U.S. patent application number 12/273497 was filed with the patent office on 2009-03-12 for high throughput quadrupolar ion trap.
Invention is credited to Viatcheslav V. Kovtoun.
Application Number | 20090065691 12/273497 |
Document ID | / |
Family ID | 38924014 |
Filed Date | 2009-03-12 |
United States Patent
Application |
20090065691 |
Kind Code |
A1 |
Kovtoun; Viatcheslav V. |
March 12, 2009 |
High throughput quadrupolar ion trap
Abstract
A method and apparatus are provided for operating a linear ion
trap. A linear ion trap configuration is provided that allows for
increased versatility in functions compared to a conventional
three-sectioned linear ion trap. In operation, the linear ion trap
provides multiple segments, the segments spatially portioning an
initial population of ions into at least a first and a second ion
population. Each segment is effectively independent and ions
corresponding to the first ion population are able to be
manipulated independently from ions corresponding to ions
corresponding to the second ion population; the ions having been
generated by an ion source under the same conditions. The ions can
then be expelled from the ion trap.
Inventors: |
Kovtoun; Viatcheslav V.;
(Santa Clara, CA) |
Correspondence
Address: |
THERMO FINNIGAN LLC
355 RIVER OAKS PARKWAY
SAN JOSE
CA
95134
US
|
Family ID: |
38924014 |
Appl. No.: |
12/273497 |
Filed: |
November 18, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11485055 |
Jul 11, 2006 |
7456389 |
|
|
12273497 |
|
|
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Current U.S.
Class: |
250/282 |
Current CPC
Class: |
H01J 49/427 20130101;
H01J 49/423 20130101; H01J 49/4225 20130101; H01J 49/4295
20130101 |
Class at
Publication: |
250/282 |
International
Class: |
B01D 59/44 20060101
B01D059/44 |
Claims
1. A method for operating a linear ion trap, the method comprising:
a. trapping an initial population of ions in the ion trap; b.
spatially partitioning the initial population of ions into at least
two ion populations, including at least a first and a second ion
population; c. manipulating at least a portion of the ions
corresponding to the first ion population independently from at
least a portion of the ions corresponding to the second ion
population, prior to expelling the ions from the linear ion trap.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of and claims the
priority benefit under 35 U.S.C. .sctn. 120 of U.S. patent
application Ser. No. 11/485,055 entitled "High Throughput
Quadrupolar Ion Trap" and filed Jul. 11, 2006, the entire
disclosure of which is incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The disclosed embodiments of the present invention relates
generally to apparatus and methods for operating a linear ion
trap.
BACKGROUND OF THE INVENTION
[0003] Linear ion traps are finding many applications in many areas
of mass spectrometry. These applications typically demand
facilitation of tandem mass spectrometry (MS/MS) techniques,
measurement of high mass-to-charge (m/z) ratios, large dynamic
range, precision, high quality data and throughput. This is
particularly the case for biological or biochemical applications.
In the proteomic field for example, where analytical instruments
are required to identify both small and large molecules and to
determine molecular structure, and required to do so quickly whilst
providing high quality results. These instruments are required to
identify thousands of peptides covering a large dynamic range from
a single sample. Peptide identifications based on tandem mass
spectrometry or MS/MS fragmentation of the peptides are also
required. In addition, this particular field of technology
typically dictates a high level of automation to accommodate a vast
amount of data in minimal time. For these reasons new apparatus and
methods which allow linear ion traps to respond to such demands are
therefore sought.
SUMMARY
[0004] In accordance with the present invention, an apparatus and a
method are disclosed for providing increased versatility in
functions compared to a conventional three-sectioned linear ion
trap. A linear ion trap is provided which is spatially
partitionable into at least two segments, including a first and a
second segment. Each segment is effectively independent has the
benefit of manipulating ions stored in these segments
independently, the ions having been generated by an ion source
under the same conditions. The ions can then be expelled from the
ion trap.
[0005] Manipulation of the ions can be carried out simultaneously
in two or more segments. Manipulation can take the form of
fragmentation, isolation, or any other process that influences the
behavior of ions.
[0006] The linear ion trap can have a plurality of electrodes, each
electrode being divided into sections. Each section can comprise a
three-section electrode assembly.
[0007] This arrangement is advantageous as it allows for tandem
(MS/MS) mass spectrometry experimentation to be performed rapidly
with only one fill from the ion source being required. Moreover,
dividing the precursor ions into increasingly narrow ranges of m/z
values allow the ion capacity of the trapping regions to be
optimized within their space charge limits.
