Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
CA 02436583 2003-08-05
MASS SPECTROMETER
The present invention relates to a mass
spectrometer and a method of mass spectrometry.
A common form of tandem mass spectrometry (MS/MS)
involves transmitting ions emitted from an ion source
through a mass filter arranged upstream of a gas
collision cell. The mass filter is set so that only
ions having a specific mass to charge ratio are onwardly
transmitted to the gas collision cell. Ions having
other mass to charge ratios are attenuated by the mass
filter. Ions transmitted by the mass filter then enter
the gas collision cell and are induced to fragment.
Fragment ions formed within the gas collision cell exit
the gas collision cell and are then mass analysed by,
for example, an orthogonal acceleration Time of Flight
mass analyser arranged downstream of the gas collision
cell. Analysis of the fragment ions provides an
effective means of identifying the parent ion which
fragmented to produce the fragment ions.
A problem with known tandem mass spectrometers is
that the duty cycle can be relatively poor in
applications where there is a need to identify or
quantify many different components from a sample. The
poor duty cycle is due to the fact that whilst parent
ions having a desired mass to charge ratio are
transmitted through the mass filter all other parent
ions are effectively attenuated by the mass filter and
are lost. The duty cycle and hence sensitivity further
decreases as the number of components to be analysed
increases.
CA 02436583 2011-06-06
2 -
According to an aspect of the present invention
there is provided a mass spectrometer comprising:
an ion trap comprising a plurality of electrodes,
wherein said ion trap has an entrance for receiving ions
and an exit from which ions exit in use, and wherein at
a first time tl ions enter said ion trap and wherein at a
second later time t2 four or more axial trapping regions
are formed or created along at least a portion of the
length of said ion trap, and wherein at said second time
t2 at least some ions have travelled from said entrance
at least 50% of the axial length of said ion trap
towards said exit.
The preferred embodiment relates to an ion trap
which is capable of fractionating ions. Ions preferably
enter the ion trap having been temporally or spatially
separated according to a physico-chemical property such
as, for example, mass to charge ratio or ion mobility in
gas phase. According to other less preferred
embodiments the ions may be.separated according to
another property such as, for example, elution time,
hydrophobicity, hydrophilicity, migration time,
chromatographic retention time, solubility, molecular
volume or size, net charge, charge state, ionic charge,
composite observed charge state, isoelectric point (pI),
dissociation constant (pKa), antibody affinity,
electrophoretic mobility, ionisation potential, dipole
moment, hydrogen-bonding capability or hydrogen-bonding
capacity.
Ions having been separated according to a physico-
chemical property then become trapped and stored in a
series of axial ion. trapping potential wells or axial
ion trapping regions along the length of the ion trap.
The ions are preferably stored in the ion trap for
CA 02436583 2011-06-06
3 -
subsequent analysis or experimentation. For example,
the ions stored in one or more of the axial potential
wells may be subsequently released for mass analysis,
for fragmentation and subsequent mass analysis, or for
mass selection, fragmentation and mass analysis.
The preferred ion trap when incorporated into a
mass spectrometer enables a high duty cycle to be
obtained for both MS and MS/MS modes of operation.
According to one embodiment at least 5 axial
trapping regions are created or formed at time t2.
According to the preferred embodiment the plurality of
axial trapping regions are preferably created at
substantially the same time t2. However, according to
less preferred embodiments the axial trapping regions
may be created in stages i.e. some axial trapping
regions may be created at time t2 and then further axial
trapping regions may be created or formed after a slight
delay.
At the first time tl in the region intermediate the
entrance and exit of the ion trap no axial trapping
regions are preferably provided along at least the
intermediate portion of the ion trap. The entrance
and/or exit may be maintained at a potential such that
ions entering the ion trap are prevented from exiting
the ion trap. However, even if ions are prevented from
exiting the ion trap at the entrance and/or the exit
such an arrangement only constitutes a single axial
trapping region. According to the preferred embodiment
ions enter the ion trap and even if they are prevented
from exiting the ion trap, the ions are not initially
fractionated within the ion trap. After a certain delay
period though, multiple axial trapping regions are then
newly created or formed which preferably fractionate the
CA 02436583 2011-06-06
- 4 -
ions. For the avoidance of any doubt, the term
"fractionate" should be understood to mean that ions
having different physico-chemical properties are divided
into separate fractions wherein all the ions in a
particular fraction have similar physico-chemical
properties. This is, of course, entirely distinct from
fragmentation wherein parent ions collide with gas
molecules and dissociate into a plurality of fragment
ions.
According to a less preferred embodiment at the
first time tl some shallow axial trapping regions having
a first depth may be formed, created or otherwise exist
along at least a portion of the length of the ion trap.
However, at the second later time t2 the axial trapping
regions which are formed or created have a substantially
greater second depth. The shallow trapping regions
present at time tl which may provide only a very limited
trapping effect are then effectively switched fully ON
to become far more effective trapping regions. The
second depth may, for example, be preferably at least x%
deeper than the first depth, wherein x is selected from
the group consisting of (i) 1%; (ii) 2%; (iii) 5%; (iv)
10%; (v) 20%; (vi) 30%; (vii) 40%; (viii) 50%; (iv) 60%;
(x) 70%; (xi) 80%; (xii) 90%; (xiii) 100%; (xiv) 150%;
(xv) 200%; (xvi) 250%; (xvii) 300%.
The ion trap has an entrance for receiving ions and
an exit from which ions exit in use and wherein at the
second time t2 when axial trapping regions are formed or
created at least some ions (e.g. ions having the lowest
mass to charge ratios or highest ion mobilities) will
preferably have travelled from the entrance at least
55% of the axial length of the ion trap towards the
exit.
CA 02436583 2003-08-05
- 5 -
The difference between t2 and tl i.e. the delay time
between ions first entering the ion trap and a plurality
of axial trapping regions first substantially appearing
(which preferably fractionate the ions) is preferably 1-
100 s, 100-200 s, 200-300 s, 300-400 s, 400-500 s,
500-600 s, 600-700 s, 700-800 s, 800-900 s or 900-
1000 ps. According to another embodiment the difference
between t2 and tl is preferably in the range 1-2 ms, 2-3
ms, 3-4 ms, 4-5 ms, 5-6 ms, 6-7 ms, 7-8 ms, 8-9 ms, 9-10
ms, 10-11 ms, 11-12 ms, 12-13 ms, 13-14 ms, 14-15 ms,
15-16 ms, 16-17 ms, 17-18 ms, 18-19 ms, 19-20 ms, 20-21
ms, 21-22 ms, 22-23 ms, 23-24 ms, 24-25 ms, 25-26 ms,
26-27 ms, 27-28 ms, 28-29 ms, 29-30 ms, or > 30 ms.
According to another aspect of the present
invention there is provided a mass spectrometer
comprising:
an ion trap comprising a plurality of electrodes,
wherein in use ions received within the ion trap are
trapped in one or more axial trapping regions within the
ion trap and wherein the one or more axial trapping
regions are translated along at least a portion of the
axial length of the ion trap with an initial first
velocity and wherein in a mode of operation the first
velocity is progressively reduced to a velocity less
than 50 m/s. The first velocity is preferably
progressively reduced to a velocity less than or equal
to 40 m/s, 30 m/s, 20 m/s, 10 m/s, 5 m/s or
substantially zero.
According to another aspect of the present
invention there is provided a mass spectrometer
comprising:
CA 02436583 2003-08-05
- 6 -
an ion trap comprising a plurality of electrodes,
wherein in use ions received within the ion trap are
trapped in one or more axial trapping regions within the
ion trap and wherein the one or more axial trapping
regions are translated along at least a portion of the
axial length of the ion trap with an initial first
velocity and wherein the first velocity is progressively
reduced to substantially zero.
