Mass spectrometer

Details Mass spectrometer Mass spectrometer

2003-05-30

2004-10-05

Wells, Nikita (Department: 2881)

Radiant energy

Ionic separation or analysis

C250S286000, C250S287000, C250S282000, C250S290000, C250S292000

Reexamination Certificate

active

06800846

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a mass spectrometer and a method of mass spectrometry.
2. Discussion of the Prior Art
A known collision cell comprises a plurality of electrodes with an RF voltage applied between neighbouring electrodes so that ions are radially confined within the collision cell. Ions are arranged to enter the collision cell with energies typically in the range 10-1000 eV and undergo multiple collisions with gas molecules within the collision cell. These collisions cause the ions to fragment or decompose.
Gas reaction cells are also similarly known wherein ions are arranged to enter the reaction cell with energies typically in the range 0.1-10 eV. The ions undergo collisions with gas molecules but instead of fragmenting the ions tend to react with the gas molecules forming product ions.
When an ion collides with a gas molecule it may get scattered and lose kinetic energy. However, the ion is not lost from the collision cell since it is radially confined within the collision cell by the applied RF voltage. If an ion undergoes a large number of collisions, perhaps more than 100 collisions, then the ion will effectively lose all its forward kinetic energy. Such ions will now have a mean energy substantially equal to that of the surrounding gas molecules i.e. they will have become thermalized. The thermalized ions will now appear to move randomly within the gas due to continuing random collisions with gas molecules. Some ions may therefore be expected to remain within the collision cell for a relatively long period of time.
In practice ions are nonetheless observed to exit the collision cell after some delay. It is generally thought that ions continue to move relatively slowly forwards through the collision cell due to the bulk movement of gas which effectively forces ions through the collision cell. It is also thought that space charge effects caused by the continual ingress of ions into the collision cell also act to force ions through the collision cell. Ions within the collision cell therefore experience electrostatic repulsion from ions arriving from behind and this effectively pushes the ions through the collision cell.
As will be appreciated from the above, ion transit times through known RF collision and reaction cells can be relatively long due to ions losing their forward kinetic energy through multiple collisions with the collision gas. The continued presence or absence of an incoming ion beam and any surface charging leading to axial potential barriers can further adversely affect the transit time.
A relatively long ion transit time through a collision cell can significantly affect the performance of a mass spectrometer. For example, ions are required to have a relatively fast transit time through a collision cell when performing Multiple Reaction Monitoring (MRM) experiments using a triple quadrupole mass spectrometer. A fast transit time is also required when rapidly switching to different product ion spectra acquisitions using a hybrid quadrupole—Time of Flight mass spectrometer. When a mass spectrometer switches rapidly between various different parent ions, then if the resultant fragment ions formed within the collision cell exit the collision cell relatively slowly then significant quantities of fragment ions may still be present in the subsequent acquisition. This therefore causes a memory effect or crosstalk.
A known method of reducing crosstalk is to reduce the RF voltage to a low enough level in the period between measurements so that ions are no longer confined within the collision cell and consequently leak away. However, it takes a certain amount of time for the collision cell to re-fill with ions after the RF voltage has been reduced and hence if short inter-acquisition times are desired then the collision cell may not be sufficiently full before the next acquisition commences. This has the effect of reducing sensitivity which becomes more acute at shorter acquisition times.
Another situation where ions need to be rapidly transmitted through the collision cell is when a mass spectrometer is operated in a parent ion scanning mode. According to this made of operation only a specific fragment ion is set to be transmitted by a mass filter downstream of a collision cell of a tandem mass spectrometer (e.g. a triple quadrupole mass spectrometer) whilst a mass analyser upstream of the collision cell is scanned. When a specific fragment ion is observed, the parent ion which was fragmented to produce the specific fragment ion can then be determined. In theory a large number of parent ions admitted to the collision cell could have given rise to the specific fragment ion. The aim of such experiments is to screen for all components belonging to a particular class of compounds that may be recognised by a common fragment ion or to discover all parent ions that may contain a particular sub-component such as the phosphate functional group in phosphorylated peptides. However, if the transit time of ions through the collision cell is relatively long then the parent ions appear to become smeared across a number of masses and consequently resolution is reduced together with sensitivity. This effect is particularly exacerbated when the mass analyser upstream of the collision cell is scanned at a relatively high scan rate when sensitivity may be completely lost.
Neutral loss/gain scanning modes of operation are also used wherein both the mass analyser upstream of the collision cell and the mass filter/analyser downstream of the collision cell are scanned synchronously with a constant mass offset to identify those parent ions which fragment through loss of a specific functional group or react to form a specific product ion with a specific mass difference. A long transit time for ions through the collision cell may cause peak smearing but since the mass analyser downstream of the collision cell is scanning the smearing is not observed. The resultant effect is a loss of sensitivity and resolution (even though the loss of resolution may be obscured) which is again exacerbated at higher scan rates.
Long transit times are also a problem with reaction cells. Ions are typically injected into reaction cells with relatively low energies and RF confinement is used to cause the ions to interact with a background buffer gas and/or a reagent gas. Any axial velocity component above thermal levels is effectively lost and the ions can become effectively stranded within the reaction cell. In some situations, such as with short reaction cells, the ions may be deliberately trapped by application of trapping voltages at the entrance and exit of the reaction cell. This prolongs the ion-molecule interaction times but when the trapping voltages are removed the ions have no specific impetus towards the exit. Some ions will eventually diffuse to the exit but the duty cycle is poor and there is a risk of crosstalk with subsequent trapping cycles. It is therefore known to reduce the RF voltage applied to the reaction cell between experiments to a level such that ions are no longer confined within the reaction cell.
With pulsed ion sources such as Laser Desorption Ionisation (“LDI”) and Matrix Assisted Laser Desorption Ionization (“MALDI”) ion sources the impetus of ions being effectively pushed through the collision cell by the space charge repulsion from continual ingress of ions is either not effectively present or is severely reduced consequently, ions from one pulse, or laser shot, can become merged with those from the next pulse and so on. Pulsed ion sources can advantageously be coupled to a discontinuous mass analyser such as a Time of Flight mass spectrometer, an ion trap mass spectrometer or a Fourier Transform Ion Cyclotron Resonance (“FTICR”) mass spectrometer so that the operation of the mass analyzer can be synchronised with the pulses of ions emitted from the ion source. This enables the duty cycle for sampling ions and therefore sensitivity to be maximised. The smearing of each pulse of ions and the subsequent merging

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