U.S. patent application number 09/565250 was filed with the patent office on 2001-12-13 for ion transfer from multipole ion guides into multipole ion guides and ion traps.
Invention is credited to Gulcicek, Erol, Whitehouse, Craig M..
Application Number | 20010050335 09/565250 |
Document ID | / |
Family ID | 21783597 |
Filed Date | 2001-12-13 |
United States Patent
Application |
20010050335 |
Kind Code |
A1 |
Whitehouse, Craig M. ; et
al. |
December 13, 2001 |
Ion transfer from multipole ion guides into multipole ion guides
and ion traps
Abstract
A multipole ion guide is configured to improve the transmission
efficiency of ions which traverse the length of one ion guide and
enter either another multipole ion guide such as a quadrupole mass
analyzer or a three dimensional ion trap. The ion transfer
multipole ion guide radial dimensions are reduced such that the
pole assembly and an appropriately shaped exit lens can be
positioned within a portion of the internal space defined by the
larger radius second multipole ion guide poles. Ions exiting the
first ion guide of reduced size find themselves inside the second
ion guide close to the centerline. In this manner ions can be
efficiently transferred from one ion guide to another, even for
those ions with low kinetic energies. In a second embodiment of the
invention, the exit region of a multipole ion guide is configured
such that the multipole ion guide poles can be extended into a
counterbore of a three dimensional ion trap end cap electrode. With
this configuration, ions (including those with low kinetic
energies) can be transferred into a three dimensional ion trap with
increased trapping efficiency.
Inventors: |
Whitehouse, Craig M.;
(Branford, CT) ; Gulcicek, Erol; (Cheshire,
CT) |
Correspondence
Address: |
Morris E Cohen Esq
Levison Lerner Berger & Langsam
757 Third Ave Ste 2400
New York
NY
10017
US
|
Family ID: |
21783597 |
Appl. No.: |
09/565250 |
Filed: |
May 5, 2000 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
09565250 |
May 5, 2000 |
|
|
|
08857191 |
May 15, 1997 |
|
|
|
6121607 |
|
|
|
|
60017619 |
May 14, 1996 |
|
|
|
Current U.S.
Class: |
250/288 |
Current CPC
Class: |
H01J 49/063 20130101;
H01J 49/067 20130101; H01J 49/424 20130101 |
Class at
Publication: |
250/288 |
International
Class: |
H01J 049/00 |
Claims
We claim:
1. An apparatus for transferring ions within a mass spectrometer,
comprising: a multipole ion guide for transferring ions, said
multipole ion guide having a first set of poles; and, a three
dimensional ion trap having an entrance endcap, wherein said ion
trap comprises a counterbore in said entrance endcap, and wherein
said first set of poles extends into said counterbore.
2. An apparatus for transferring ions within a mass spectrometer,
comprising: a first multipole ion guide having a first set of
poles; and, a second multipole ion guide; and wherein said first
multipole ion guide and said second multipole ion guide are
configured such that said first multipole ion guide extends into
said second multipole ion guide, such that a portion of said first
set of poles is located within said second multipole ion guide.
3. An apparatus for transferring ions within a mass spectrometer,
comprising: a first multipole ion guide having an exit end; a
hat-shaped electrostatic lens, said lens having a lens face, said
exit end of said first multipole ion guide being located within
said hat shaped lens; and, a second multipole ion guide having an
entrance end, wherein said lens face of said hat-shaped
electrostatic lens is located in proximity to said entrance end of
said second multipole ion guide.
Description
RELATED APPLICATIONS
[0001] This application claims the priority of U.S. Nonprovisional
Application Ser. No. 08/857,191 filed May 15, 1997, and the
priority of U.S. Provisional Patent Application Ser. No.
60/017,619, filed May 14, 1996, the disclosures of which are fully
incorporated herein by reference.
FIELD OF INVENTION
[0002] The present invention relates to an apparatus and method for
increasing the efficiency of ion transport from ion sources into a
multipole ion guide, a quadrupole mass analyzer or a three
dimensional ion trap. Multipole ion guides have been effectively
used to capture and transport ions which are delivered into vacuum
from Atmospheric Pressure Ion (API) sources such as Electrospray
(ES) and Atmospheric Pressure Chemical Ionization (APCI). Ions
whose mass to charge (m/z) values fall within the stability region
of the multipole ion guide are transmitted through the length of
the guide and delivered to the entrance region of a mass analyzer.
Specifically, the present invention addresses the ion transfer from
a multipole ion guide into either a subsequent multipole ion guide
such as a quadrupole mass analyzer or a three dimensional ion guide
mass analyzer. Atmospheric Pressure Ion Source mass spectrometry
(API-MS) has emerged as a sensitive method for detecting sample ion
solutions with both discrete sample and on-line sample introduction
methods. The invention improves performance with quadrupole mass
and ion trap mass spectrometers for both on-line and off-line
applications. In addition, the apparatus and methods described can
be configured to improve quadrupole and ion trap mass analysis
performance with ion sources other than API sources.
BACKGROUND OF INVENTION
[0003] Multipole ion guides have been used to efficiently transfer
ions through vacuum or partial vacuum into mass analyzers. In
particular, multipole ion guides have been configured to transport
ions from an Atmospheric Pressure Ion (API) Source through one or
more vacuum pumping stages and into a mass analyzer. Quadrupole,
magnetic sector, Fourier Transform (FTMS), three dimensional ion
trap and Time-Of-Flight (TOF) mass analyzers each have different
entrance ion optics criteria which must be satisfied by any ion
source ion transport or focusing system. The present invention
addresses optimization of the transfer of ions from one multipole
ion guide into a subsequent multipole ion guide, quadrupole mass
analyzer or a three dimensional quadrupole ion trap. Multipole ion
guides and ion traps operate with sinusoidal voltages and separate
or combined DC voltages applied to one or more electrodes. The
sinusoidal voltage wave forms are usually referred to as AC or RF
because the frequency of these wave forms generally fall within the
radio frequency range. The combination of AC and DC voltages
applied to the rods of a multipole ion guide or the endcaps and
ring electrode of a three dimensional quadrupole ion trap can be
selected to establish stable ion trajectories for some mass to
charge (m/z) values while rejecting others. Mass selection for mass
analysis can be achieved in this manner, or ions can be trapped
while colliding with background gas to achieve Collisional Induced
Dissociation (CID) ion fragments from trapped ions or from ions
traversing the length of the ion guide. Ions whose m/z values do
not have a stable trajectory for the AC and DC potentials applied
to the rods of a multipole ion guide will be rejected from the ion
guide before reaching the ion guide exit. The AC and DC voltages
applied to the poles of a multipole ion guide can be selected to
achieve the functions of selective m/z ion transmission and ion
rejection for those ions within the ion guide; however, the fields
created by the applied voltages can pose some difficulty for ions
trying to enter the ion guide. AC and DC voltages applied to the
poles of a commercial analytical quadrupole can reach hundreds of
volts and even kilovolt potentials. Similarly, the trajectories of
ions attempting to enter a three dimensional quadrupole ion trap
are greatly influenced by the RF fields produced from voltages
applied to the ring electrode appearing at the ion guide endcap
entrance orifice. Ion transport into a multipole ion guide will be
considered first.
