U.S. patent application number 13/827685 was filed with the patent office on 2014-02-06 for systems and methods for ms-ms-analysis.
This patent application is currently assigned to Agilent Technologies, Inc.. The applicant listed for this patent is AGILENT TECHNOLOGIES, INC.. Invention is credited to Alexander Mordehai, Kenneth R. Newton.
Application Number | 20140034827 13/827685 |
Document ID | / |
Family ID | 49957927 |
Filed Date | 2014-02-06 |
United States Patent
Application |
20140034827 |
Kind Code |
A1 |
Mordehai; Alexander ; et
al. |
February 6, 2014 |
SYSTEMS AND METHODS FOR MS-MS-ANALYSIS
Abstract
A mass spectrum is acquired by accumulating parent ions in an
ion trap, ejecting parent ions of a selected m/z ratio into a
collision cell, producing fragment ions from the parent ions, and
analyzing the fragment ions in a mass analyzer. The other parent
ions remain stored in the ion trap, and thus the process may be
repeated by mass-selectively scanning parent ions from the ion
trap. In this manner, the full mass range of parent ions or any
desired subset of the full mass range may be analyzed without
significant ion loss or undue time expenditure. The collision cell
may provide a large ion acceptance aperture and relatively smaller
ion emission aperture. The collision cell may pulse ions out to the
mass analyzer. The mass analyzer may be a time-of-flight analyzer.
The timing of pulsing of ions out from the collision cell may be
matched with the timing of pulsing of ions into the time-of-flight
analyzer.
Inventors: |
Mordehai; Alexander;
(Loveland, CO) ; Newton; Kenneth R.; (Loveland,
CO) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
AGILENT TECHNOLOGIES, INC. |
Loveland |
CO |
US |
|
|
Assignee: |
Agilent Technologies, Inc.
Loveland
CO
|
Family ID: |
49957927 |
Appl. No.: |
13/827685 |
Filed: |
March 14, 2013 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
61677945 |
Jul 31, 2012 |
|
|
|
Current U.S.
Class: |
250/283 ;
250/287; 250/290 |
Current CPC
Class: |
H01J 49/004 20130101;
H01J 49/02 20130101; H01J 49/429 20130101; H01J 49/40 20130101 |
Class at
Publication: |
250/283 ;
250/290; 250/287 |
International
Class: |
H01J 49/00 20060101
H01J049/00; H01J 49/40 20060101 H01J049/40 |
Claims
1. A method for acquiring a mass spectrum, the method comprising:
(a) accumulating a plurality of parent ions having a range of m/z
ratios in an ion scanning trap; (b) ejecting parent ions of a
selected first m/z ratio from the ion scanning trap into a
collision cell, wherein other parent ions of different m/z ratios
remain stored in the ion scanning trap during ejection of the
selected parent ions; (c) producing fragment ions from at least
some of the selected parent ions in the collision cell; (d)
confining the selected parent ions and the fragment ions to an ion
confinement region that converges from an ion acceptance aperture
to an ion emission aperture of the collision cell, wherein the ion
emission aperture is smaller than the ion acceptance aperture; (e)
transmitting the fragment ions from the cell exit into a mass
analyzer to acquire spectral data; and (h) repeating steps (b)-(e)
one or more times for other parent ions accumulated in the ion
scanning trap having one or more selected m/z ratios different from
the first m/z ratio, wherein a plurality of fragment ion spectra
are acquired from a corresponding plurality of parent ions of
different respective m/z ratios.
2. The method of claim 1, comprising adjusting a collision energy
of the parent ions in the collision cell by adjusting a DC
potential applied between a cell entrance and a cell exit of the
collision cell, or by adjusting a DC potential applied between the
collision cell and an ion optics component preceding the collision
cell.
3. The method of claim 1, comprising collecting the parent ions in
an ion storage trap, storing the collected parent ions in the ion
storage trap, and transmitting at least some of the stored parent
ions from the ion storage trap to the ion scanning trap for
accumulation.
4. The method of claim 3, comprising, after ejecting the selected
parent ions from the ion scanning trap, transmitting at least some
of the parent ions remaining in the ion storage trap into the ion
scanning trap for accumulation.
5. The method of claim 1, comprising loading a desired number of
parent ions into an ion storage trap and transmitting the parent
ions into the ion scanning trap for accumulation, wherein the
desired number is one that minimizes space-charge effects in the
ion scanning trap.
6. The method of claim 1, comprising producing a plurality of
parent ions having an initial range of m/z ratios in an ion source
and transmitting the parent ions into an ion storage trap, storing
the parent ions in the ion storage trap, and transmitting parent
ions of a selected range of m/z ratios from the ion storage trap
into the ion scanning trap, wherein the plurality of parent ions
accumulated in the ion scanning trap has a range of m/z ratios that
is a subset of the initial range of m/z ratios transmitted into the
ion storage trap.
7. The method of claim 6, comprising, after ejecting the parent
ions of the subset from the ion scanning trap, transmitting parent
ions of a different range of m/z ratios from the ion storage trap
into the ion scanning trap, wherein the different range is a
different subset of the initial range of m/z ratios transmitted
into the ion storage trap.
8. The method of claim 1, wherein transmitting the fragment ions
into the mass analyzer comprises transmitting the fragment ions
into a pulser of a time-of-flight analyzer.
9. The method of claim 8, wherein transmitting the fragment ions
into the pulser comprises performing pulsed ejection of sequential
packets of the fragment ions from the collision cell, and the
timing of the pulsed ejection is matched with the timing of pulsed
extraction of packets of the fragment ions from the pulser into a
flight tube of the time-of-flight analyzer.
10. A mass spectrometry system, comprising a sequential arrangement
of an ion scanning trap, a collision cell and a mass analyzer, and
configured to perform the method of claim 1.
11. A mass spectrometry system, comprising: an ion scanning trap
comprising a plurality of trap electrodes surrounding an ion
trapping region and configured for generating a radio frequency
(RF) ion trapping field in the ion trapping region, and a trap exit
communicating with the ion trapping region; a device configured for
applying an RF trapping voltage to the trap electrodes; a device
configured for scanning ions from the ion trapping region and
through the trap exit on a mass-selective basis; a collision cell
comprising a cell entrance communicating with the trap exit, a cell
exit, and a plurality of cell electrodes arranged around a cell
axis and between the cell entrance and the cell exit, wherein the
cell electrodes surround an ion confining region and are configured
for generating an RF ion confining field in the ion confining
region such that the ion confining region converges in
cross-section in a direction from the cell entrance to the cell
exit; a device for applying an RF confining voltage to the cell
electrodes; and a mass analyzer communicating with the cell
exit.
12. The mass spectrometry system of claim 11, wherein the cell
electrodes are elongated in the direction from the cell entrance to
the cell exit and oriented at an angle relative to the cell axis
such that one or more opposing pairs of the cell electrodes
converge toward the cell exit.
13. The mass spectrometry system of claim 11, wherein the cell
electrodes are elongated in an axial direction from the cell
entrance to the cell exit and have respective diameters that vary
along the axial direction such that a cross-sectional area of the
ion trapping region is greater at the cell entrance than at the
cell exit.
14. The mass spectrometry system of claim 11, wherein the cell
electrodes are plate-shaped and axially spaced along the cell axis,
and the cell electrodes have respective apertures, and wherein the
apertures have respective cross-sectional areas that are
successively reduced in the direction from the cell entrance to the
cell exit.
15. The mass spectrometry system of claim 11, wherein the plurality
of cell electrodes comprises a plurality of first cell electrodes
disposed on a first substrate and a plurality of second cell
electrodes disposed on a second substrate in radial opposition to
the first cell electrodes relative to the cell axis, the first cell
electrodes are elongated along the first substrate in the direction
from the cell entrance to the cell exit, the second electrodes are
elongated along the second substrate in the direction from the cell
entrance to the cell exit, and the first cell electrodes and the
second cell electrodes are oriented at an angle relative to the
cell axis such that the first cell electrodes and the second cell
electrodes converge toward the cell exit.
