Patent Publication Number: US-6703607-B2

Title: Axial ejection resolution in multipole mass spectrometers

Description:
FIELD OF INVENTION 
     The invention generally relates to mass spectrometers, and more particularly to optimized axial ejection techniques in a linear ion trap. 
     BACKGROUND OF INVENTION 
     The linear ion trap is characterized by an elongate multi-pole rod set in which a two dimensional RF field is used to radially trap ions that are contained axially by a DC barrier or trapping field at an exit lens. The linear ion trap has a number of advantages over quadrupole or three-dimensional ion traps, including reduced space charge effects. Linear ion traps are described, inter alia, in U.S. Pat. No. 6,177,668 issued Jan. 23, 2001 to Hager (the “Hager patent”), the entire contents of which are incorporated herein by reference. The Hager patent teaches a variety of axial ejection techniques, in which ions are mass-selectively scanned out of the trap by overcoming the potential barrier at the exit lens. The efficiency, sensitivity, and resolution of particular instances of the axial ejection techniques are briefly discussed. 
     SUMMARY OF INVENTION 
     The invention relates to improved axial ejection techniques, and in particular to maximizing the resolution of axial ejection over a wide range of ionic masses. 
     Broadly speaking, the invention accomplishes this by varying the DC potential barrier between the rods and the exit member of linear ion trap as a function of mass. This is carried out in conjunction with the manipulation of other fields used to axially eject ions mass-selectively. The magnitude of the potential barrier is preferably controlled to vary generally linearly as a function of ion mass-to-charge ratios (m/z), over a pre-determined m/z range. Outside the bounds of the pre-determined m/z range, the barrier field preferably remains stable. 
     According to one aspect of the invention an improved method of operating a linear ion trap is provided. The linear ion trap includes a DC potential barrier between the rods of the trap and an exit member adjacent to an exit end of the trap. Ions are axially ejected in the improved trap by energizing trapped ions of a selected m/z value and setting the magnitude of the potential barrier based on the selected m/z value in accordance with a pre-determined function, to thereby mass selectively eject at least some ions of a selected n/z value axially from the rod set past the exit member. In the preferred function, the magnitude of the potential barrier is substantially linearly related to the magnitude of the n/z value. 
     According to another aspect of the invention, there is provided a method of operating a mass spectrometer having an elongated rod set which has an entrance end, an exit end and a longitudinal axis. The method includes: (a) admitting ions into the entrance end of the rod set; (b) trapping at least some of the ions in the rod set by producing a barrier field at an exit member adjacent to the exit end of the rod set and by producing an RF field between the rods of the rod set adjacent at least the exit end of the rod set, wherein the RF and barrier fields interact in an extraction region adjacent to the exit end of the rod set to produce a fringing field; (c) energizing ions in at least the extraction region and varying a potential barrier between the exit member and rod set to mass selectively eject at least some ions of a selected mass-to-charge ratio axially from the rod set past said barrier field; and (d) and detecting at least some of the axially ejected ions. The magnitude of the potential barrier is preferably substantially linearly related to the selected ion mass-to-charge ratio. 
     In the preferred embodiment, an auxiliary dipole or quadrupole AC voltage is applied to the rod set to assist in axial ejection. The population of ions contained by the linear ion trap is preferably axially ejected therefrom by simultaneously ramping or scanning the RF field, the auxiliary AC field and the DC voltage on the exit lens (or alternatively or additionally a DC offset voltage applied to the rod set). The ions may thus be axially ejected orderly by increasing or decreasing m/z values, depending on the direction (upward or downward) of the ramping, thereby facilitating a mass scan or the collection of mass spectra. 
    
    
     BRIEF DESCRIPTION OF DRAWINGS 
     The foregoing and other aspects of the invention will become more apparent from the following description of specific embodiments thereof and the accompanying drawings which illustrate, by way of example only and not intending to be limiting, the principles of the invention. In the drawings: 
     FIG. 1 is a schematic diagram of a relatively simple mass spectrometer apparatus with which the invention may be used; 
     FIG. 1 a  is an end view of a rod set of FIG.  1  and showing electrical connections to the rod set; 
     FIG. 2 is a schematic diagram of a more complex mass spectrometer apparatus with which the invention may be used; 
     FIG. 3 is a timing diagram showing, in schematic form, signals applied to a quadrupole rod set of the apparatus of FIG. 2 in order to inject, trap, and mass-selectively eject ions axially from the rod set; 
     FIGS. 4A-a,  4 A-b,  4 B-a,  4 B-b,  4 C-a,  4 C-b,  4 D-a and  4 D-b are charts which show mass spectrums obtained from the apparatus of FIG. 2 for ions of various m/z values under differing DC voltages applied to an exit lens associated with the rod set; 
     FIG. 5 is a graph illustrating optimal DC voltages on the exit lens as a function of mass (when a DC offset is applied to the rods) for maximizing the resolution of ion signals produced by axial ejection; and 
     FIG. 6 is a graph, corresponding to the graph of FIG. 5, showing the optimal potential barriers. 
    