[0004] For a geometrically ideal multipole ion guide, there is no
net electric field at the very centerline of the ion guide except
for the common DC offset potential applied equally to all ion guide
poles. Ions of a given polarity attempting to enter a device whose
electrodes have an AC voltage applied can encounter a retarding or
rejecting electric field gradient during a portion of the AC
voltage phase. Multipole ion guides with an even number of
symmetrically spaced parallel poles or rods ideally have no net AC
(or RF) field at the centerline or axis of the assembly. Ion beams,
however, have a finite cross section and most ions will enter a
multipole ion guide such as a quadrupole mass analyzer at some
radial distance off the centerline. Consequently, the trajectory of
these ions will be influenced by an AC and an asymmetric DC field.
Depending on the phase of the AC field, the asymmetric DC field off
the centerline and the ion kinetic energy in the axial direction,
an approaching ion may successfully enter the ion guide and
maintain a stable trajectory, or may be rejected from entering the
multipole ion guide or may enter the ion guide with an unstable
trajectory. The more time an ion spends in the fringing fields
while attempting to enter a multipole ion guide, the more cycles of
AC voltage it can be exposed to and thus the more likely that it
may be potentially driven into an unfavorable trajectory. For a
given average ion energy, the higher an ion m/z value, the lower
its velocity. Consequently, the larger the m/z value of an ion, the
more time an ion will spend traversing the entrance region of a
multipole ion guide while entering the rod assembly. Similarly, if
the average ion kinetic energy is reduced, ions of a given m/z
value will spend more time traversing the fringing fields of the
multipole ion guide as they enter the ion guide. The AC voltages
applied to the rods of a multipole ion guide with an even number of
poles generally have equal RF amplitude but opposite phase for each
adjacent rod or pole. For example, the opposing rods of a
quadrupole ion guide have the same phase, which is itself 180
degrees out of phase from the AC voltage applied to each
neighboring rod or pole.
[0005] One means used to achieve quadrupole mass analyzer m/z
selection, is to apply RF and positive and negative polarity DC
voltage to the rods with a selected RF to DC amplitude ratio. The
DC voltage is equal in amplitude but opposite in polarity on
adjacent rods. When quadrupole mass analyzers are scanned in this
mass selective mode to acquire a mass spectrum, the AC and DC
amplitudes increase proportionally with selected m/z during a scan.
Consequently, an ion with a higher m/z value and a slower velocity
than a lower m/z value, moves more slowly through the entrance
fringing fields and must traverse a higher AC and DC fringing field
amplitude in entering the quadrupole in scan mode. Ion transmission
efficiency in quadrupole mass analyzers can decrease with
increasing m/z, due in part to a decreased efficiency of ions
entering the quadrupole. The positive and negative DC voltage
components may be added to form a common offset voltage. This DC
offset potential can be set to aid in accelerating ions into the
quadrupole. In some applications, an additional low amplitude AC
wave form, which has a lower frequency than the RF voltage
component, is capacitively added to the RF voltage. This additional
low amplitude AC voltage of a selected frequency or frequency set
is added to the RF voltage to provide resonant frequency excitation
for specific ion m/z rejection or fragmentation. With the exception
of the DC offset voltage component, the effective AC and DC field
strength decreases the closer an ion is positioned to the ion guide
centerline. The invention improves the ion transport into a
multipole ion guide such as a quadrupole mass analyzer by
minimizing the fringing field effects and insuring that ions are
delivered close to the multipole ion guide centerline with angular
trajectories within the acceptance window of the multipole ion
guide.
[0006] A quadrupole is the most commonly used multipole ion guide
configuration for conducting mass analysis. Quadrupoles can achieve
higher mass to charge resolving power compared with hexapoles,
octapoles or ion guides with higher numbers of poles. Hexapoles or
octapoles have been used in AC or RF only operating mode where ion
transport with little or no m/z selection is desired. Hexapoles or
octapoles may be used as the ion guide in which Collision Induced
Dissociation occurs in what is generically referred to as a triple
"quadrupole" mass spectrometer. Although the invention can be
applied to improve the ion transfer efficiency into any multipole
ion guide configured and used in RF only mode, as an ion trap, as a
CID region or as a mass filter, a quadrupole will be described as
an example. As was described above, ion losses can occur in the
entrance region when transferring ions into a quadrupole ion guide
or mass analyzers due to the electric fields which influence the
ion trajectories as they approach and enter the quadrupole ion
guide. Peter H. Dawson (Chapter 2, Quadrupole Mass Spectrometry and
Its Applications, Elsevier Scientific Publishing Company, New York,
1976) describes the effective quadrupole mass filter aperture and
acceptance for an ion approaching the quadrupole entrance with both
AC and DC electric fields applied to the poles. The effective
entrance aperture through which ions may enter the quadrupole
decreases with increasing resolution, increasing distance from the
centerline, and trajectories with increasing off-axis angle and
velocity. The success of an ion attempting to enter the quadrupole
ion guide at a position off the centerline will be highly dependent
on the phase and amplitude of the AC voltage component and the
amplitude of the DC voltage component of the applied electric
fields. In addition, ions approaching the quadrupole entrance can
enter unstable trajectories due to fringing field affects. The more
time an ion spends in the quadrupole fringing fields the more
chance it has of being driven into an unstable trajectory. Once an
ion establishes a stable trajectory in the ion guide, the more RF
cycles the ion is exposed to while traversing the quadrupole
length, and the higher the mass selection resolution that is
achievable. This relationship between maximum resolution achievable
as function of the number of RF cycles an ion is exposed to while
traversing the length of a quadrupole can be expressed by the
empirical relation,
M/.DELTA.M=(1/K)N.sup.n
[0007] (Chapter 6, Dawson).