16. The mass spectrometry system of claim 11, wherein the plurality
of cell electrodes comprises a plurality of first cell electrodes
disposed on a first substrate and a plurality of second cell
electrodes disposed on a second substrate in radial opposition to
the first cell electrodes relative to the cell axis, the first cell
electrodes are spaced from each other along the first substrate in
the direction from the cell entrance to the cell exit, the second
electrodes are spaced from each other along the second substrate in
the direction from the cell entrance to the cell exit, and the
first cell substrate and the second substrate are oriented at an
angle relative to the cell axis such that a transverse spacing
between the first cell electrodes and the second cell electrodes in
the radial direction is reduced in the direction from the cell
entrance to the cell exit.
17. The mass spectrometry system of claim 11, comprising a device
for ejecting ions from the cell exit in pulses wherein discrete ion
packets enter the mass analyzer.
18. The mass spectrometry system of claim 17, wherein the device
for ejecting ions from the cell exit is configured for applying a
potential barrier at the cell exit and adjusting the potential
barrier to alternately permit and prevent transmission of ions
through the cell exit.
19. The mass spectrometry system of claim 17, wherein the mass
analyzer is a time-of-flight (TOF) analyzer comprising a pulser,
and further comprising a device for matching the timing of the
device for ejecting ions from the cell exit with the timing of the
pulser to minimize loss of ions in the pulser.
20. The mass spectrometry system of claim 11, comprising an ion
storage trap configured for selectively storing ions and
transmitting ions into the ion scanning trap.
Description
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Patent Application Ser. No. 61/677,945, filed Jul. 31, 2012, titled
"SYSTEMS AND METHODS FOR MS-MS ANALYSIS," the content of which is
incorporated by reference herein in its entirety.
TECHNICAL FIELD
[0002] The present invention relates to acquisition of
spectrometric data by tandem mass spectrometry (MS) or MS-MS.
BACKGROUND
[0003] A mass spectrometry (MS) system in general includes an ion
source for ionizing components of a sample of interest, a mass
analyzer for separating the ions based on their differing
mass-to-charge ratios (or m/z ratios, or more simply "masses"), a
ion detector for counting the separated ions, and electronics for
processing output signals from the ion detector as needed to
produce a user-interpretable mass spectrum. Typically, the mass
spectrum is a series of peaks indicative of the relative abundances
of detected ions as a function of their m/z ratios. To elucidate
additional information regarding a sample, the MS system may be
configured for carrying out tandem MS, or MS-MS, experiments. In
this case, selected ions produced by the ion source, or "parent"
ions, are dissociated into fragment ions (or "daughter" ions) in a
collision cell. A mixture of the parent ions and fragment ions may
then be transferred into the mass analyzer, and the resulting mass
spectrum thus includes the fragment spectra.
[0004] Tandem MS may be implemented in a triple quadrupole (or QQQ)
MS system, which includes three quadrupole devices in series. The
first quadrupole is utilized for mass selection, the second
quadrupole is an RF-only device enclosed in a gas chamber and
utilized as the collision cell, and the third quadrupole is
utilized as the mass analyzer. Tandem MS may also be implemented in
a quadrupole time-of-flight (or qTOF) MS system, the main
difference being that the mass analyzer is a TOF analyzer instead
of a quadrupole device. In either system, the first quadrupole is
operated as a mass filter and thus is capable of passing only a
single parent ion at a time. All other ions are lost, eliminating
the opportunity to use these ions to contribute to signal
intensity. The sample introduced to the ion source may, however,
yield hundreds to thousands of different parent ions (parent ions
having differing m/z ratios), and each parent ion in turn may yield
tens of different fragment ions in the collision cell. In the QQQ
or qTOF system, obtaining fragment spectra from several parent ions
requires repeating the ion selection, fragmentation and analysis
sequence for each parent ion several times. The number of
experimental repetitions needed or desired may not, however, be
compatible with the time constraints imposed on the MS system. This
is particularly the case when the MS system is employed to analyze
sample components eluting from the column of a liquid chromatograph
(LC) or gas chromatograph (GC). On the other hand, simply loading
parent ions having a range of m/z ratios into a collision cell
simultaneously is typically not an acceptable solution, as this
approach typically does not enable the identification of which
parent ion created which fragment ion.
[0005] Therefore, there is a need for MS-MS systems and methods
that enable the collection and mass spectral analysis of all
combinations of parent ions (or any desired subset of parent ions)
and fragment ions from a sample of interest. There is also a need
for MS-MS systems and methods capable of performing such ion
collection and analysis within the time constraints imposed by any
sample introduction process that may be done at the front end such
as, for example, LC or GC elution.
SUMMARY
[0006] To address the foregoing problems, in whole or in part,
and/or other problems that may have been observed by persons
skilled in the art, the present disclosure provides methods,
processes, systems, apparatus, instruments, and/or devices, as
described by way of example in implementations set forth below.
[0007] According to one embodiment, a method for acquiring a mass
spectrum includes accumulating a plurality of parent ions having a
range of m/z ratios in an ion scanning trap; ejecting parent ions
of a selected first m/z ratio from the ion scanning trap into a
collision cell, wherein other parent ions of different m/z ratios
remain stored in the ion scanning trap during ejection of the
selected parent ions; producing fragment ions from at least some of
the selected parent ions in the collision cell; confining the
selected parent ions and the fragment ions to an ion confinement
region that converges from an ion acceptance aperture to an ion
emission aperture of the collision cell, wherein the ion emission
aperture is smaller than the ion acceptance aperture; transmitting
the fragment ions from the cell exit into a mass analyzer to
acquire spectral data; and repeating the foregoing steps one or
more times for other parent ions accumulated in the ion scanning
trap having one or more selected m/z ratios different from the
first m/z ratio, wherein a plurality of fragment ion spectra are
acquired from a corresponding plurality of parent ions of different
respective m/z ratios.
[0008] According to another embodiment, the parent ions are
transmitted into the ion scanning trap along a trap axis, ejecting
the selected parent ions from the ion scanning trap includes
ejecting the selected parent ions through an aperture of an
electrode of the ion scanning trap in a direction either in-line
with or transverse to the trap axis.
[0009] According to another embodiment, the ion scanning trap
includes a two-dimensional arrangement of electrodes coaxially
disposed about a trap axis and axially disposed between a trap
entrance and a trap exit in-line with an entrance of the collision
cell, and ejecting the selected parent ions from the ion scanning
trap includes ejecting the selected parent ions through the trap
exit.
[0010] According to another embodiment, a mass spectrometry system
includes an ion scanning trap comprising a plurality of trap
electrodes surrounding an ion trapping region and configured for
generating a radio frequency (RF) ion trapping field in the ion
trapping region, and a trap exit communicating with the ion
trapping region; a device for applying an RF trapping voltage to
the trap electrodes; a device for scanning ions from the ion
trapping region and through the trap exit on a mass-selective
basis; a collision cell comprising a cell entrance communicating
with the trap exit, a cell exit, and a plurality of cell electrodes
arranged around a cell axis and between the cell entrance and the
cell exit, wherein the cell electrodes surround an ion confining
region and are configured for generating an RF ion confining field
in the ion confining region such that the ion confining region
converges in cross-section in a direction from the cell entrance to
the cell exit; a device for applying an RF confining voltage to the
cell electrodes; and a mass analyzer communicating with the cell
exit.
[0011] According to another embodiment, the plurality of trap
electrodes includes a pair of end cap electrodes spaced from each
other along a trap axis, and a ring electrode coaxially disposed
about the trap axis between the end cap electrodes.
[0012] According to another embodiment, the plurality of trap
electrodes are elongated in parallel with a trap axis and disposed
at a radial distance from the trap axis. In some embodiments, the
trap exit is located at an axial end of the trap electrodes, and
the device for scanning ions is configured for ejecting ions
through the trap exit along the trap axis. In other embodiments,
the trap exit is an aperture through one of the trap electrodes,
and the device for scanning ions is configured for ejecting ions
through the trap exit along a radial direction relative to the trap
axis.
[0013] According to another embodiment, the device for scanning
ions is configured for scanning a magnitude or a frequency of the
RF trapping voltage.
[0014] According to another embodiment, the device for scanning
ions is configured for applying an AC supplemental voltage between
at least two of the trapping electrodes, and for scanning one or
more of the following parameters: a magnitude of the RF trapping
voltage, a frequency of the RF trapping voltage, a magnitude of the
AC supplemental voltage, and a frequency of the AC supplemental
voltage.
