Note: Descriptions are shown in the official language in which they were submitted.
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MASS SPECTROMETER
Field
This invention relates to ion mobility spectrometers.
Background
With the decoding of the 20-30,000 genes that
compose the human genome, emphasis has switched to the
identification of the translated gene products that
comprise the proteome. Mass spectrometry has firmly
established itself as the primary technique for
identifying proteins due to its unparalleled speed,
sensitivity and specificity. Strategies can involve
either analysis of the intact protein, or more commonly
digestion of the protein using a specific protease that
cleaves at predictable residues along the peptide
backbone. This provides smaller stretches of peptide
sequence that are more amenable to analysis via mass
spectrometry.
The mass spectrometry technique providing the
highest degree of specificity and sensitivity is
Electrospray ionisation ("ESI") interfaced to a tandem
mass spectrometer. These experiments involve separation
of the complex digest mixture by microcapillary liquid
chromatography with on-line mass spectral detection
using automated acquisition modes whereby conventional
MS and MS/MS spectra are collected in a data dependant
manner. This information can be used directly to search
databases for matching sequences leading to
identification of the parent protein. This approach can
be used to identify proteins that are present at low
endogenous concentrations. However, often the limiting
factor for identification of the protein is not the
quality of the MS/MS spectrum produced but is the
initial discovery of the multiply charged peptide
precursor ion in the MS mode. This is due to the level
of background chemical noise, largely singly charged in
nature, which may be produced in the ion source of the
mass spectrometer. Fig. 1 shows a typical conventional
mass spectrum and illustrates how doubly charged species
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may be obscured amongst a singly charged background. A
method whereby the chemical noise is reduced so that the
mass spectrometer can more easily target peptide related
ions would be highly advantageous for the study of
protein digests.
A known method used to favour the detection of
multiply charged species over singly charged species is
to use an Electrospray ionisation orthogonal
acceleration time of flight mass analyser ("ESI-oaTOF").
The orthogonal acceleration time of flight mass analyser
counts the arrival of ions using a Time to Digital
Converter ("TDC") which has a discriminator threshold.
The voltage pulse of a single ion must be high enough to
trigger the discriminator and so register the arrival of
an ion. The detector producing the voltage may be an
electron multiplier or a Microchannel Plate detector
("MCP"). These detectors are charge sensitive so the
size of signal they produce increases with increasing
charge state. Discrimination in favour of higher charge
states can be accomplished by increasing the
discriminator voltage level, lowering the detector gain,
or a combination of both. Fig. 2(a) shows a mass
spectrum obtained with normal detector gain and Fig.
2(h) shows a comparable mass spectrum obtained with a
reduced detector gain. An important disadvantage of
lowering the detector gain (or of increasing the
discriminator level) is that the sensitivity is lowered.
As can be seen from the ordinate axes of Figs. 2(a) and
(b), the sensitivity is reduced by a factor of -x4 when
a lower detector gain is employed. Using this method it
is also impossible to pick out an individual charge
state. Instead, the best that can be achieved is a
reduction of the efficiency of detection of lower charge
states with respect to higher charge states.
Another ionisation technique that has been recently
coupled to tandem mass spectrometers for biological mass
spectrometry is Matrix Assisted Laser Desorption
Ionisation ("MALDI"). When a MALDI ion source is used
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high levels of singly charged matrix related ions and
chemical noise are generated which make it difficult
to identify candidate peptide ions.
Summary
It is therefore desired to provide an improved mass
spectrometer and method of mass spectrometry which does
not suffer from some or all of the disadvantages of the
prior art.
According to a first aspect of present invention
there is provided a method of mass spectrometry
comprising: providing a pulse of ions and performing the
following steps before providing another pulse of ions:
(a) temporally separating at least some of the ions
according to their ion mobility in a first device; (b)
mass filtering at least some of the ions according to
their mass to charge ratio in a second device; and (c)
progressively varying a mass filtering characteristic
of the second device so that ions having a first charge
state are onwardly transmitted in preference to ions
having a second different charge state.
The preferred embodiment is particularly
advantageous in that it allow ions with a chosen charge
state to be selected from a mixture of ions having
differing charge states. Another advantage is that
sensitivity for this technique is greater than the known
discriminator level technique as the detector can be run
at full gain and all ions present may be counted.
According to the preferred embodiment, multiply
charged ions (which may include doubly, triply and
quadruply charged ions and ions having five or more
charges) may be preferentially selected and transmitted
whilst the intensity of singly charged ions may be
reduced. In other embodiments any desired charged state
or states may be selected. For example, two or more
multiply charged states may be transmitted.
The first device preferably comprises an ion
mobility spectrometer or other ion mobility device.
Ions in an ion mobility spectrometer may be subjected
to an electric field in the presence of a buffer gas so
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that different species of ion acquire different
velocities and are temporally separated according to
their ion mobility. The mobility of an ion in an ion
mobility spectrometer typically depends inter alia upon
its mass and its charge. Heavy ions with one charge
tend to have lower mobilities than light ions with one
charge. Also an ion of a particular mass to charge
ratio with one charge tends to have a lower mobility
than an ion with the same mass to charge ratio but
carrying two (or more) charges.
The ion mobility spectrometer may be similar to a
known ion mobility spectrometer comprising a drift tube
together with one or more electrodes for maintaining an
axial DC voltage gradient along at least a portion of
the drift tube.
Alternatively, the ion mobility spectrometer may
comprise a Field Asymmetric Ion Mobility Spectrometer
("FAIMS"). In one embodiment a FAIMS may comprise two
axially aligned inner cylinders surrounded by a long
outer cylinder. The outer cylinder and a shorter inner
cylinder are preferably held at the same electrical
potential. A longer inner cylinder may have a high
frequency high voltage asymmetric waveform applied to
it, thereby establishing an electric field between the
inner and outer cylinders. A compensation DC voltage is
also applied to the longer inner cylinder. A FAIMS acts
like a mobility filter and may operate at atmospheric
pressure.
However, according to a particularly preferred
embodiment, a new form of ion mobility spectrometer is
contemplated comprising a plurality of electrodes having
apertures wherein a DC voltage gradient is maintained
across at least a portion of the ion mobility
spectrometer and at least some of the electrodes are
connected to an AC or RF voltage supply. The new form
of ion mobility spectrometer is particularly
advantageous in that the addition of an AC or RF voltage
to the electrodes (which may be ring like or otherwise
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annular) results in radial confinement of the ions
passing through the ion mobility spectrometer. Radial
confinement of the ions results in higher ion
transmission compared with conventional ion mobility
spectrometers of the drift tube type.