[0008] .DELTA.M is the mass spectral peak width at mass to charge
value M for a singly charged ion. N is the number of cycles of the
RF field and n and K are constants equal to approximately 2 and 20
respectively. An ion entering with lower axial velocity or energy
will be exposed to more RF cycles during the time it spends in the
quadrupole than an ion with higher energy. An ion with lower
kinetic energy will also spend more time in the fringing fields at
the quadrupole entrance and consequently have an increased chance
of being driven into an unfavorable trajectory. Various lens
configurations have been developed which attempt to overcome these
opposing ion entrance and mass analysis criteria to achieve
improved quadruple sensitivity and resolution performance. Ideally,
it is desirable to introduce ions into a quadrupole ion guide with
trajectories parallel to the centerline, with a minimum radial
displacement and with a low ion energy.
[0009] When transferring ions from one multipole ion guide to
another multipole ion guide, as occurs in triple "quadrupole" mass
analyzers, losses can occur in the interface regions between each
multipole ion guide. Commercial triple quadrupole instrument,
typically have one or more electrostatic lenses located between two
sequential ion guides and are configured not only to minimize the
fringing electric fields at the entrance of the downstream ion
guide but also to minimize the fringing fields at the exit end of
the upstream ion guide. An electrostatic lens element is commonly
used at the entrance of a multipole ion guide operated as either a
mass analyzer or a Collisionally Induced Dissociation (CID) ion
transport region. Commercially available multipole ion guide
electrostatic entrance optics have included a flat plate entrance
lens with an orifice positioned on the centerline which is located
as close as possible along the axis to the entrance face of the
multipole ion guide rods to minimize fringing effects. A second
commercially available lens, known as a Turner-Kruger lens, has a
ground or fixed DC potential entrance face with a tube section
projecting into the quadrupole rod assembly. DC voltage is applied
to a concentrically positioned inner tube and the DC voltage
amplitude is varied proportional to the scanned quadrupole AC and
DC voltages during a mass spectrum acquisition. A third
commercially available electrostatic entrance lens assembly
incorporates the use of a "leaky" dielectric material to reduce the
quadrupole entrance fringing field effects. A cylindrical lens of
semiconductor material is positioned to extend into the entrance
region of a quadrupole rod assembly. The "leaky" dielectric
semiconductor material is positioned to reduce the amplitude of the
fringing fields experienced by ions entering the quadrupole
assembly. Configurations of one or more flat plate electrostatic
lens are commonly used to transfer ions from one multipole ion
guide to another. The flat plate lenses are positioned in close
proximity to the exit rod face of one multipole ion guide and the
entrance rod face of the next multipole ion guide to minimize exit
and entrance fringing field effects. The orifice size in these flat
plate electrostatic lenses is configured as an optimization of
opposing criteria. The smaller the orifice size, the less the
fringing field penetration will effect the trajectory of an
approaching ion. A larger orifice is desired, however, to avoid
interfering with the ion beam cross section and reducing
sensitivity. AC only sections or Brubaker lenses have also been
added to the entrance and even the exit ends of analytical
quadrupoles to reduce the DC fringing field effects for ions
entering and exiting the quadrupole. Electrostatic entrance lenses
have been configured with Brubaker lenses in commercial quadrupole
analyzers to improve the efficiency of ion transport into a
multipole ion guide particularly at reduced ion energies.
[0010] Each of these multipole ion guide entrance lens
configurations help to reduce the effect of fringing fields but
have variable ion transfer efficiencies into the ion guide
depending on ion energy, ion m/z value, ion angular divergence, the
radial position of the ion from the centerline and the AC and DC
voltages applied to the ion guide poles. For example, as the
resolution is increased for a quadrupole mass analyzer, the radial
and angular acceptance window for an ion entering the ion guide may
decrease and hence contribute to a reduction in sensitivity during
mass analysis. Electrostatic entrance lens configurations do not
fully compensate for the variations in entrance conditions
encountered with quadrupole ion guide mass analysis operation. The
present invention improves the efficiency of ion transport into ion
guides by overcoming several of the performance problems
encountered when using electrostatic lens systems. The invention
improves the efficiency of ion transport into a multipole ion guide
by extending the rods of one multipole ion guide into the entrance
region of the next multipole ion guide rod assembly. This nested
multipole ion guide configuration effectively reduces fringing
field losses observed with electrostatic entrance lens
configurations.
[0011] A second embodiment of the invention improves the ion
transfer efficiency from a multipole ion guide into a three
dimensional quadrupole ion trap. In this second embodiment, a
multipole ion guide of reduced radial dimensions is positioned such
that the ion guide rods extend into a counterbore in the entrance
end cap of a three dimensional ion trap. The bottom of the
counterbore is configured to be the multipole ion guide exit lens
or an additional electrostatic lens can be added between the ion
guide exit and the end cap. Without the additional electrostatic
lens, the end cap aperture at the counterbore bottom serves as the
multipole ion guide exit aperture and the ion trap entrance
aperture. A portion of the ions unable to enter the ion trap due to
rejection by the RF fringing field phase may remain trapped by the
ion guide exit region. When the changing ion trap AC phase allows
ions to enter the trap by creating a more favorable electric field
at the ion trap entrance aperture, the ion guide releases ions into
the ion trap. The offset potential of the multipole ion guide can
be reduced relative to the three dimensional ion trap end cap
voltage to trap ions in the ion guide during ion trap mass
analysis. For example if the ion kinetic energy is established by
the ion guide DC offset potential, lowering this offset potential
below the DC potential set on the ion trap entrance endcap will
prevent ions from leaving the ion guide, effectively trapping the
ions within the multipole ion guide rod assembly internal volume.