[0008] In one aspect of the invention, the initial ion population
can be spatially partitioned, for example my mass to charge ratio,
before entering the linear ion trap. In this instance, the linear
ion trap operates to maintain the spatial partitioning of the
initial population within the linear ion trap by partitioning the
initial population.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] For a better understanding of the nature and objects of the
invention, reference should be made to the following detailed
description, taken in conjunction with the accompanying drawings,
in which:
[0010] FIG. 1 shows a mass spectrometer configuration including a
linear ion trap.
[0011] FIG. 2 is a perspective view illustrating the basic design
of a two-dimensional linear ion trap.
[0012] FIG. 3 shows a mass spectrometer configuration including a
linear ion trap according to an aspect of the invention.
[0013] FIGS. 4a, 4b and 4c are schematic illustrations showing how
a linear ion trap can be configured to provide segments according
to the invention.
[0014] FIG. 5 is a flow diagram illustrating a method according to
an aspect of the invention.
[0015] FIGS. 6a to 6d illustrates how one way in which the
partitioning process can provide for segmentation of the ion
population.
[0016] FIG. 7 illustrates another way in which the partitioning
process can provide for segmentation of the ion population.
[0017] FIG. 8 is a schematic illustration showing a segmented
linear ion trap configuration according to yet another aspect of
the invention.
[0018] FIG. 9 is a flow diagram illustrating a method according to
another aspect of the invention.
[0019] Like reference numerals refer to corresponding parts
throughout the several views of the drawings.
DETAILED DESCRIPTION OF EMBODIMENTS
[0020] FIG. 1 illustrates a typical linear ion trap mass
spectrometer configuration 100. The configuration 100 includes a
suitable ion source 110 such as an electrospray ion source in a
chamber 120. Ions formed in the chamber 120 are conducted to a
second chamber 130 via a heated capillary 140 and directed by the
lens arrangement 150 into a third chamber 160. The ions entering
the third chamber 160 are guided by quadrupole ion guide 170 and
directed towards a two-dimensional (linear) quadrupolar ion trap
180, housed in a vacuum chamber 190. Ions generated by the ion
source 110 proceed directly or indirectly to the ion trap 180.
[0021] Quadrupole ion traps use substantially quadrupole fields to
trap the ions. In pure quadrupole fields, the motion of the ions is
described mathematically by the solutions to a second order
differential equation called the Mathieu equation. Solutions can be
developed for a general case that applies to all radio frequency
(RF) and direct current (DC) quadrupole devices including both
two-dimensional and three-dimensional quadrupole ion traps. A two
dimensional quadrupole trap is described in U.S. Pat. No.
5,420,425, which is incorporated in its entirety by reference.
[0022] FIG. 2 illustrates a quadrupole electrode/rod structure of a
linear or two-dimensional (2D) quadrupole ion trap 200. The
quadrupole structure includes two sets of opposing electrodes
including rods that define an elongated internal volume having a
central axis along a z direction of a coordinate system. An X set
of opposing electrodes includes rods 215 and 220 arranged along the
x axis of the coordinate system, and a Y set of opposing electrodes
includes rods 205 and 210 arranged along the y axis of the
coordinate system. As illustrated, each of the rods 205, 210, 215,
220 is cut into a main or center section 230 and front and back
sections 235, 240.
[0023] The ions are radially contained by the RF quadrupole
trapping potentials applied to the X and Y electrode/rod sets under
the control of a controller 290. A Radio Frequency (RF) voltage is
applied to the rods with one phase applied to the X set, while the
opposite phase is applied to the Y set. This establishes a RF
quadrupole containment field in the x and y directions and will
cause ions to be trapped in these directions.
[0024] To constrain ions axially (in the z direction), the
controller 290 can be configured to apply or vary a DC voltage to
the electrodes in the center segment 230 that is different from
that in the front and back segments 235, 240. Thus a DC "potential
well" is formed in the z direction in addition to the radial
containment of the quadrupole field resulting in containment of
ions in all three dimensions.
[0025] An aperture 245 is defined in at least one of the center
sections 230 of one of the rods 205, 210, 215, 220. Through the
aperture 245, the controller 290 can further facilitate trapped
ions can be selectively expelled based on their mass-to-charge
ratios in a direction orthogonal to the central axis by causing an
additional AC dipolar electric field to be applied or varied in
this direction. In this example, the apertures and the applied
dipole electric field are on the X rod set. Other appropriate
methods may be used to cause the ions to be expelled, for example,
the ions may be ejected between the rods.
