Abstract:
The invention relates to an ion guide consisting of RF multipole segments to transfer ions from an ion source into a mass analyzer. The invention consists in having movable RF multipole segments in the ion guide which extend or electrically connect other RF multipole segments along the axis of the ion guide, in which spaces have arisen as a result of a change in configuration of the mass spectrometer, comprising ion source, ion guide and mass analyzer. The moved RF multipole segments bridge the spaces which have arisen between the components of the mass spectrometer and facilitate the transfer of the ions from the ion source to the mass analyzer.

Description:
FIELD OF THE INVENTION  
       [0001]     The invention relates to an ion guide consisting of RF multipole segments to transfer ions from an ion source into a mass analyzer.  
       BACKGROUND OF THE INVENTION  
       [0002]     Electric RF multipole fields have long been used to guide ions in ion guides without the use of magnetic fields. These RF multipole fields can easily be generated with at least two pairs of long, thin, parallel rods or tubes distributed uniformly on a surface of a cylinder. Neighboring rod-shaped or tubular electrodes are supplied with the two phases of an RF voltage. This creates a pseudopotential between the rod-shaped or tubular electrodes, which keeps the ions in the interior of the cylinder. With two pairs of rod-shaped or tubular electrodes, a quadrupole field is created between the electrodes; with more than two pairs of rods, hexapole, octopole, decapole fields, etc. are created. The rod-shaped or tubular electrodes used to guide ions have a diameter of less than one millimeter and are typically 10 to 50 centimeters long. The interior formed by the electrodes is very narrow and has a diameter of only 2 to 4 millimeters, by means of which sufficiently strong multipole fields can be generated with low RF voltages.  
         [0003]     Apart from these rod-shaped or tubular electrodes, other shapes of electrodes are described in DE 195 23 895 A1 and U.S. Pat. No. 5,572,035A with which an ion-guiding pseudopotential can be generated.  
         [0004]     Nowadays, ion guides are used in almost all mass spectrometers in which the ions are generated outside the vacuum (out-of-vacuum ion sources), for example by ESI (electrospray ionization) or APCI (atmospheric pressure chemical ionization). The ion guides here often comprise several electrically isolated RF multipole segments of these rod-shaped or tubular electrodes, which can differ with respect to the number and arrangement of the electrodes, and the frequency and amplitude of the RF voltage, for example.  
         [0005]     Some of the mass analyzers can only be operated under ultra-high vacuum conditions (p&lt;10 −6  Pa). In contrast, the out-of-vacuum ion sources are operated at up to atmospheric pressure. If generated out-of-vacuum, the ions are first transferred from the region of the ion source through an opening or capillary into the vacuum system and conveyed on to the mass analyzer. The residual gas originating from the ion source is evacuated in several differential pump stages until the operating pressure of the mass analyzer is reached. The chambers of adjacent differential pump stages are interconnected only via small openings. The rod-shaped or tubular electrodes are often limited to the chamber; the ion guide then consists of several RF multipole segments separated from each other.  
         [0006]     For some types of mass analyzer, particularly for ion cyclotron resonance spectrometers (ICR MS), the ultra-high vacuum region can be separated from the ion source by means of a valve. Sliding valves, which have thicknesses of around 30 millimeters in the direction of the axis of the ion guide, are the preferred option here because they are small. Separation by means of a valve is necessary in order to protect the ultra-high vacuum in the mass analyzer from contamination when the ion source and adjacent regions of the ion guide are cleaned or serviced. The availability of the mass spectrometer is increased because the sensitive ultra-high vacuum of the mass analyzer is maintained during cleaning or servicing and does not have to be produced again in a protracted process. The insertion of a valve means that the two adjacent RF multipole segments of the ion guide have a separation which, when the valve is open, the ions can bridge only with a lens system, given the current prior art.  
         [0007]     The method of operation of the ICR MS means that a strong magnetic field is required in the mass analyzer. The transfer of the ions from the region where there is no magnetic field into the strong magnetic field of the mass analyzer is demanding because the ions are reflected, as if in a magnetic bottle, at the magnetic field of the mass analyzer if they do not move close to the axis and parallel to the lines of the magnetic field. Outside the mass analyzer there is a magnetic stray field which can neither be completely avoided nor shielded sufficiently. The separating valve can modify the magnetic stray field in such a way that the valve has to be taken into consideration in the design of the lens system.  