[0015] Other devices, apparatus, systems, methods, features and
advantages of the invention will be or will become apparent to one
with skill in the art upon examination of the following figures and
detailed description. It is intended that all such additional
systems, methods, features and advantages be included within this
description, be within the scope of the invention, and be protected
by the accompanying claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The invention can be better understood by referring to the
following figures. The components in the figures are not
necessarily to scale, emphasis instead being placed upon
illustrating the principles of the invention. In the figures, like
reference numerals designate corresponding parts throughout the
different views.
[0017] FIG. 1 is a schematic view of an example of a mass
spectrometry (MS) system according to one embodiment.
[0018] FIG. 2 is a schematic side view of an example of a collision
cell according to one embodiment.
[0019] FIG. 3 is a schematic side view of an example of a collision
cell according to another embodiment.
[0020] FIG. 4 is a schematic end view of the collision cell
illustrated in FIG. 3.
[0021] FIG. 5 is a schematic side view of an example of a collision
cell according to another embodiment.
[0022] FIG. 6 is a cut-away perspective view of an example of a
collision cell according to another embodiment.
[0023] FIG. 7 is a cross-sectional side view of an example of a
collision cell according to another embodiment.
[0024] FIG. 8 is a schematic view of an example of an MS system
according to another embodiment.
[0025] FIG. 9 illustrates the envelope of ion ejection count
(number of ions) as a function of ion ejection time (ns) for a
single mass (the peak curve), and the ejection energy (eV) of each
individual ion as a function of the ion's ejection time (the series
of dots).
[0026] FIG. 10 is a zoomed-in view of one of the pulses illustrated
in FIG. 9.
[0027] FIG. 11 is a cross-sectional view of an example of a linear
ion trap that may be deployed as an ion scanning trap according to
the present disclosure.
[0028] FIG. 12 is a cross-sectional view of a portion of a trap
electrode of the linear ion trap illustrated in FIG. 11, at which a
device for adjusting ion energy is located.
[0029] FIG. 13, is a cross-sectional view similar to FIG. 12 with
equipotential lines and ion trajectories added.
DETAILED DESCRIPTION
[0030] The present disclosure describes methods, apparatus and
systems for acquiring spectrometric data from analyte ions by way
of tandem mass spectrometry (MS) or MS-MS. The methods, apparatus
and systems enable the collection and mass spectral analysis of all
combinations of parent ions (or any desired subset of parent ions)
and fragment ions from a sample of interest. Moreover, ion
collection and analysis may be performed within the time
constraints imposed by any sample introduction process typically
done at the front end such as, for example, chromatographic
elution. The methods, apparatus and systems may accomplish this
without any significant loss of ions, instrumental sensitivity and
dynamic range, and may improve upon these figures of merit.
Examples of embodiments are described below in conjunction with
FIGS. 1-8.
[0031] FIG. 1 is a schematic view of an example of a mass
spectrometry (MS) system 100 according to one embodiment. The MS
system 100 generally includes an ion source 104, an ion scanning
trap 108, a collision cell 112, a mass spectrometer 116, and a
system controller 120.
[0032] The ion source 104 may be any type of continuous-beam or
pulsed ion source suitable for tandem MS operations. Examples of
ion sources 104 include, but are not limited to, electrospray
ionization (ESI) sources, other atmospheric pressure ionization
(API) sources, photo-ionization (PI) sources, electron ionization
(EI) sources, chemical ionization (CI) sources, laser desorption
ionization (LDI) sources, and matrix-assisted laser desorption
ionization (MALDI) sources. Depending on the type of ionization
implemented, the ion source 104 may reside in a vacuum chamber or
may operate at or near atmospheric pressure. Sample material to be
analyzed may be introduced to the ion source 104 by any suitable
means, including hyphenated techniques in which the sample material
is the output of an analytical separation instrument such as, for
example, a gas chromatography (GC) or liquid chromatography (LC)
instrument (not shown).
[0033] The ion scanning trap 108 generally includes a plurality of
trap electrodes 124 arranged about a trap axis 126 and surrounding
an interior region of the ion scanning trap 108, a trap entrance
(or ion entrance) 128 into the interior region, and a trap exit (or
ion exit) 130 out from the interior region. The ion scanning trap
108 is enclosed in a vacuum chamber (not shown). The trap
electrodes 124 are in signal communication with an appropriate
voltage source 134, which includes a radio frequency (RF) voltage
source and typically also a direct current (DC) voltage source. In
response to applying an RF voltage of appropriate parameters (RF
drive frequency and magnitude), and typically also a DC voltage of
appropriate magnitude superposed on the RF voltage, the trap
electrodes 124 are configured to generate an RF quadrupole trapping
field that confines ions of a desired mass range (m/z range) to the
interior region for a desired period of time. The trap electrodes
124 are also configured to scan the trapped ions such that they are
ejected from the ion scanning trap 108 on a mass-selective basis.
Scanning may be done by scanning (varying) at least one of the
trapping voltage parameters. In some embodiments scanning is done
by resonant excitation, in which a relatively weak supplementary
alternating current (AC) voltage of a certain frequency is applied
between two opposing trap electrodes 124. At least one trapping
voltage parameter is then scanned until the secular frequency of an
ion of selected mass comes into resonance with a frequency that is
directly or parametrically driven by the supplemental wave
frequency. In this way, the selected ion can gain sufficient energy
to overcome the repulsive force imparted by the RF trapping field
and exit through the trap exit 130. Scanning may also be done by
triple resonant ejection by adding a dipole component to the
trapping field and a quadrupole and/or dipole component to the
excitation field, as described for example in U.S. Pat. Nos.
5,714,755 and 7,034,293, the entire contents of which are
incorporated herein by reference. As appreciated by persons skilled
in the art, other ion ejection techniques may alternatively be
implemented, such as mass-selective instability as described for
example in U.S. Pat. No. 4,540,884, the entire contents of which
are incorporated herein by reference.
[0034] In some embodiments, the trap electrodes 124 are arranged in
a two-dimensional (2D) configuration (or linear configuration). As
an example of a 2D ion trap, the trap electrodes 124 may include a
multipole arrangement of four or more electrodes (generally, 2N
electrodes where N is an integer equal to 2 or greater) that are
parallel to the trap axis 126, elongated in the direction of the
trap axis 126, positioned at a radial (transverse) distance from
the trap axis 126, and circumferentially spaced from each other
about the trap axis 126. The trap electrodes 124 may be cylindrical
rods, or may present hyperbolic surfaces having foci that face the
interior region, or in some cases may be plates. The RF trapping
field is typically generated by applying an RF voltage to one pair
of opposing trap electrodes 124, and an RF voltage 180 degrees out
of phase with the first RF voltage to at least one other pair of
opposing trap electrodes 124. For clarity only two trap electrodes
124 are shown in FIG. 1, with the understanding that two or more
pairs of opposing trap electrodes 124 may be provided. The trap
entrance 128 typically corresponds to the "upstream" axial end of
the trap electrodes 124, and leads to the axially elongated
interior region. Ions are confined to an elongated ion-occupied
volume, or ion cloud, along the trap axis by the RF trapping field,
which in this case is a 2D trapping field that limits ion excursion
in radial directions. The ion cloud may be further reduced by
introducing an inert damping gas (e.g., helium, nitrogen, argon,
etc.) into the interior region. DC voltages may be applied to ion
optics (not shown) at the axial ends of the 2D ion trap to prevent
ions from escaping through the axial ends. The 2D ion trap may be
configured for radial ejection in which case the trap exit 130 is
typically an aperture (or slot) formed through one of the trap
electrodes 124. Alternatively, if the 2D ion trap is configured for
axial ejection of ions, the trap exit 130 may correspond to the
axial end opposite to the trap entrance 128, as schematically
depicted in FIG. 1. Axial ion ejection is described, for example,
in U.S. Pat. No. 6,177,668, the entire contents of which are
incorporated herein by reference.
[0035] In other embodiments, the trap electrodes may be arranged in
a three-dimensional (3D) configuration (not specifically shown). As
an example of a 3D ion trap, the trap electrodes may include a pair
of hyperbolic end-cap electrodes spaced apart from each other along
the trap axis 126, and a hyperbolic ring electrode positioned
between the end-cap electrodes and coaxially swept about the trap
axis 126. The respective foci of the end-cap electrodes face each
other and thus face the interior region of the 3D ion trap, and the
focus of the ring electrode also faces the interior region.