A device for temporally, spatially or otherwise
dispersing a group of ions according to a physico-
chemical property is preferably provided. The device is
preferably arranged upstream of the ion trap. The
physico-chemical property may, for example, be mass to
charge ratio.
A field free region may be arranged upstream of the
ion trap wherein ions which have been accelerated to
have substantially the same kinetic energy become
dispersed according to their mass to charge ratio. The
field free region may be provided within an ion guide.
The ion guide may comprise a quadrupole rod set, a
hexapole rod set, an octopole or higher order rod set,
an ion tunnel ion guide comprising a plurality of
electrodes having apertures through which ions are
transmitted (the apertures being substantially the same
size), an ion funnel ion guide comprising a plurality of
electrodes having apertures through which ions are
transmitted (the apertures becoming progressively
smaller or larger), or a segmented rod set.
A pulsed ion source may be provided wherein in use
a packet of ions emitted by the pulsed ion source enters
the field free region.
Additionally and/or alternatively, an ion trap may
be arranged upstream of the field free region wherein in
CA 02436583 2003-08-05
7 -
use the ion trap releases a packet of ions which enters
the field free region.
According to another embodiment ions may be
arranged to become temporarily or spatially dispersed
according to their ion mobility in the gas phase.
A drift region may be arranged, for example,
upstream of the ion trap wherein ions become dispersed
according to their ion mobility. The drift region may
be provided within an ion guide. The ion guide may
comprise a quadrupole rod set, a hexapole rod set, an
octopole or higher order rod set, an ion tunnel ion
guide comprising a plurality of electrodes having
apertures through which ions are transmitted (the
apertures being substantially the same size), an ion
funnel ion guide comprising a plurality of electrodes
having apertures through which ions are transmitted (the
apertures becoming progressively smaller or larger), or
a segmented rod set.
A pulsed ion source may be provided wherein in use
a packet of ions emitted by the pulsed ion source enters
the drift region.
Alternatively and/or additionally, an ion trap may
be arranged upstream of the drift region wherein in use
the ion trap releases a packet of ions which enters the
drift region.
The ion trap preferably has an entrance for
receiving ions and an exit disposed at the other end of
the ion trap to the entrance and wherein at a point in
time the one or more axial trapping regions may be
translated towards the entrance.
The ion trap preferably has an entrance for
receiving ions and an exit disposed at the other end of
the ion trap to the entrance and wherein at a point in
CA 02436583 2003-08-05
- 8 -
time the one or more axial trapping regions may be
translated towards the exit.
A potential barrier between two or more trapping
regions may be removed so that the two or more trapping
regions form a single trapping region or a potential
barrier between two or more trapping regions may be
lowered so that at least some ions are able to be move
between the two or more trapping regions.
In use, one or more transient DC voltages or one or
more transient DC voltage waveforms may be progressively
applied to the electrodes so that ions are urged along
the ion trap.
In use an axial voltage gradient may be maintained
along at least a portion of the length of the ion trap
and the axial voltage gradient preferably varies with
time.
The ion trap may comprise a first electrode held at
a first reference potential, a second electrode held at
a second reference potential, and a third electrode held
at a third reference potential, wherein at a time T1 a
first DC voltage is supplied to the first electrode so
that the first electrode is held at a first potential
above or below the first reference potential. At a
later time T2 a second DC voltage is supplied to the
second electrode so that the second electrode is held at
a second potential above or below the second reference
potential. At a yet later time T3 a third DC voltage is
supplied to the third electrode so that the third
electrode is held at a third potential above or below
the third reference potential.
At the time T1 the second electrode may be at the
second reference potential and the third electrode may
be at the third reference potential. At the time T2 the
CA 02436583 2003-08-05
- 9 -
first electrode may be at the first potential and the
third electrode may be at the third reference potential.
At the time T3 the first electrode may be at the first
potential and the second electrode may be at the second
potential.
According to another embodiment, at the time T1 the
second electrode may be at the second reference
potential and the third electrode is at the third
reference potential. At the time T2 the first electrode
is preferably no longer supplied with the first DC
voltage so that the first electrode is returned to the
first reference potential and the third electrode is at
the third reference potential. At the time T3 the
second electrode is preferably no longer supplied with
the second DC voltage so that the second electrode is
returned to the second reference potential and the first
electrode is at the first reference potential.
The first, second and third reference potentials
may be substantially the same and/or the first, second
and third DC voltages may be substantially the same
and/or the first, second and third potentials may be
substantially the same.
The ion trap may comprise 3, 4, 5, 6, 7, 8, 9, 10,
11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24,
25, 26, 27, 28, 29, 30 or >30 segments, wherein each
segment preferably comprises 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, 30 or >30 electrodes and wherein
the electrodes in a segment are preferably maintained at
substantially the same DC potential. A plurality of
segments may be maintained at substantially the same DC
potential. Each segment may be maintained at
substantially the same DC potential as the subsequent
CA 02436583 2003-08-05
- 10 -
nth segment wherein n is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,
12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,
26, 27, 28, 29, 30 or >30.
Ions may be confined radially within the ion trap
by an AC or RF electric field. Ions may be radially
confined within the ion trap in a pseudo-potential well
and may be constrained axially by a real potential
barrier or well.
The transit time of ions through the ion trap (i.e.
the time taken for ions to be stored and then released)
is preferably less than or equal to 20 ms, less than or
equal to 10 ms, less than or equal to 5 ms, less than or
equal to 1 ms, or less than or equal to 0.5 ms.
The ion trap and/or a drift region upstream of the
ion trap are preferably maintained, in use, at a
pressure selected from the group consisting of: (i)
greater than or equal to 0.0001 mbar; (ii) greater than
or equal to 0.0005 mbar; (iii) greater than or equal to
0.001 mbar; (iv) greater than or equal to 0.005 mbar;
(v) greater than or equal to 0.01 mbar; (vi) greater
than or equal to 0.05 mbar; (vii) greater than or equal
to 0.1 mbar; (viii) greater than or equal to 0.5 mbar;
(ix) greater than or equal to 1 mbar; (x) greater than
or equal to 5 mbar; and (xi) greater than or equal to 10
mbar.
The ion trap and/or the drift region preferably is
maintained, in use, at a pressure selected from the
group consisting of: (i) less than or equal to 10 mbar;
(ii) less than or equal to 5 mbar; (iii) less than or
equal to 1 mbar; (iv) less than or equal to 0.5 mbar;
(v) less than or equal to 0.1 mbar; (vi) less than or
equal to 0.05 mbar; (vii) less than or equal to 0.01
mbar; (viii) less than or equal to 0.005 mbar; (ix) less
CA 02436583 2003-08-05
- 11 -
than or equal to 0.001 mbar; (x) less than or equal to
0.0005 mbar; and (xi) less than or equal to 0.0001 mbar.
The ion trap and/or the drift region preferably is
maintained, in use, at a pressure selected from the
group consisting of: (i) between 0.0001 and 10 mbar;
(ii) between 0.0001 and 1 mbar; (iii) between 0.0001 and
0.1 mbar; (iv) between 0.0001 and 0.01 mbar; (v) between
0.0001 and 0.001 mbar; (vi) between 0.001 and 10 mbar;
(vii) between 0.001 and 1 mbar; (viii) between 0.001 and
0.1 mbar; (ix) between 0.001 and 0.01 mbar; (x) between
0.01 and 10 mbar; (xi) between 0.01 and 1 mbar; (xii)
between 0.01 and 0.1 mbar; (xiii) between 0.1 and 10
mbar; (xiv) between 0.1 and 1 mbar; and (xv) between 1
and 10 mbar.