         [0008]     Ion guides are also used for types of ionization in which the ions are generated within the vacuum (in-vacuum ion source), such as matrix-assisted laser desorption and ionization MALDI. The ion sources which operate on the MALDI principle are used in ion trap mass spectrometers (IT MS), ion cyclotron resonance spectrometers (ICR MS) and time-of-flight mass spectrometers (TOF MS).  
         [0009]     When using in-vacuum ion sources, the ion guides are used mainly in cases where the ions are not only guided but the ion guide also fulfils further objectives during the conditioning of the ions. These objectives consist in cooling the ions in a damping gas, in the dissociation of the ions by molecular collisions (CID=collision induced dissociation) or by electron capture (ECD=electron capture dissociation), in the intermediate storage of the ions, or in the selection in mass filters, for example. The differences in the objectives also result in the ion guide being subdivided into RF multipole segments because the individual RF multipole segments have different operating parameters. The most important operating parameters here are the number and arrangement of the electrodes, the frequency and the voltage amplitude of the RF voltage, additional DC voltage between and along the rod-shaped electrodes, and the pressure conditions in the interior between the electrodes. The operating parameters of an individual RF multipole segment are adapted to suit its specific objective, but are also determined by the mass spectrometer, comprising ion source, ion guide and mass analyzer.  
         [0010]     The ions collide with the neutral molecules of a collision gas in a fragmentation cell and dissociate (CID). If the ions have low kinetic energy, the collisions in the gas do not lead to a fragmentation but only to a damping of the ion motion and cooling of the ions. The fragmentation or damping cells are often separated from the neighboring RF multipole segments in order to maintain the required vacuum conditions in the other RF multipole segments and in the mass analyzer. As is the case with the differential pump stages of an out-of-vacuum ion source, these gas-filled cells are only connected to the neighboring chambers via small openings and separate the RF multipole segments of the ion guide.  
         [0011]     At the transition between the RF multipole segments of the ion guide, the fringing fields cause the ions at the ends of the RF multipole segments to be partially reflected, resulting in loss of transmission. These transmission losses during the passage between the RF multipole segments can be minimized by interposing diaphragms and lenses. An ion guide comprising a single RF multipole segment has lower losses and increases the sensitivity of the mass spectrometer.  
         [0012]     If the diaphragms or lenses are put at a repelling DC potential for a certain period, then the pseudopotential of the RF multipole field and the DC potential of the diaphragms or lenses temporarily store the ions in the interior, which is defined by the rod-shaped or tubular electrodes and the diaphragms or lenses.  
         [0013]     Mass spectrometers have been described in DE 196 29 134 C1 and DE 199 37 439 C1 which make it possible to choose between more than one ion source by sliding or turning movable RF multipole segments of the ion guide. It is therefore possible to change the configuration of the mass spectrometer without having to ventilate it. In both publications, an individual movable RF multipole segment has no electrical contact to other RF multipole segments of the ion guide. In order to avoid losses as the ions pass between the RF multipole segments of the ion guide, the distance between adjacent RF multipole segments must be as small as possible without causing electrical flashovers or crosstalk. Nevertheless, there are losses at the electric fringing fields between the RF multipole segments. In addition, each movable RF multipole segment of the ion guide must be individually connected to an RF voltage.  
       SUMMARY OF THE INVENTION  
       [0014]     The invention provides an ion guide made of RF multipole segments with which ions in a mass spectrometer can be guided from the ion source to the mass analyzer after a change in the configuration has created spaces between the segments of the ion guide. There are movable RF multipole segments in the ion guide which extend or electrically interconnect other RF multipole segments, between which spaces (gaps) have arisen as a result of a change in configuration of the mass spectrometer. The moved RF multipole segments fill the gaps created in the ion guide and thus form variable “ion bridges”. This requires that the electrodes of the movable RF multipole segments are congruent with the electrodes of the RF multipole segments that are being extended or bridged. After extension or connection, a moved RF multipole segment is in electrical contact with at least one other RF multipole segment. This electrical contact supplies the moved RF multipole segment with an RF voltage and generates an RF multipole field which guides the ions in the interior of the moved RF multipole segment with low losses. According to the invention, the movable RF multipole segments do not each require their own voltage supply, which reduces cost. If two stationary RF multipole segments are electrically connected by a movable RF multipole segment, then only one of the stationary RF multipole segments requires a power supply in order to generate an ion-guiding RF multipole field in the interior of the three RF multipole segments. This means that an additional power supply for a stationary RF multipole segment is not required, and that the respective electrodes of the three RF multipole segments are exactly in phase with each other. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0015]     The above and further advantages of the invention may be better understood by referring to the following description in conjunction with the accompanying drawings in which:  
         [0016]      FIG. 1  shows a schematic representation of a mass spectrometer comprising an ion source, an ion guide with a separating valve and an ICR mass analyzer.  