Application of the RF trapping voltage thus generates a 3D trapping
field that constrains the motion of ions to an ion cloud in the
center of the interior region, which may be further reduced by a
damping gas. The trap entrance 128 and trap exit 130 may be one or
more apertures typically formed through the end-cap electrodes.
Examples of the structure and operation of 3D as well as 2D ion
traps are described, for example, in above-referenced U.S. Pat. No.
7,034,293.
[0036] The collision cell 112 generally includes an ion guide
enclosed in a collision gas chamber 138. The ion guide includes a
plurality of cell electrodes 142 arranged about a cell axis 144 and
surrounding an interior region of the ion guide, a cell entrance
(or ion entrance) 148 into the interior region, and a cell exit (or
ion exit) 150 out from the interior region. A gas inlet 152 admits
a neutral collision gas (e.g., helium, nitrogen, argon, etc.) into
the collision gas chamber 138 to enable ion fragmentation by
collision-induced dissociation (CID). A voltage source 154 applies
an RF voltage or composite of RF/DC voltage to the cell electrodes
142 to confine parent ions along the cell axis 144. DC voltages are
also utilized to accelerate the ions from the cell entrance 148 and
cell exit 150, during which time parent ions collide with the
collision gas to produce fragment ions as appreciated by persons
skilled in the art. The collision cell 112 may be configured to
output fragment ions, or a mixture of fragment ions and
non-fragmented parent ions. Some specific examples of embodiments
of the collision cell 112 are described below in conjunction with
FIGS. 2-7.
[0037] The mass spectrometer 116 generally includes a mass analyzer
158 and an ion detector 162 enclosed in a vacuum chamber. The mass
analyzer 158 may have a design suitable for collecting a full mass
range of fragment ions (or fragment and parent ions) from the
collision cell 112 with high efficiency and minimal loss, and
mass-selectively sorting the ions with high resolution in
accordance with the present teachings. Accordingly, a
time-of-flight (TOF) analyzer is presently considered to be an
example of a suitable mass analyzer 158. The ion detector 162
receives the ions and produces ion detection signals from which a
mass spectrum of the detected fragment ions (or fragment and parent
ions) may be generated, as appreciated by persons skilled in the
art.
[0038] The system controller 120 is schematically depicted as
representing one or more modules configured for controlling,
monitoring and/or timing various functional aspects of the MS
system 100 such as, for example, controlling the operation of the
ion source 104; controlling the application of voltages to the ion
scanning trap 108 and setting and adjusting the voltage parameters
for loading, storing and scanning out parent ions; controlling the
application of voltages to the collision cell 112 and setting and
adjusting the voltage parameters for collecting parent ions,
adjusting ion energies, accelerating ions toward the cell exit,
ejecting ions in either a continuous or pulsed manner, and
adjusting collision gas flow and/or pressure; controlling any ion
optics (not shown) provided between the illustrated components; and
controlling vacuum pumps. The system controller 120 may also be
configured for receiving the ion detection signals from the ion
detector 162 and performing other tasks relating to data
acquisition and signal analysis as necessary to generate a mass
spectrum characterizing the sample under analysis. The system
controller 120 may include a computer-readable medium that includes
instructions for performing any of the methods disclosed herein.
For all such purposes, the system controller 120 is schematically
illustrated as being in signal communication with various
components of the MS system 100 via wired or wireless communication
links represented by dashed lines. Also for these purposes, the
system controller 120 may include one or more types of hardware,
firmware and/or software, as well as one or more memories and
databases. The system controller 120 typically includes a main
electronic processor providing overall control, and may include one
or more electronic processors configured for dedicated control
operations or specific signal processing tasks. The system
controller 120 may also schematically represent all voltage sources
not specifically shown, as well as timing controllers, clocks,
frequency/waveform generators and the like as needed for applying
voltages to various components of the MS system 100. The system
controller 120 may also be representative of one or more types of
user interface devices, such as user input devices (e.g., keypad,
touch screen, mouse, and the like), user output devices (e.g.,
display screen, printer, visual indicators or alerts, audible
indicators or alerts, and the like), a graphical user interface
(GUI) controlled by software, and devices for loading media
readable by the electronic processor (e.g., logic instructions
embodied in software, data, and the like). The system controller
120 may include an operating system (e.g., Microsoft Windows.RTM.
software) for controlling and managing various functions of the
system controller 120.
[0039] It will be understood that FIG. 1 is a high-level schematic
depiction of the MS system 100 disclosed herein. Other components,
such as additional structures, ion optics, ion guides and
electronics may be included needed for practical
implementations.
[0040] An example of a method for acquiring a mass spectrum from a
sample of interest will now be described with reference to FIG. 1.
The sample is introduced in the ion source 104 and the ion source
104 produces a plurality of parent ions having m/z ratios spanning
some initial mass range. The parent ions are transmitted into and
accumulated in the ion scanning trap 108. After accumulation, the
ion scanning trap 108 ejects parent ions of a selected first m/z
ratio (or "first parent ions"), and the first parent ions are
transmitted into and through the collision cell 112. While moving
through the collision cell 112, at least some of the first parent
ions undergo OD whereby fragment ions of a range of m/z ratios are
produced. After dissociation, fragment ions and non-fragmented
first parent ions may undergo collisional cooling (or
thermalization) as they approach the cell exit 150. The fragment
ions (and any non-fragmented first parent ions) are then
transmitted into the mass spectrometer 116 and spectral data is
generated.
[0041] While the first parent ions are transmitted through the
collision cell 112 and the resulting fragment ions (and any
non-fragmented first parent ions) are sorted in the mass
spectrometer 116, the ion scanning trap 108 continues to store the
other parent ions (having m/z ratios different from the first
parent ions) from the initial mass range that was originally
collected from the ion source 104. This is in contrast to a
conventional MS-MS system in which the ion selection device is a
quadrupole mass filter that transmits parent ions of a single m/z
ratio and allows all other parent ions of different m/z ratios to
be lost. Thus in the present method, while the first parent ions
are being processed, the trapping parameters of the ion scanning
trap 108 may be adjusted to scan out parent ions of a selected
second m/z ratio (or "second parent ions"), which are then
processed in the collision cell 112 to produce fragment ions. These
fragment ions (and any non-fragmented second parent ions) are then
processed in the mass spectrometer 116 to produce spectral data as
described above. This process may be repeated for all other parent
ions of desired m/z ratios that continue to be stored in the ion
scanning trap 108. In this manner, a mass spectrum may be
constructed from all combinations of parent ions (or any desired
subset of parent ion m/z ratios) obtained from the sample of
interest and from all fragment ions derived from each parent ion
m/z ratio. Moreover, as described by way of examples below, the
collision cell 112 may be configured to increase the efficiency of
ion collection from the ion scanning trap 108 and transmission into
the mass spectrometer 116, thereby reducing the loss of ions and
increasing the sensitivity of the mass spectrometer 116.
[0042] FIG. 2 is a schematic side view of an example of a collision
cell 200 according to one embodiment. As noted above, the collision
cell 200 includes a plurality of cell electrodes 242 enclosed in a
collision gas chamber (not shown). For clarity, only two cell
electrodes 242 are shown. The cell electrodes 242 are arranged
about a cell axis 244 and surround an interior region of the
collision cell 200. One axial end of the cell electrodes 242
corresponds to a cell entrance (or ion entrance) 248 into the
interior region, and the other axial end corresponds to a cell exit
(or ion exit) 250 out from the interior region. Ions are
accelerated from the cell entrance 248 to the cell exit 250 in the
presence of a collision gas by imparting a DC potential across the
axial length of the cell electrodes 242. Depending on how the cell
electrodes 242 are configured, the DC potential may be generated by
applying a DC voltage to the cell electrodes 242 (as depicted by a
DC voltage source 264), or to one or more entrance lenses 266 and
exit lenses 268 at the cell entrance 248 and cell exit 250,
respectively (as depicted by DC voltage sources 272 and 274). The
cell electrodes 242, exit lens(es) 268, or both, may be configured
for pulsing fragment ions (or a mixture of fragment ions and
non-fragmented parent ions) out from the collision cell 200. The
timing of this pulsing may be matched with the timing of ion
injection into the mass analyzer 116 as described below.