The ion trap and/or the drift region preferably are
maintained, in use, at a pressure such that a viscous
drag is imposed upon ions passing through the ion trap
and/or drift region.
The field free region is preferably maintained, in
use, at a pressure selected from the group consisting
of: (i) greater than or equal to 1x10-7 mbar; (ii)
greater than or equal to 5x10-7 mbar; (iii) greater than
or equal to 1x10-6 mbar; (iv) greater than or equal to
5x10-6 mbar; (v) greater than or equal to 1x10-5 mbar;
and (vi) greater than or equal to 5x10-5 mbar.
The field free region is preferably maintained, in
use, at a pressure selected from the group consisting
of: (i) less than or equal to 1x10-4 mbar; (ii) less than
or equal to 5x10-5 mbar; (iii) less than or equal to
1x10-5 mbar; (iv) less than or equal to 5x10-6 mbar; (v)
less than or equal to 1x10-6 mbar; (vi) less than or
equal to 5x10-7 mbar; and (vii) less than or equal to
1x10-7 mbar.
CA 02436583 2003-08-05
- 12 -
The field free region is preferably maintained, in
use, at a pressure selected from the group consisting
of: (i) between 1x10-' and 1x10-4 mbar; (ii) between 1x10-
' and 5x10-5 mbar; (iii) between 1x10-7 and 1x10-5 mbar;
(iv) between 1x10-7 and 5x10-6 mbar; (v) between 1x10-7
and 1x10-6 mbar; (vi) between 1x10-7 and 5x10-7 mbar;
(vii) between 5x10-7 and 1x10-4 mbar; (viii) between 5x10-
' and 5x10-5 mbar; (ix) between 5x10-7 and 1x10-5 mbar;
(x) between 5x10-7 and 5x10-6 mbar; (xi) between 5x10-7
and 1x10-6 mbar; (xii) between 1x10-6 mbar and 1x10-4
mbar; (xiii) between 1x10-6 and 5x10-5 mbar; (xiv)
between 1x10-6 and 1x10-5 mbar; (xv) between 1x10-6 and
5x10-6 mbar; (xvi) between 5x10-6 mbar and 1x1.0-4 mbar;
(xvii) between 5x10-6 and 5x10-5 mbar; (xviii) between
5x10-6 and 1x10-5 mbar; (xix) between 1x10-5 mbar and
1x10-4 mbar; (xx) between 1x10-5 and 5x105 mbar; and
(xxi) between 5x10-5 and 1x10-4 mbar.
In use one or more transient DC voltages or one or
more transient DC voltage waveforms are preferably
applied to electrodes at a first axial position along
the ion trap and are then subsequently provided at
second, then third different axial positions along the
ion trap.
In use one or more transient DC voltages or one or
more transient DC voltage waveforms preferably are
arranged to move from one end of the ion trap to another
end of the ion trap so that ions are urged along the ion
trap. The one or more transient DC voltages or one or
more transient DC voltage waveforms are preferably
arranged to be progressively applied to the ion trap and
along the ion trap so that ions are urged along the ion
trap.
CA 02436583 2003-08-05
- 13 -
The one or more transient DC voltages preferably
create: (i) a potential hill or barrier; (ii) a
potential well; (iii) multiple potential hills or
barriers; (iv) multiple potential wells; (v) a
combination of a potential hill or barrier and a
potential well; or (vi) a combination of multiple
potential hills or barriers and multiple potential
wells.
The one or more transient DC voltage waveforms
preferably comprise a repeating waveform, e.g. a square
wave.
The amplitude of the one or more transient DC
voltages or the one or more transient DC voltage
waveforms may remain substantially constant with time or
the amplitude of the one or more transient DC voltages
or the one or more transient DC voltage waveforms may
vary with time.
The amplitude of the one or more transient DC
voltages or the one or more transient DC voltage
waveforms may either increase with time, increase then
decrease with time, decrease with time, or decrease then
increase with time.
The ion trap may comprise an upstream entrance
region, a downstream exit region and an intermediate
region, wherein in the entrance region the amplitude of
the one or more transient DC voltages or the one or more
transient DC voltage waveforms may have a first
amplitude. In the intermediate region the amplitude of
the one or more transient DC voltages or the one or more
transient DC voltage waveforms may have a second
amplitude. In the exit region the amplitude of the one
or more transient DC voltages or one or more transient
DC voltage waveforms may have a third amplitude.
CA 02436583 2003-08-05
- 14 -
The entrance and/or exit region preferably comprise
a proportion of the total axial length of the ion trap
selected from the group consisting of: (i) < 5%; (ii) 5-
1096; (iii) 10-15%; (iv) 15-20%; (v) 20-25%; (vi) 25-30%;
(vii) 30-35%; (viii) 35-40%; and (ix) 40-45%.
The first and/or third amplitudes preferably are
substantially zero and the second amplitude is
substantially non-zero. The second amplitude preferably
is larger than the first amplitude and/or the second
amplitude preferably is larger than the third amplitude.
The one or more axial trapping regions may be
translated along the ion trap with a first velocity and
cause ions within the ion trap to pass along the ion
trap with a second velocity.
The difference between the first velocity and the
second velocity is selected preferably from the group
consisting of: (i) less than or equal to 50 m/s; (ii)
less than or equal to 40 m/s; (iii) less than or equal
to 30 m/s; (iv) less than or equal to 20 m/s; (v) less
than or equal to 10 m/s; (vi) less than or equal to 5
m/s; and (vii) less than or equal to 1 m/s.
The first velocity preferably is selected from the
group consisting of: (i) 10-250 m/s; (ii) 250-500 m/s;
(iii) 500-750 m/s; (iv) 750-1000 m/s; (v) 1000-1250 m/s;
(vi) 1250-1500 m/s; (vii) 1500-1750 m/s; (viii) 1750-
2000 m/s; (ix) 2000-2250 m/s; (x) 2250-2500 m/s; (xi)
2500-2750 m/s; (xii) 2750-3000 m/s; (xiii) 3000-3250
m/s; (xiv) 3250-3500 m/s; (xv) 3500-3750 m/s; (xvi)
3750-4000 m/s; (xvii) 4000-4250 m/s; (xviii) 4250-4500
m/s; (xix) 4500-4750 m/s; (xx) 4750-5000 m/s; and (xxi)
> 5000 m/s.
The second velocity preferably is selected from the
group consisting of: (i) 10-250 m/s; (ii) 250-500 m/s;
CA 02436583 2003-08-05
- 15 -
(iii) 500-750 m/s; (iv) 750-1000 m/s; (v) 1000-1250 m/s;
(vi) 1250-1500 m/s; (vii) 1500-1750 m/s; (viii) 1750-
2000 m/s; (ix) 2000-2250 m/s; (x) 2250-2500 m/s; (xi)
2500-2750 m/s; (xii) 2750-3000 m/s; (xiii) 3000-3250
m/s; (xiv) 3250-3500 m/s; (xv) 3500-3750 m/s; (xvi)
3750-4000 m/s; (xvii) 4000-4250 m/s; (xviii) 4250-4500
m/s; (xix) 4500-4750 m/s; (xx) 4750-5000 m/s; and (xxi)
> 5000 m/s.
The second velocity is preferably substantially the
same as the first velocity.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms passed along the ion
trap or applied to the electrodes preferably have a
frequency, and wherein the frequency remains
substantially constant, varies, increases, increases
then decreases, decreases, or decreases then increases.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms passed along the ion
trap or applied to the electrodes preferably have a
wavelength, and wherein the wavelength, remains
substantially constant, varies, increases, increases
then decreases, decreases, or decreases then increases.