[0026] One method for obtaining a mass spectrum of the contained
ions is to change the trapping parameters so that trapped ions of
increasing values of mass-to-charge ratio become unstable.
Effectively, the kinetic energies of the ions are excited in a
manner that causes them to become unstable. These unstable ions
develop trajectories that exceed the boundaries of the trapping
structure and leave the quadrupolar field through an aperture or
series of apertures in the electrode structure.
[0027] The sequentially expelled ions typically strike a dynode 195
and secondary particles emanating therefrom are emitted to the
subsequent elements of the detector arrangement. The placement and
type of detector arrangement may vary, the detector arrangement for
example extending along the length of the ion trap. Throughout this
description, the dynode is considered to be part of the detector
arrangement, the other elements being elements such as
electromultipliers, pre-amplifiers, and other such devices.
[0028] It should be recognized that different arrangements for the
mass analyzing system may be used, as is well known by the art. For
example, analyzing device may be configured such that ions are
expelled axially from the ion trap rather than radially. The
available axial direction could be used to couple the linear ion
trap to another mass analyzer such as a Fourier Transform RF
Quadrupole Analyzer, Time of Flight Analyzer, three-dimensional ion
trap, Orbitrap.TM. or other type of mass analyzer in a hybrid
configuration.
[0029] FIG. 3 shows a mass spectrometer configuration 300 including
a linear ion trap 380 according to an aspect of the invention. It
can be seen that this configuration exhibits all the features of
the configuration shown and described in FIG. 1, with the exception
of the linear ion trap 380 and the dynodes 395. In this
configuration, the linear ion trap 380 comprises multiple segments,
and there is a plurality of dynodes 395 disposed adjacent each
discrete segment. In this particular configuration, dynodes 395 are
disposed on either side of the multi-segmented linear ion trap,
enabling substantially all ions that are expelled from the ion trap
to be detected. It will appreciated that the number of dynodes, and
their disposition is not limited to that illustrated, and that
dynodes may, as in FIG. 1, be disposed on one side of the linear
ion trap only, be disposed adjacent every other segment, or include
a dynode disposed axially for example. In this respect, it should
be noted that FIG. 3 is not necessarily representative of the
direction in which the ions are expelled from the ion trap
(typically being ejected and/or extracted), but merely of the fact
that they are expelled, whether that be axially and/or radially.
The trajectory of the expulsion will be dependent amongst other
things upon the configuration adopted.
[0030] In operation, the linear ion trap configuration of FIG. 3
provides for the simultaneous expulsion of ions from the
multi-segmented linear ion trap 380, the expelled ions being
detected by a plurality of dynodes 395. In the event that ions are
not expelled from all segments of the multi-sectioned linear ion
trap 380 simultaneously, but that groups of at least two segments
have their ions expelled at any one time, the results of the second
and other subsequent expulsions can be summed with those of the
first expulsion to produce a single mass spectrum.
[0031] The use of a multi-segmented quadrupolar ion trap allows for
increased versatility in functionality compared to that of a
conventional three-sectioned linear ion trap as illustrated in FIG.
1, and described in detail in U.S. Pat. No. 5,420,425. Spatially
partitioning the linear ion trap into multiple quasi-independent
segments provides an architecture facilitating the ions stored in
these segments to be manipulated independently, and allows the
processing of ions in separate segments to be carried out
simultaneously. In addition, it allows predetermined populations of
ions that emanate from the same source under the same conditions,
at around the same time, to be manipulated, detected or otherwise
processed or analyzed simultaneously. Each ion population can also
be independently manipulated prior to subsequent detection,
processing or analysis.
[0032] One application where improvement in quality of mass
spectrum data may be achieved is optimization of scanning out an
extended mass range. Another application where improvement in
quality of mass spectrum data may be achieved is when trying to
reduce the scan time for a given scan rate. A few of these
applications will be described in more detail later.
[0033] Two implementations of a linear ion trap according to the
invention are illustrated by FIGS. 4a, 4b and 4c. The linear ion
trap 380 is configurable to provide a plurality of (at least two)
substantially discrete trapping volumes or segments 410, each of
these segments 410 or combination of segments being electrically
isolated from one another when an electrical and/or magnetic
isolation mechanism is activated, and capable of acting in
combination as a continuous device when the segments are
"assembled" or the electrical isolation means has been deactivated.