[0043] The cell electrodes 242 may also be configured for
generating an ion confining region (or ion beam) 278 that converges
in the direction of the cell exit 250, in response to application
of an RF voltage or RF/DC composite voltage (as depicted by an RF
voltage source 280). Accordingly, the collision cell 200 may be
described as defining an ion acceptance aperture 284 at the cell
entrance 248 and an ion emittance aperture 286 at the cell exit
250, wherein the ion acceptance aperture 284 is greater in
cross-sectional area than the ion emittance aperture 286. In this
manner, the ion confining region 278 tapers (its cross-sectional
area is reduced or compressed in the radial direction) along the
length of the collision cell 200 toward the cell exit 250. This
convergence is useful for matching the output geometry of the ion
scanning trap 108 with the input geometry of the mass analyzer 116,
increasing the efficiency of both ion collection from the ion
scanning trap 108 and ion injection into the mass analyzer 116, and
consequently increasing the sensitivity of the mass analyzer 116.
In the case of a TOF analyzer, the convergence is also useful for
reducing the spread of the radial velocity of the ions. Generally,
the cross-sectional area of the ion acceptance aperture 284 should
be large enough to maximize the efficiency of collection of ions
from the ion scanning trap 108 (or from any intervening ion
optics), particularly in cases where the ion beam from the ion
scanning trap 108 is somewhat dispersed or divergent. The
cross-sectional area of the ion emittance aperture 286 should be
small enough to maximize the efficiency of transmission of ions
into the mass analyzer 116 (or into any intervening ion optics),
but without creating instability in ions of relatively low mass. In
some embodiments, the cross-sectional area of the ion acceptance
aperture 284 may range from about 0.7 mm.sup.2 to about 600
mm.sup.2, and the cross-sectional area of the ion emittance
aperture 286 may range from about 0.03 mm.sup.2 to about 0.5
mm.sup.2. An arrangement of cell electrodes 242 configured for
generating a converging ion confining region 278 may be referred to
as an "ion funnel," examples of which are described below with
reference to FIGS. 3-6.
[0044] FIG. 3 is a schematic side view of an example of a collision
cell 300 according to another embodiment. FIG. 4 is a schematic end
view of the collision cell 300. The collision cell 300 includes a
plurality of cell electrodes 342 enclosed in a collision gas
chamber (not shown). The cell electrodes 342 are arranged about a
cell axis 344 and surround an interior region. One axial end of the
cell electrodes 342 corresponds to a cell entrance 348 and the
other axial end corresponds to a cell exit 350. The collision cell
300 may also include one or more axially positioned entrance and
exit lenses (not shown) as noted above. In this embodiment, the
cell electrodes 342 have a multipole configuration in which each
cell electrode 342 is elongated generally in a direction from the
cell entrance 348 to the cell exit 350. For clarity, only one
opposing pair of cell electrodes 342 is shown in FIG. 3. By way of
example, FIG. 4 illustrates a quadrupole arrangement in which two
opposing pairs of cell electrodes 342 are provided. It will be
understood, however, that more than two opposing pairs of cell
electrodes 342 may be provided to realize a higher-order multipole
arrangement. In typical implementations, the RF confining field is
produced by applying RF voltages to each cell electrode 342 such
that the RF voltage on any given cell electrode 342 is 180 degrees
out of the phase with the RF voltage on the adjacent cell
electrode(s) 342, as schematically depicted by RF voltage sources
480 and 482. DC voltages may be applied to some or all of the cell
electrodes 342 and/or to entrance and exit lenses as needed to
control the axial motion of the ions, including pulsing out to the
mass analyzer 116 if desired. Also in this embodiment, the cell
electrodes 342 are oriented so as to converge toward each other in
the direction of the cell exit 350, i.e., at an angle to the cell
axis 344, such that the cross-sectional area of the interior region
at the cell entrance 348 is greater than the cross-sectional area
at the cell exit 350. In some embodiments, the cell electrodes 342
may be oriented at an angle ranging from about 0.5 degrees to about
10 degrees relative to the cell axis 344. This electrode geometry
generates a converging ion confining region as described above in
conjunction with FIG. 2.
[0045] In another embodiment, the cell electrodes 342 may be
generally parallel but their diameters are varied along the axial
direction such that the cross-sectional area of the interior region
at the cell entrance 348 is greater than the cross-sectional area
at the cell exit 350, thereby providing a converging ion confining
region as described above. In another embodiment, the cell
electrodes 342 may be physically converging as shown in FIG. 3 and
also have varying diameters.
[0046] FIG. 5 is a schematic side view of an example of a collision
cell 500 according to another embodiment. The collision cell 500
includes a plurality of cell electrodes 542 enclosed in a collision
gas chamber (not shown). The cell electrodes 542 are arranged about
a cell axis 544 and surround an interior region. One axial end of
the cell electrodes 542 corresponds to a cell entrance 548 and the
other axial end corresponds to a cell exit 550. The collision cell
500 may also include one or more axially positioned entrance and
exit lenses (not shown) as noted above. In this embodiment, the
cell electrodes 542 include a series of plate-shaped electrodes
arranged transversely to the cell axis 544 and axially spaced from
each other. Each cell electrode 542 has an aperture 584 that is
typically centered on the cell axis 544. The aperture 584 of a
first cell electrode 586 at the cell entrance 548 has the largest
cross-sectional area, the aperture 584 of a last cell electrode 588
at the cell exit 550 has the smallest cross-sectional area, and the
apertures 584 of the intermediate cell electrodes 542 have one or
more intermediate cross-sectional areas. The electrode apertures
584 reduce in cross-sectional area (e.g., reduce in diameter in the
case of circular apertures)--and thus the cross-sectional area of
the interior region tapers--in the direction of the cell exit 550,
resulting in an ion funnel configuration. The apertures 584 may be
circular or elliptical, or alternatively may be polygonal (e.g.,
rectilinear), as desired for best accommodating the output geometry
of the ion scanning trap 108 and/or the input geometry of the mass
analyzer 116. For example, a rectilinear aperture may be found to
be advantageous for efficiently receiving an ion beam from a
rectilinear or slot-shaped trap exit 130, which is often provided
in linear ion traps configured for radial ion ejection. In typical
implementations, the RF confining field is produced by applying RF
voltages to each cell electrode 542 such that the RF voltage on any
given cell electrode 542 is 180 degrees out of the phase with the
RF voltage on the adjacent cell electrode(s) 542. DC voltages may
be applied to the first cell electrode 586, last cell electrode
588, and one or more of the intermediate cell electrodes 542 as
needed to control the axial motion of the ions, including pulsing
out to the mass analyzer 116 if desired. This electrode geometry
generates a converging ion confining region as described above in
conjunction with FIG. 2.
[0047] FIG. 6 is a cut-away perspective view of an example of a
collision cell 600 according to another embodiment. The collision
cell 600 may be characterized as providing a longitudinal "RF
carpet" arrangement with converging geometry. The collision cell
600 includes a plurality of cell electrodes enclosed in a collision
gas chamber (not shown). The cell electrodes are arranged about a
cell axis 644 and surround an interior region. One axial end of the
cell electrodes corresponds to a cell entrance 648 and the other
axial end corresponds to a cell exit 650. The collision cell 600
may also include one or more axially positioned entrance lenses 666
and exit lenses 668 as noted above. In this embodiment, the cell
electrodes are elongated generally in a direction from the cell
entrance 648 to the cell exit 650 and have a relatively small
cross-sectional dimension (e.g., width in the case of a rectilinear
cross-section, or diameter in the case of a circular
cross-section). Additionally, the cell electrodes are disposed on
(or formed on, or supported by) two or more substrates. Thus, in
the illustrated example, the collision cell 600 includes a first
substrate 672 on which a plurality of first cell electrodes 674 are
disposed, and an opposing second substrate 680 on which a plurality
of second cell electrodes (not shown) are disposed. The collision
cell 600 may also include a third substrate 682 on which a
plurality of third cell electrodes 684 are disposed, and an
opposing fourth substrate (not shown) on which a plurality of
fourth electrodes (not shown) are disposed. Alternatively,
contiguous conductive layers may be substituted for one of the
opposing sets of cell electrodes. The third substrate 682 and
fourth substrate may be oriented in planes orthogonal to those of
the first substrate 672 and second substrate 680. The first
substrate 672 and second substrate 680 may be disposed on
respective bases or walls 686 and 688, which in FIG. 6 are shown to
be detached for illustrative purposes. The third substrate 682 may
similarly be disposed on a base or wall 690, as well as the fourth
substrate (not shown).