Two or more transient DC voltages or two or more
transient DC voltage waveforms may be arranged to be
applied to the electrodes or passed substantially
simultaneously along the ion trap. The two or more
transient DC voltages or the two or more transient DC
voltage waveforms may be arranged to move in the same
direction, in opposite directions, towards each other or
away from each other.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms may be repeatedly
generated and applied to the electrodes or passed in use
CA 02436583 2003-08-05
- 16 -
along the ion trap, and wherein the frequency of
generating the one or more transient DC voltages or the
one or more transient DC voltage waveforms, remains
substantially constant, varies, increases, increases
then decreases, decreases, or decreases then increases.
The mass spectrometer preferably further comprises
a Time of Flight mass analyser comprising an electrode
for injecting ions into a drift region, the electrode
being arranged to be energised in use in a substantially
synchronised manner with a pulse of ions emitted from
the exit of the ion trap.
The ion trap may comprise an ion funnel comprising
a plurality of electrodes having apertures therein
through which ions are transmitted, wherein the diameter
of the apertures becomes progressively smaller or
larger, an ion tunnel comprising a plurality of
electrodes having apertures therein through which ions
are transmitted, wherein the diameter of the apertures
are substantially constant or a stack of plate, ring or
wire loop electrodes.
The ion trap preferably comprises a plurality of
electrodes, wherein at least 100, 20%, 30%, 40%, 50%,
60%, 70%, 800, 90%, 95% or 100% of the electrodes have
an aperture, preferably circular, through which ions are
transmitted in use. Each electrode preferably has a
single aperture through which ions are transmitted in
use, although according to other embodiments multiple
apertures may be provided.
The diameter of the apertures of at least 500, 60%,
70%, 80%, 90%, 95% or 100% of the electrodes forming the
ion trap is preferably selected from the group
consisting of: (i) less than or equal to 10 mm; (ii)
less than or equal to 9 mm; (iii) less than or equal to
CA 02436583 2003-08-05
- 17 -
8 mm; (iv) less than or equal to 7 mm; (v) less than or
equal to 6 mm; (vi) less than or equal to 5 mm; (vii)
less than or equal to 4 mm; (viii) less than or equal to
3 mm; (ix) less than or equal to 2 mm; and (x) less than
or equal to 1 mm.
At least 50%, 60%, 70%, 80%, 90%, 95% or 100% of
the electrodes forming the ion trap preferably have
apertures which are substantially the same size or area.
According to another embodiment the ion trap may
comprise a segmented rod set.
The ion trap may consist of: (i) 10-20 electrodes;
(ii) 20-30 electrodes; (iii) 30-40 electrodes; (iv) 40-
50 electrodes; (v) 50-60 electrodes; (vi) 60-70
electrodes; (vii) 70-80 electrodes; (viii) 80-90
electrodes; (ix) 90-100 electrodes; (x) 100-110
electrodes; (xi) 110-120 electrodes; (xii) 120-130
electrodes; (xiii) 130-140 electrodes; (xiv) 140-150
electrodes; or (xv) more than 150 electrodes. According
to a less preferred embodiment the ion trap may comprise
< 10 electrodes.
The thickness of at least 50%, 60%, 70%, 80%, 90%,
95% or 100% of the electrodes forming the ion trap
preferably is selected from the group consisting of: (i)
less than or equal to 3 mm; (ii) less than or equal to
2.5 mm; (iii) less than or equal to 2.0 mm; (iv) less
than or equal to 1.5 mm; (v) less than or equal to 1.0
mm; and (vi) less than or equal to 0.5 mm.
The ion trap preferably has a length selected from
the group consisting of: (i) less than 5 cm; (ii) 5-10
cm; (iii) 10-15 cm; (iv) 15-20 cm; (v) 20-25 cm; (vi)
25-30 cm; and (vii) greater than 30 cm.
CA 02436583 2003-08-05
- 18 -
At least 10%, 20%, 30%, 40%, 50%, 600, 70%, 800,
90%, 950 or 100% of the electrodes preferably are
connected to both a DC and an AC or RF voltage supply.
Axially adjacent electrodes are preferably supplied
with AC or RF voltages having a phase difference of
180 . According to an embodiment one or more AC or RF
voltage waveforms may be applied to at least some of the
electrodes so that ions are urged along at least a
portion of the length of the ion trap. This may be in
addition to or instead of applying DC voltages to the
ion trap to form axial trapping regions.
The mass spectrometer may comprise an ion source
selected from the group consisting of: (i) an
Electrospray ("ESI") ion source; (ii) an Atmospheric
Pressure Chemical Ionisation ("APCI") ion source; (iii)
an Atmospheric Pressure Photo Ionisation ("APPI") ion
source; (iv) an Inductively Coupled Plasma ("ICP") ion
source; (v) an Electron Impact ("EI) ion source; (vi) an
Chemical Ionisation ("CI") ion source; (vii) a Fast Atom
Bombardment ("FAB") ion source; (viii) a Liquid
Secondary Ions Mass Spectrometry ("LSIMS") ion source;
(ix) a Matrix Assisted Laser Desorption Ionisation
("MALDI") ion source; and (x) a Laser Desorption
Ionisation ("LDI") ion source.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms may pass in use
along the ion trap with a velocity which remains
substantially constant, varies, increases, increases
then decreases, decreases, decreases then increases,
reduces to substantially zero, reverses direction, or
reduces to substantially zero and then reverses
direction.
CA 02436583 2011-06-06
- 19 -
In use pulses of ions preferably emerge from an exit (or
entrance) of the ion trap.
A complex mixture of ions may be trapped within the ion
trap in use. The complex mixture may comprise, for example,
at least 5, 10, 15, 20, 25, 30, 35, 40, 50, 55, 60, 65, 70,
75, 80, 90, 95, 100, 150, 200, 250, 300, 350, 400, 450, 500,
550, 600, 650, 700, 750, 800, 850, 900, 950 or 1000 different
species of ions, each species of ions having a substantially
different mass to charge ratio.
A Matrix Assisted Laser Desorption Ionisation (MALDI)
ion source is particularly preferred.
According to the preferred embodiment, a complex mixture
of ions is fractionated in use along the length of the ion
trap and one or more fractions are stored in separate axial
trapping regions.
Ions may be ejected or allowed to exit from one or more
axial trapping regions as desired for subsequent mass
analysis or for further experimentation such as fragmentation
and/or mass to charge ratio separation and/or ion mobility
separation.
According to another aspect of the present invention
there is provided a method of mass spectrometry comprising:
providing an ion trap comprising a plurality of
electrodes, wherein said ion trap has an entrance for
receiving ions and an exit from which ions exit in use, and
wherein at a first time t, ions enter said ion trap; and
forming or creating four or more axial trapping regions
at a second later time t2 along at least a portion of the
length of said ion trap, wherein at said second time t2 at
least some ions have travelled from said entrance at least
50% of the axial length of said ion trap towards said exit.
According to another aspect of the present invention
there is provided a method of mass spectrometry comprising:
CA 02436583 2011-06-06
20 -
providing an ion trap comprising a plurality of
electrodes;
receiving ions within the ion trap;
trapping the ions in one or more axial trapping
regions within the ion trap;
translating the one or more axial trapping regions
along at least a portion of the axial length of the ion
trap with an initial first velocity; and
progressively reducing the first velocity to a
velocity less than or equal to 50 m/s.