The linear ion trap 380 enables an initial population of ions 420
as shown in FIG. 4a to be influenced or physically subdivided, such
that predetermined populations of ions may be spatially localized
in one or more segments 410 of the multi-segmented ion trap, as
illustrated in FIGS. 4b and 4c.
[0034] The multiple segments of the linear ion trap can be provided
by creating potential barriers which spatially divide the linear
ion trap 380. In one aspect of the invention, the segments can be
generated or activated by the activation of a corresponding
multipole rod assembly 430, such as a quadrupole rod assembly
including four rod electrodes. Each of the multiple rod assemblies
defining at least partially (that is, defining at least one end of)
a segment or trapping volume about an axis of the multi-segmented
linear ion trap. These multipole rod assemblies may comprise single
section or continuous rods, or include multi-sectioned rods. In
this trapping volume, ions can be radially and axially confined in
one or more of the sections by application of a combination of RF
and DC electric potentials to the multipole rod assemblies.
[0035] In one aspect of the invention, as illustrated in FIG. 4b,
the segments of the linear ion trap 380 are configured by
three-sectioned multipole rod assemblies 440 and 450. The first
three-sectioned multipole rod assembly 440 is capable in operation
of generating a trapping volume 410a confined primarily to the
centre section of the assembly 440. The second three-sectioned
multipole rod assembly 450 is capable in operation of generating a
trapping volume 410b confined primarily to the center section of
the assembly 450.
[0036] In another aspect of the invention, as illustrated in FIG.
4c, the segments of the linear ion trap 380 are once again
configured by three-sectioned multipole rod assemblies 460, 470 and
480. However, in this instance the third section of first
three-sectioned multipole rod assembly 460 also functions as the
first section of the second three-sectioned multipole rod assembly
470. Similarly, the third section of the second three-sectioned
multipole rod assembly 470 also functions as the first section of
the third three-sectioned multipole rod assembly 480. The
three-sectioned multipole rod assemblies effectively overlap, yet
in operation are capable of generating trapping volumes 410c, 410d
and 410e, more trapping volumes than in the configuration
illustrated in FIG. 4b.
[0037] The individual multipole rod assemblies are each supplied
with their own RF, DC and supplemental excitation voltages.
Generally, end sections will be configured to minimize fringing
field effects on ions entering or leaving the ion trap. Once the
ions have been trapped in the trap, the application of RF, DC
and/or supplemental voltage components can be used to influence the
trapped ions to distribute themselves along the length of the ion
trap in a predetermined manner. Modification of the RF, DC and/or
supplemental voltage components can then be further employed to
influence ions to move from one segment to another within the ion
trap, to vacate a segment of ions, or minimize coupling of ions
between adjacent segments.
[0038] In general, a control unit applies a corresponding set of RF
voltages to segments of the multi-segmented ion trap to generate an
RF multipole potential to confine ions radially in the trapping
volume about the axis of the linear ion trap. The control unit also
applies various DC offsets to the segments of the ion trap to trap
ions in any of or combination of the segments axially along the
trapping volume of the ion trap.
[0039] One or more rods of the multipole rod assemblies may be
provided with slots or apertures to enable ions to pass to the
multiple detector arrangements if so desired.
[0040] Expulsion of ions from the ion trap may be achieved by
applying a supplementary AC voltage across the relevant segment of
a pair of the rods causing ions in that particular segment to
resonate and leave the ion trap. Application of such an AC voltage
may affect ions in other segments, so compensation for this may be
required. This is due to the fact that the applied AC voltage will
have an affect not only on the ions within that particular segment,
but its fringing effects will couple to the ions in the adjacent
segment also.
[0041] A method for operating a linear ion trap according to one
aspect of the current invention is illustrated in FIGS. 5 and 6 by
a series of steps. The steps of the method may include trapping an
initial population of ions (420) in the multi-segmented linear ion
trap (step 510); spatially partitioning the initial ion population
(420) into at least two ion populations (step 520), including a
first population and a second population; and simultaneously
expelling ions corresponding to the first and second ion
populations from the multi-segmented linear ion trap (step 530).
Ions corresponding to the first and second ion populations include
ions from or derived from the first and second ion populations
respectively. At least a portion of the ions corresponding to the
first population can be subsequently detected by a first detector
arrangement, and at least a portion of the ions corresponding to
the second population of ions can be detected by a second detector
arrangement. In some instances the first and second detector
arrangements may share some elements. Alternatively they may be
discrete.