The technique of trapping ions in a multipole ion guide using a
separate ion guide exit lens potential and releasing ions into a
three dimensional ion trap has been described by Douglas in U.S.
Pat. No. 5,179,278. Douglas, however, does not teach the
configuration of extending the rods of a multipole ion guide into a
counterbore of a three dimensional ion trap endcap to improve the
trapping efficiency by recapturing ions within the ion guide that
have been rejected by the ion trap entrance orifice. The invention
also allows the transfer of low energy ions into the three
dimensional ion trap, which aids in increasing the trapping
efficiency of ions once they enter the ion trap. Also, due to the
sharing of the end cap aperture, ions can be efficiently
transferred back into the multipole ion guide from the ion trap to
achieve improved sensitivity as well as a variety of enhanced scan
functions.
SUMMARY OF INVENTION
[0012] A multipole ion guide has been configured with a reduced
diameter such that the ion guide with the appropriately shaped exit
lens can be positioned inside a larger diameter multipole ion
guide. Ions exiting the smaller multipole ion guide pass through
the exit lens and are focused to the centerline already inside the
larger ion guide. Since the ions leaving the exit lens aperture of
the multipole ion guide with reduced dimensions are already inside
the larger ion guide, high ion transfer efficiencies can be
achieved even with ions having low axial translational energies.
Improved mass analysis resolution at higher sensitivities can be
achieved with this ion transfer optic when ions are transferred
into a quadrupole mass analyzer. The smaller ion guide can be
configured to extend continuously through more than one vacuum
stages or reside entirely within one vacuum stage. The smaller ion
guide can be configured to reside in a different vacuum stage than
that of the downstream larger ion guide with the smaller ion guide
exit lens serving as the vacuum partition. Alternatively, all
multipole ion guides can be configured to reside in the same vacuum
pumping stage.
[0013] In a second embodiment of the invention, a multipole ion
guide with reduced radial dimensions is positioned such that the
rods of the multipole ion guide extend into a counterbore of the
entrance endcap of a three dimensional quadrupole ion trap. The
entrance aperture in the ion trap endcap as serves as the multipole
ion guide exit lens. During the ion trap filling cycle, a portion
of the ions rejected from entering the entrance aperture of the
three dimensional ion trap due to unfavorable RF phase electric
fields can be retrapped by the multipole ion guide. Ions ejected
out of the entrance endcap by the three dimensional ion trap during
mass analysis scanning can also be retrapped by the multipole ion
guide. To increase duty cycle and sensitivity, the ion trap endcap
voltage can be set higher than the kinetic energy of the ions
exiting the multipole ion guide to trap ions in the multipole ion
guide during a three dimensional ion trap mass analysis cycle. The
multipole ion guide rod potentials can be set to reduce the m/z
stability window. In this manner, ions with undesirable m/z values
can be ejected from the multipole ion guide and prevented from
entering the three dimensional ion trap, thus reducing space charge
effects in the ion trap. The multipole ion guide can be configured
to extend continuously into more than one vacuum pumping stage.
BRIEF DESCRIPTION OF DRAWINGS
[0014] FIG. 1 is a drawing of a multipole ion guide configured to
accept ions from an atmospheric pressure ion source and deliver
them into a quadrupole mass analyzer through two vacuum pumping
stages. The multipole ion guide and a portion of its exit lens
extends into the inside diameter of the quadrupole mass analyzer
rod assembly.
[0015] FIG. 2 is a diagram of the quadrupole entrance region with a
multipole ion guide assembly extended into the quadrupole analyzer
AC only entrance section.
[0016] FIG. 3 is an end view cross section diagram of the hexapole
ion guide with surrounding exit lens and insulator positioned
inside a quadrupole mass analyzer rod assembly.
[0017] FIG. 4 is a diagram of a quadrupole entrance region having
no AC only sections with a multipole ion guide assembly extended
into the quadrupole rod assembly.
[0018] FIGS. 5a and 5b are mass spectra of singly charged ions of
Hexatyrosines. FIG. 5b shows the improved results acquired the ion
guide entrance lens configuration of the present invention, as
opposed to the results obtained from the prior art assembly which
is shown in FIG. 5a.
[0019] FIG. 6 is a diagram of a multipole ion guide configured such
that the ion guide exit lens is the entrance endcap of a three
dimensional ion trap mass analyzer.
[0020] FIG. 7 is a diagram of a multipole ion guide configured such
that the ion guide and its exit lens extends into the counter bore
of a three dimensional ion trap endcap lens.
DESCRIPTION OF THE INVENTION
[0021] A preferred embodiment of the invention is shown in FIG. 1.
A multipole ion guide is configured with a small radial diameter
such that the ion guide and a surrounding hat shaped electrostatic
exit lens element and insulator can fit within a larger multipole
ion guide, in this case illustrated as a quadrupole mass analyzer.
The hat shaped exit lens is surrounded by an electrically
insulating material to prevent the exit lens from contacting and
electrically shorting to the larger multipole ion guide rods. Ions
exiting the smaller ion guide through its exit lens are focused to
the centerline of the larger ion guide and efficiently trapped even
at low ion kinetic energies. The multipole ion guide with reduced
radial dimensions produces a very small diameter ion beam which
enters the larger ion guide close to the centerline. Ions can exit
the small ion guide at very low kinetic energies relative to the
offset potential of the larger ion guide and are trapped in the
radial direction by the RF of the large ion guide. Ions whose m/z
values fall within the stability window set by the potentials
applied to the larger multipole ion guide have trajectories which
remain close to the centerline. Operation with the configuration
shown in FIG. 1 results in high ion transport efficiencies from the
smaller ion guide into the larger diameter ion guide even for low
ion kinetic energies. The ability to efficiently transfer a low
energy ion beam into a quadrupole mass analyzer with reduced m/z
discrimination improves mass analysis performance. Significant
improvements in sensitivity and resolution have been achieved with
the configuration shown in FIG. 1 when compared with ion transfer
through electrostatic lenses mounted external to the quadrupole
rods. In the preferred embodiment shown, ions which are transferred
from the smaller ion guide through the exit lens are already inside
the quadrupole mass analyzer rod assembly close to the centerline
with a minimum angular divergence. The effective radial trapping
efficiency of the quadrupole is high for ion m/z values which fall
within the stability window set by the potentials applied to the
quadrupole rods.