    
     DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS 
     Referring to FIG. 1, a mass spectrometer apparatus  10  with which the invention may be used is shown. The system  10  includes a sample source  12  (normally a liquid sample source such as a liquid chromatograph) from which sample is supplied to a conventional ion source  14 . Ion source  14  may be an electro-spray, an ion spray, or a corona discharge device, or any other known ion source. An ion spray device of the kind shown in U.S. Pat. No. 4,861,988 issued Aug. 29, 1989 to Cornell Research Foundation Inc. is suitable. 
     Ions from ion source  14  are directed through an aperture  16  in an aperture plate  18 . Plate  18  forms one wall of a gas curtain chamber  19  which is supplied with curtain gas from a curtain gas source  20 . The curtain gas can be argon, nitrogen or other inert gas and is described in the above-mentioned U.S. Pat. No. 4,861,988. The ions then pass through an orifice  22  in an orifice plate  24  into a first stage vacuum chamber  26  evacuated by a pump  28  to a pressure of about 1 Torr. 
     The ions then pass through a skimmer orifice  30  in a skimmer plate  32  and into a main vacuum chamber  34  evacuated to a pressure of about 2 milli-Torr by a pump  36 . 
     The main vacuum chamber  34  contains a set of four linear conventional quadrupole rods  38 . The rods  38  may typically have a rod radius r=0.470 cm, an inter-rod dimension r 0 =0.415 cm, and an axial length  1 =20 cm. 
     Located about 2 mm past an exit end  40  of the rods  38  is an exit lens  42 . The lens  42  is simply a plate with an aperture  44  therein, allowing passage of ions through aperture  44  to a conventional detector  46  (which may for example be a channel electron multiplier of the kind conventionally used in mass spectrometers). 
     The rods  38  are connected to the main power supply  50  which applies a DC offset voltage to all the rods  38  and also applies RF in conventional manner between the rods. The power supply  50  is also connected (by connections not shown) to the ion source  14 , the aperture and orifice plates  18  and  24 , the skimmer plate  32 , and to the exit lens  42 . 
     By way of example, for positive ions the ion source  14  may typically be at +5,000 volts, the aperture plate  18  may be at +1,000 volts, the orifice plate  24  may be at +250 volts, and the skimmer plate  32  may be at ground (zero volts). The DC offset applied to rods  38  may be −5 volts. The axis of the device, which is the path of ion travel, is indicated at  52 . 
     Thus, ions of interest which are admitted into the device from ion source  14  move down a potential well and are allowed to enter the rods  38 . Ions that are stable in the applied main RF field applied to the rods  38  travel the length of the device undergoing numerous momentum dissipating collisions with the background gas. However a trapping DC voltage, typically −2 volts DC, is applied to the exit lens  42 . This yields a potential barrier of 3 volts, being the difference between DC voltage on the exit lens  42  (−2 volts) and the DC offset applied to rods  38  (−5 volts). Normally the ion transmission efficiency between the skimmer  32  and the exit lens  42  is very high and may approach 100%. Ions that enter the main vacuum chamber  34  and travel to the exit lens  42  are thermalized due to the numerous collisions with the background gas and have little net velocity in the direction of axis  52 . The ions also experience forces from the main RF field which confines them radially. Typically the RF voltage applied is in the order of about 450 volts (unless it is scanned with mass) and is of a frequency of the order of about 816 kHz. No resolving DC field is applied to rods  38 . 
     When a DC trapping or barrier field is created at the exit lens  42  by applying a DC voltage which is higher than the DC voltage applied to the rods  38 , the ions stable in the RF field between the rods  38  are effectively trapped. 
     However ions in region  54  in the vicinity of the exit lens  42  will experience fields that are not entirely quadrupolar, due to the nature of the termination of the main RF and DC fields near the exit lens. Such fields, commonly referred to as fringing fields, will tend to couple the radial and axial degrees of freedom of the trapped ions. This means that there will be axial and radial components of ion motion that are not mutually orthogonal. This is in contrast to the situation at the center of rod structure  38  further removed from the exit lens and fringing fields, where the axial and radial components of ion motion are not coupled or are minimally coupled. 
     Since the fringing fields couple the radial and axial degrees of freedom of the trapped ions, ions may be scanned mass dependently axially out of the ion trap constituted by rods  38 , by the application to the exit lens  42  of a low voltage auxiliary AC signal of appropriate frequency. The auxiliary AC signal may be provided by an auxiliary AC supply  56 , which for illustrative purposes is shown as forming part of the main power supply  50 . The auxiliary AC voltage is in addition to the trapping DC voltage applied to exit lens  42 , and creates an auxiliary AC field which couples to both the radial and axial secular ion motions. When the frequency of the auxiliary AC field matches a radial secular frequency of an ion in the vicinity of the exit lens  42 , the ion will absorb energy and will now be capable of traversing the potential barrier present on the exit lens due to the radial/axial motion coupling. When the ion exits axially, it will be detected by detector  46 . 