[0048] On any given substrate (e.g., 672, 680, 682), each cell
electrode is parallel to the other cell electrodes. In typical
implementations, the RF confining field is produced by applying RF
voltages to each cell electrode such that the RF voltage on any
given cell electrode is 180 degrees out of the phase with the RF
voltage on the adjacent cell electrode(s) on the same substrate. In
some embodiments, the RF voltage may be applied to only one pair of
opposing electrode sets, such as only to the first cell electrodes
674 and second cell electrodes, or only to the third cell
electrodes 684 and fourth cell electrodes. DC voltages may be
applied to some or all of the cell electrodes and/or to entrance
lenses 666 and exit lenses 668 as needed to control the axial
motion of the ions, including pulsing out to the mass analyzer 116
if desired. In some embodiments, DC voltages may be applied to only
one pair of opposing electrode sets or to one pair of opposing
contiguous conductive layers. In the illustrated embodiment, the
first substrate 672 and the second substrate 680 (and thus the
first cell electrodes 674 and second cell electrodes) are oriented
so as to converge in the direction of the cell exit 650, i.e., at
an angle to the cell axis 644, such that the cross-sectional area
of the interior region at the cell entrance 648 is greater than the
cross-sectional area at the cell exit 650. In some embodiments, the
cell electrodes may be oriented at an angle ranging from about 0.5
degrees to about 10 degrees relative to the cell axis 644. The
third substrate 682 and the fourth substrate (and thus the third
cell electrodes 684 and fourth cell electrodes) may likewise
converge toward each other relative to the cell axis 644, or
alternatively may be parallel to each other. In either case, the
electrode geometry illustrated in FIG. 6 generates a converging ion
confining region 678 as described above in conjunction with FIG.
2.
[0049] As one non-limiting example, the substrates of the collision
cell 600 are composed of a suitable dielectric material and the
cell electrodes are formed on the substrates by any suitable
fabrication or microfabrication technique. Each cell electrode may
have a cross-sectional dimension (e.g., width or diameter) ranging
from about 5 .mu.m to about 500 .mu.m, a thickness (or height above
the substrate) ranging from about 0.1 .mu.m to about 50 .mu.m, and
a pitch (i.e., spacing between adjacent electrodes) ranging from
about 10 .mu.m to about 1000 .mu.m.
[0050] More generally, the cell electrodes have relatively small
dimensions as compared, for example, to conventional multipole
arrangements of rod-type electrodes. As a result, the RF confining
field is maintained in comparative close proximity to the cell
electrodes and their respective substrates. This in turn results in
the field-free or near field-free region through which the cell
axis 644 passes being larger in comparison to that established by
conventional electrode geometries. The resulting spatial form of
the electric field may facilitate the generation of a converging
ion confining region 678 that has a large ion acceptance aperture
and a small ion emittance aperture. Moreover, this configuration
may prevent the establishment of a reflective RF field at the cell
exit 650 that might undesirably reflect ions back toward the cell
entrance 648.
[0051] FIG. 7 is a cross-sectional side view of an example of a
collision cell 700 according to another embodiment. The collision
cell 700 may be characterized as providing a transverse "RF carpet"
arrangement with converging geometry. The collision cell 700
includes a plurality of cell electrodes enclosed in a collision gas
chamber (not shown). The cell electrodes are arranged about a cell
axis 744 and surround an interior region. One axial end of the cell
electrodes corresponds to a cell entrance 748 and the other axial
end corresponds to a cell exit 750. The collision cell 700 may also
include one or more axially positioned entrance and exit lenses
(not shown) as noted above. The cell electrodes have a relatively
small cross-sectional dimension as in the case of the electrodes
described above in conjunction with FIG. 6. In this embodiment,
however, the cell electrodes are oriented in a direction orthogonal
to those illustrated in FIG. 6, i.e., orthogonal to the X-Z plane
depicted in FIG. 7. In the illustrated example, the collision cell
700 includes a first substrate 772 on which a plurality of first
cell electrodes 774 are disposed, and an opposing second substrate
782 on which a plurality of second cell electrodes 784 are
disposed. The collision cell 700 may also include a third substrate
786 on which a contiguous conductive layer 788 is disposed, and an
opposing fourth substrate (not shown) on which a contiguous
conductive layer (not shown) is disposed. Alternatively, a
plurality of third cell electrodes (not shown) and a plurality of
fourth electrodes (not shown) may be disposed on the third
substrate 786 and fourth substrate, respectively. The third
substrate 786 and fourth substrate may be oriented in planes
orthogonal to those of the first substrate 772 and second substrate
782. The first substrate 772 and second substrate 782 may be
disposed on respective bases or walls 788 and 790, as well as the
third substrate 786 and fourth substrate (not shown).
[0052] On any given substrate (e.g., 772, 782, 786), each cell
electrode is parallel to the other cell electrodes. In typical
implementations, the RF confining field is produced by applying RF
voltages to each cell electrode such that the RF voltage on any
given cell electrode is 180 degrees out of the phase with the RF
voltage on the adjacent cell electrode(s) on the same substrate. In
some embodiments, the RF voltage may be applied to only one pair of
opposing electrode sets, such as only to the first cell electrodes
774 and second cell electrodes 784, or only to the third cell
electrodes and fourth cell electrodes (if provided). DC voltages
may be applied to some or all of the cell electrodes and/or to
entrance and exit lenses as needed to control the axial motion of
the ions, including pulsing out to the mass analyzer 116 if
desired. In some embodiments, DC voltages may be applied to only
one pair of opposing electrode sets or to one pair of opposing
contiguous conductive layers. In the illustrated embodiment, the
first substrate 772 and the second substrate 782 (and thus the
first cell electrodes 774 and second cell electrodes 784) are
oriented so as to converge in the direction of the cell exit 750,
i.e., at an angle to the cell axis 744, such that the
cross-sectional area of the interior region at the cell entrance
748 is greater than the cross-sectional area at the cell exit 750.
In some embodiments, the cell electrodes may be oriented at an
angle ranging from about 0.5 degrees to about 10 degrees relative
to the cell axis 744. The third substrate 786 and the fourth
substrate (and thus any cell electrodes provided thereon) may
likewise converge toward each other relative to the cell axis 744,
or alternatively may be parallel to each other. In either case, the
electrode geometry illustrated in FIG. 7 generates a converging ion
confining region 778 as described above in conjunction with FIG.
2.
[0053] Similar to the embodiment illustrated in FIG. 6, the cell
electrodes have relatively small dimensions, resulting in an RF
confining field that is maintained in close proximity to the cell
electrodes and their respective substrates. This configuration may
have advantages as noted above. In FIG. 7, the RF confining field
is depicted by equipotential lines 792 distributed around each cell
electrode. Similarly distributed equipotential lines could be
visualized around the cross-section of each cell electrode in the
embodiment of FIG. 6.
[0054] In the examples illustrated in FIGS. 6 and 7, the ion
acceptance aperture and the ion emittance aperture are each
rectilinear in cross-section. In some embodiments, the ion
acceptance aperture has a height ranging from about 1 mm to about 3
mm and a width ranging from about 7.5 mm to about 20 mm. In some
embodiments, the ion emittance aperture has a height ranging from
about 0.05 mm to about 1 mm and a width ranging from about 5 mm to
about 15 mm.
[0055] In another embodiment (not shown), the cell electrodes of
the collision cell may generally have a parallel, elongated
multipole configuration as shown in FIG. 2. The converging ion
confining region 278 may be generated by varying the RF confining
field such that it has a predominant higher-order multipole field
component (e.g., a hexapole component) at the cell entrance 248 and
a predominant lower-order multipole field component (e.g., a
quadrupole component) at the cell exit 250. This may be
accomplished by applying appropriate RF voltages to the cell
electrodes 242, which in some embodiments may be axially segmented
to facilitate varying the RF confining field for this purpose. A
fuller description of this approach and additional examples of
electrode arrangements, albeit not in the context of a collision
cell, are provided in U.S. Pat. No. 8,124,930 the entire contents
of which are incorporated herein by reference.