[0022] FIG. 1 illustrates one embodiment for the vacuum ion optics
region of an API source interfaced to a quadrupole mass analyzer.
The API source can be but is not limited to an Electrospray (ES),
Atmospheric Pressure Chemical Ionization (APCI) or an Inductively
Coupled Plasma (ICP) source. Ions produced in the API source enter
vacuum through orifice 1 in capillary tube 2.
[0023] The ions exit capillary 2 at exit end 4 and enter the first
vacuum pumping stage 3. A portion of the ions pass through orifice
20 of skimmer 5 and enter multipole ion guide assembly 7 at its
entrance 15. Multipole ion guide 7, as illustrated, extends
continuously into multiple vacuum stages. This multiple vacuum
stage multipole ion guide configuration efficiently transports ions
passing through skimmer 5 orifice 20 into quadrupole mass analyzer
14 located in the fourth vacuum pumping stage 9. Multipole ion
guide 7, as illustrated, is configured as a hexapole with rods 16,
but could also be configured as a quadrupole or as a multipole ion
guide with more than six poles. When AC only voltage with a common
DC offset voltage is applied to multipole ion guide 7, a broad
range of m/z values fall within the ion guide stability region and
are transmitted from entrance 15 in the second vacuum pumping stage
6 to exit end 21 which is located in the third vacuum pumping stage
8 surrounded by vacuum housing 22. In the embodiment shown, the
neutral gas pressure at the entrance 15 of ion guide 7 is high
enough to cause collisional damping of the ion translational
energies for those ions trapped by the AC or RF only field within
ion guide 7. This collisional damping of ion kinetic energies
effectively reduces the ion energy spread. Typically, ion beams
with energy spreads of less than +/-0.4 electron volts have been
achieved for all m/z values transmitted, with the ion guide 7
configuration shown in FIG. 1.
[0024] The neutral gas is pumped away along the length of ion guide
7 through progressive vacuum stages 6, 8 and 9. Ions exiting ion
guide 7 at exit lens 10 orifice 13 typically enter a background
pressure in the 10.sup.-5 or 10.sup.-6 torr range or lower. The
first vacuum stage 3 is typically evacuated by a rotary vacuum pump
which maintains the background pressure in the range from 0.2 to 3
torr. Vacuum stage 6 background pressure can range from less than 1
millitorr to over 180 millitorr depending on the vacuum pump
pumping speed and vacuum stage 8 generally is maintained in the
10.sup.-4 to 10.sup.-5 torr range. Vacuum stage 6 is separated from
vacuum stage 8 by partition 23. Vacuum stage 8 is separated from
vacuum stage 9 by partition 18 and ion guide exit lens 10. In the
embodiment shown in FIG. 1 the average ion energy is set by the
offset potential of ion guide 7 due to neutral gas collisional
energy damping as the ions traverse the ion guide 7 length. Ions
leaving exit end 21 of ion guide 7 pass through orifice 13 of the
hat shaped exit lens 10 and into quadrupole 14 located in vacuum
stage 9. For positive polarity ions, multipole ion guide 7 exit
lens 10 voltage is set lower than the ion guide 7 offset potential
to draw the ions out of ion guide 7 and focus them to the
centerline of quadrupole mass analyzer 14. For example the ion
guide 7 offset potential may be set at 0.5 volts and the ion guide
exit lens 10 potential set at -5.0 volts to allow ion transfer with
focusing into quadrupole 14. Voltage settings for negative ion
transmission should have reverse polarities. Rods 17 of quadrupole
assembly 14 are shown in cross section with the front two rods or
poles 17 removed. Each quadrupole rod 17 has an AC only entrance
end 12 or Brubaker lens attached. The offset or common DC potential
applied to the AC only sections is set relative to the applied exit
lens 10 voltage and the ion guide 7 offset potential to focus the
ions exiting ion guide 7 to an optimal position along the
quadrupole centerline. The AC component applied to the AC only
sections 12 aids in moving ions which fall within the quadrupole
stability region toward the centerline before entering the
analytical portion of quadrupole mass analyzer 14. Ceramic
insulator 11 prevents contact between exit lens 10 and poles 12 or
vacuum partition 18 during operation.
[0025] Schematics of the embodiment of the invention shown in FIG.
1 are given in FIGS. 2 and 3 for clarity. In FIG. 2, poles 42 of
ion guide exit end 44 of multipole ion guide 30 are surrounded by
hat shaped exit lens 31 which forms a vacuum partition with
insulator 32 and vacuum chamber partition 33 between vacuum stages
37 and 40. Exit lens face 36 is located even with or just inside
the plane set by the face 45 of quadrupole rods 46 RF sections 43.
A cross sectional view looking down the centerline of multipole ion
guide 30 is shown in FIG. 3. Quadrupole rod 46 RF sections 43 are
positioned around ion guide exit lens 31, hexapole rod assembly 42
of multipole guide 30 and insulator 32. Insulator 32 surrounds exit
lens tube section 47 preventing multipole ion guide 30 and exit
lens 31 from coming electrically contacting quadrupole rod RF
sections 43. In this embodiment, the ion guide 30 centerline is
approximately aligned with quadrupole centerline 41. In practice it
has been found that the ion guide and quadrupole mass analyzer
centerline alignment is not critical to achieve efficient ion
transmission into quadrupole 35.
[0026] Ions 34 traversing ion guide 30 having m/z values falling
within the multipole ion guide operating stability m/z range are
trapped radially by the AC and DC voltages applied to guide rods 42
but are free to move in the axial direction. Ions exiting ion guide
30 at exit end 44 pass through exit lens 31 orifice 38 and into
quadrupole rod assembly 35. Ions 34 are initially focused to
quadrupole 35 centerline 41 by setting the relative potentials of
the DC offset of ion guide 30, and exit lens 31 and the DC offset
potential of quadrupole 35 AC only section 43. Ions exiting ion
guide 30 along centerline 41, where the net quadrupole 35 AC field
strength is low, are initially focused toward quadrupole centerline
41 by what is effectively a three element electrostatic lens
assembly. The RF applied to the quadrupole RF only section 43
continues to move ions close to centerline 41 whose m/z values are
within the stability window. Ion beam 34 exiting exit lens orifice
38 can be focused to a point along the centerline downstream from
orifice 38 where the quadrupole 35 RF field can prevent the beam
from diverging after the focal point. Ions exiting through exit
orifice 38 are initially shielded from the quadrupole RF fringing
field defocusing effects by exit lens face 36. As ions move
downstream from orifice 38, they are well within the quadrupole rod
assembly 35 as the quadrupole RF and DC fields begin to drive the
ion trajectories in the radial direction. The embodiment shown in
FIGS. 1 and 2 effectively reduces the negative effect of the
quadrupole fringing fields for ions transmitted into quadrupole
mass analyzer 14 or 35.