[0042] Optionally, as indicated by step 525, the ions in any of the
segments or combination of segments of the multi-segmented linear
ion trap may be manipulated if so desired, before they are
extracted and passed to the detector arrangement. Ions
corresponding to the first ion population may be manipulated
independently from those corresponding to the second ion
population, and simultaneously if so desired. Manipulation may take
the form of fragmentation, isolation, or any other such operation
or influence that ions typically respond to.
[0043] FIG. 6 illustrates a configuration in which each segment of
the multi-segmented linear ion trap 380 is provided by a
three-sectioned multipole electrode structure 610, 615, 620. As
illustrated, the expulsion of ions from the multi-segmented linear
ion trap 380 is carried out in a direction that is substantially
orthogonal to the axial direction 625. Alternatively, the
extraction of ions may be carried out in a combination of
substantially parallel to and orthogonal to the axial direction
625.
[0044] One manner in which the ion population can be spatially
partitioned is according to mass to charge ratio (m/z) or m/z
range. For example, the third segment 620 of the multi-segmented
linear ion trap 380 can be configured to trap ion in the mass range
M.sub.range1, this range including masses below mass m.sub.1. The
second segment 615 of the multi-segmented linear ion trap 380 can
be configured to trap ion in the mass range M.sub.range2, which is
for masses between masses m.sub.1 and m.sub.2. The first segment
610 can be configured to trap ions in the mass range M.sub.range3
between masses m.sub.2 and m.sub.3, where
m.sub.3>m.sub.2>m.sub.1.
[0045] There are several ways in which this may be achieved, one of
which is by applying an axial excitation AC voltage that varies
axially. This essentially enables ions to travel along the trap
until they reach a segment where no excitation is applied that
affects the range of m/z accommodated by the segment, there they
lose energy in collisions and stay in this segment.
[0046] For example, the initial ion population 605 comprises
M.sub.range1+M.sub.range2+M.sub.range3. These ions enter the
multi-segmented ion trap at the left hand side of the figure as
viewed by the reader. The first segment 610 captures incoming ions
(preferably, a continuous stream) and, at the same time excites
ions within the second mass range M.sub.range2 and the third mass
range M.sub.range1 for example the m/z range (150-200 Th) and m/z
(200-2000) to overcome the potential barrier separating the first
and the second segments 610, 615. The potential barrier can be
formed by a combination of DC, and optionally, RF fields. The
excitation can be provided by an AC field added to the potential
barrier so that resonant axial oscillations of ions above a
particular mass to charge ratio are excited. Ions corresponding to
the first population of ions in the first segment 610 will acquire
energy in the axial direction until sufficient energy has been
acquired to overcome the potential barrier separating segments 610
and 615 and reach the second segment 615 (M.sub.range3). To avoid
losing ions through the entrance aperture of the first segment 610
additional DC potential may be applied to the aperture reflecting
ions back into the segment 610.
[0047] As mentioned earlier, FIG. 6 illustrates a configuration in
which each segment of the multi-segmented linear ion trap 380 is
provided by a multi-sectioned quadrupole rod assembly 610, 615,
620, so an excitation voltage can be applied to the first three
sections of the x-electrodes of the multi-segmented linear ion trap
380 providing a potential of V.sub.210 to the sections 630, 635,
640. The amplitude of the excitation voltage is large enough to
excite ions that have mass to charge ratios that are outside the
mass range of M.sub.range3 forwards and axially along the
multi-segmented linear ion trap 380, so ions in the mass range
M.sub.range2 and M.sub.range1 propagate forwards in the direction
625. Ions corresponding to the first population of ions, which are
ions in the mass range M.sub.range3 are trapped and do not
propagate further than the third section 640 of the first
multi-sectioned quadrupole rod assembly 610. As indicated in FIG.