According to another aspect of the present invention
there is provided a method of mass spectrometry
comprising:
providing an ion trap comprising a plurality of
electrodes;
receiving ions within the ion trap;
trapping the ions in one or more axial trapping
regions within the ion trap;
translating the one or more axial trapping regions
along at least a portion of the axial length of the ion
trap with an initial first velocity; and
progressively reducing the first velocity to
substantially zero.
The present invention also provides a mass spectrometer
as claimed in claim 97 and a method of mass spectrometry as
claimed in claim 98.
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 an embodiment wherein ions emitted from an
ion source are dispersed according to their mass to charge
ratio in a field free region before entering an AC or RF ion
trap according to the preferred embodiment;
Fig. 2 shows the distribution of ions having various
mass to charge ratios as a function of distance
CA 02436583 2003-08-05
- 21 -
along the ion trap according to a first main mode of
operation wherein ions enter an AC or RF ion trap and
then after a delay time DC potentials are applied to the
electrodes forming the ion guide/trap in order to
generate a plurality of axial trapping regions which
fractionate the ions within the ion guide/trap;
Fig. 3 shows the distribution of ions having
various mass to charge ratios as a function of time
according to a second main mode of operation wherein
ions are received within the ion trap and wherein a
plurality of axial trapping regions are translated along
the length of the ion trap at progressively slower
speeds; and
Fig. 4 shows a mass spectrometer incorporating a
preferred ion trap.
A preferred embodiment will now be described with
reference to Fig. 1. Ions may be released from e.g. a
pulsed ion source 1 such as a laser ablation or a Matrix
Assisted Laser Desorption/Ionisation (MALDI) ion source
1. Alternatively, a pulse of ions may be released from
an ion trap (not shown). The pulse of ions is then
preferably accelerated through a constant potential
difference so that the ions gain a constant energy. The
ions are then preferably transmitted to a field free
region 2 which is preferably maintained at a relatively
low pressure (e.g. < 10-4 mbar). Ions having different
mass to charge ratios will travel through the field free
region 2 at different velocities and the ions will
therefore become temporally dispersed according to their
mass to charge ratios.
The ions upon reaching the end of the field free
region 2 are then arranged to exit the field free region
2 and enter an AC or RF ion guide/ion trap 3 operated
CA 02436583 2003-08-05
- 22 -
according to the preferred embodiment. Ions having
relatively low mass to charge ratios will have acquired
relatively high velocities in the field free region 2
and hence will have arrived at the AC or RF ion
guide/ion trap 3 before other ions having relatively
high mass to charge ratios (and which will have had
relatively low velocities through the field free region
2). Once the ions emitted from the field free region 2
have entered the AC or RF ion guide/ion trap 3 and have
travelled some way along the AC or RF ion guide/ion trap
3, DC potentials are then applied to at least some of
the electrodes forming the AC or RF ion guide/ion trap 3
so that a plurality of axial trapping regions are
effectively instantaneously created or generated along
the length of the AC or RF ion guide/ion trap 3. The
ions thus become collected in (real) axial potential
wells which are formed along the length of the AC or RF
ion guide/ion trap 3. The ions are also radially
confined within the AC or RF ion guide/ion trap 3 in
pseudo-potential wells by the AC or RF voltage applied
to the electrodes forming the AC or RF ion guide/ion
trap 3. The effect of creating or forming a plurality
of axial trapping regions after a certain delay period
following ions first entering the AC or RF ion guide/ion
trap 3 is such that the ions will be collected in groups
or will be otherwise fractionated according to their
mass to charge ratio.
The ions once fractionated are then stored in the
various axial trapping regions formed within and along
the AC or RF ion guide/ion trap 3 and can then be
released in a controlled manner for subsequent analysis
or further experimentation. Advantageously, since all
the ions in a particular axial trapping region will have
CA 02436583 2003-08-05
- 23 -
a relatively narrow spread of mass to charge ratios then
the ions released from a particular axial trapping
region can be arranged to be passed to a mass analyser
and be mass analysed by, for example, an orthogonal
acceleration Time of Flight mass analyser with a
relatively high duty cycle. The relatively narrow
spread of mass to charge ratios of ions in a particular
trapping region may preferably ensure that essentially
all the ions will be present in an orthogonal or other
extraction region of a Time of Flight mass analyser at
substantially the same time when an extraction pulse is
applied to the ions in the extraction region. The high
duty cycle achievable when operating the preferred ion
trap in conjunction with, for example, an orthogonal
acceleration Time of Flight mass analyser is
particularly advantageous.
The temporal separation of ions according to their
mass to charge ratios before arrival at the AC or RF ion
guide/ion trap 3 preferably occurs in a field free
region 2 which is preferably formed within an ion guide.
The ion guide preferably comprises an AC or RF ion guide
such as a multipole rod set e.g. a quadrupole or
hexapole rod set with zero axial DC electric field.
Alternatively, the ion guide may comprise a ring stack
or ion tunnel ion guide comprising a plurality of
electrodes having apertures through which ions are
transmitted in use and again preferably with zero
average axial DC electric field. According to less
preferred embodiments, other ion guides such as those
employing guide wires may also be used.
According to a slightly less preferred but
nonetheless still important embodiment, the field free
region 2 may be replaced with a drift region maintained
CA 02436583 2003-08-05
- 24 -
at a relatively higher pressure e.g. at least 10-3 mbar.
Ions are preferably urged through the relatively high
pressure drift region by e.g. an axial DC voltage
gradient or by means of DC and/or AC/RF voltages being
applied to electrodes surrounding the drift region which
cause axial trapping regions to be created and then
translated along the drift region so as to urge ion
through the drift region. The ions preferably separate
according to their ion mobility in the presence of the
relative high pressure background gas and hence more
mobile ions reach the end of the drift region before
less mobile ions.
The preferred ion trap 3 may be operated in two
main different modes of operation. According to a first
main mode of operation which has already been briefly
described above ions arrive and are received within the
AC or RF ion guide/ion trap 3. The ions effectively
occupy different positions along the length of the AC or
RF ion guide/ion trap 3 according to their mass to
charge ratios (or less preferably their ion mobility).
No significant axial trapping regions are preferably
provided when ions initially enter the AC or RF ion
guide/ion trap 3. Ions with relatively low mass to
charge ratios (or less preferably relatively high ion
mobilities) will preferably have travelled further into
the AC or RF ion guide/ion trap 3 than ions having
relatively high mass to charge ratios (or less
preferably relatively low ion mobilities). Once ions
have been received within the AC or RF ion guide/ion
trap 3 a series of DC voltages is then applied to
certain electrodes forming the AC or RF ion guide/ion
trap 3 so that a series of real axial potential wells or
barriers are created along the length of the AC or RF
CA 02436583 2003-08-05
- 25 -
ion guide/ion trap 3. For example, a DC potential may
be applied to one or more electrodes along the AC or RF
ion guide/ion trap 3 so as to form a potential hill.
The potential hill may be repeated at regular intervals
along the length of the AC or RF ion guide/ion trap 3 so
as to create a repeating pattern of potential wells
separated by potential hills. The potential wells or
barriers may according to less preferred embodiments be
spaced at non-regular intervals.
The height of the potential hills (or depth of the
potential wells) is preferably arranged so as to trap
ions positioned between neighbouring potential hills or
wells so that ions are trapped or otherwise stored in
the different potential wells or trapping regions along
the length of the AC or RF ion guide/ion trap 3. Ions
are therefore preferably fractionated according to their
mass to charge ratio (or less preferably according to
their ion mobility in the gas phase).