The second device may preferably take one of two
main forms. The first main preferred embodiment uses a
quadrupole rod set mass filter and the second main
preferred embodiment uses an axial time of flight drift
region and a synchronised pusher electrode.
With regards the first main preferred embodiment,
the quadrupole mass filter may be operated as a high
pass mass to charge ratio filter so as to transmit
substantially only ions having a mass to charge ratio
greater than a minimum value. In this embodiment
multiply charged ions can be preferentially transmitted
compared to singly charged ions (i.e. doubly, triply,
quadruply and ions having five or more charges may be
transmitted whilst singly charged ions are attenuated).
According to another embodiment, the quadrupole
mass filter may be operated as a band pass mass to
charge ratio filter so as to substantially transmit only
ions having a mass to charge ratio greater than a
minimum value and smaller than a maximum value. This
embodiment is particularly advantageous in that multiply
charged ions of a single charge state e.g. triply
charged, may be preferentially transmitted whilst ions
having any other charge state are relatively attenuated.
However, according to another embodiment ions having two
or more neighbouring charge states (e.g. doubly and
triply charged ions) may be transmitted and all other
charge states may be attenuated. Embodiments are also
contemplated wherein non-neighbouring charge states are
selected (e.g. doubly and quadruply charged ions).
The quadrupole mass filter is preferably scanned so
that the minimum mass to charge ratio cut-off is
progressively increased during a cycle (which is defined
as the period between consecutive pulses of ions being
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admitted into the ion mobility spectrometer). The
quadrupole mass filter may be scanned in a substantially
continuous (i.e. smooth) manner or alternatively the
quadruple mass filter may be scanned in a substantially
stepped manner.
According to the second main preferred embodiment,
the second device may comprise a drift region,
preferably free of any buffer gas and preferably an
axial drift region, having an axis and an injection
electrode for injecting at least some ions in a
direction substantially orthogonal to the axis. The
injection electrode may comprise a pusher and/or puller
electrode of an orthogonal acceleration time of flight
mass analyser.
A particularly preferred feature is to provide an
ion trap upstream of the drift region. This ion trap is
separate to an ion trap which may be provided preferably
upstream of the ion mobility spectrometer. The ion trap
may preferably store and periodically release ions so
that a pulsed (rather than a continuous) source of ions
is admitted or otherwise inputted in to the drift
region. The injection electrode is arranged to inject
ions a predetermined period of time after ions have
first been released from the ion trap upstream of the
drift region. The period of time is set so that only
ions having a desired mass to charge ratio or a mass to
charge ratio within a desired range are substantially
injected by the injection electrode in an orthogonal
direction and are hence onwardly transmitted.
In a preferred embodiment a single packet of ions
is released from the ion trap and then the predetermined
time delay is slightly increased. The process of
increasing the time delay may be repeated a number of
times (e.g. 40-50 times) during one cycle of ions being
input into the ion mobility spectrometer.
According to another embodiment, a number of
packets of ions (e.g. 4-5 packets) may be repeatedly
released from the ion trap before the predetermined time
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delay is progressively increased. As with the other
embodiment, the process of increasing the time delay may
be repeated a number of times during one cycle.
At the upstream end of the mass spectrometer, the
ion source may be a pulsed ion source such as a Matrix
Assisted Laser Desorption Ionisation ("MALDI") ion
source. The pulsed ion source may alternatively
comprise a Laser Desorption Ionisation ion source which
is not matrix assisted.
Alternatively, and more preferably, a continuous
ion source may be used in which case an ion trap for
storing ions and periodically releasing ions is also
preferably provided. Continuous ion sources which may
be used include Electrospray, Atmospheric Pressure
Chemical Ionisation ("APCI"), Electron Impact ("EI"),
Atmospheric Pressure Photon Ionisation ("APPI") and
Chemical Ionisation ("CI") ion sources. Other
continuous or pseudo-continuous ion sources may also be
used. In an embodiment the mass spectrometer may be a
Fourier Transform mass spectrometer or a Fourier
Transform Ion Cyclotron Resonance mass spectrometer.
A collision cell may be provided in both the main
preferred embodiments. In one mode of operation at
least some ions entering the collision cell are caused
to fragment.
An orthogonal acceleration time of flight mass
analyser is particularly preferred for both main
preferred embodiments, although another type of mass
analyser such as a quadrupole mass analyser or a 3D ion
trap are also contemplated.
According to a second aspect of the present
invention, there is provided a method of mass
spectrometry comprising: providing a pulse of ions;
separating at least some of the ions according to their
ion mobility in an ion mobility spectrometer; using a
mass filter having a variable mass to charge ratio cut-
off to mass filter at least some of the ions; and
progressively increasing the mass to charge ratio cut-
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off in synchronisation with the ion mobility
spectrometer.
According to a third aspect of the present
invention, there is provided a method of mass
spectrometry comprising: separating at least some ions
according to their ion mobility; mass filtering at least
some ions; and arranging for multiply charged ions to be
transmitted and for singly charged ions to be
attenuated.
According to a fourth aspect of the present
invention, there is provided a method of reducing
unwanted singly charged ions from a mass spectrum,
comprising: separating ions in an ion mobility
spectrometer; passing the ions to a mass filter; and
arranging the mass filter to have a mass to charge ratio
cut-off which increases in time, the cut-off being
predetermined based upon the known drift times of singly
and doubly charged ions through the ion mobility
spectrometer.
According to a fifth aspect of the present
invention, there is provided a method of mass
spectrometry, comprising: providing a pulse of ions;
temporally separating at least some of the ions
according to their ion mobility in an ion mobility
spectrometer; providing a quadrupole rod set mass
filter; and progressively increasing a mass to charge
ratio cut-off of the mass filter so that multiply
charged ions are onwardly transmitted in preference to
singly charged ions.
According to a sixth aspect of the present
invention, there is provided a method of mass
spectrometry, comprising: providing a pulse of ions;
temporally separating at least some of the ions
according to their ion mobility in an ion mobility
spectrometer; providing a drift region and an injection
electrode; repeatedly pulsing ions into the drift region
and causing the injection electrode to inject at least
some of the ions in a substantially orthogonal direction
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after a delay time; and repeatedly increasing the delay
time; wherein multiply charged ions are onwardly
transmitted in preference to singly charged ions.
According to a seventh aspect of the present
invention, there is provided a mass spectrometer
comprising: a first device for temporally separating
ions according to their ion mobility; a second device
for mass filtering at least some of the ions according
to their mass to charge ratio; and a controller which is
arranged to progressively vary a mass filtering
characteristic of the second device so that ions having
a first charge state are onwardly transmitted in
preference to ions having a second charge state.