[0056] FIG. 8 is a schematic view of an example of a mass
spectrometry (MS) system 800 according to another embodiment. The
MS system 800 generally includes an ion source 804, an ion scanning
trap 808, a collision cell 812, a mass spectrometer 816, and a
system controller (not shown). The foregoing devices which may be
the same or similar to the corresponding devices described above in
conjunction with FIG. 1. In this embodiment, the collision cell 812
is configured for establishing a converging ion confining region,
and thus may be configured as described above and illustrated in
FIGS. 2-7. Also in this embodiment, the mass spectrometer 816 is a
time-of-flight (TOF) mass spectrometer. The MS system 800 may
additionally include an ion storage trap 822 as described further
below. The MS system 800 may also include a suitable ion guide 826
between the ion source 804 and the ion storage trap 822, such as an
RF-only multipole ion guide or a system of electrostatic lenses.
The MS system 800 may also include ion optics between various
components as needed to control or enhance the transmission of ions
through the MS system 800. For example, an automatic gain control
(AGC) gate 832 may be located between the ion guide 826 and the ion
storage trap 822, which is useful for maintaining the total charge
(ion count) in the ion storage trap 822 at a constant level to
prevent space-charge effects that may distort the trapping field.
One or more ion lenses 836 may also be located between the ion
storage trap 822 and the ion scanning trap 808, and one or more ion
lenses 840 may be located between the ion scanning trap 808 and the
collision cell 812.
[0057] In this embodiment, the mass spectrometer 816 includes a TOF
analyzer 858 and an ion detector 862. The TOF analyzer 858 includes
an ion pulser (or ion extraction region) 846 and a flight tube 856.
The ion pulser 846 includes a set of electrodes (e.g., grids or
apertured plates) communicating with voltage sources for applying a
pulsed electric field sufficient to extract ions from the ion
pulser 846 into the flight tube 856. The flight tube 856 defines an
electric field-free drift region through which ions drift toward
the ion detector 862. The ion detector 862 may be any detector
suitable for use in the TOF mass spectrometer 816, a few
non-limiting examples being an electron multiplier with a flat
dynode and a microchannel plate detector. The ion detector 862
detects the arrival of ions (or counts the ions) and produces
representative ion detection signals. In the present example, the
TOF mass spectrometer 816 is arranged as an orthogonal TOF MS--that
is, the direction in which ions are extracted and drift through the
flight tube 856 is generally orthogonal (or at least at an
appreciable angle) to the direction in which ions are transmitted
into the ion pulser 846. In other examples, the TOF mass
spectrometer 816 may be on-axis with the path of ions ejected from
the collision cell 812. Also in the present example, the TOF mass
spectrometer 816 includes a single- or multi-stage ion reflector
(or reflectron) 860 that turns the path of the ions generally 180
degrees to focus their kinetic energy before their arrival at the
detector 862, as appreciated by persons skilled in the art. The
resulting ion flight path in this example is generally indicated at
862. In other embodiments, the reflector 860 is not utilized and
the ion pulser 846 and detector 862 may be located at opposite ends
of the flight tube 856.
[0058] The MS system 800 may also include ion optics 866 between
the collision cell 812 and the mass spectrometer 816. The ion
optics 866 may be configured as an ion slicer that ensures that the
geometry of the ion beam from the collision cell 812 matches the
acceptance area of ion pulser 846 and that the transverse energy
distribution is a desired (low) value. However, in some embodiments
the low emittance provided by the collision cell 812 as described
herein is effective enough that the ion slicer is not needed.
[0059] The ion storage trap 822 generally may have any
configuration suitable for collecting ions from the ion source 804,
storing the ions for a desired period of time (e.g., the duration
of the ion scanning trap cycle), and transferring ions of a
selected mass range out to the ion scanning trap 808. Hence, the
ion storage trap 822 may have a 2D or 3D configuration similar to
any of those described above in relation to the ion scanning trap
808, including RF and DC voltage sources, and may be enclosed in a
vacuum chamber (not shown). Ion ejection from the ion storage trap
822 may be axial or radial.
[0060] Another example of a method for acquiring a mass spectrum
from a sample of interest will now be described with reference to
FIG. 8. Parent ions are transmitted from the ion source 804,
through the ion guide 826, and into the ion storage trap 822. The
ion count in the ion storage trap 822 may be controlled by the AGC
gate 832 as noted above to avoid accumulating an excessive number
of parent ions. The parent ions may be transmitted into the ion
storage trap 822 essentially any time other than when the ion
storage trap 822 is in the process of transmitting ions into the
ion scanning trap 808. The ion storage trap 822 may hold the parent
ions until the ion scanning trap 808 is ready to receive them. The
ion storage trap 822 then transmits the parent ions into the ion
scanning trap 808, which may be done essentially any time other
than when the ion scanning trap 808 is in the process of
transmitting ions into the collision cell 812. The inclusion of the
ion storage trap 822 enables ion transfer efficiency to approach
100%. In some embodiments, however, the ion storage trap 822 may be
eliminated and the AGC gate 832 utilized to control loading
directly into the ion scanning trap 808. In this latter case, an
upper limit on ion transfer efficiency is set by the loading/duty
cycle of the ion scanning trap 808, but the efficiency may still be
greater than 90%.
[0061] After accumulation, the ion scanning trap 808 transfers
first parent ions into the collision cell 812 where at least some
of the first parent ions dissociate into fragment ions as described
above. The parent ions exiting the ion scanning trap 808 may have a
wide range of energies, for example ranging from less than 1 eV to
several keV. The energy range may scale linearly with m/z ratio.
For example, ions of m/z=100 may have energies ranging from about 0
eV to about 150 eV, and ions of m/z=1000 may have energies ranging
from about 0 eV to about 150 eV. The parent ions may be permitted
to enter the collision cell 812 with the full range of exit
energies. Alternatively, the ion lens(es) 840 may be configured to
adjust the energy range to higher or lower scales as desired, such
as by adjusting the DC voltage(s) applied to the ion lens(es) 840
and the collision cell 812. In either case, the ion funnel
configuration of the collision cell 812 enables high collection
efficiency for both parent and fragment ions that have a wide
energy spread.
[0062] After dissociation, fragment ions and non-fragmented first
parent ions are then transferred into the ion pulser 846 of the TOF
analyzer 858, and the ion pulser 846 injects ion packets into the
flight tube 856 at a controlled pulse rate. In some embodiments,
the collision cell 812 is likewise configured to eject the ions in
pulses. The timing of the ejection pulses from the collision cell
812 may be matched with the timing of the injection pulses into the
flight tube 856 from the ion pulser 846 so as to minimize duty
cycle losses in the ion pulser 846 and retain or improve the
resolution of the resulting mass spectrum.
[0063] As noted previously in the present disclosure, the
above-described process may be repeated for all other parent ions
held in the ion scanning trap 808 to obtain a mass spectrum from
all combinations of parent ions (or any desired subset of parent
ion m/z ratios) and from all fragment ions derived from each parent
ion m/z ratio. As an example, the ion scanning trap 808 may be
capable of scanning a full mass range of 2000 Da in about 0.04 s to
about 2 s, with corresponding trap scan rates ranging from about
50,000 Da/s down to about 1000 Da/s. Collision cell mixing times
may range, for example, from about 10 .mu.s to about 1000 .mu.s.
The number of TOF transients per Da of trap scan time may range
from 1 to 5, and TOF pulse periods may range from about 20 .mu.s to
about 200 .mu.s. The faster scan rates, shorter scan times, shorter
TOF pulse periods, and smaller collision cell mixing times all
contribute to improving the spectral dynamic range of the MS system
800. The improved values for these parameters are enabled at least
in part by the use of the ion scanning trap 808 as the ion
selection device in front of the collision cell 812 and by the use
of an ion funnel design for the collision cell 812. In practice,
the dynamic range may be increased by as much as a factor of 40 or
more in comparison to conventional systems.
[0064] As described above, the ion loading time into the ion
storage trap 822 may be controlled to enable a desired number of
parent ions (e.g., 10.sup.4 ions) to be accumulated in the ion
storage trap 822, after which all of the parent ions may be
transferred into the ion scanning trap 808 without exceeding its
trap capacity (as may be dictated by space-charge effects). The ion
storage trap 822 may also be utilized to pre-select a desired
subset of the full mass range originated in the ion source 804, and
transfer the ions in this selected mass range to the ion scanning
trap 808. This may be desirable for loading a larger number of ions
in the selected mass range into the ion scanning trap 808 without
exceeding its trap capacity.