         [0017]      FIG. 2  shows a schematic representation of a separating valve with a lens system.  
         [0018]      FIG. 3  shows a schematic representation of a separating valve with a movable RF multipole segment.  
         [0019]      FIG. 4  shows preferred embodiments of movable RF multipole segments with rod-shaped and tubular electrodes.  
         [0020]      FIG. 5  shows a further preferred embodiment of a movable RF multipole segment with rod-shaped electrodes. 
     
    
     DETAILED DESCRIPTION  
       [0021]      FIG. 1  shows a mass spectrometer comprising an ion source, an ion guide and an ICR mass analyzer. The ions are generated in the out-of-vacuum electrospray ion source  101 . The RF multipole segments  105 ,  108  and  113  of the ion guide are located in the vacuum chambers  106 ,  109  and  114 . The mass spectrometric measurement is carried out in the ICR measuring cell  116 . The strong magnetic field required for the measurement in the ICR mass analyzer is generated in a magnet  115 . Outside the magnet  115  there is a magnetic stray field. The ion guide allows transfer of the ions generated in the out-of-vacuum ion source  101  into the ICR measuring cell  116  with low losses.  
         [0022]     The ions are generated in the out-of-vacuum ion source  101  by electrospray ionization (ESI) and introduced through an inlet capillary  102  with a diameter of approx. 0.5 millimeters and a length of 160 millimeters into the first chamber  103  of the vacuum system. An electric field draws the ions to the tapered skimmer  104 , and they enter the vacuum chamber  106  through a central opening. The gas from the out-of-vacuum ion source  101 , which also flows in through the inlet capillary  102 , is deflected outwards by the tapered gas skimmer  104  and evacuated through the vacuum connection  117  down to a residual pressure of around 100 Pa. The chambers  106 ,  109  and  114  are separated by the diaphragms  107  and  110  and connected to a pump system via the vacuum connections  118 ,  119  and  120  respectively. The small aperture diameters of the diaphragms mean that the chambers  106 , 109  and  114  form a differential pump section with typical pressures of 10 −1  Pa, 10 −5  Pa or 10 −8  Pa. The first RF multipole segment  105  of the ion guide begins directly behind the opening in the skimmer  104 . This segment consists of rod-shaped or tubular electrodes arranged in a hexapole or octopole, as are the RF multipole segments  108  and  113 . The RF multipole segments  105  and  108  convey the ions to the aperture  110 .  
         [0023]     In  FIG. 1 , the separating valve  111  is closed and completely separates the chambers  109  and  114  from each other. The mounting dimensions of the separating valve mean that the RF multipole segments  108  and  113  are separated by a distance of some 30 millimeters when the separating valve is open. Without the lens systems  110  and  112 , the ions cannot pass through this space when the separating valve is open without incurring extremely large losses. The separating valve protects the ultra-high vacuum in the ICR measuring cell  116  (p&lt;10 −7  Pa) from contamination when the upstream parts of the ion guide are cleaned or serviced. The availability of the mass spectrometer is increased by the separation of the vacuum system because the sensitive ultra-high vacuum of the ICR mass analyzer is maintained during cleaning or servicing and does not have to be produced again in a protracted process. After the lens system  112 , the ions are conveyed through the RF multipole segment  113  to the ICR measuring cell  116 .  
         [0024]     The specialist is aware that RF multipole segments can carry out other functions apart from ion transport, for example ion storage, selection according to ion mass, cooling or fragmentation of ions, if the corresponding operating parameters for the RF multipole segments are selected. The number of such RF multipole segments in a mass spectrometer is obviously not limited to the three segments  105 ,  108  and  113  in  FIG. 1 .  
