strength E(x). rupole MS/MS instrument, the ion trap can perform multiple stage mass spectrometry (MSn) simply by the use of additional operations which are performed sequentially in time. The triple quadrupole has the advantage of access to parent F=f(x)2 ion and neutral loss scans, and ana- E=f(x) Φ lytically useful versions of the Field = E = - d dx MS/MS experiment; however, MSn experiments can only be performed X in multi-quadrupole instruments. Although ion/molecule reactions can be studied in both instruments, (vi) ions of high mass/charge are Comparisons of the Ion Trap the reaction time can only be varied accessible using resonance ex- with the Triple Quadrupole in the ion trap. This allows the ki- periments, and netics and equilibrium of ion-mole- The differences in operating cule reactions to be studied. On the (vii) non-destructive detection is principles of the linear quadrupole other hand, the triple-quadrupole available using Fourier trans- and the ion trap have just been de- instrument provides good control form techniques. scribed. In comparing their per- over the kinetic energies of the ions F4 Potential used for trap- ping ions (A) in the radial direction and (B) in the ax- ial direction. An ion in the (A) position shown is acceler- ated away from the trap center in the axial direc- tion at the rf phase V shown in (A) and towards it in (B) (Adapted from ref- erence 13). -Z o ro Z -r Axial Dimensiono o Radial Dimension (B) V -Z o ro Z -r Axial Dimensiono o Radial Dimension F5 If it were possible to employ a az The Mathieu stability Operating line for system of electrodes and construct a diagram for the quadru- pole ion trap. Ions are mass selective instability one-dimensional quadrupole field, stable in both the r- then the potential distribution and and the z-direction if their Mathieu parame- the field strength would be as ters az and qz fall within 0.4 shown in F3. Ions located an in- the shaded area in the diagram. The common creasing distance from the center mode of mass analysis z stability would be subjected to a force which is the mass-selective in- would increase linearly with dis- stability scan in which 1.0 the rf potential is raised 0.2 0.8 placement and which would tend to to increase the value of 0.7 0.1 q = 0.908 return the ions to the center of the qz to the instability point 0.6 eject qz = 0.908, while az =0.