[0027] A wide range of ion beam average ion energies can be
efficiently transmitted into quadrupole 14 or 35 with the
embodiment shown in FIGS. 1, 2 and 3. Ions with energies as low as
0.1 volts relative to the quadrupole 35 offset voltage have been
efficiently transmitted from ion guide 30 into quadrupole ion guide
35. Typically, ion energies of 0.5 to 2.0 volts will be set to
achieve maximum sensitivity and resolution with quadrupole 35. It
was found that operating with the configuration shown in FIG. 1,
the mass resolving power set for quadrupole 14 could be increased
over a substantial range with little reduction in ion signal
amplitude. The exit lens 31 voltage can be set from a few volts
below the offset voltage of ion guide 30 down to 100 volts below
said offset voltage depending on the focusing conditions desired.
Quadrupole 35 may or may not include AC only pole pieces which form
an AC only entrance section 43. The embodiment of the invention
shown in FIGS. 1 and 2 can efficiently transmit ions into a
quadrupole mass analyzer which incorporates or does not incorporate
AC only rod sections at the entrance of the quadrupole. FIG. 4 is a
schematic of a multipole ion guide 100 with the rods 101 and hat
shaped exit lens 102 extending into quadrupole 103 with rod
assembly 104. Insulator 105 surrounds nose portion 106 of exit lens
102 and forms a vacuum seal with vacuum partition 107. Ion beam 108
traversing multipole ion guide 100 exits through exit aperture 109
into quadrupole 103. Multipole ion guide 100 and exit lens face 110
effectively focus the ion beam into quadrupole 103 minimizing the
defocusing effects of the quadrupole fringing fields.
[0028] When operating with the ion transfer optics assembly shown
in FIGS. 1, 2, 3 and 4, higher resolution and higher sensitivity
can be achieved when compared to electrostatic ion transfer and
focusing lenses and ion guides which do not extend into the
downstream ion guide. FIG. 5b shows a mass spectrum of singly
charged protonated Hexatyrosine electrosprayed into a quadrupole
mass analyzer with the ion transfer optics shown in FIG. 1. FIG. 5a
is a mass spectrum of singly charged protonated Hexatyrosine
electrosprayed using the same Electrospray ion source and
quadrupole mass analyzer as was used in acquiring the data in FIG.
5b. An electrostatic lens assembly with no multipole ion guide was
used to transfer ions from the Electrospray ion source into the
quadrupole mass analyzer for the data acquired in FIG. 5a. The
amplitude of the partially resolved protonated monoisotopic singly
charged peak 120 in FIG. 5a has an intensity of 9338. The
unresolved isotope peak 122 at Full Width Half Mass (FWHM) is 1.73
Daltons wide. Note that the unresolved C.sub.13 isotope peak 121 in
FIG. 5a does not have the correct theoretical relative intensity
compared to the monoisotopic peak. This relative amplitude error
was due to unresolved peak blending. Monoisotopic peak 123 in FIG.
5b has an amplitude of 93101, nearly a factor of 10 higher than
that of peak 120. The FWHM of peak 123 and 124 is 0.29 Daltons wide
and the relative amplitudes of isotope peaks 123 and 124 is close
to the predicted theoretical value. The resolution achieved by the
quadrupole analyzer for the peaks shown in FIG. 5b was actually
higher than that recorded. The recorded resolution was reduced by
the data system limit in data point density of 20 points per
Dalton. Comparing the results in FIGS. 5a and 5b, the multipole ion
guide ion transfer optics shown in FIGS. 1, 2 and 3 improves the
sensitivity and the resolution attainable with a quadrupole mass
analyzer when compared with that which can be achieved with
conventional electrostatic lens transfer ion optics assembly. As
shown in the FIGS. 5a and 5b, the increase in resolution and
sensitivity is considerable. Higher resolution is achievable due to
the lower ion translational energies which can be transferred into
a quadrupole mass analyzer with the embodiment shown in FIGS. 1, 2
and 3.
[0029] Ion guide transfer optics from API sources to quadrupole
mass analyzers are currently commercially available. One such
configuration is, for example, described by Douglas and French in
U.S. Pat. No. 4,963,736. Transferring ions from one ion guide to
another sequentially, where one ion guide does not extend into the
bore of the next, is not as efficient, particularly for ions with
low translational energies, as that which can be achieved by
operating with the embodiment shown in FIG. 1. Ions are more
exposed to the trajectory disrupting and rejection effects of
fringing fields when they are transferred from an upstream ion
guide which abuts to a downstream ion guide with an electrostatic
lens or lenses in between each ion guide. These ions transferred
through sequential but separated multipole ion guides are exposed
to more pronounced fringing fields when they leave the upstream
multipole ion guide and when they attempt to enter the downstream
multipole ion guide than they experience in a nested multipole ion
guide configuration.
[0030] System performance is enhanced when the upstream ion guide
begins just at the face or extends into the downstream ion guide to
facilitate ion transfer. When this configuration is used to
transfer ions into the downstream quadrupole mass analyzer, the
resolution performance of the downstream quadrupole ion guide can
be increased with little or no decrease in sensitivity. For the
configuration shown in FIG. 2 or 4, the ion guide 30 or 100 can be
used to trap and hold ions by raising the voltage on exit lens 31
or 102. The AC and DC voltages applied to ion guide 30 can also be
set to limit the m/z range of ions which can traverse the ion guide
length either during trapping or in the ion transmission mode.