         [0025]      FIG. 2   a  shows a section from an ion guide in which the vacuum chambers  201  and  208  are separated by a valve. In  FIG. 2   b , the cap  204  of the valve has been moved into the secondary chamber  205  and the valve is open. The chamber  201  and the chamber  208  are evacuated through the vacuum connections  209  and  210  respectively and can be ventilated independently of each other when the valve is closed. The RF multipole segments  202  and  207  consist of rod-shaped or tubular electrodes arranged on a surface. Neighboring electrodes are each supplied with an antiphase RF voltage.  FIGS. 2   a  and  2   b  show only the surfaces in whose interior the ions are guided by the RF multipole fields. The RF multipole segments  202  and  207  are roughly 30 to 50 millimeters apart. When the valve is open, the ions coming from the RF multipole segment  202  move in the field of the lens systems  203  and  206  to the RF multipole segment  207 . Without the field of the lens systems  203  and  206  only a very small fraction of the ions would overcome the space between the RF multipole segments  202  and  207 .  
         [0026]      FIGS. 3   a  and  3   b  show a schematic representation of an embodiment according to the invention. As is the case with  FIGS. 2   a  and  2   b , these illustrations also depict a section from an ion guide in which there is a valve between the vacuum chambers  301  and  307 . The two chambers can be evacuated and ventilated separately via the vacuum connections  308  and  309 . The RF multipole segments  302  and  306  consist of rod-shaped or tubular electrodes arranged on a surface which is shown here. Neighboring electrodes are each supplied with an antiphase RF voltage. In contrast to  FIGS. 2   a  and  2   b  there are no lens systems. When the valve is closed, the electrodes of the movable RF multipole segment  303  are situated near the stationary RF multipole segment  302 . The two preferred embodiments in  FIGS. 4 and 5  illustrate how the rod-shaped or tubular electrodes of movable RF multipole segments are inserted into other RF multipole segments. In  FIG. 3   b , the movable RF multipole segment  303  has been moved out of the segment  302  in the direction of the segment  306  when the valve is open. The three RF multipole segments  302 ,  303  and  306  are electrically interconnected, producing a multipole field in the interior of the movable RF multipole segment  303 , in which the ions move from segment  302  to segment  306 . When used as a variable “ion bridge” the movable RF multipole segment has advantages over the lens system in  FIGS. 2   a  and  2   b . The ion losses and the susceptibility to external influences, such as the magnetic field of an ICR measuring cell, are lower, and the acceptance of the ions with respect to the spatial and velocity distribution is better.  
         [0027]      FIGS. 4   a  to  4   d  illustrate a preferred embodiment for a movable RF multipole segment.  FIG. 4   b  shows two stationary RF octopole segments  410  and  430  as well as a movable RF octopole segment  420 . The stationary segments  410  and  430  consist of eight tubular electrodes. The movable RF octopole segment  420  is constructed from eight rod-shaped electrodes, whose diameters correspond to the inside diameter of the tubular electrodes of the segments  410  and  430 , and which can be slid along the axis of the electrodes. The electrodes of the RF octopole segments  410 ,  420  and  430  are all made of conductive material. In  FIG. 4   a , the rod-shaped electrodes of the segment  420  are pushed into the tubular electrodes of the segment  410 , and in  FIG. 4   b , they are pushed out. There is an antiphase RF voltage across the neighboring tubular electrodes of a stationary segment ( 410  or  430 ). In  FIG. 4   b , the movable electrode  421  electrically connects the two electrodes  411  and  431 . The same applies to the corresponding electrodes of the three RF octopole segments  410 ,  420  and  430 . An octopole field is generated in the interior of all three RF octopole segments  410 ,  420  and  430 , and this field guides the ions along the whole length of the electrically connected RF octopole segments  410 ,  420  and  430 .  