     The Hager patent discloses a number of other scanning techniques, including: 
     Modulating a DC offset voltage applied to the rods  38 , to thereby simulate an auxiliary AC signal applied to the exit lens  42  (i.e., no auxiliary AC signal is applied to the exit lens  42 , only the trapping DC field). 
     Scanning the amplitude of a supplementary or auxiliary AC dipole or quadrupole voltage applied to rods  38  (as indicated by dotted connection  57  in FIG.  1 ), to produce varying fringing fields which will eject ions axially in the manner described. As is well known, when an auxiliary dipole voltage is used, it is usually applied between an opposed pair of the rods  38 , as indicated in FIG. 1 a.    
     Scanning the RF signal applied onto the rods  38  while keeping a DC potential barrier on the exit lens  42  (but with no AC field on the exit lens  42 , no modulation of the DC offset on rods  38 , and no auxiliary AC signal on rods  38 ). This technique was stated to be somewhat inefficient in that, while ions in the fringing fields at the downstream ends of rods  38  will leave axially mass dependently and be detected, most of the ions upstream of the fringing fields will leave radially and be wasted. 
     Applying a fixed, low level, auxiliary dipolar or quadrupolar AC field to the rods  38  and then scanning the amplitude of the RF field. 
     Scanning the frequency of an auxiliary dipolar or quadrupolar AC field applied to the rods  38  while keeping the RF field fixed. 
     In each of the foregoing techniques, a DC potential barrier exists between the rods  38  and the exit lens  42 . The ions must overcome this potential barrier in order to be axially ejected. Through experiments described in greater detail below, the inventors have determined that the foregoing and/or other axial ejection techniques may be improved by varying the DC potential barrier in conjunction with the manipulation of one or more of the other fields enumerated above required to axially eject ions mass-selectively. The magnitude of the potential barrier is preferably controlled to vary generally linearly as a function of ion mass-to-charge ratios (m/z), over a predetermined mass range. Outside the bounds of the pre-determined m/z range, the potential barrier preferably remains stable. 
     FIG. 2 illustrates a mass spectroscopy apparatus  10 ′ similar to that shown in FIG. 1 upon which a number of experiments were conducted to determine the optimal magnitude of the exit barrier field for maximizing the resolution of axial ejection. In FIGS. 1 and 2, corresponding reference numerals indicate corresponding parts, and only the differences from FIG. 1 are described. FIG. 3 is a timing diagram which shows, in schematic form, signals applied to the “Q 3 ” rod set of the apparatus  10 ′ in order to inject, trap, and mass-selectively eject ions axially from Q 3 . 
     In apparatus  10 ′, ions pass through the skimmer plate  32  into a second differentially pumped chamber  82 . Typically, the pressure in chamber  82 , often considered to be the first chamber of the mass spectrometer, is about 7 or 8 mTorr. 
     In the chamber  82 , there is a conventional RF-only multipole ion guide Q 0 . Its function is to cool and focus the ions, and it is assisted by the relatively high gas pressure present in the chamber  82 . This chamber also serves to provide an interface between the atmospheric pressure ion source  14  and the lower pressure vacuum chambers, thereby serving to remove more of the curtain gas from the ion stream, before further processing. 
     An inter-quad aperture IQ 1  separates the chamber  82  from a second main vacuum chamber  84 . A quadrupole rod set Q 1  is located in the vacuum chamber  84 , which is evacuated to approximately 1 to 3×10 −5  Torr. A second quadrupole rod set Q 2  is located in a collision cell  86 , supplied with collision gas  88 . The collision cell  86  is designed to provide an axial field toward the exit end as taught by Thomson and Jolliffe in U.S. Pat. No. 6,111,250, the entire contents of which are incorporated herein by reference. The cell  86  is typically maintained at a pressure in the range 5×10 −4 to 10 −2  Torr and includes inter-quad apertures IQ 2 , IQ 3  at either end. Following Q 2  is located a third quadrupole rod set Q 3 , and an exit lens  42 ′. Opposite rods in Q 3  are preferably spaced apart approximately 8.5 mm, although other spacings are contemplated and may be used in practice. The distance between the ends of the rods in Q 3  and the exit lens  42 ′ is approximately  3  mm, although other spacings are contemplated and may be used in practice, since this is not an essential parameter. The pressure in the Q 3  region is nominally the same as that for Q 1 , namely 1 to 3×10 −5  Torr. Detector  46  is provided for detecting ions exiting through the exit lens  40 . 