According to an eighth aspect of the present
invention, there is provided a mass spectrometer
comprising: an ion mobility spectrometer; a quadrupole
mass filter; and control means for progressively
increasing the mass to charge ratio cut-off of the
quadrupole mass filter in synchronisation with the ion
mobility spectrometer.
According to a ninth aspect of the present
invention, there is provided a mass spectrometer
comprising: an ion source; an ion mobility spectrometer
for separating ions according to both their mass and
charge state; a mass filter; control means for
controlling the ion mobility spectrometer and the mass
filter; and a mass analyser; wherein the control means
is arranged to control the ion mobility spectrometer and
the mass filter to attenuate ions having a first charge
state so that there is a higher proportion of ions
having a second charge state to ions having the first
charge state downstream of the ion mobility spectrometer
and the mass filter compared with upstream of the ion
mobility spectrometer and the mass filter.
According to a tenth aspect of the present
invention, there is provided a mass spectrometer
comprising: an ion source; a mass filter; an ion
mobility spectrometer arranged downstream of the mass
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filter; and a mass analyser; wherein the mass filter and
the ion mobility spectrometer are operated, in use, so
that doubly and/or other multiply charged ions are
transmitted to the mass analyser and singly charged ions
are attenuated.
According to an eleventh aspect of the present
invention, there is provided a mass spectrometer
comprising: a continuous ion source; a first ion trap;
an ion mobility spectrometer downstream of the first ion
trap, the ion mobility spectrometer comprising a
plurality of electrodes having apertures therein through
which ions may be transmitted, wherein in use a DC
voltage gradient is maintained across at least a portion
of the ion mobility spectrometer and at least some of
the electrodes are supplied with an AC or RF voltage,
and wherein at least some of the electrodes are housed
in a vacuum chamber maintained in use at a pressure
within the range 0.1-10 mbar; a quadrupole mass filter
downstream of the ion mobility spectrometer; and an
orthogonal time of flight mass analyser comprising a
pusher and/or puller electrode, orthogonal drift region
and detector, the orthogonal time of flight mass
analyser being arranged downstream of the quadrupole
mass filter.
According to a twelfth aspect of the present
invention, there is provided a mass spectrometer
comprising: a continuous ion source; a first ion trap;
an ion mobility spectrometer downstream of the first ion
trap, the ion mobility spectrometer comprising a
plurality of electrodes having apertures therein through
which ions may be transmitted, wherein in use a DC
voltage gradient is maintained across at least a portion
of the ion mobility spectrometer and at least some of
the electrodes are supplied with an AC or RF voltage,
and wherein at least some of the electrodes are housed
in a vacuum chamber maintained in use at a pressure
within the range 0.1-10 mbar; a second ion trap
downstream of the ion mobility spectrometer, the second
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ion trap comprising a plurality of electrodes having
apertures through which ions may be transmitted, at
least some of the electrodes being supplied in use with
an AC or RF voltage; an axial drift region downstream of
the second ion trap; and an orthogonal time of flight
mass analyser comprising a pusher and/or puller
electrode, orthogonal drift region and detector, the
orthogonal time of flight mass analyser being arranged
downstream of the axial drift region.
According to an thirteenth aspect of the present
invention, there is provided an ion mobility
spectrometer for separating ions according to their ion
mobility, the ion mobility spectrometer comprising: a
plurality of electrodes having apertures wherein a DC
voltage gradient is maintained across at least a portion
of the ion mobility spectrometer and at least some of
the electrodes are connected to an AC or RF voltage
supply.
The ion mobility spectrometer preferably extends
between two vacuum chambers so that an upstream section
comprising a first plurality of electrodes having
apertures is arranged in a vacuum chamber and a
downstream section comprising a second plurality of
electrodes having apertures is arranged in a further
vacuum chamber, the vacuum chambers being separated by a
differential pumping aperture.
At least some of the electrodes in the upstream
section are preferably supplied with an AC or RF voltage
having a frequency within the range 0.1-3.0 MHz. A
frequency of 0.5-1.1 MHz is preferred and a frequency of
780 kHz is particularly preferred. The upstream section
is preferably arranged to be maintained at a pressure
within the range 0.1-10 mbar, preferably approximately 1
mbar.
At least some of the electrodes in the downstream
section are preferably supplied with an AC or RF voltage
having a frequency within the range 0.1-3.0 MHz. A
frequency of 1.8-2.4 MHz is preferred and a frequency of
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2.1 MHz is particularly preferred. The downstream
section is preferably arranged to be maintained at a
pressure within the range 10-3-10-2 mbar.
The voltages applied to the electrodes in the
upstream section may be such that a first DC voltage
gradient is maintained in use across at least a portion
of the upstream section and a second different DC
voltage gradient may be maintained in use across at
least a portion of the downstream section, the first DC
voltage gradient being preferably greater than the
second DC voltage gradient. Either voltage gradient
does not necessarily have to be linear and indeed a
stepped voltage gradient is particularly preferred.
Preferably, the ion mobilityspectrometer comprises
at least 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100
electrodes. Preferably, at least 60%, 65%, 70%, 75%,
80%, 85%, 90%, 95% of the electrodes forming the ion
mobility spectrometer have apertures which are of
substantially the same size or area.
Other embodiments are contemplated wherein the
second device comprises either a 2D ion trap (e.g. a rod
set with front and/or rear trapping electrodes) or a 3D
ion trap (e.g. a central ring electrode with front and
rear endcap electrodes).
According to a fourteenth aspect of the present
invention, there is provided a method of mass
spectrometry, comprising:
scanning a Field Asymmetric Ion Mobility
Spectrometer ("FAIMS"); and
trapping ions in a 2D or 3D ion trap.
Preferably, the FAIMS is scanned by varying a DC
compensation voltage applied to the Field Asymmetric Ion
Mobility Spectrometer.
The Field Asymmetric Ion Mobility Spectrometer is
preferably selected from the group consisting of: (i)
two parallel plates; and (ii) at least one inner
cylinder and an outer cylinder.
According to a fifteenth aspect of the present
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invention, there is provided a mass spectrometer
comprising:
a Field Asymmetric Ion Mobility Spectrometer
("FAIMS"); and
a 2D or 3D ion trap;
wherein the Field Asymmetric Ion Mobility
Spectrometer is scanned in use.
According to a sixteenth aspect of the present
invention, there is provided a method of mass
spectrometry, comprising:
filtering ions using a Field Asymmetric Ion
Mobility Spectrometer ("FAIMS") so that a first group of
ions having a first mobility are transmitted;
mass filtering or trapping at least some of the
first group of ions so that ions having a desired charge
state(s) are onwardly transmitted;
varying the Field Asymmetric Ion Mobility
Spectrometer so that a second group of ions having a
second mobility different to the first mobility are
transmitted; and
mass filtering or trapping at least some of the
second group of ions so that ions having a desired
charge state(s) are onwardly transmitted.