         [0028]      FIG. 4   c  illustrates the cross-section of the electrodes  411 ,  421  and  431 . In this case, electrodes  401  and  411 ,  402  and  421 , and  403  and  431  correspond. The arrow indicates that the rod-shaped electrode  402  is movable with respect to the stationary tubular electrodes  401  and  403  and electrically connects the two stationary tubular electrodes  401  and  403  after a translation movement. The wall thickness of the tubular electrodes  401  and  403  must be kept as small as possible, as otherwise the discontinuities at the transition between the electrodes  401  and  402  or  402  and  403  cause fringing fields with axial field components at which the ions are partially reflected.  FIG. 4   d  shows the cross-section of electrodes of another preferred embodiment of a movable RF octopole segment. Unlike  FIG. 4   c , the rod-shaped electrodes  404  and  406  here are stationary, and the movable electrode  405  is tubular in shape. After a translation movement of the electrode  405 , the three electrodes  404 ,  405  and  406  are electrically interconnected. In both embodiments, the movable RF octopole segment can be accommodated near a stationary RF octopole segment, providing a great space-saving advantage, and only one single translation movement of the RF octopole segment  420  (“sliding multipole”) is required to bridge the two stationary RF octopole segments.  
         [0029]      FIGS. 5   a  to  5   c  illustrate a further preferred embodiment for a movable RF multipole segment.  FIGS. 5   a  to  5   c  show two stationary RF quadrupole segments  510  and  530  as well as a movable RF quadrupole segment  520 . In  FIG. 5   a , the rod-shaped electrodes of the movable segment  520  are situated between the rod-shaped electrodes of the stationary segment  530 . The electrodes of the RF quadrupole segments  510 ,  520  and  530  are all made of conductive material. From  FIG. 5   a  to  5   b  the movable segment  520  is slid by means of a translation movement into the space between the two stationary segments  510  and  530 . After a rotational movement, the movable electrode  521  electrically connects the two rod-shaped electrodes  511  and  531  with each other (see  FIG. 5   c ). The same applies for the other corresponding electrodes of the RF quadrupole segments  510 ,  520  and  530 . Applying an antiphase RF voltage to a stationary segment ( 510  or  530 ) generates a quadrupole field in the interior of the three electrically connected segments  510 ,  520  and  530 , in which the ions are guided from segment  510  to segment  530 .  
         [0030]      FIG. 5   d  illustrates an embodiment of the movable electrode  521  of the RF quadrupole segment  520  in cross-section. The stationary electrodes  501  and  507  correspond to the stationary electrodes  511  and  531  in  FIG. 5   c . The movable electrode  521  has a rod-shaped main body  504  with end bores into which contact bodies  502  and  506  are introduced. The contact bodies  502  and  506  are connected to the main body  504  by means of the springs  503  and  505  respectively, and are pressed into the bores of the main body  504  by the movement shown in  FIG. 5   d . The contact bodies  502  and  506  are electrically connected to the main body  504 . If the movable electrode  521  is slid between the stationary electrodes  511  and  531 , then the two stationary electrodes  511  and  531  are electrically connected via the end surface of the contact bodies  502  and  506  and the main body  504 . A recess on the end of the electrodes  501  and  507  provides a connection between the electrodes  501 ,  504  and  507 .  
         [0031]     The RF quadrupole segment  520  (“revolver multipole”) forms a variable “ion bridge” between stationary RF multipole segments, as does the RF octopole segment  420  (“sliding multipole”) in  FIG. 4 . Compared to a lens system, the revolver multipole offers the same advantages as a “sliding multipole”. Comparing the “revolver multipole” to the “sliding multipole” shows that with the “revolver multipole”, two movements are necessary in order to make the connection between the stationary RF multipole segments, and that the space between the stationary electrodes limits the number of movable electrodes. However, the transitions between the RF multipole segments in the case of the “revolver multipole” are more favorable with respect to the homogeneity of the multipole field generated.  
         [0032]     The embodiments in  FIGS. 4 and 5  illustrate rod-shaped or tubular electrodes in quadrupole and octopole arrangements. It is apparent to the specialist that other RF multipole electrodes can also be used. Furthermore, in the embodiments shown in FIGS.  1  to  3 , only the separation between two RF multipole segments is bridged, this separation being caused by a separating valve. Without limiting the generality, the movable RF multipole segments according to the invention are capable of bridging any space in an ion guide which arises from a change in configuration.  
         [0033]     The automatic connection of the RF multipole segments by the bridging RF multipole segment has the further advantage that no vacuum feedthroughs for the RF voltage are needed for the connected RF multipole segment. It may however be necessary to switch the RF generator to a state better adapted to the now higher capacitive load.