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Quadrupole Ion Trap MS

Overview; Ion Trapping; Ion Excitation and Ejection; Multiple Stages of Mass Spectrometry (MSn); Resolution; Limitations; Recent Developments;


A quadrupole ion trap is a sensitive and versatile mass spectrometer, roughly the size of a tennis ball [Paul, 1990, March, 1997, Jonscher, 1997]. The mass range of commercial LC-traps is well matched to the range of m/z values typically generated from the electrospray ionization process and the unit resolution provided throughout the mass range affords charge state identification of multiply-charged peptide ions. Quadrupole ion trap mass spectrometers can analyze peptides from a tryptic digest present at the 20-100 fmol level. Perhaps the greatest strength of the ion trap technique lies in the ability to perform multiple stages of mass spectrometry, unlike a triple quadrupole instrument or a standard TOF-MS. Up to 12 stages of tandem mass spectrometry (MS12) have been performed using an ion trap, greatly increasing the amount of structural information obtainable for a given molecule. Three hyperbolic electrodes, consisting of a ring and two endcaps, form the core of this instrument.

Ion Trapping

Transmission into the Trap:

Ions created by electrospray ionization are focused using an octupole transmission system into the ion trap. Ions may be gated into the trap through the use of a pulsing lens or through a combination of rf potentials applied to the ring electrode. The pulsed transmission of ions into the trap differentiates ion traps from "beam" instruments such as quadrupoles where ions continually enter the mass analyzer. The time during which ions are allowed into the trap, termed the "ionization period" , is set to maximize signal while minimizing space-charge effects. The ion trap is typically filled with helium to a pressure of about 1 mtorr. Collisions with helium dampen the kinetic energy of the ions and serve to quickly focus trajectories toward the center of the ion trap, enabling trapping of injected ions [Louris, 1987, Louris, 1989].

Stable Focusing of Ions in the Trap:

Trapped ions are further focused toward the center of the trap through the use of an oscillating voltage, called the fundamental rf, applied to the ring electrode. An ion will be stably trapped depending upon the values for the mass and charge of the ion, the radial size of the ion trap (r), the oscillating frequency of the fundamental rf (w), and the amplitude of the voltage on the ring electrode (V). The dependence of ion motion on these parameters is described by the dimensionless parameter qz:

qz = 4eV/mr2w2

An analogous parameter az describes the effect on the motion of ions when a DC potential is applied to the ring electrode.

In order to create an ideal quadrupole field, r2=2z2 is required, where z is the axial distance from the center of the trap to the endcap electrode. A number of groups over the past several years have discovered that, by moving the electrodes farther apart or changing the asymptotic angle between the electrodes, the higher multipole fields inside the trap may be accessed. Use of these fields has led to increases in performance such as higher resolution and more efficient ion excitation and ejection.

The "stability diagram" shows a theoretical region where radial and axial stability overlap. Depending upon the amplitude of the voltage placed on the ring electrode, an ion of a given m/z will have az, qz values that will fall within the boundaries of the stability diagram, and the ion will be trapped. If the az, qz values at that voltage falls outside of the boundaries of the stability diagram, the ion will hit the electrodes and be lost. Commercial ion traps work along the line az=0.

Mass Range for Trapping Ions:

Ions of different m/z values may have stable orbits at the same time. Because ion trajectories become unstable at a particular value for qeject, a well-defined low-mass cutoff is created for a given value of the amplitude of the applied rf voltage, V. No ions below that mass will be trapped, but ions above that mass will be trapped with trapping efficiency decreasing for larger m/z values. The high mass cutoff for detection depends in part on the amplitude and frequency of an auxiliary potential placed on the endcap electrodes. In this manner, the nominal mass range of the instrument has been extended to m/z 4,000 - 6,000 [Kaiser, 1989]. This mass range is considerably higher than that typically obtainable on a quadrupole instrument but lower than that achievable on a time-of-flight mass spectrometer (TOF-MS).

Ion Excitation and Ejection

Ejection and Detection:

Ions oscillate in the trap with a frequency known as the secular frequency that is determined by the values for az and qz and by the frequency of the fundamental rf. A mass spectrum is generated by sequentially ejecting fragment ions from low m/z to high m/z. This is done by scanning the amplitude of the fundamental rf voltage to make ion trajectories sequentially become unstable. Ions are ejected through holes in the endcap electrode and detected using a collision dynode and electron multiplier system [Stafford, 1984].