Ions may oscillate within each potential well or
axial trapping region but according to the preferred
embodiment the ions may be subsequently dampened by the
introduction of a gas into the AC or RF ion guide/ion
trap 3 once some or all the axial trapping regions have
been created. The damping gas may, for example, be
provided at a pressure of at least 10-3 mbar. The
introduction of a gas into the AC or RF ion guide/ion
trap 3 will result in collisions between the ions and
the gas molecules so that ions will lose energy through
such collisions. The energy of the ions within the AC
or RF ion guide/ion trap 3 will therefore preferably be
reduced to that of the background gas within the AC or
RF ion guide/ion trap 3 i.e. the ions will become
thermalised. As the ions lose energy they will also
CA 02436583 2003-08-05
- 26 -
tend to occupy the lowest positions within the potential
wells and hence will become more radially confined and
will occupy average positions closer to the axis of the
AC or RF ion guide/ion trap 3. The collisionally cooled
ions preferably remain stored in the potential wells or
axial trapping regions until it is desired to release
the ions either for subsequent mass analysis or for
subsequent experimentation (e.g. fragmentation).
Fig. 2 illustrates how ions having different mass
to charge ratios will be distributed along the length of
the AC or RF ion guide/ion trap 3 according to the first
main mode of operation at the point in time when axial
trapping potentials are applied to the AC or RF ion
guide/ion trap 3 subsequent to ions having been
separated according to their mass to charge ratio being
received within the AC or RF ion guide/ion trap 3. In
the example illustrated by Fig. 2, the length Ll of the
upstream ion guide 2 which provides the field free
region 2 is 150 mm and the length L2 of the AC or RF ion
guide/ion trap 3 to which trapping DC potentials are
applied after a certain delay time is also 150 mm. The
DC voltages applied to the AC or RF ion guide/ion trap 3
are such that according to the embodiment described in
relation to Fig. 2 ten axial potential wells are formed
along the length of the AC or RF ion guide/ion trap 3.
The axial potential wells are spaced at regular
intervals of 15 mm e.g. the potential barriers are
located at 0, 15, 30, 45, 60, 75, 90, 105, 120, 135 and
150 mm from the entrance. The ion energy was assumed to
be 3 eV and the trapping potentials along the AC or RF
ion guide/ion trap 3 were assumed to be applied some 315
as after a pulse of ions first entered the field free
region 2. In this illustration the ions collected in
CA 02436583 2003-08-05
- 27 -
the (tenth) potential well PW10 which is the potential
well closest to the entrance of the AC or RF ion
guide/ion trap 3 (i.e. in the region 0-15 mm from the
entrance of the ion trap 3) will have ions having mass
to charge ratios in the range 2100-2550. Ions collected
in the first potential well PW1 furthest from the
entrance to the ion guide 3 (i.e. in the region 135-150
mm from the entrance of the ion trap 3) will have ions
having mass to charge ratios in the range 640-700. Fig.
2 also illustrates the range of mass to charge ratios of
ions trapped in the other intermediate potential wells
PW2-PW9.
According to a second main mode of operation,
described with reference to Fig. 3, the ions may arrive
at the AC or RF ion guide/ion trap 3 on which a
travelling DC potential voltage or voltage waveform has
been superimposed i.e. axial trapping DC potentials are
not created after a delay period after ions enter the AC
or RF ion guide/ion trap 3, but rather a series of DC
potentials are applied to the AC or RF ion guide/ion
trap 3 so that a series of axial ion trapping regions
are being continuously created and are being translated
along the length of the AC or RF ion guide/ion trap 3 as
ions arrive. As the ions arrive at the entrance to the
AC or RF ion guide/ion trap 3 they are preferably
arranged to coincide with the appearance of a first
potential well PWla which is being translated in the
same direction as the ions. These ions will therefore
be translated along the AC or RF ion guide/ion trap 3
within the first potential well PW1a. Ions with
slightly higher mass to charge ratios (or less
preferably slightly lower ion mobilities) will arrive at
the AC or RF ion guide/ion trap 3 at a slightly later
CA 02436583 2003-08-05
- 28 -
time but will still travel within the first potential
well PW1a. However, after,a relatively short period of
time (30 s) a second (new) potential hill or barrier
will emerge in the vicinity of the entrance of the AC or
RF ion guide/ion trap 3 to form a second axial trapping
region PW2a. This axial trapping region PW2a will also
be travelling in the same direction as the ions. Ions
arriving after the second potential hill has been
created will therefore be prevented from being collected
and trapped within the first axial trapping region PWla
and hence will therefore be collected and travel within
the second axial trapping region PW2a. Third and
further potential wells or axial trapping regions PW3a-
PW10a are preferably created as ions continue to arrive
at the AC or RF ion guide/ion trap 3.
As will be appreciated, each new potential well or
axial trapping region will therefore collect a series of
ions with an average range of mass to charge ratios
slightly higher than the previous potential well (or
less preferably ion mobilities slightly lower than the
previous potential well). Ions may oscillate within
each potential well or axial trapping region but their
ion motion may preferably be subsequently dampened by
the introduction of a gas into the AC or RF ion
guide/ion trap 3.
The axial length of the potential wells which are
preferably created along the length of the AC or RF ion
guide/ion trap 3 may be varied so that the range of mass
to charge ratios (or less preferably ion mobilities)
that are collected in each potential well can be
arranged as desired. Fig. 3 shows the range of ions
collected in each of the axial trapping regions over the
period 300-600 s subsequent to ions first entering the
CA 02436583 2003-08-05
29 -
field free region 2. A new ion trapping region is
created every 30 s after 300 gs have elapsed. The
axial trapping regions are translated with a constant
velocity and have a constant axial length. In the
example illustrated by Fig. 3 the length of the field
free region L1 and the length of the AC or RF ion trap 3
are both 150 mm. Axial trapping regions are created
having a length of 15 mm. The ion energy was assumed to
be 1 eV in this particular example. Ions collected in
the first potential well PWla (during the period 300-330
ps) have mass to charge ratios in the range 780-920.
Ions collected in the last potential well PW10a (during
the time period 570-600 ps) have mass to charge ratios
in the range 2790-3100. In the example shown in Fig. 3
further potential wells or axial trapping regions are
generated after 330ps, 360}is, 390ps, 420ps, 450ps,
480ps, 510Ms, 540ps and 570}is.
According to a particularly preferred embodiment
described in more detail below the velocity that the
axial trapping regions are translated along the AC or RF
ion trap 3 may progressively slow down to substantially
match the ever decreasing velocity of the ions arriving
at the entrance of the AC or RF ion guide/ion trap 3.
The velocity of ions already trapped in the potential
wells or axial trapping regions being translated along
the AC or RF ion guide/ion trap 3 will also preferably
decrease to match that of the axial trapping regions.
Ion motion may be dampened by the presence or
introduction of a buffer gas into the AC or RF ion
guide/ion trap 3. Under the right conditions the
velocity of the ions in the axial trapping regions can
be made to decrease at the same rate as that of the
axial trapping regions.
CA 02436583 2003-08-05
30 -
In the following analysis it is assumed that ions
are released from a pulsed ion source 1, for example a
laser ablation or MALDI ion source, or are released from
an ion trap. Ions then travel through an AC or RF ion
guide 2 with zero axial DC electric field (i.e. a field
free region 2) and then enter an AC or RF ion guide/ion
trap 3 with a superimposed travelling DC voltage wave or
voltage waveform according to the preferred embodiment
i.e. axial trapping regions are created and are then
translated along the AC or RF ion guide/ion trap 3. The
ion guide 2 with zero axial DC electric field is
preferably maintained at a relatively low pressure (e.g.
less than 0.0001 mbar) and the AC or RF ion guide/ion
trap 3 according to the preferred embodiment is
preferably maintained at an intermediate pressure (e.g.
between 0.0001 and 100 mbar, preferably between 0.001
and 10 mbar).