Preferably, at least some of the ions having the
desired charge(s) which are onwardly transmitted are
subsequently mass analysed.
According to a seventeenth aspect of the present
invention, there is provided a mass spectrometer,
comprising:
a Field Asymmetric Ion Mobility Spectrometer
("FAIMS") arranged to filter ions so that a first group
of ions having a first mobility are transmitted;
a mass filter or ion trap operated so that at least
some of the first group of ions having a desired charge
state(s) are onwardly transmitted;
a controller for varying the Field Asymmetric Ion
Mobility Spectrometer so that a second group of ions
having a second mobility different to the first mobility
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are transmitted wherein the mass filter or ion trap
is operated so that at least some of the second group
of ions having a desired charge state(s) are onwardly
transmitted.
According to an eighteenth aspect of the present
invention, there is provided a mass spectrometer
comprising:
a Field Asymmetric Ion Mobility Spectrometer
("FAIMS") coupled to a mass filter so as to
preferentially select ions having a desired charge
state(s). Preferably, the Field Asymmetric Ion Mobility
Spectrometer is not scanned. The mass filter may be a
quadrupole, 2D or 3D ion trap or other mass filter.
Brief Description of the Drawings
Various embodiments of the present invention will
now be described, by way of example only, and with
reference to the accompanying drawings in which:
Fig. 1 shows a conventional mass spectrum;
Fig. 2(a) shows a conventional mass spectrum
obtained with normal detector gain, and Fig. 2(b) shows
a comparable conventional mass spectrum obtained by
lowering the detector gain;
Fig. 3(a) shows the known relationship between
flight time in a time of flight mass analyser drift
region versus drift time in an ion mobility spectrometer
for various singly and doubly charged ions, and Fig.
3(b) shows an experimentally determined relationship
between the mass to charge ratio of a sample of ions and
their drift time through an ion mobility spectrometer;
Fig. 4 illustrates the general principle of
filtering out singly charged ions according to a
preferred embodiment of the present invention;
Fig. 5 illustrates the general principle of
selecting ions having a specific charge state according
to a preferred embodiment of the present invention;
Fig. 6 shows a first main preferred embodiment of
the present invention;
Fig. 7(a) illustrates a preferred embodiment of an
ion trap, ion gate and ion mobility spectrometer, Fig.
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7(b) illustrates the various DC voltages which may be
applied to the ion trap, ion gate and ion mobility
spectrometer, Fig. 7(c) illustrates how the DC voltage
applied to the ion gate may vary as a function of time,
and Fig. 7(d) illustrates how a quadrupole mass filter
may be scanned according to a preferred embodiment;
Fig. 8 shows a second main preferred embodiment
of the present invention;
Fig. 9 shows how ions of differing mass to charge
ratios become temporally separated in an axial drift
region;
Fig. 10 illustrates how the duty cycle of an ion
trap-time of flight mass analyser increases to -100% for
a relatively narrow mass to charge ratio range compared
with a typical maximum duty cycle of -25% obtained by
operating the time of flight mass analyser in a
conventional manner;
Fig. 11(a) shows a conventional mass spectrum and
Fig. 11(b) shows a comparable mass spectrum obtained
according to a preferred embodiment of the present
invention; and
Fig. 12(a) shows another conventional mass spectrum
and Fig. 12(b) shows a comparable mass spectrum obtained
according to a preferred embodiment of the present
invention.
Detailed Description
Various embodiments of the present invention will
now be described. Fig. 3(a) shows the known
relationship of flight time in a drift region of a time
of flight mass analyser versus drift time in an ion
mobility spectrometer for various singly and doubly
charged ions. An experimentally determined relationship
between the mass to charge ratio of ions and their drift
time through an ion mobility spectrometer is shown in
Fig. 3(b). This relationship can be represented by an
empirically derived polynomial expression. As can be
seen from these figures, a doubly charged ion having
the same mass to charge ratio as a singly charged ion
will take less time to drift through an ion mobility
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spectrometer compared with a singly charged ion.
Although the ordinate axis of Fig. 3(a) is given as the
flight time through the drift region of a time of flight
mass analyser, it will be appreciated that this
correlates directly with the mass to charge ratio of the
ion.
The present inventors have recognised that if a
mass filter is provided in combination with an ion
mobility spectrometer, and if the mass filter is scanned
(i.e. the transmitted range of mass to charge ratios is
varied) in synchronisation with the drift of ions
through the ion mobility spectrometer, then it is
possible to arrange that only ions having a particular
charge state (e.g. multiply charged ions) will be
transmitted onwardly e.g. to a mass analyser. The
ability to be able to substantially filter out singly
charged background ions and/or to select ions of one or
more specific charge states for analysis represents a
significant advance in the art.
Fig. 4 illustrates an embodiment of the present
invention. The known data of Fig. 3(a) and the
experimentally derived data of Fig. 3(b) can be
interpreted such that all ions having the same charge
state can be considered to fall within a distinct region
or band of a 2D plot of mass to charge ratio versus
drift time through an ion mobility spectrometer. In
Fig. 4 singly and doubly charged ions are shown as
falling within distinct bands with an intermediate
region therebetween where very few ions of interest are
to be found. Triply and quadruply charged ions etc. are
not shown for ease of illustration only. The large area
below the "scan line" can be considered to represent
singly charged ions and the other area can be considered
to represent doubly charged ions.
According to a preferred embodiment, a mass filter
is provided which is synchronised with the operation of
an ion mobility spectrometer. Considering Fig. 4, it
can be seen that at a time around 4 ms after ions have
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first entered or been admitted to the drift region of
the ion mobility spectrometer, ions may be emerging from
the ion mobility spectrometer with various different
mass to charge ratios. Those ions which emerge with a
mass to charge ratio of approximately 1-790 are most
likely to be singly charged ions whereas those ions
emerging with a mass to charge ratio of approximately
1070-1800 are most likely to be doubly charged ions.
Very few, if any, ions will emerge at that point of time
with a mass to charge ratio between 790-1070 (which
corresponds with the intermediate region of the graph).
Therefore, if the mass filter is set at this particular
point in time so as to transmit only ions having a mass
to charge ratio > 790 then it can be assumed that the
majority of the singly charged ions will not be onwardly
transmitted whereas doubly charged ions (and ions having
a higher charge state) will be substantially onwardly
transmitted. If the mass filter is operated as a high
pass mass filter and if the minimum cut-off mass to
charge ratio of the mass filter follows in real time the
"scan line" shown in Fig. 4 (i.e. if it tracks the upper
predetermined mass to charge ratio for singly charged
ions as a function of time) then it will be appreciated
that only multiply charged ions will substantially be
onwardly transmitted.