     Power supplies  90  are connected to the quadrupoles Q 0 , Q 1 , Q 2 , and Q 3 , as shown. Q 0  is an RF-only multi-pole ion guide. Q 1  is a standard resolving RF/DC quadrupole, the RF and DC voltages being chosen to transmit only precursor ions of interest or a range of ions into Q 2 . Q 2 , functioning within a collision cell, is operated as an RF-only multi-pole guide. Q 3  operates as a linear ion trap. Ions are scanned out of Q 3  in a mass dependent manner using an axial ejection technique, described in greater detail below. 
     In the experiments discussed below, the ion source was an ion spray device which produced ions from a standard calibration solution, including ions of known m/z values, supplied by a syringe pump. Q 1  was operated as an RF-only multi-pole ion guide, and the DC potential difference between Q 1  and IQ 2  was controlled to provide collisional energies of about 15 eV. Q 3  therefore trapped the precursor ions as a well as disassociated fragments thereof. 
     FIG. 3 shows the timing diagrams of waveforms applied to the quadrupole Q 3  in greater detail. In an initial phase  100 , a DC blocking potential on IQ 3  is dropped so as to permit the linear ion trap to fill for a time preferably in the range of approximately 5×1000 ms, with 50 ms being preferred. 
     Next, an optional cooling phase  102  follows in which the ions in the trap are allowed to cool or thermalize for a period of approximately  10  ms in Q 3 . The cooling phase is optional, and may be omitted in practice. 
     A mass scan or mass analysis phase  104  follows the cooling phase, in which ions are axially scanned out of Q 3  in a mass dependent manner. In the illustrated embodiment, an auxiliary dipole AC voltage, superimposed over the RF voltage used to trap ions in Q 3 , is applied to one set of pole pairs, in the x or y direction. The frequency of the auxiliary AC voltage is preferably set to a predetermined frequency ω ejec  known to effectuate axial ejection. (Each linear ion trap may have a somewhat different frequency for optimal axial ejection based on its exact geometrical configuration.) Simultaneously, the amplitudes of the Q 3  RF voltage and the Q 3  auxiliary AC voltage are ramped or scanned. Experiments were conducted to find the optimal DC potential barrier that would maximize the resolution of axial ejection. 
     The experimental data is shown FIGS. 4A-4D. In each of these drawings, the top frame show the DC voltage applied to the exit lens  42 ′ (i.e., the “exit lens voltage”) being ramped, followed by frames showing the spectra that span a mass of interest. The masses of interest are m/z=322, m/z=622, m/z=922 and m/z=1522, respectively shown in FIGS. 4A-4D. (Note that in these spectrograms the ions of interest were produced as a result of fragmentation in the collision cell. The spectrograms are this MS/MS spectra, with the precursor ions not shown.) 
     Each of the spectra are related to a specific barrier voltage. For example, in FIG. 4A, the mass of interest is m/z=322 and the exit lens voltage changes from −188 V to −150 V, as seen in the top frame  140   a . The total ion current is plotted as a function of exit lens voltage. A constant DC offset voltage of −190 V is applied to the rods of Q 3 , so the potential barrier that must be overcome by the ions in order to be axially ejected is equal to the exit lens voltage minus the DC offset voltage applied to the rods. For instance, an exit lens voltage of −160 V corresponds to a potential barrier of 30 volts. 
     The 2 nd  frame  140   b  indicates that when the exit lens voltage is at −163 V, no m/z=322 ions are ejected. The 3 rd  frame  140   c  indicates that ions are ejected when the exit lens voltage is at −173 V. The 4 th  frame  140   d  shows the ion signal when the exit lens voltage is at −183 V. 
     In FIG. 4B, the mass of interest is m/z=622 and the exit lens voltage changes from −188 V to −150 V, as seen in top frame  142   a . Frames  142   b - 142   e  show the spectra recorded at exit lens voltages of −153.1 V, −163.1 V, −173.1 V, and −183.1 V, respectively. 
     In FIG. 4C, the mass of interest is m/z=922 and the exit lens voltage changes from −190 V to −130 V, as seen in top frame  144   a . Frames  144   b - 144   f  show the spectra recorded at exit lens voltages of −143 V, −153 V, −163 V, −173 and −183 V, respectively. 
     In FIG. 4D, the mass of interest is m/z=1522 and the exit lens voltage changes from −190 V to −100 V, as seen in top frame  146   a . Frames  146   b - 146   f  show the spectra recorded at exit lens voltages of −143 V, −153 V, −163 V, −173 and −183 V, respectively. 
     From FIGS. 4A-4D, it will be seen that there is an optimum exit lens voltage for each of the different m/z values which maximizes the resolution of the ion signal, as determined by the full width half maximum value (FWHM) or m/Δm of each spectrum. The exit lens voltage increases as a function of mass, but only to a certain extent. Once the optimum exit lens voltage is reached, increasing the magnitude of the potential barrier further only reduces the signal resolution. For example, the optimized exit lens values for the specific geometry of apparatus  10 ′ are shown in Table 1 below: 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 (data acquired at 1000 amu/s scan speed) 
               