The distance in meters from the pulsed ion source 1
(or ion trap) to the entrance of the travelling wave AC
or RF ion guide/ion trap 3 (i.e. the length of the field
free region 2) is L1, the length of the travelling wave
AC or RF ion guide/ion trap 3 is L2 and the distance
from the exit of the travelling wave AC or RF ion
guide/ion trap 3 to the centre of an orthogonal
acceleration Time of Flight acceleration region arranged
downstream of the AC or RF ion guide/ion trap 3 is L3.
The ions are preferably accelerated through a voltage
difference of V1 at the ion source (or ion trap) so that
they have an energy E1 of zeV1 electron volts upon
entering the field free region 2. Accordingly, for ions
having a mass to charge ratio m/z the arrival time T1
(in ps) of ions arriving at the entrance to the
CA 02436583 2003-08-05
- 31 -
travelling wave AC or RF ion guide/ion trap 3 after they
have entered the field free region 2 is given by:
T, =72L, m
ze V,
The velocity v of the ions emerging from the field
free region 2 and entering the AC or RF ion guide/ion
trap 3 will be:
V = L,
T,
The AC or RF ion guide/ion trap 3 is preferably
maintained at an intermediate pressure such that the gas
density is sufficient to impose a viscous drag on ions
entering the AC or RF ion guide/ion trap 3 and hence the
gas will appear as a viscous medium to the ions and will
act to slow the ions down.
According to the preferred embodiment the velocity
vwave of a travelling DC voltage wave or voltage waveform
superimposed on the electrodes forming the AC or RF ion
guide/ion trap 3 (i.e. the velocity that the axial
trapping regions are translated along the AC or RF ion
guide/ion trap 3) is arranged to substantially equal the
velocity v of the ions arriving at the entrance to the
AC or RF ion guide/ion trap 3. Since the velocity of
the ions arriving at the entrance to the AC or RF ion
guide/ion trap 3 is inversely proportional to the
elapsed time T1 from the release of ions from the ion
source 1 (or ion trap), then the velocity vwave of the
travelling DC voltage wave or the speed at which the
axial trapping regions are translated preferably also
decreases with time in the same way.
CA 02436583 2003-08-05
- 32 -
Since the travelling DC voltage wave velocity VWave
is equal to A/T where 2\ is the wavelength (or length of
an axial trapping region) and T is the cycle time of the
DC voltage waveform (or repetition rate at which axial
trapping regions are created) then it follows that the
cycle time T should also preferably vary in proportion
to the elapsed time T1, assuming that the wavelength
(i.e. length of the axial trapping regions) is kept
constant. Accordingly, for the DC voltage wave velocity
to always substantially equal the velocity of the ions
arriving at the entrance to the AC or RF ion guide/ion
trap 3, the travelling DC voltage wave cycle time T
(i.e. the time taken between creating axial trapping
regions) should preferably increase substantially
linearly with time.
Since the travelling DC voltage wave velocity Vwave
(or the velocity of translating the axial trapping
regions) preferably continuously slows then it may be
thought that the ions might travel faster than the axial
trapping region which is slowing down and that the ions
might oscillate within the axial trapping region.
However, the viscous drag resulting from frequent
collisions with gas molecules in the AC or RF ion
guide/ion trap 3 preferably prevents the ions from
building up excessive velocity. Consequently, the ions
will tend to ride on or travel with the travelling DC
voltage wave (i.e. with the translating axial trapping
regions) rather than run ahead of the travelling DC
voltage wave and execute excessive oscillations within
the potential wells being translated along the length of
the AC or RF ion guide/ion trap 3.
If, in time 5t, the ions travel a distance 51
within the AC or RF ion guide/ion trap 3 then:
CA 02436583 2003-08-05
- 33 -
81=v5t
If the time at which the ions exit the AC or RF ion
guide/ion trap 3 is T2 then the distance AL travelled
within the AC or RF ion guide/ion trap 3 is:
AL vSt
AL = rT Ll 8t
t
AL = L, (In (T2) - 2I n (T))
AL=L, In 2
,
Since the length of the AC or RF ion guide/ion trap
3 is L2 and hence AL = L2 then:
L2 =L, In T2
,
c2
T2=T, e L'
The velocity of the ions vX as they exit the AC or
RF ion guide/ion trap 3 is equal to that of the
travelling DC voltage wave (or speed of the axial
trapping region) at the time the ions exit the AC or RF
ion guide/ion trap 3 which in turn equals the velocity
CA 02436583 2003-08-05
- 34 -
of the ions being received at the entrance to the AC or
RF ion guide/ion trap 3 and hence:
V = L,
X T2
L LZ
vX= 'e lL1
T,
L 2-
vY = ve- LI
Since the energy E1 of the ions entering the AC or
RF ion guide/ion trap 3 is:
E, = zeV,
and since:
E, =2mv2
then if the energy of the ions exiting the AC or RF ion
guide/ion trap 3 is E2 then:
1 2
E2=2mvX
1 Lz
E2 = -mv2e-2 L,
2
LZ
E2 = E,e-2 L,
CA 02436583 2003-08-05
- 35 -
It is therefore apparent from considering the above
equations that when the velocity of travelling DC
voltage wave (or axial trapping regions) substantially
matches the velocity of the ions arriving at the
entrance of the AC or RF ion guide/ion trap 3 then both
the energy and the velocity of ions within the axial
trapping regions decays substantially exponentially with
distance travelled along the length of the AC or RF ion
guide/ion trap 3.
The gas in the AC or RF ion guide/ion trap 3
preferably causes frequent ion-molecule collisions which
in turn cause the ions in the AC or RF ion guide/ion
trap 3 to lose kinetic energy. In the presence of an RF
confining field both the axial and radial kinetic
energies will therefore be reduced. It has been shown
that the axial and radial energies also happen to decay
approximately exponentially with distance travelled
along an AC or RF ion guide (see J. Am. Soc. Mass
Spectrom., 1998, 9, pp 569-579). From computer
simulations it is estimated that the kinetic energies of
ions in both their axial and radial directions reduce to
about l00 of their initial value when ions pass through
a nitrogen gas pressure-distance product of
approximately 0.1 mbar-cm. Since both the velocity of
translating the axial trapping regions and the kinetic
energies of ions within the axial trapping regions are
preferably arranged to decay exponentially with distance
along the AC or RF ion guide/ion trap 3, the exponential
decay rate imposed by slowing down the speed of
translating the axial trapping regions can be arranged
so as to substantially match the inherent decay of the
ion kinetic energy with distance due to collisional
CA 02436583 2003-08-05
- 36 -
cooling of the ions with gas molecules within the AC or
RF ion guide/ion trap 3. Advantageously, it is
therefore possible to arrange for the axial trapping
regions to progressively slow down at a rate which
substantially equals the collisional cooling of the ions
so as to avoid ions gaining excessive energy and being
fragmented within the ion guide/ion trap 3.
As the ions enter the AC or RF ion guide/ion trap 3
then the ions will preferably be grouped such that each
axial trapping region contains ions having a limited
range of mass to charge ratios (or less preferably ion
mobilities). Each axial trapping region will have ions
with mass to charge ratios higher (or less preferably
lower ion mobilities) than those of the preceding axial
trapping region. After the last ions of interest have
entered the AC or RF ion guide/ion trap 3 the axial
trapping regions can then effectively be halted.