According to other embodiments the mass filter may
track the lower predetermined mass to charge ratio for
doubly charged ions. The cut-off mass to charge ratio
may also lie for at least a portion of a cycle within
the intermediate region which separates the regions
comprising singly and doubly charged ions. The minimum
cut-off mass to charge ratio of the mass filter may also
vary in a predetermined or random manner between the
upper threshold of the singly charged ion region, the
intermediate region and the lower threshold of the
doubly charged ion region. It will also be appreciated
that according to less preferred embodiments, the
minimum cut-off mass to charge ratio may fall for at
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least a portion of time within the region considered to
comprise either singly or doubly charged ions. In such
circumstances, ions of a potentially unwanted charge
state may still be transmitted, but the intensity of
such ions will nonetheless be reduced.
According to a preferred embodiment the minimum
cut-off mass to charge ratio is varied smoothly, and is
preferably increased with time. Alternatively, the
minimum cut-off mass to charge ratio may be increased in
a stepped manner.
Fig. 5 illustrates how the basic embodiment
described in relation to Fig. 4 may be extended so that
ions of a specific charge state(s) may be selected. In
the embodiment illustrated in Fig. 5 the mass filter is
operated as a band pass mass to charge ratio filter so
as to select ions of a specific charge state (in this
case triply charged ions) in preference to ions having
any other charge state. At a time T after ions have
first been admitted or introduced into the ion mobility
spectrometer, the mass filter, being operated in a band
pass mode, is set so as to transmit ions having a mass
to charge ratio > P and < Q, wherein P preferably lies
on the upper threshold of the region containing doubly
charged ions and Q preferably lies on the lower
threshold of the region containing quadruply charged
ions. The upper and lower mass cut-offs P,Q are
preferably smoothly increased with time so that at a
later time T', the lower mass to charge ratio cut-off of
the band pass mass to charge ratio filter has been
increased from P to P' and the upper mass to charge
ratio cut-off of the band pass mass to charge ratio
filter has been increased from Q to Q. As with the
embodiment described in relation to Fig. 4, the upper
and lower mass to charge ratio cut-offs do not need to
follow the lower and upper thresholds of any particular
charge state region, and according to the other
embodiments the upper and lower cut-offs may fall within
one or more intermediate regions and/or one or more of
CA 02714930 2010-09-17
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the bands in which ions having a particular charge state
are to be found. For example, in one embodiment, the
lower and upper mass to charge ratio cut-offs may simply
follow the thresholds of the region comprising doubly,
triply, quadruply etc. charged ions. According to other
embodiments two, three, four or more charge states may
be selected in preference to any other charge state
(e.g. doubly and triply charged ions may be
transmitted). Embodiments are also contemplated wherein
non-neighbouring charge states (e.g. doubly and
quadruply charged ions) are transmitted but not any
other charge states.
Fig. 6 shows a first main preferred embodiment of
the present invention. An ion mobility spectrometer 4
is provided. A pulse of ions is admitted to the ion
mobility spectrometer 4. A continuous ion source, e.g.
Electrospray ion source, preferably generates a beam of
ions 1 which are trapped in an ion trap 2 upstream of
the ion mobility spectrometer 4 and are then pulsed out
of the ion trap 2 by the application of an extraction
voltage to an ion gate 3 at the exit of the ion trap 2.
The ion trap 2 may comprise a quadrupole rod set
having a length of approximately 75 mm. However,
according to a more preferred embodiment the ion trap
may comprise an ion tunnel comprising a plurality of
electrodes having apertures therein. The apertures are
preferably all the same size. In other embodiments at
least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the
electrodes have apertures which are substantially the
same size. The ion tunnel may preferably comprise
approximately 50 electrodes. Adjacent electrodes are
preferably connected to opposite phases of an AC or RF
voltage supply so that ions are radially confined in use
within the ion tunnel.
The voltage applied to the ion gate 3 may be
dropped for a short period of time thereby causing ions
to be ejected from the ion trap 2 in a substantially
pulsed manner into the ion mobility spectrometer 4.
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In less preferred embodiments, a pulsed ion source
such as a Matrix Assisted Laser Desorption Ionisation
("MALDI") ion source or a Laser Desorption Ionisation
ion source may be used instead of a continuous ion
source. If a pulsed ion source is used, then ion trap 2
and ion gate 3 may be omitted.
The ion mobility spectrometer 4 is a device which
causes ions to become temporally separated based upon
their ion mobility. A number of different forms of ion
mobility spectrometer may be used.
In one embodiment, the ion mobility spectrometer 4
may comprise a conventional ion mobility spectrometer
consisting of a drift tube having a number of guard
rings distributed within the drift tube. The guard
rings may be interconnected by equivalent valued
resistors and connected to a DC voltage source. A
linear DC voltage gradient is generated along the length
of the drift tube. The guard rings are not connected to
an AC or RF voltage source.
In another embodiment, the ion mobility
spectrometer 4 may comprise a Field Asymmetric Ion
Mobility Spectrometer ("FAIMS").
According to a particularly preferred embodiment, a
new form of ion mobility spectrometer 4 is preferably
provided. According to this embodiment the ion mobility
spectrometer 4 comprises a number of ring/annular or
plate electrodes, or more generally electrodes having an
aperture therein through which ions are transmitted.
The apertures are preferably all the same size and are
preferably circular. In other embodiments at least 60%,
65%, 70%, 75%, 80%, 85%, 90% or 95% of the electrodes
have apertures which are substantially the same size or
area. A schematic example of the new form of ion
mobility spectrometer 4 is shown in Fig. 7(a). The ion
mobility spectrometer 4 may comprise a plurality of
electrodes 4a,4b which are either arranged in a single
vacuum chamber, or, as shown in Fig. 7(a), are arranged
in two adjacent vacuum chambers separated by a
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differential pumping aperture Apl. In one embodiment,
the portion of the ion mobility spectrometer 4a in an
upstream vacuum chamber may have a length of
approximately 100 mm, and the portion of the ion
mobility spectrometer 4b in a downstream vacuum chamber
may have a length of approximately 85 mm. The ion trap
2, ion gate 3 and upstream portion 4a of the ion
mobility spectrometer 4 are all preferably provided in
the same vacuum chamber which is preferably maintained,
in use, at a pressure within the range 0.1-10 mbar.
According to less preferred embodiments, the vacuum
chamber housing the upstream portion 4a may be
maintained at a pressure greater than 10 mbar up to a
pressure at or near atmospheric pressure. Also,
according to less preferred embodiments, the vacuum
chamber may alternatively be maintained at a pressure
below 0.1 mbar.