Generally, higher m/z selection resolving power can be achieved
with quadrupoles compared to hexapoles or octapole. With ion guide
30 configured as quadrupole, narrow m/z range selection can be
achieved prior to the downstream multipole ion guide or additional
quadrupole mass analyzer 35. If the background pressure in
multipole ion guide 35 is increased or the neutral gas pressure is
increased along a portion of the length of ion guide 30, CID
fragmentation can occur within multipole ion guide 30 or 35. CID
fragmentation within ion guide 30 can be achieved by applying an AC
excitation voltage to rods 42 of multipole ion guide 30 whose
frequency or frequencies corresponds to the resonant excitation
frequencies of the ions selected for fragmentation. Ion m/z values
whose trajectories are accelerated in the radial direction by the
resonant excitation frequencies, collide with background gas which
leads to Collisionally Induced Dissociation within multipole ion
guide 30. In this manner, multipole ion guide 30 can be operated in
a mass selective and CID fragmentation mode and even a trapping
mode prior to transferring ions to the downstream multipole ion
guide or mass analyzer 35. Consequently, ion guide 30 and 35
combined can be used to achieve MS/MS analysis provided the
background pressure in ion guide 30 is sufficient to cause CID
fragmentation of ions as they traverse the ion guide length.
[0031] In another embodiment, ion guide 30 can be configured as the
first analytical quadrupole and ion guide 35 as the CID AC only ion
guide in a mass analyzer with MS/MS capability. In this embodiment,
it would be required to set the background pressure in multipole
ion guide 35 sufficiently high to enable CID fragmentation of ions
accelerated into multipole ion guide 35. The embodiment of the
invention as shown in FIGS. 1, 2 and 4 can also be configured such
that both ion guides 30 and 35 are located in the same vacuum
pumping stage. This would typically be the case in a multipole ion
guide configuration where m/z selection is followed by a CID
section followed by m/z selection. Configured with a chamber that
surrounds the second multipole ion guide, the local background
pressure in the second multipole ion guide can be maintained at a
level to achieve efficient CID conditions. In commercially
available "triple quadrupoles", generally all three ion guides of
an MS/MS analyzer reside in the same vacuum stage.
[0032] An alternative embodiment of the invention can be configured
to improve the transmission efficiency of ions from a multipole ion
guide into a three dimensional quadrupole ion trap mass analyzer
and allow the recapture of ions ejected from the three dimensional
ion trap. This alternative embodiment of the invention is shown in
FIG. 6. Multipole ion guide 50 is configured to have a smaller
radial dimension and is positioned to extend into counterbore 65 in
three dimensional quadrupole ion trap 62 endcap or endplate 64. In
the embodiment shown, multipole ion guide 50 extends continuously
into multiple vacuum stages. Ion guide 50 could also be configured
to reside entirely in one vacuum pumping stage. Alternatively, the
three dimensional ion trap 62 endcap or endplate 64 can be
configured as a vacuum stage partition with multipole ion guide 50
and ion trap 62 residing in different vacuum pumping stages. Ion
guide 50 can also be configured to reside in the same vacuum
pumping stage as ion trap 62. Commercially available three
dimensional ion traps generally have ring and endplate electrode
configurations whose dimensions differ from that which would
produce purely quadrupole fields. The distorted ion trap electrode
shapes create non-quadrupole electric field components within the
ion trap. For convenience in this discussion such three dimensional
"quadrupole" ion traps will be generically referred to as three
dimension ion traps.
[0033] Referring to FIG. 6, ion guide 50 extends continuously from
vacuum stage 53 into vacuum stage 60 through the vacuum chamber
partition 52 and insulator 54. Voltages are applied to multipole
ion guide 50 poles 51 to establish stable ion transmission for
large or narrow ranges of m/z or to trap ions in the multipole ion
guide before transferring said ions into the three dimensional ion
trap 62. In the embodiment of the invention shown in FIG. 6, ion
trap 62 entrance end cap 64 is bored from the outside surface with
bore 65 (also referred to herein as a "counterbore") terminating in
ion trap entrance aperture 57. Exit end 59 of ion guide 50 is
positioned to extend into counterbore 65 of entrance endcap 64.
Exit end 66 of ion guide rods 51 are positioned in bored hole 65
such that the bottom of bore 65 with aperture 57 serves as the exit
lens for ion guide 50. Ions exiting ion guide 50 pass through the
ion trap entrance aperture 57 and move into ion trap 62 during a
portion of the AC waveform cycle resulting from the AC voltage
applied to ring electrode 56. The AC or RF voltage applied to ion
trap ring electrode 56 during operation creates varying electric
fields at entrance aperture 57 which enable ions to enter region 61
of ion trap 62, reject ions attempting to enter or modify the ion
trajectories in a manner that will prevent the effective trapping
of the ions by ion trap 62. The ion polarity, ion kinetic energy,
the RF amplitude phase of the electric field and the ion trap
endcap potentials will determine whether an ion can enter ion trap
62 and be successfully trapped. The embodiment shown in FIG. 6
allows a portion of the ions which are rejected from ion trap 62
during the ion trap fill period to be recaptured in multipole ion
guide 50. These ions retrapped by multipole ion guide 50 can
subsequently be reinjected into ion trap 62. During the scan or
mass analysis step of ion trap 62, ions must be rejected from the
ion trap 62 to be detected. To detect ions trapped in ion trap 62,
the ions must be driven into an unstable trajectory so they will be
ejected from the ion trap through the endcap orifices 57 and 67.
Ions exiting through exit aperture 67 in exit endcap 58 are
detected by a detector appropriately positioned to detect these
ions. Ions which are simultaneously ejected through entrance
aperture 57 of endcap 64 can be recaptured in multipole ion guide
50. All or a portion of these recaptured ions can then be
transferred back into region 61 of ion trap 62 during the next
appropriate fill cycle. Ions which are retrapped in multipole ion
guide 50 are not lost during a fill and scan cycle. This method
where ions ejected through or rejected from ion trap entrance
aperture 57 are retrapped in multipole ion guide 50 can be used to
improve overall duty cycle and hence sensitivity of mass analysis
with three dimensional ion traps.
