An ion trap mass spectrometer is described in Paul et al. U.S. Pat. No. 2,939,952. In general, an electrode structure provides an ion storage trap region where a substantially quadrupole field traps and stores ions. Ion trap mass spectrometers are also described in Dawson et al. U.S. Pat. No. 3,527,939; McIver U.S. Pat. No. 3,742,212; McIver et al. U.S. Pat. No. 4,104,917; and Stafford et al. U.S. Pat. No. 4,540,884.
Ion traps are devices in which ions are introduced into or formed and contained within a trapping chamber formed by at least two electrode structures by means of substantially quadrupolar electrostatic fields generated by applying RF voltages, DC voltages or a combination thereof to the electrodes. To form a substantially quadrupole field, the electrode shapes have typically been hyperbolic.
Mass storage and analysis are generally achieved by operating the ion trap electrodes with values of RF voltage V, RF frequency f, DC voltage U, and device size r.sub.0 such that ions having their mass-to-charge ratios (m/e) within a finite range are stably trapped inside the device. The aforementioned parameters are sometimes referred to as trapping or scanning parameters and have a relationship to the m/e ratios of the trapped ions.
Quadrupole devices are dynamic. Instead of constant forces acting on ions, ion trajectories are defined by a set of time-dependent forces. As a result, an ion is subject to strong focusing in which the restoring force, which drives the ion back toward the center of the device, increases linearly as the ion deviates from the center. For two-dimensional ion trap mass spectrometers, the restoring force drives the ion back toward the center axis of the device.
Motion of ions in quadrupole fields is described mathematically by the solutions to a particular second-order linear differential equation called the Mathieu equation. Solutions are developed for the general case, the two-dimensional case of the quadrupole mass filter, and the standard three-dimensional case of the quadrupole ion trap. Thus, in general, for any direction u where u represents x, y, or z, ##EQU1## where V=magnitude of radio frequency (RF) voltage
U=amplitude of applied direct current (d.c.) voltage PA1 e=charge on an ion PA1 m=mass of an ion PA1 r.sub.0 =device-dependent size PA1 .omega.=.pi.f PA1 f=frequency of RF voltage PA1 K.sub.a =device-dependent constant for a.sub.u PA1 K.sub.q =device-dependent constant for q.sub.u PA1 k=integer where k={0, .+-.1, .+-.2, .+-.3, . . . } PA1 f=frequency of the RF component of the substantially quadrupole field PA1 f.sub.u =fundamental frequency for the secular motion of a given ion at q.sub.u eject along the u coordinate axis, and f.sub.u &lt;f.
Stability diagrams which represent a graphical illustration of the solutions of the Mathieu equation use a.sub.u as the ordinate and q.sub.u as the abscissa.
For a substantially quadrupole field defined by U, V, r.sub.0 and .omega. the locus of all possible m/e ratios maps onto the stability diagram as a single straight line running through the origin with a slope equal to -2 U/V. This locus is also referred to as the scan operating line. For ion traps, the portion of the locus that maps within the stability region defines the range of ions that are trapped by the applied field.
FIG. 3 shows a stability diagram representative of the operation of a three-dimensional ion trap mass spectrometer. Knowledge of the diagram is important to the understanding of the operation of quadrupole ion trap mass spectrometers. The stable region is shown bounded by .beta..sub.x =0, .beta..sub.x =1.0, .beta..sub.y =0, and .beta..sub.y =1.0.
The ion masses that can be trapped depend on the numerical values of the trapping parameters U, V, r.sub.0, and .omega.. The relationship of the trapping parameters to the m/e ratio of the ions that are trapped is described in terms of the parameters "a" and "q" in FIG. 1. The type of trajectory a charged ion has in a quadrupole field depends on how the specific m/e ratio of the ion and the applied trapping parameters, U, V, r.sub.0 and .omega. combine to map onto the stability diagram. If these trapping parameters combine to map inside the stability envelope then the given ion has a stable trajectory in the defined field.
By properly choosing the magnitudes of U and V, the range of specific masses of trappable ions can be selected. If the ratio of U to V is chosen so that the locus of possible specific masses maps through an apex of the stability region, then only ions within a very narrow range of specific masses will have stable trajectories. However, if the ratio of U to V is chosen so that the locus of possible specific masses maps through the "middle" (a.sub.u =0) of the stability region, then ions of a broad range of specific masses will have stable trajectories.
Ions having a stable trajectory in a substantially quadrupole field are constrained to an orbit about the center of the field. Typically, the center of the field is substantially along the center of the trapping chamber.
This invention is used with several known methods of mass analysis. One method is mass selective instability scan. One embodiment of this method is described in U.S. Pat. No. 4,540,884, which is incorporated herein by reference. In this method, a wide mass range of ions of interest is created and stored in the ion trap during an ionization step. The RF voltage applied to the ring electrode of the substantially quadrupole ion trap is then increased and trapped ions of increasing specific masses become unstable and either exit the ion trap or collide on the electrodes. The ions that exit the ion trap can be detected to provide an output signal indicative of the m/e (mass to charge ratio) of the stored ions and the number of ions.
Another method of mass analysis is an enhanced form of the mass selective instability scan which incorporates resonance ejection. Refer to U.S. Pat. Nos. 4,736,101 and RE34,000. They demonstrate that introducing a supplemental AC field in the ion trap mass spectrometer facilitates the separation and ejection of adjacent m/e ions. The frequency f.sub.res of the supplemental AC source determines the q.sub.u at which ions will be ejected. If the frequency f.sub.res of the supplemental AC field matches a secular component frequency of motion of one of the m/e ion species in the ion occupied volume, the supplemental field causes those specific ions (e.g., those ions at the specific q) to oscillate with increased amplitude. The magnitude of the supplemental field determines the rate of increase of the ion oscillation. Small magnitudes of the supplemental field will resonantly excite ions, but they will remain within the substantially quadrupole field. Large magnitudes of the supplemental field will cause those ions with the selected resonant frequency to be ejected from or onto the trapping chamber. In some commercial ion traps, a value of 2 to 10 volts peak-to-peak measured differentially between the two end caps have been used to resonantly eject ions.