In the preferred embodiment the electrodes
comprising the ion trap 2 are maintained at a DC voltage
Vrfl = Ion gate 3 is normally held at a higher DC voltage
Vtrap than Vrfl, but the voltage applied to the ion gate 3
is periodically dropped to a voltage Vextrac, which is
preferably lower than Vrti thereby causing ions to be
accelerated out of the ion trap 2 and to be admitted
into the ion mobility spectrometer 4.
Adjacent electrodes which form part of the ion trap
2 are preferably connected to opposite phases of a first
AC or RF voltage supply. The first AC or RF voltage
supply preferably has a frequency within the range 0.1-
3.0 MHz, preferably 0.5-1.1 MHz, further preferably 780
kHz.
Alternate electrodes forming the upstream section
4a of the ion mobility spectrometer 4 are preferably
capacitively coupled to opposite phases of the first AC
or RF voltage supply.
The electrodes comprising the ion trap 2, the
electrodes comprising the upstream portion 4a of the ion
mobility spectrometer 4 and the differential pumping
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aperture Apl separating the upstream portion 4a from the
downstream portion 4b of the ion mobility spectrometer 4
are preferably interconnected via resistors to a DC
voltage supply which in one embodiment comprises a 400 V
supply. The resistors interconnecting electrodes
forming the upstream portion 4a of the ion mobility
spectrometer 4 may be substantially equal in value in
which case an axial DC voltage gradient is obtained as
shown in Fig. 7(b). The DC voltage gradient is shown
for ease of illustration as being linear, but may
preferably be stepped. The applied AC or RF voltage is
superimposed upon the DC voltage and serves to radially
confine ions within the ion mobility spectrometer 4.
The DC voltage Vt,p or Vextract applied to the ion gate 3
preferably floats on the DC voltage supply. The first
AC or RF voltage supply is preferably isolated from the
DC voltage supply by a capacitor.
In a similar manner, alternate electrodes forming
the downstream portion 4b of the ion mobility
spectrometer 4 are preferably capacitively coupled to
opposite phases of a second AC or RF voltage supply.
The second AC or RF voltage supply preferably has a
frequency in the range 0.1-3.0 MHz, preferably 1.8-2.4
MHz, further preferably 2.1 MHz. In a similar manner to
the upstream portion 4a, a substantially linear or
stepped axial DC voltage gradient is maintained along
the length of the downstream portion 4b of the ion
mobility spectrometer 4. As with the upstream portion
4a, the applied AC or RF voltage is superimposed upon
the DC voltage and serves to radially confine ions
within the ion mobility spectrometer 4. The DC voltage
gradient maintained across the upstream portion 4a is
preferably not the same as the DC voltage gradient
maintained across the downstream portion 4b. According
to a preferred embodiment, the DC voltage gradient
maintained across the upstream portion 4a is greater
than the DC voltage gradient maintained across the
downstream portion 4b.
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The pressure in the vacuum chamber housing the
downstream portion 4b is preferably in the range 10-3 to
10-2 mbar. According to less preferred embodiments, the
pressure may be above 10-2 mbar, and could be similar in
pressure to the pressure of the vacuum chamber housing
the upstream portion 4a. It is believed that the
greatest temporal separation of ions occurs in the
upstream portion 4a due to the higher background gas
pressure. If the pressure is too low then the ions will
not make enough collisions with gas molecules for a
noticeable temporal separation of the ions to occur.
The size of the orifice in the ion gate 3 is
preferably of a similar size or is substantially the
same internal diameter or size as the differential
pumping aperture Apl. Downstream of the ion mobility
spectrometer 4 another differential pumping aperture Ap2
may be provided leading to a vacuum chamber housing a
quadrupole mass filter 5. Pre- and post-filters 14a,14b
may be provided. The apertures of the electrodes
forming the ion mobility spectrometer 4 are preferably
all the same size. In other embodiments at least 6096,
659s, 70%-, 7596, 8096, 85%-, 90 6 or 9596 of the electrodes
have apertures which are substantially the same size.
In another preferred embodiment of the present
invention the ion mobility spectrometer 4 may comprise
an ion tunnel comprised of a plurality of segments. In
one embodiment 15 segments may be provided. Each
segment may comprise two electrodes having apertures
interleaved with another two electrodes having
apertures. All four electrodes in a segment are
preferably maintained at the same DC voltage but
adjacent electrodes are connected to opposite phases of
the AC or RF supply. The DC and AC/RF voltage supplies
are isolated from one another. Preferably, at least 90%
of all the electrodes forming the ion tunnel comprised
of multiple segments have apertures which are
substantially similar or the same in size.
Typical drift times through the ion mobility
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spectrometer 4 are of the order of a few ms. After all
the generated ions have traversed the ion mobility
spectrometer 4 a new pulse of ions may be admitted which
marks the start of a new cycle of operation. Many
cycles may be performed in a single experimental run.
An important feature of the preferred embodiment is
the provision of a mass filter which is varied in a
specified manner in conjunction with the operation of
the ion mobility spectrometer 4. In the first main
preferred embodiment a quadrupole rod set mass filter 5
is used.
If the mass filter 5 is synchronised to the start
of the pulse of ions being admitted into the ion
mobility spectrometer 4, then the mass filter 5 can be
set to transmit (in conjunction with the operation of
the ion mobility spectrometer 5) only those ions having
a mass to charge ratio that corresponds at any
particular point in time with the charge state of the
ions of interest. Preferably, the mass filter should be
able to sweep the chosen mass to charge ratio range on
at least the time scale of ions drifting through the
drift region. In other words, the mass filter should be
able to be scanned across the desired mass to charge
ratio range in a few milliseconds. Quadrupole mass
filters 5 are capable of operating at this speed.
According to the first main preferred embodiment,
either the AC (or RF) voltage and/or the DC voltage
applied to the quadrupole mass filter 5 may be swept in
synchronisation with the pulsing of ions into the ion
mobility spectrometer 4. As discussed above in relation
to Figs. 4 and 5, the quadrupole mass filter 5 may be
operated in either a high pass or band pass mode
depending on whether e.g. multiply charged ions are
preferred in general, or whether ions having a specific
charge state are preferred. The varying of a mass
filtering characteristic of the quadrupole mass filter 5
is such that ions having a favoured charge state (or
states) are preferably onwardly transmitted, preferably
CA 02714930 2010-09-17
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to the at least near exclusion of other charge states,
for at least part of the cycle time Tm between pulses of
ions being injected into the ion mobility spectrometer
4. Figs. 7(c) and (d) show the inter-relationship
between ions being pulsed out of the ion trap 2 into the
ion mobility spectrometer 4, and the scanning of the
mass filter 5. Synchronisation of the operation of the
mass filter 5 with the drift times of desired ions
species through the ion mobility spectrometer 4 enables
a duty cycle of -10096 to be obtained for ions having the
charge state(s) of interest.