Further damping of the ion motion may be performed
whilst the ions are trapped within the AC or RF ion
guide/ion trap 3 and for as long as the buffer gas
pressure in the AC or RF ion guide/ion trap 3 is
maintained. Ions can then be released from one or more
of the ion trapping regions for subsequent analysis or
experimentation as desired.
Once ions have been stored and effectively brought
to a halt within the ion trap 3 they may then be
released from the series of potential wells either from
the end to which the ions were originally travelling or
according to another embodiment from the entrance of the
AC or RF ion guide/ion trap 3. In the former case the
ions will be released in increasing order of mass to
charge ratio value (or less preferably decreasing ion
mobility) starting with those ions having the lowest
CA 02436583 2003-08-05
37 -
mass to charge ratios (or less preferably highest ion
mobilities). In the latter case ions once trapped are
reversed in direction so as to be released from the end
of the AC or RF ion guide/ion trap 3 through which they
entered. In this case ions will be released in
decreasing order of mass to charge ratio (or less
preferably increasing ion mobilities) starting with
those ions having the highest mass to charge ratios (or
less preferably lowest ion mobilities).
Ions may be released, for example, from the AC or
RF ion guide/ion trap 3 by lowering the potential hill
or barrier retaining the ions within the AC or RF ion
guide/ion trap 3 and optionally accelerating the ions
out in the required direction. Alternatively, ions may
be released by moving the axial trapping region along
one wavelength (or axial trapping region spacing) in the
required direction. This will push out the ions in the
group nearest the exit (or entrance) of the AC or RF ion
guide/ion trap 3 and at the same time all the other ions
in their respective groups will be translated one
wavelength (or axial trapping region spacing) closer to
the exit.
The preferred AC or RF ion guide/ion trap 3
according to both the first and second main modes of
operation enables a large number of ions from a complex
mixture of ions to be subsequently analysed in, for
example, a tandem mass spectrometer by means of
collision induced fragmentation and subsequent mass
analysis of the fragment ions. The preferred AC or RF
ion guide/ion trap 3 together with preferably an
upstream field free region 2 or drift region enables the
components to be separated, or at least partially
separated, into groups according to their mass to charge
CA 02436583 2003-08-05
38 -
ratio (or less preferably ion mobility) and then stored
in a series of separate potential wells or axial
trapping regions. The ions can then be subsequently
analysed in groups, one group at a time. According to
an embodiment the ions exiting the preferred AC or RF
ion guide/ion trap 3 may be mass filtered so that ions
having a precise mass to charge ratio from each group
may be selected to be fragmented and the resulting
fragment ions mass analysed.
An embodiment of the present invention will now be
described with reference to Fig. 4. A pulse of ions may
be emitted from an ion source 1 and collected and cooled
in an AC or RF ion trapping device 4. The AC or RF ion
trapping device 4 may, for example, comprise a segmented
AC or RF ion guide which in a mode of operation
functions as an ion trap by virtue of being able to be
programmed with different DC potentials along its
length. When used to trap ions the AC or RF ion
trapping device 4 may be programmed to have an axial
potential well at some point along its length. The AC
or RF ion trapping device 4 may alternatively comprise a
segmented multipole rod set, a stacked ring set, a
stacked plate set in the form of a sandwich of
electrodes, or some combination of these devices. The
AC or RF ion trapping device 4 may use a buffer gas to
cool the ions thereby helping to improve the trapping
efficiency of the device 4 whilst at the same time
cooling energetic ions emitted from the ion source 1.
If it is only required to mass analyse the trapped
ions then the ions may be released from the ion trapping
device 4 and passed to downstream to an ion guide 5 and
further downstream mass analyser 6. The mass analyser 6
may comprise, for example, a quadrupole mass filter, a
CA 02436583 2003-08-05
- 39 -
2D (linear) or 3D (Paul) quadrupole ion trap, a Time of
Flight mass analyser, a FTICR mass analyser or a
magnetic sector mass analyser. According to a preferred
embodiment the mass analyser comprises an orthogonal
acceleration Time of Flight mass analyser.
Alternatively, if it is desired to fragment and
analyse a number of different ions from the mixture of
ions released from the ion source 1 and subsequently
collected and collisionally cooled in the AC or RF ion
trapping device 4, then the ions may be released from
the AC or RF ion trapping device 4 in a single pulse and
passed upstream through an RF quadrupole ion guide 2.
The RF quadrupole ion guide 2 is preferably operated in
an RF only mode so that it acts as an ion guide not as a
mass filter. The RF quadrupole ion guide 2 is
preferably operated at a pressure (e.g. < 10-4 mbar) such
that the RF quadrupole ion guide 2 forms a field free
region 2 within the ion guide. Ions therefore become
temporally separated according to their mass to charge
ratio as they pass through the RF quadrupole ion guide.
The ions emerging from the field free region 2 within
the RF quadrupole ion guide are received by an ion trap
3 operated according to either the first or second main
modes of operation. Ions preferably become collected
and stored within the ion trap 3 in groups according to
their mass to charge ratios as described previously.
The ion trap 3 may, for example, be provided with a
progressively slowing travelling DC voltage wave as
described above with reference to the second main mode
of operation of the preferred ion trap 3. Ions
therefore enter the ion trap 3 and are received within
axial trapping regions which are translated away from
the exit of the ion trap 3. Potential barriers are
CA 02436583 2003-08-05
40 -
therefore repeatedly created around the entrance region
of the ion trap 3 so as to create further ion trapping
regions which are similarly translated away from the
entrance of the ion trap 3 but preferably with ever
decreasing velocity so as to match the decreasing
velocity of ions arriving at the ion trap 3. The axial
trapping regions are preferably brought to a halt or
standstill.
Ions may then be released from the series of
potential wells in the preferred ion trap 3 in reverse
order i.e. ions having the highest mass to charge ratios
which are the last to enter the ion trap 3 and hence are
stored in axial trapping regions closest to the entrance
of the ion trap 3 may be the first ions to be released
from the preferred ion trap 3. Ions in a first group
are preferably released from the preferred ion trap 3
and are preferably ejected back through the RF
quadrupole ion guide 2 and preferably pass into and
through the AC or RF ion trapping device 4. The RF
quadrupole ion guide 2 may either be operated in the
non-resolving (i.e. RF only) mode such as to transmit
all the ions released from an axial trapping region
within the preferred ion trap 3. Alternatively, the RF
quadrupole ion guide 2 may be operated in the resolving
(i.e. mass filtering) mode of operation so as to
transmit only ions having a specific or a limited range
of mass to charge ratios and to attenuate ions having
other mass to charge ratios.
Ions transmitted through the RF quadrupole ion
guide 2 and received in the AC or RF ion trapping device
4 may be fragmented by collision activation with a
buffer gas within the AC or RF ion trapping device 4.
The fragment ions may then preferably be trapped in the
CA 02436583 2003-08-05
- 41 -
AC or RF ion trapping device 4 and may be subsequently
released and passed downstream through an optional
further ion guide 5 before being passed to a mass
analyser 6 arranged downstream of the AC or RF ion
trapping device 4 and optional further ion guide S.
The procedure of releasing ions from the ion trap 3
and optionally fragmenting some or all the parent ions
released in a group of ions from an axial trapping
region within the preferred ion trap 3 may be repeated
multiple times until all the desired ions have been
fragmented or mass analysed. The preferred ion trap 3
may therefore be operated as a fraction collection
device for fractionating ions according to their mass to
charge ratios. The embodiment shown and described in
relation to Fig. 4 allows many different fragmentation
and mass analyses to be performed from the original
mixture of ions and enables a high duty cycle to be
obtained especially when the mass spectrometer is
operated in a MS/MS mode.
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.