Resonance Ejection:

Resonance conditions are induced by matching the frequency of a supplementary potential applied on the endcap electrodes to the secular frequency (as determined by qz) of the ion.

If the amplitude of the resonance signal is large enough, ions will be ejected from the trap. Resonance ejection occurs at qz values lower than those typically required for ejection at qeject. Since qz is inversely proportional to m, ions of larger molecular weight can be ejected under resonance conditions.

Resonance Excitation:

Individual ions are isolated by the application of a waveform signal across the endcap electrodes. Structural information is obtained by the application of a low amplitude resonance signal termed the tickle voltage across the endcap electrodes. The ion motion between the endcaps increases, leading to ion dissociation due to thousands of collisions with the helium damping gas. This process causes random fragmentation along the peptide backbone in a manner analogous to that obtained using a triple quadrupole mass spectrometer.

Multiple Stages of Mass Spectrometry (MSn):

FTICR and quadrupole ion traps are unique in their ability to perform multiple stages of mass spectrometry, enormously increasing the amount of information obtainable from a molecule. For both types of instruments, waveforms are constructed to isolate an ion, induce its fragmentation, then isolate one of the products, induce its fragmentation, etc. Finally, the resultant ions from all of the manipulations are ejected from the trap and detected [Soni, 1994]. Typically a maximum of 3 stages of mass spectrometry are performed for peptide analysis [Louris, 1990].


The mass resolution of the ion trap is a function of the number of rf cycles that the ion spends interacting with the trapping field. Resolution is increased to provide charge state determination for multiply-charged peptide ions by decreasing the scan speed of the ejection voltage. Typical mass resolutions can be unit or better depending on the scan speed of the instrument and the width of the mass window investigated. Mass resolutions as high as 30,000 have been reported but are not typical [Cooks, 1992]. Charge-state determination is not possible using a triple quadrupole mass spectrometer under the conditions normally used for high sensitivity peptide analysis.

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  • A limitation of the ion trap is that the alternate scan modes of triple quadrupole mass spectrometers, such as precursor ion and neutral loss scans, are currently not possible. These scan modes are particularly useful for identifying the presence of trace components in complex mixtures.
  • The upper limit on the ratio between the precursor mass and the lowest trapped fragment ion mass is approximately 0.3 (dependent on the qz value). The fragment ions with masses in the lower third of the mass range will not be detected, therefore the first several b- and y-type fragment ions may not be observed for a given peptide. The newly-released tandem Q-TOFs have improved capability for performing de novo sequencing since all fragment ions may be detected at high resolution.
  • The dynamic range of ion traps is limited because, when there are too many ions in the trap, space charge effects lead to diminished performance. Automated scans are used to rapidly count the ions before they go into the trap so that the time ions are allowed to enter the trap is dependent on the ion flux. This ensures only a certain number of ions get in. This can be a problem when trace elements in particularly dirty matrices are analyzed because the trap fills with both matrix ions (large number) and trace sample ions (very small number).

Recent Developments

  • ESI sources generate multiply-charged ions, making molecular weight assignment difficult when peptide mixtures are analyzed off-line. Several groups constructed MALDI-ion traps in an effort to simplify off-line mixture analysis by generating singly-charged molecules. These traps have been found to be particularly useful in phosphopeptide analysis. For example, pSer and pThr were observed to routinely lose 98 amu from the molecular ion, while pTyr lost 80 amu. The difference between the mass of the phosphorylated molecular ion and its unphosphorylated analog provided a fingerprint to help confirm the presence of a phosphopeptide in the mixture.
  • An interesting configuration utilizes the MSn capabilities of ion traps and the rapid scanning of TOFs to create very powerful hybrid mass spectrometers [Chen, 1999, Huang, 2000]. These IT-reTOFs, coupled with capillary LC ion sources, provide an alternative method to identify proteins from complex mixtures. Since gel electrophoresis is not required, sample losses due to gel-related restrictions and peptide extraction post-digestion are minimized. Typically, more protein coverage is obtained by this technique than is observed when conventional MALDI-TOF is used [He, 1997].
  • The role of quadrupole ion traps is expanding from traditional pharmaceutical applications into the revolutionary field of proteomics, where identification of native and post-translationally modified proteins provides insight into complex biological systems [Haynes, 2000]. Although most proteomics experiments involve the use of MALDI-TOF to screen tryptic digests of in gel digested proteins, the ion trap has proven itself in its ability to generate high sensitivity fragmentation spectra when the MALDI method gives inconclusive identification [Qin, 1997 #356].
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