Referring back to Fig. 6, a collision (or gas) cell
6 may be provided preferably downstream of the ion
mobility spectrometer 4 and preferably downstream of the
quadrupole mass filter 5. Ions may be arranged so that
they are sufficiently energetic when they enter the
collision cell 6 so that they collide with gas molecules
present in the gas cell 6 and fragment into daughter
ions. Subsequent mass analysis of the daughter ions
yields valuable mass spectral information about the
parent ion(s). Ions may also be arranged so that they
enter the gas or collision cell 6 with much less energy,
in which case they may not substantially fragment. The
energy of ions entering the collision cell 6 can be
controlled e.g. by setting the level of a voltage
gradient experienced by the ions prior to entering the
collision cell 6. Since the voltage gradient can be
switched near instantaneously, the collision cell 6 can,
in effect, be considered to be switchable between a
relatively high fragmentation mode and a relatively low
fragmentation mode.
Ion optical lenses 7 are preferably provided
downstream of the collision cell 6 to guide ions through
a further differential pumping aperture Ap3 and into an
analyser chamber containing a mass analyser. According
to a particularly preferred embodiment, the mass
analyser comprises an orthogonal acceleration time of
flight mass analyser 11 having a pusher and/or puller
CA 02714930 2010-09-17
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electrode 8 for injecting ions into an orthogonal drift
region. A reflectron 9 is preferably provided for
reflecting ions travelling through the orthogonal drift
region back towards a detector 10. As is well known in
the art, at least some of the ions in a packet of ions
entering an orthogonal acceleration time of flight mass
analyser will be orthogonally accelerated into the
orthogonal drift region. Ions will become temporally
separated in the orthogonal drift region in a manner
dependent upon their mass to charge ratio. Ions having
a lower mass to charge ratio will travel faster in the
drift region and will reach the detector 10 prior to
ions having a higher mass to charge ratio. The time it
takes an ion to drift through the drift region and to
reach the detector 10 can be used to accurately
determine the mass to charge ratio of the ion in
question. The intensity of ions and their mass to
charge ratios can be used to produce a mass spectrum.
Fig. 8 shows a second main preferred embodiment of
the present invention. The ion mobility spectrometer 4,
optional ion trap 2 and ion gate 3 may take any of the
forms described in relation to the first main preferred
embodiment of the present invention. Similarly, the ion
sources described in relation to the first main
preferred embodiment may also be used in relation to the
second main preferred embodiment.
The second main preferred embodiment differs
primarily from the first main preferred embodiment in
that the quadrupole mass filter 5 is replaced with a
different form of mass filter, namely an axial time of
flight or drift region having a length Li and an
injection electrode 8. Ions are preferably pulsed into
the axial time of flight region and the injection
electrode 8 is operated in conjunction with the pulsing
of ions into the axial time of flight region so that
only ions having a specific mass to charge ratio are
injected by the injection electrode 8 and hence onwardly
transmitted to e.g. the detector 10. The injection
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electrode 8 preferably comprises the pusher and/or
puller electrode 8 of an orthogonal acceleration time of
flight mass analyser 11.
In order to pulse ions into the axial time of
flight region, a second ion trap 12 and optionally a
second ion gate 13 are preferably provided. Ions
received from the ion mobility spectrometer 4 are
trapped in the second ion trap 12. Packets of ions are
then preferably periodically released from the second
ion trap 12, for example, by lowering the DC voltage
applied to the second ion gate 13 in a similar manner to
the way ions may be released from the first ion gate 3.
In other embodiments, however, the second ion trap 12
may trap and release ions without requiring a distinct
second ion gate 13.
The second ion trap 12 preferably comprises an ion
tunnel ion trap comprising a plurality of electrodes
having apertures therein. The electrodes may take the
form of rings or other annular shape or rectangular
plates. As with the ion mobility spectrometer 4,
preferably at least 60%, 65%, 70%, 80%, 85%, 90% or 95%
of the electrodes forming the ion tunnel ion trap have
apertures which are substantially the same size or area.
Adjacent electrodes are preferably connected to opposite
phases of an AC or RE voltage supply so that ions are
radially confined within the second ion trap 12. A
particular advantage of an ion tunnel ion trap is that
the DC voltage supplied to each electrode can be
individually controlled. This enables numerous
different axial DC voltage profiles to be created along
the length of the ion tunnel ion trap 12. A
particularly preferred embodiment is to provide, in one
mode of operation, a V-shaped DC potential profile
comprising an upstream portion having a negative DC
voltage gradient and a downstream portion having a
positive DC voltage gradient so that (positive) ions
become trapped towards the centre of the ion trap 12.
If the positive DC voltage gradient maintained across
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the downstream portion of the ion trap 12 is then
changed to a zero gradient or more preferably to a
negative gradient, then (positively charged) ions will
be accelerated out the ion trap 12 as a pulse of ions.
In this particular embodiment a distinct second ion gate
13 may then become redundant.
According to other embodiments, the second ion trap
12 may comprise a 3D-quadrupole ion trap comprising a
central doughnut shaped electrode together with two
endcap electrodes. According to another embodiment, the
second ion trap 12 may comprise a hexapole ion guide.
However, this embodiment is less preferred since no
axial DC voltage gradient is present to urge ions out of
the hexapole ion guide. It is for this reason that an
ion tunnel ion trap is particularly preferred.
The drift region Li between the second ion gate 13
(or exit of the second ion trap 12) and the centre of
the pusher/puller electrode 8 is such that the ions in a
packet of ions released from the second ion trap 12 will
become temporally dispersed by the time that they arrive
at the pusher electrode 8. Ions having a smaller mass
to charge ratio will reach the pusher/puller electrode 8
before ions having a larger mass to charge ratio. The
pusher/puller electrode 8 can be set so as to inject
ions into the orthogonal acceleration time of flight
mass analyser 11 at a predetermined time after they were
first released from the second ion trap 12. Since the
time of arrival of an ion at the pusher/puller electrode
8 is dependent upon its mass to charge ratio, it can be
arranged that only ions having a certain mass to charge
ratio will be injected by the pusher/puller electrode 8
into the orthogonal drift region of the orthogonal
acceleration time of flight mass analyser 11 by
appropriate setting of the time delay.
Fig. 9 illustrates how the axial time of flight
region in combination with the pusher electrode 8 may
act as a mass filter. Ll is the distance from the exit
of the second ion trap 12 or second ion gate 13 to the
CA 02714930 2010-09-17
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centre of the pusher electrode 8. Wb is the width of
the pusher electrode. At a time T=0, ions are released
for a period W from the exit of the second ion trap 12.