The frequency of the supplemental AC field f.sub.res is selected such that the ions of specific m/e ratios can develop trajectories that will make the ion leave the ion occupied volume. The resonant frequency f.sub.res =kf.+-.f.sub.u where,
The expression for f.sub.res represents the frequency components of the solutions of the exact equations of ion motion in a harmonic RF potential. Typically, k=0 so that f.sub.res =f.sub.u and smaller applied AC amplitude potentials are required; however, any frequency satisfying the general expression for f.sub.res and of sufficient amplitude will cause ions to leave the trapping chamber.
A third method of mass analysis is the use of a supplemental field with the MS/MS method, described in U.S. Pat. Nos. 4,736,101 and RE34,000, which are incorporated herein by reference. Essentially, MS/MS involves the use of at least two distinct mass analysis steps. First, a desired m/e is isolated (typically with a mass window of .+-.0.5 amu). Ejection of undesired ions during the isolation step is accomplished by, and not limited to, several techniques: (i) applying DC to the ring, (ii) applying an RF electric field with a supplemental AC field, and (iii) scanning the RF so that undesirable ions pass through and are ejected by a resonance frequency. This is MS.sup.1. After undesired ions are ejected, the RF (and possibly DC) voltage is lowered to readjust the m/e range of interest to include lower m/e ions. Fragments, or product ions can then be formed when a neutral gas, such as helium, argon, or xenon, is introduced in the ion trapping chamber in combination with a resonance excitation potential applied to the end caps. These fragments remain in the ion trapping chamber. In the second mass analysis step, the mass selective instability scan is used, with or without resonance ejection, to eject the fragment ions into a detector. This is MS.sup.2. Thus, at least two mass spectrometry steps were performed in one device. Repetitive tandem MS techniques (i.e. (MS).sup.n) may also be employed for n distinct mass spectrometry steps.
The MS.sup.2 step can be accomplished as follows: A supplemental AC field is applied after the primary RF field is decreased at the end of the first scan and prior to the second scan to eject undesired ions of a specific m/e ratio. Upon ejection, the supplemental AC field is turned off and the primary RF field is increased to eject desired ions into a detector. Variations of this technique, as disclosed in U.S. Pat. Nos. 4,736,101 and RE34,000, can be used. Thus, manipulation of the RF amplitude, RF frequency, supplemental AC field amplitude, supplemental AC field frequency, or a combination thereof promotes ejection of ions for detection after the formation and trapping of product ions. For example, the supplemental AC field can be turned on during the second scan of the primary RF field. Alternatively, instead of a second scan period, the RF field is kept constant while the frequency of the supplemental AC field is varied. Ejection can also be achieved by changing the magnitude of the supplemental AC field while changing the amplitude of the RF component of the substantially quadrupole field.
When operating a mass spectrometer, the amount of ions entering the ion trap for analysis varies. In the prior art the ionization times have remained relatively constant. Thus, when the amount of ions exceeds a certain threshold level, sample saturation and space charge effects may result in the loss of mass resolution and sensitivity and errors in mass assignment.
Space charge is the perturbation in an electrostatic field due to the presence of an ion or ions. This perturbation forces the ion to follow trajectories not predicted by the applied field. If the perturbation is great, the ion may be lost and/or the mass spectral quality may degrade. Spectral degradation refers to broad peaks giving lower resolution (m/.DELTA.m), a loss of peak height reducing the signal-to-noise ratio, and/or a change in the measured relative ion abundances. Space charge thus limits the number of ions one can store while still maintaining useful resolution and detection limits.
To minimize the effects of space charge, increase the dynamic range, increase sensitivity, and improve detection limits, an automatic ion supply control feature may be used to control the number of ions introduced into the mass spectrometer. Thus, in a simplified illustration, ions are initially introduced into the mass spectrometer by "turning on" a focusing lens system to gate ions. The ions are trapped in the mass spectrometer by a substantially quadrupole field. Total ion content is then measured by collecting and processing ejected ions. A computer, through an algorithm, assesses the total ion content and determines how many additional ions, if any, should be formed in the mass spectrometer and still be below the space charge level but above the lower level detection limit. This total ion content information is then used to calculate a new gate time. The focusing lens system turns on for a length of time equal to this new gate time to gate a substantially optimum number of ions into the mass spectrometer.
Various external ionization methods may be employed in this invention. A representative, and not exhaustive, list of ionization methods include electron impact ionization (EI), chemical ionization (CI), field ionization/desorption, photon impact, fast atom bombardment (FAB), electrospray ionization, and thermospray ionization, atmospheric pressure ionization (API), atmospheric pressure chemical ionization (APCI), particle beam liquid chromatography, and supercritical fluid chromatography. These ionization methods are well-known by their names alone and are well represented in the literature.
U.S. Pat. No. 5,107,109, assigned to Finnigan Corporation, shows one application of feedback for mass spectrometers. However, this particular patent uses feedback for internal ionization. External ionization, through its many techniques, has been an effective and popular means of introducing ions into mass spectrometers because of its many benefits, including minimizing ion-molecule reactions. Several embodiments of the invention, as claimed and disclosed in this patent application, shows the use of feedback for external ionization. For those cases where external ionization is employed in mass analysis, the present invention, through its embodiments, provides an effective means of obtaining improved performance in mass spectrometer systems.