[0065] In another embodiment, an additional ion funnel device (not
shown) may be positioned between the ion scanning trap 808 and the
collision cell 812. The additional ion funnel device may be
utilized to collect the parent ions of a selected mass from the ion
scanning trap 808 and cool them down into a smaller energy
distribution, and then transfer them into the ion funnel of the
collision cell 812 for fragmentation.
[0066] As noted above, it may be desirable to provide a device (or
means) for adjusting the energy distribution (or energy range) of
ions ejected from the ion scanning trap 808. For the case of
transverse ejection from a linear ion trap or ejection from a 3D
ion trap, the ejected ions appear in pulses at a frequency equal to
the secular frequency of those ions in the trap just prior to
ejection. It has been found that within each pulse, the ion energy
may vary over a wide range but depends on the precise time (or
phase) of ejection within the RF cycle. As an example, FIG. 9
illustrates the envelope of ion ejection count (number of ions) as
a function of ion ejection time (ns) for a single mass (the peak
curve), and the ejection energy (eV) of each individual ion as a
function of the ion's ejection time (the series of dots). FIG. 10
is a zoomed-in view of one of these pulses, and shows that the
average ion energy within each pulse follows a time-dependent
function. In some implementations, it is desirable to compress or
narrow the energy distribution of the ions before they undergo
fragmentation in a collision cell, as schematically depicted by
arrows in FIG. 10. The narrower energy distribution may provide one
or more advantages, such as increasing ion collection efficiency or
facilitating better control over preferred fragmentation pathways
in the collision cell.
[0067] In accordance with the present disclosure, a device (or
means) for adjusting the ion energy distribution is provided. In
some embodiments, the device may include a combination of ion
optics elements (e.g., lenses, electrodes, or the like) that are
positioned at (i.e., at or proximate to) the trap exit of the ion
scanning trap, or at some distance between the trap exit and the
collision cell. In some embodiments, such a device is schematically
represented by the ion lens(es) 840 illustrated in FIG. 8. Another
embodiment is illustrated in FIGS. 11-13. FIG. 11 is a
cross-sectional view of an example of a linear ion trap 1108 (in
the transverse plane, relative to the elongated dimension) that may
be deployed as an ion scanning trap in the manner described earlier
in this disclosure. The linear ion trap 1108 includes a quadrupolar
arrangement of trap electrodes 1124, which in the illustrated
example have hyperbolic profiles. The linear ion trap 1108 is
configured for transverse (or radial) ejection, and accordingly one
of the trap electrodes 1124 includes an elongated aperture serving
as a trap exit 1130. In this embodiment, a device 1140 for
adjusting ion energy distribution is integrated with the linear ion
trap 1108. The device 1140 may include one or more lenses, one or
more of which may be positioned in the trap exit 1130. FIG. 12 is a
cross-sectional view of a portion of the trap electrode 1124 at
which the device 1140 is located. In this example, the device 1140
includes a first exit lens 1252, a second exit lens 1254 and a
third exit lens 1256. One or more RF potentials and DC offsets may
be applied to one or more of the lenses 1252, 1254 and 1256 as
needed to adjust ion energy and focus the ion beam. For example, RF
potentials, phases and offsets may be applied to the first exit
lens 1252 and second exit lens 1254, and adjusted to selected
values to both focus ions exiting the linear ion trap 1108 and
re-adjust their energies to pass through the third lens 1256 (to
which a DC voltage may be applied) at close to the same energy.
This is illustrated by example in FIG. 13, which includes some
equipotential lines 1362 and ion trajectories 1364 generated by ion
simulation software.
[0068] In other embodiments, a device for adjusting ion energy
distribution such as the device 1140 may be adapted for use with a
3D ion trap.
[0069] For any of the devices described herein that utilize axially
elongated electrodes (or rods), one or more of such electrodes may
have a composite structure that includes a central electrically
conductive core (or conductive layer surrounding a central core of
another material), an electrically insulating layer coaxially
surrounding the conductive core or layer, and an outer electrically
resistive layer coaxially surrounding the insulating layer.
Electrical interconnections may be made from voltage sources to
both the conductive core or layer and the resistive layer. Such
electrode configurations are described in further detail in U.S.
Pat. No. 7,064,322, the entire contents of which are incorporated
herein by reference.
[0070] It will be understood that one or more of the processes,
sub-processes, and process steps described herein may be performed
by hardware, firmware, software, or a combination of two or more of
the foregoing, on one or more electronic or digitally-controlled
devices. The software may reside in a software memory (not shown)
in a suitable electronic processing component or system such as,
for example, the system controller 120 schematically depicted in
FIG. 1. The software memory may include an ordered listing of
executable instructions for implementing logical functions (that is
"logic" that may be implemented in digital form such as digital
circuitry or source code, or in analog form such as an analog
source such as an analog electrical, sound, or video signal). The
instructions may be executed within a processing module, which
includes, for example, one or more microprocessors, general purpose
processors, combinations of processors, digital signal processors
(DSPs), or application specific integrated circuits (ASICs).
Further, the schematic diagrams describe a logical division of
functions having physical (hardware and/or software)
implementations that are not limited by architecture or the
physical layout of the functions. The examples of systems described
herein may be implemented in a variety of configurations and
operate as hardware/software components in a single
hardware/software unit, or in separate hardware/software units.
[0071] The executable instructions may be implemented as a computer
program product having instructions stored therein which, when
executed by a processing module of an electronic system (e.g., the
system controller 120 in FIG. 1), direct the electronic system to
carry out the instructions. The computer program product may be
selectively embodied in any non-transitory computer-readable
storage medium for use by or in connection with an instruction
execution system, apparatus, or device, such as a electronic
computer-based system, processor-containing system, or other system
that may selectively fetch the instructions from the instruction
execution system, apparatus, or device and execute the
instructions. In the context of this disclosure, a
computer-readable storage medium is any non-transitory means that
may store the program for use by or in connection with the
instruction execution system, apparatus, or device. The
non-transitory computer-readable storage medium may selectively be,
for example, an electronic, magnetic, optical, electromagnetic,
infrared, or semiconductor system, apparatus, or device. A
non-exhaustive list of more specific examples of non-transitory
computer readable media include: an electrical connection having
one or more wires (electronic); a portable computer diskette
(magnetic); a random access memory (electronic); a read-only memory
(electronic); an erasable programmable read only memory such as,
for example, flash memory (electronic); a compact disc memory such
as, for example, CD-ROM, CD-R, CD-RW (optical); and digital
versatile disc memory, i.e., DVD (optical). Note that the
non-transitory computer-readable storage medium may even be paper
or another suitable medium upon which the program is printed, as
the program can be electronically captured via, for instance,
optical scanning of the paper or other medium, then compiled,
interpreted, or otherwise processed in a suitable manner if
necessary, and then stored in a computer memory or machine
memory.
[0072] It will also be understood that the term "in signal
communication" as used herein means that two or more systems,
devices, components, modules, or sub-modules are capable of
communicating with each other via signals that travel over some
type of signal path. The signals may be communication, power, data,
or energy signals, which may communicate information, power, or
energy from a first system, device, component, module, or
sub-module to a second system, device, component, module, or
sub-module along a signal path between the first and second system,
device, component, module, or sub-module. The signal paths may
include physical, electrical, magnetic, electromagnetic,
electrochemical, optical, wired, or wireless connections. The
signal paths may also include additional systems, devices,
components, modules, or sub-modules between the first and second
system, device, component, module, or sub-module.
[0073] More generally, terms such as "communicate" and "in . . .
communication with" (for example, a first component "communicates
with" or "is in communication with" a second component) are used
herein to indicate a structural, functional, mechanical,
electrical, signal, optical, magnetic, electromagnetic, ionic or
fluidic relationship between two or more components or elements. As
such, the fact that one component is said to communicate with a
second component is not intended to exclude the possibility that
additional components may be present between, and/or operatively
associated or engaged with, the first and second components.
[0074] It will be understood that various aspects or details of the
invention may be changed without departing from the scope of the
invention. Furthermore, the foregoing description is for the
purpose of illustration only, and not for the purpose of
limitation--the invention being defined by the claims.
* * * * *