After a period of time Td ions of mass to charge ratio
M2 have reached the pusher/puller electrode 8 and the
pusher/puller electrode 8 is preferably energised so
that ions of a mass to charge ratio M2 are injected into
the orthogonal drift region of the time of flight mass
analyser 11. This results in a duty cycle of -100% for
ions of mass to charge ratio M2. Ions having a mass to
charge ratio M1 which is greater than M2 have not
reached the pusher/puller electrode 8 by the time that
the pusher/puller electrode 8 is energised, and hence
these ions are not injected into the orthogonal
acceleration time of flight mass analyser 11.
Similarly, ions having a mass to charge ratio M3 which
is smaller than M2 have already passed the pusher
electrode 8 by the time that the pusher/puller electrode
8 is energised, and hence these ions are also not
injected into the orthogonal acceleration time of flight
mass analyser 11.
Preferably, after a pulse of ions has been admitted
into the axial drift region the pusher electrode 8 is
energised after a predetermined time delay Td to inject
only certain ions. The predetermined time delay Td is
then increased and the process repeated. Embodiments
are also contemplated wherein, for example, 4-5 packets
of ions are admitted into the axial drift region and the
pusher electrode duly energised 4-5 times before the
predetermined time delay Td is increased. For sake of
illustration only, if a single pulse of ions is released
from the second ion trap 12 and the pulse takes a
maximum of -100 As to drift through the axial drift
region, then the delay time Td may be increased
approximately every 100 As. If a cycle is taken to be
about 5 ms (i.e. the maximum time for an ion to drift
through the ion mobility spectrometer 4), then the
predetermined delay time Td may be increased
CA 02714930 2010-09-17
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approximately 50 times per cycle.
By adjusting the length of the extraction pulse W
and the predetermined time delay Td it is possible to
optimise the transmission for any particular mass to
charge ratio (or limited mass to charge ratio range) as
desired. The period W may be adjusted such that the
size of the packet of ions released from the second ion
trap 12 exactly fills the pusher electrode 8 for a
particular mass to charge ratio. The improvement in
duty cycle for this method over a continuously pulsing
orthogonal acceleration time of flight mass analyser is
shown in Fig. 10.
As will be appreciated, the second ion trap 12,
second ion gate 13, drift region Li and pusher electrode
8 operate to act as a mass filter with a high duty cycle
over a limited mass to charge ratio range.
For ease of illustration only, a collision (or gas)
cell 6 is not shown in Fig. 8. However, a separate
collision cell 6 as described in relation to the first
main preferred embodiment may be provided upstream or
downstream of the second ion trap 12. According to a
particularly preferred embodiment, the second ion trap
12 may act both as an ion trap and as a collision cell
in both main preferred embodiments. The ion tunnel ion
trap/collision cell may comprise a plurality of segments
(e.g. 15 segments), each segment comprising four
electrodes interleaved with another four electrodes.
All eight electrodes in a segment are preferably
maintained at the same DC voltage, but adjacent
electrodes are preferably supplied with opposite phases
of an AC or RF voltage supply. A collision gas
preferably nitrogen or argon may be supplied to the
collision cell at a pressure preferably of 10-3-10-2 mbar.
Ions may be trapped and/or fragmented in the ion
trap/collision cell by appropriate setting of the DC
voltages applied to the electrodes and the energy that
ions are arranged to have upon entering the ion
trap/collision cell.
CA 02714930 2010-09-17
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Some experimental results are shown in Figs. 11(a)
and (b). Fig. 11(a) shows a conventional mass spectrum
i.e. without any charge state selection being performed.
Fig. 11(b) shows a comparable mass spectrum obtained
with charge state selection according to the preferred
embodiment. As can be seen, singly charged ions are
substantially absent from the mass spectrum. Similarly,
Fig. 12(a) shows another conventional mass spectrum and
Fig. 12(b) shows a comparable mass spectrum obtained
with charge state selection according to the preferred
embodiment. Again, it can be seen that singly charged
ions are substantially absent from the mass spectrum.
In both the first main preferred embodiment and the
second main preferred embodiment, the mass filter (e.g.
quadrupole 5 or axial time of flight region and
injection electrode 8) are shown and described as being
downstream of the ion mobility spectrometer 4. However,
according to other embodiments the mass filter (e.g.
quadrupole 5 or axial time of flight region and
injection electrode 8) may be arranged upstream of the
ion mobility spectrometer 4.
Furthermore, although the first and second main
preferred embodiments have been described in relation to
being able to filter out e.g. singly charged ions in
preference to multiply charged ions, other embodiments
are contemplated wherein singly charged ions are
preferentially selected and onwardly transmitted whilst
other charge state(s) are attenuated.
Other embodiments are contemplated wherein the AC
or RF voltage supplied to electrode(s) in an ion tunnel
(either an ion mobility spectrometer and/or ion trap)
may be non-sinusoidal and may, for example, take the
form of a square wave.
Yet further embodiments are contemplated wherein
other types of mass filter are used instead (or in
addition to) a quadrupole mass filter or an axial drift
region in combination with an injection electrode as
described in relation to the two main preferred
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embodiments. In particular, embodiments are
contemplated wherein a RF hexapole, octapole or other
multipole rod set mass filter is used. Alternatively, a
RF ring set or a RF ion trap (either 2D or 3D) may be
used.
According to a preferred embodiment both the
upstream ion trap 2 and the ion mobility spectrometer 4
may comprise an ion tunnel i.e. a plurality of
electrodes wherein each electrode has an aperture
therein through which ions are transmitted. The
electrodes, preferably having substantially similar
sized apertures, forming each ion tunnel may comprise
essentially a square or rectangular plate or a ring. In
either case the apertures are preferably circular.
According to various embodiments, the ion tunnel ion
trap and/or ion mobility spectrometer may comprise at
least 10, 20, 30, 40, 50, GO, 70, 80, 90 or 100
electrodes of which at least 60%, 65%, 70%, 75%, 80%,
85%, 90% or 95% have apertures which are substantially
the same size or area. As will be appreciated, the
construction of an ion tunnel which preferably comprises
a large number of plate like electrodes is quite
distinct from a multipole rod set ion guide.
Embodiments of the invention are also contemplated
wherein the DC voltage profile along the length of the
ion mobility spectrometer and/or ion trap and/or
collision cell is not strictly linear, but rather has a
stepped profile.
Although the present invention has been described
with reference to preferred embodiments, it will be
understood by those skilled in the art that various
changes in form and detail may be made without departing
from the scope of the invention as set forth in the
accompanying claims.