6, the excitation voltage applied to the first three sections 630,
635, 640 can be applied such that the polarity alternates between
adjacent sections, in the form of -V.sub.210, +V.sub.210,
-V.sub.210. Hence the ions in mass range M.sub.range3 are
effectively trapped in the middle section, section two, 635. In
this manner, the ions in mass range M.sub.range3 are less
influenced by ions in the adjacent 4.sup.th section 645, and also
less likely to return back to the source. Utilizing the method
described above, not only can all ions which do not belong in the
mass range M.sub.range3 be moved from segment 610, but in addition
to this all ions of this mass range can be collected in segment 610
rather than allow ions in the mass range M.sub.range3 be
distributed between segments 610, 615 and 620. A small positive DC
voltage can be applied along the length of the ion trap in the
axial direction dragging ions mass-independently to the points with
lowest DC potential located at the left-most point of assembly, say
section 630. This transfers ions of mass range M.sub.range3 that
may reside in any of the segments 610, 615, 620 into the segment
610. Similarly, this applies to ions of other m/z ranges but the
excitation amplitude provided by the axial AC field is chosen to
provide enough axial energy to push ions out from segment 610 (for
M.sub.range1 and M.sub.range2) and from segments 610, 615 for
M.sub.range1. The same consideration in terms of a DC voltage also
applies to ions of other mass ranges, the DC created field tends to
collect ions on the left side of assembly but the axial AC created
field excites them mass-dependently in the opposite direction until
they end up in the segment without resonant AC field, cool down and
reside in this region. These ions will not spread out further into
the regions without resonant AC voltage being applied because above
mentioned DC field created will oppose this motion.
[0048] Similarly, the excitation voltage applied to the second set
of three sections (the second multi-sectioned quadrupole rod
assembly 615) is applied such that ions in the mass range
M.sub.range1 propagate away from the source in the direction 625
and to the other end of the multi-segmented ion trap 380. Ions
corresponding to the second ion population, ions within the mass
range M.sub.range2, are trapped and do not propagate further than
the third section 655 of the second multi-sectioned quadrupole rod
assembly 615. These ions are out of resonance with the AC field
that exists therein, and the ions get stored in this segment 615
due to further loss of their energy in collisions with gas. The
voltage V.sub.10 that is applied is not sufficient to enable the
ions in the range of M.sub.range2 to traverse the potential barrier
and enter the subsequent segment 620 of the multi-segmented linear
ion trap 380. Once again, the excitation voltage applied to the
second multi-sectioned quadrupole rod assembly 615 is applied with
the polarity between adjacent sections 645, 650, 655 alternating as
+V.sub.10, -V.sub.10, +V.sub.10. Hence, ions in the mass range
M.sub.range2 are effectively trapped in the middle of these three
sections, the 5.sup.th section from the left 650. In this manner,
ions corresponding to the second population of ion, the ions in the
mass range M.sub.range2 are less influenced by the ions in the
adjacent 4.sup.th and 6.sup.th sections 645,655.
[0049] Similar explanations can be made for the third
multi-sectioned quadrupole rod assembly 620 of the multi-segmented
linear ion trap 380 configuration illustrated. With ions
corresponding to the third ion population, ions within the mass
range M.sub.range1 being trapped in the 8.sup.th section in a
similar manner to that described above.
[0050] Alternatively, ions can be expelled or extracted from a
particular segment by applying resonant dipolar or quadrupolar
field between rods in the interface between segments. Coupling
between radial and axial motion stimulates ions to move axially,
but only those which are in resonance with the applied AC voltage.
The same idea with positive DC gradient can also be applied to
promote collection of ions in the segment where partitioning based
on m/z ratio is initiated.
[0051] Utilizing the described configuration, once the ion
populations have been spatially positioned and segmented in this
manner, not only can the expulsion be carried out such that a
different mass range is scanned out from the first segment than the
mass range scanned out from the second segment, but the scans can
be performed substantially simultaneously requiring either one or
two separate detectors arrangements. This would require separate AC
signals to be applied differentially to the first and second
segments of the multi-segmented linear ion trap respectively.
[0052] One of the applications where improvement in quality of mass
spectrometry data may be achieved is during the scanning out of an
extended mass range, for example up to 6000 Th. Consider an
experiment in which one desires to scan out a mass range of
150-4000 Th. If the same RF generator is used for this extended
mass range, up to 4000 Th, as for a normal mass range (150-2000
Th), as currently dictated by the prior art, the ejection q
parameter must be reduced approximately by factor of 2. If the same
scan-out rate (the rate at which ions are expelled from the ion
trap, the speed of analysis) is used, the quality of data is
normally lower compared to a normal mass range of 150-2000 Th. This
data will have worse mass resolution, mass accuracy and sensitivity
unless the speed of analysis is significantly reduced. This is
particularly the case for the high mass range ions that are
typically scanned in the region of at least three times slower than
ions having an m/z below 2000 Th.