[0034] Ion trap 62 with entrance end cap 64, exit end cap 58 and
ring electrode 56 can be operated as a mass analyzer or as an ion
trap with ion pulsing into a time-of-flight mass analyzer. The
invention configures aperture 57 with the dual role of ion guide
exit lens and ion trap endplate entrance aperture. The focusing of
the ion beam entering the ion trap is established by optimizing the
relative DC end caps 64 and 58 voltages with ion guide 50 DC offset
potential and the ion kinetic energy. Low energy ions can be
efficiently transferred into the ion trap, effectively increasing
the trapping efficiency of these transferred ions particularly for
ions of higher m/z values. Increased ion trap 62 trapping
efficiency directly results in higher sensitivity. Higher dynamic
range can be achieved in the trap if multipole ion guide 50 is
operated in a manner which reduces the m/z range of ions which are
transferred to ion trap 62. Unwanted ion m/z values such as low m/z
contamination ions can be prevented from filling the trap while the
ions of interest located in a different portion of the m/z scale
can be transmitted into ion trap 62 for mass analysis. The offset
potential of ion guide 50 can be lowered relative to the endplate
64 voltage, trapping ions in the ion guide during the time period
where ion trap 62 is conducting a mass analysis. When ion trap 62
has completed its analysis, the multipole ion guide 50 offset
potential can be increased relative to the endplate 64 voltage,
allowing ions to pass from multipole ion guide 50 into three
dimensional ion trap 62. For example if the kinetic energy of
positive ions is 2 volts, the DC potential applied to endcap 64
must be greater than 2 volts higher than the ion guide 50 offset
potential to trap the positive ions within multipole ion guide
50.
[0035] Alternatively, three dimensional ion trap 50 can be operated
such that ion trap 62 RF, resonant AC potentials and end cap DC
potentials are set relative to the ion guide 50 DC offset potential
to allow ions to pass from volume 61 of ion trap 62 into multipole
ion guide 50. In this manner, a portion of the ions rejected from
ion trap 62, for example in an MS/MS experiment, can be recaptured
by multipole ion guide 50 and transferred back into ion trap 62 for
a subsequent analysis. This method of transferring ions back into
multipole ion guide 50 may also be employed to achieve higher
energy CID conditions by accelerating selected ions trapped in ion
trap 62 back into multipole ion guide 50. Ions which re-enter
multipole ion guide 50 in reverse through exit end 59 travel toward
entrance end 63 where they can collide with neutral gas molecules
in the increased background gas pressure region near ion guide
entrance end 63. As shown in FIG. 1, if the ion guide entrance were
positioned downstream of a skimmer in an API source, the pressure
at the ion guide entrance can be in excess of 10.sup.-2 torr. Ions
with sufficient kinetic energy colliding with neutral gas molecules
in the elevated pressure regions near entrance 63 of ion guide 50
would experience Collisional Induced Dissociation. The resulting
fragment ions trapped in multipole ion guide 50 could then be
transferred back into ion trap 62 for analysis. The transfer of
ions from ion trap 62 to multipole ion guide 50 can also be a means
of saving ions if ion trap 62 is overloaded and ions must be
released to avoid space charge effects during mass analysis.
[0036] An alternative embodiment of the invention is diagrammed in
FIG. 7. In this embodiment, exit lens 78 has been positioned
between ion guide 70 exit end 81 and ion trap 83 end cap aperture
84. Hat shaped exit lens 78 is positioned to extend into an ion
trap 83 end cap counterbore 79 such that exit lens 78 aperture 87
is axially aligned with end cap aperture 84 and the axis of
multipole ion guide 70. Ions 77 traveling through multipole ion
guide 70 exit through exit lens 78 at aperture 87 and are focused
through endplate 80 aperture 84 into the ion trap 83 volume 86. Ion
trap 83, consisting of endcap electrodes 85 and 80 and ring
electrode 82, traps ions transferred from multipole ion guide 70
for mass analysis and/or fragmentation. Ion guide 70 is shown to
extend continuously from vacuum stage 73 into vacuum stage 74
through vacuum partition 76 and insulator 75. Alternatively,
multipole ion guide 70 and ion trap 83 can be configured to reside
in separate vacuum stages or in a single vacuum stage.
[0037] The addition of exit lens 78 allows for improved focusing or
shaping of the ion beam consisting of ions either leaving multipole
ion guide 70 at exit end 81 or ions re-entering multipole ion guide
70 from ion trap 83 in the reverse direction through multipole ion
guide exit end 81. The ion beam exiting ion guide 70 can be focused
or shaped by setting the appropriate relative voltages on exit lens
78, ion trap endcap electrodes 80 and 85, ring electrode (i.e.
lens) 82 and the multipole ion guide rods 72. The addition of lens
78 allows flexibility in ion beam shaping with the appropriate
voltage settings yet retains an efficient means of transferring
ions from multipole ion guide 70 into an ion trap 83. By
positioning end 81 of ion guide 70 inside the counterbore 79 of end
cap 80 close to aperture 84, lower ion energies can be delivered to
the ion trap with higher efficiencies. This results in higher
sensitivity and more uniform trapping efficiencies over a larger
range of m/z values. The voltage applied to hat shaped lens 78 can
also be adjusted to trap ions in multipole ion guide 70 independent
from the potentials applied to ion trap endcaps 80 and 85. Hence
three dimensional ion trap trapping, ion fragmentation and mass
analysis functions which involve changing AC and/or DC potentials
on endcaps 80 and 85, can be run independently from the potentials
applied to ion guide exit lens 78 and ion guide 70. The various ion
transfer functions from ion guide 70 to ion trap 83 and from ion
trap 83 to ion guide 70 described for the embodiment shown in FIG.
6 can also be realized with the embodiment shown in FIG. 7. The
embodiment in FIG. 7 allows additional flexibility in relative
voltage settings between the ion trap 83 and ion guide 70. This is
due to the ability to set the potential on exit lens 78 separately
from the potentials set on ion trap endplates 80 and 85 and ring
electrode 82 and ion guide rods 72.
[0038] Having described this invention with regard to specific
embodiments, it is to be understood that the description is not
meant as a limitation since further modifications or variations
thereon may suggest themselves or may be apparent to those skilled
in the art. It is intended that the present application cover all
such modifications and variations as fall within the scope of the
appended claims.
* * * * *