            
           
           
               
               
               
            
               
                 m/z 
                 Exit Lens Voltage 
                 Potential Barrier (V) 
               
               
                   
               
            
           
           
               
               
               
            
               
                 322 
                 −177 
                 13 
               
               
                 622 
                 −168 
                 22 
               
               
                 922 
                 −157 
                 33 
               
               
                 1522 
                 −135 
                 55 
               
               
                   
               
            
           
         
       
     
     This data is plotted in FIG. 5, which shows the absolute exit lens voltage, and FIG. 6, which shows the data in terms of the relative potential barrier. 
     From the plots in FIGS. 5 and 6, it will be seen that the optimal potential barrier is substantially linearly related to the magnitude of the mass-to-charge ration of the ion selected for axial ejection. Thus, as shown in FIG. 3, by scanning or ramping the DC voltage on the exit lens  42 ′ in conjunction with the scanning or ramping of the RF auxiliary AC fields, the resolution obtained through axial ejection can be maximized over a wide mass range. It will be also be appreciated that the same effect can be accomplished by keeping the DC voltage on the exit lens constant and ramping or scanning the DC offset applied to the rods of Q 3 , since that is an alternative method of varying the potential barrier between the rods of Q 3  and the exit lens  42 ′. 
     It should also be appreciated that one of the advantages provided by apparatus  10 ′ is a relatively high efficiency of axial ejection, despite the fact that the RF field is ramped. Ordinarily, ramping the RF field in isolation results in low efficiency because most of the ions upstream of the fringing fields will leave radially and be wasted (i.e., not counted by detector  46 ). However, by simultaneously applying and ramping the auxiliary AC field and the trapping potential barrier, efficiency can be increased. This is because, during a mass scan (from low to high masses), if the potential barrier is fixed at a high level then the lower masses will not be able to overcome the barrier unless enough energy is imparted to them. However, as more energy is applied, the low masses will most likely be ejected radially before overcoming the axial barrier. By ramping the axial potential barrier with mass, the probability of axial ejection increases. Efficiencies on the order of 15% have been obtained with the apparatus  10 ′. 
     It will be understood to those skilled in the art that many of the operating parameters described herein are specific to the geometry of the mass spectrometers, and will vary depending on the geometry or dimensions of any specific product. Accordingly, the operating parameters should be understood as being illustrative only, and not intended to be limiting. Similarly, those skilled in the art will understand that numerous modifications and variations may be made to the embodiments described herein without departing from the spirit or scope of the invention.