[0053] According to an aspect of the current invention, ions having
an m/z at some low value of interest are placed at the
predetermined q value. Then the RF amplitude is scanned linearly up
to some maximum voltage which ejects ions up to some maximum m/z by
moving their q value to the ejection q. In this manner, the ions
corresponding to the first population of ions can be expelled by
shifting the ions from a region of stable ion motion to a region of
unstable ion motion in an (a,q) stability diagram for ion motion
with a first q parameter, and ions corresponding to the second
population of ions can be expelled by shifting the ions from a
region of stable ion motion to a region of unstable ion motion in
an (a,q) stability diagram with a second q parameter, the first and
second q parameters being different from one another.
[0054] By applying a second resonance ejection signal to a the
segment of the multi-segmented linear ion trap in which the higher
mass range ions reside, a fairly low q parameter value can be
utilized to ejected at this q value simultaneously with lower mass
range ions that can be ejected at a higher q value when the RF
amplitude is ramped. For example the second segment could scan m/z
150-2000 Th while the first segment could scan m/z 2000-4000 Th.
The forgoing uses four detectors. In addition, there is a reduction
in scan out time, in that the ions in the range 200-2000 Th are
scanned out at the normal rate at 0.88, but the ions in the higher
mass range of 2000-4000 Th are scanned out at q=0.44, but since the
range is over ions being scanned at this low q is smaller than the
entire range of 200-4000 Th, the scanning at this low q value can
be achieved in less time, and there can be an overall reduction in
scan-out time. Alternatively, with the same scan-out time improved
mass resolution and mass accuracy can be achieved.
[0055] Thus, the ions are dispersed throughout the multi-segmented
linear ion trap according to their m/z ratio and subsequently
trapped in appropriate sections of the three-sectioned multipolar
electrode assemblies. The use of a multi-segmented RF ion trap in
this scenario can improve the quality of mass spectral data that
can be achieved by optimizing the data throughout the extended
range. By exciting ions in a manner that is appropriate and tuned
to the particular discrete mass ranges in question, one is able to
optimize use of time without necessarily sacrificing sensitivity,
scanning speed or resolving power of the linear ion trap.
[0056] With the conventional approach, a three-sectioned linear ion
trap would have been filled for 0.01-0.1 ms for compounds in the
range of 100 fmol/uL (sub ms time for 10 fmol/uL) to reach the
allowed space charge limit about 2000 and the linear ion trap would
have been scanned for 1.5 s (scan rate 0.4 ms/Th) to cover the
required mass range of 150-4000 Th. The current invention enables
the same data to be acquired for about 50% of time because
injection time is unessential compared to scan-out time in this
example.
[0057] FIG. 6 illustrates how segmentation of a linear on trap can
be achieved utilizing multiple three-sectioned multipole rod
assemblies (similar to that of FIG. 4b), in which each section of
each multipole rod assembly has a excitation voltage applied in a
specific phase to ascertain the results required. FIG. 7
illustrates that there are other ways in which this can be
accomplished, for example utilizing a two-sectioned multipole
structure to provide segmentation, the trapping volumes being
formed in-between the sections as illustrated.
[0058] In another aspect of this invention, the ions may be
dispersed according to their m/z ratio prior to entering the
multi-segmented ion trap, and once in the multi-segmented ion trap,
the dispersion can be maintained by actuating the segments within
the multi-segmented linear ion trap. In this particular scenario,
if the previously dispersed ions travel through a field free region
at a relatively low pressure or separate in pressurized sections of
ion transfer optics based on ion specific ion mobilities, the
different m/z ratios will traverse the region and arrive at the
multi-segmented linear ion trap at different times. The lower m/z
values will therefore arrive at the ion trap before the higher m/z
values, hence enabling the dispersion to be maintained.
[0059] A variety of other mechanisms can be employed to produce
discrete potential barriers along the axial dimension of the linear
ion trap. These include, for example, as illustrated in FIG. 8,
positioning the segments or multipolar rod assemblies at varying
distances from the axis 825. Essentially, the r.sub.0 value (the
distance from the longitudinal axis 825 of the multi-segmented
linear ion trap) for one segment having a different value to the
r.sub.0 value of an adjacent segment. Referring to FIG. 3, one will
see that the r.sub.0 value for each of the multiple segments is the
same, whereas in FIG. 8 each is different, namely r.sub.1, r.sub.2,
r.sub.3, r.sub.4, r.sub.5, and r.sub.6.
[0060] In this instance, an initial ion population is trapped in
the multi-segmented linear ion trap. The initial ion population is
then spatially partitioned to create several ion populations by m/z
range (m.sub.1.SIGMA., m.sub.2.SIGMA., m.sub.3.SIGMA.,
m.sub.4.SIGMA., m.sub.5.SIGMA., m.sub.6.SIGMA.) by known methods
and/or methods described above. Voltages necessary for the creation
of the DC and AC fields to implement this partitioning have to be
tuned appropriately compared to the example with uniform r.sub.0
above. If the same RF field is applied to each segment of the
multi-segmented linear ion trap during scan-out event, ions across
the entire mass range (m.sub.1.SIGMA., m.sub.2.SIGMA.,
m.sub.3.SIGMA., m.sub.4.SIGMA., m.sub.5.SIGMA., m.sub.6.SIGMA.)
will be expelled from adjacent segments (of differing r.sub.0
values, r.sub.1, r.sub.2, r.sub.3, r.sub.4, r.sub.5, and r.sub.6)
with the same or close q parameter. This is due to the relationship
between the q parameter, mass, RF potential, frequency and r.sub.0.
In this manner optimization of the time required for complete
expulsion of the ion populations can be achieved, however a
compromise will have been made in terms of mass resolution, mass
accuracy and sensitivity.
[0061] Each segment with a specific r.sub.i can be sub-divided into
at least three sections and the same approach with combination of
axial AC and DC fields created to partition ions between segments
as before with uniform r.sub.0. Voltages for DC and AC fields to
implement this partitioning also have to be tuned correspondingly
in view of changing r.sub.i.
[0062] There are other methods by which ions can be ejected from
the ion trap, for example by applying a DC excitation voltage
between a set of rods, or merely pulsing the ions out to the
detector arrangement. Details of these procedures are not described
herein, but are known to those skilled in the art.
[0063] In yet another aspect of this invention, as illustrated in
FIG. 9, an alternative manner of operating a linear ion trap is
described. The steps of the method may include trapping an initial
population of ions in the multi-segmented linear ion trap (step
910); spatially partitioning the initial ion population into at
least two ion populations (step 920), including a first population
and a second population; and manipulating the first ion population
of ions independently of the second ion population (step 930). At
least a portion of the ions corresponding to the first and second
ion populations can be subsequently detected by a detector
arrangement. The detector arrangement may comprise separate
detectors for the first and second ion populations. In another
aspect of the invention, the manipulation of ions corresponding to
the first and second ion populations may occur substantially
simultaneously. In yet a further aspect of the invention, the ion
populations may be forwarded to a subsequent mass analyzing
device.
[0064] This method is particularly useful when carrying out tandem
mass spectrometry (MS/MS) experiments in which ions need to be
fragmented. After running a full MS scan which allows for
identification of peaks of interest, only these ions are stored in
the trap during next injection event. Alternatively, only a
fraction of the ions from the first injection event are used for
the full MS scan. The rest of them can be stored in other segments
using appropriate AC and DC potentials. The last approach is
particularly beneficial when the injection time is long. In
addition, one may spatially partition an initial ion population
into a first ion population, second ion population and optionally
more populations, all ion populations having emanated from the same
source under the same conditions. One may then manipulate each
population of ions independent of one another, for example by
isolating a different m/z in each population, and then subjecting
the two mlzs to fragmentation. Once fragmented, the content of each
segment can be forwarded to a discrete detector arrangement,
essentially providing for two fragmentation experiments to be
facilitated simultaneously utilizing one linear ion trap. All or
some of these events can occur substantially simultaneously. This
saves on time, an expensive commodity in the proteomics
industry.
[0065] The methods of the invention can be implemented in digital
electronic circuitry, or in hardware, firmware, software, or in
combinations of them. Method steps on the invention can be
performed by one or more programmable processors executing a
computer program to perform functions of the invention by operating
on input data and generating output.
[0066] The various features explained on the basis of the various
aspects can be combined to form further aspects of the
invention.
[0067] Unless otherwise defined, all technical and scientific terms
used herein have the meaning commonly understood by one of ordinary
skill in the art to which this invention belongs. The disclosed
materials, methods, and examples are illustrative only and not
intended to be limiting. Skilled artisans will appreciate that
methods and materials similar to equivalent to those described
herein can be used to practice the invention.
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