Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
CA 02433508 2003-06-25
MASS SPECTROMETER
The present invention relates to a mass
spectrometer, an ion mobility separator, a method of
mass spectrometry and a method of ion mobility
separation.
Radio Frequency (RF) ion guides are commonly used,
for confining and transporting ions. Conventionally a
plurality of electrodes are provided wherein an RF
voltage is applied between neighbouring electrodes so
that a pseudo-potential well or valley is produced. The
pseudo-potential well can be arranged to radially
confine ions and may be used to efficiently transport
ions by acting as an ion guide.
The RF ion guide is capable of functioning
efficiently as an ion guide even at relatively high
pressures wherein ions are likely to undergo frequent
collisions with residual gas molecu=Les. However,
although the collisions with gas mo~_ecules may cause the
ions to scatter and lose energy, the pseudo-potential
well generated by the RF ion guide acts to radially
confine the ions within the ion guide. RF ion guides
therefore have an advantage over guide wire types of ion
guides wherein a DC voltage is applied to a central wire
running down the centre of a conducting tube. In such
arrangements ions are held in orbit around the central
guide wire and if ions undergo many collisions with gas
molecules then they will tend to lose energy and will
eventually collapse into the central guide wire and
hence be lost. It is known to use RF ion guides to
transport ions through vacuum chambers held at
intermediate pressures (e.g. 0.001-10 mbar). For
example, the ion guide may be provided to transmit ions
_., . ... _ _... r _.. ~.,..,~ .~,, ~~~ ~~:r~,.~~..~..v"~~.___ ..._.
CA 02433508 2003-06-25
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Pram an atmospheric pressure ion source to a mass
analyser in a chamber maintained at a relatively low
pressure.
When ions collide with gas molecules they may get
scattered and lose kinetic energy. If the ions undergo
a large number of collisions, e.g. more than 100
collisions, then the ions will substantially lose all
their forward kinetic energy. The ions will therefore
possess a mean energy which is substantially equal to
that of the surrounding gas molecules. The ions will
therefore appear to move randomly within the gas due to
continuing random collisions with gas molecules.
Accordingly, under some operating conditions, ions being
transported through an RF ion guide maintained at an
intermediate gas pressure can lose substantially all
their forward motion and may remain within the ion guide
for a relatively long period of time.
In practice, ions may still continue to move
forwards for other reasons. It is normally assumed that
ions may continue to move forwards due to the bulk
movement of gas forcing the ions through the ion guide.
Space charge effects caused by the continual ingress of
ions into the ion guide and hence the electrostatic
repulsion from ions arriving from behind may also
effectively push the ions through the ion guide.
However, without these influences the ions can, in
effect, come to a substantial standstill within the ion
guide and hence not emerge at the exit.
A known means for driving ions through an RF ion
guide at intermediate pressures is th.e use of a constant
DC electric field. To ensure the ions emerge, or simply
to reduce their transit time, an axial voltage gradient
may be applied along the ion guide. For example, the
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ion guide may comprise a segmented multipole rod set ion
guide with a DC potential maintained between successive
rod segments. The axial electric :Field causes the ions
to accelerate forwards after each r_ollision with a gas
molecule. A weak electric field, _Ln the region of 0.1
to 1 V/cm, is adequate for pressures between 0.001 and
0.01 mbar. At higher pressures higher field strengths
may be used.
In the pressure region above 0.001 mbar ions in an
axial electric field will attain velocities according to
their ion mobility. Ions emitted from a pulsed ion
source can thus be arranged to separate according to
their ion mobility. Ions from a continuous ion source
may be gated into a drift region.
According to an aspect of the present invention
there is provided a mass spectrometer comprising:
an ion mobility separator for separating ions
according to their ion mobility, the ion mobility
separator comprising a plurality of electrodes wherein
in use one or more transient DC voltages or one or more
transient DC voltage waveforms are progressively applied
to the electrodes so that at least some ions having a
first ion mobility are separated from other ions having
a second different ion mobility.
According to a preferred embodiment a repeating
pattern of electrical potentials are superimposed along
the length of an ion mobility separator so as to form a
periodic waveform. The waveform is caused to travel
along the ion mobility separator in the direction in
which it is required to move the ions and at the
velocity at which it is required to move the ions.
The ion mobility separator may comprise an AC or RF
ion guide such as a multipole rod set or a stacked ring
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set. The ion guide is preferably segmented in the axial
direction so that independent transient DC potentials
can be applied to each segment. T:he transient DC
potentials are preferably superimposed on top of an AC
or RF voltage which acts to radially confine ions andlor
any constant DC offset voltage. The transient DC
potentials generate a travelling wave which moves in
the axial direction.
At any instant in time a voltage gradient is
generated between segments which acts to push or pull
ions in a certain direction. As th.e ions move in the
required direction sa does the voltage gradient. The
individual DC voltages on each of the segments may be
programmed to create a required waveform. The
individual DC voltages on each of the segments may also
be programmed to change in synchronism so that the DC
potential waveform is maintained but is translated in
the direction in Which it is required to move the ions.
The one or more transient DC voltages or one or
more transient DC voltage waveforms is preferably such
that at least 10$, 20%, 30~, 400, 5U%, 60~, 70%, 80~,
90~ or 95~ of the ions having the first ion mobility are
substantially moved along the ion mobility separator by
the one or more transient DC voltages or the one or more
transient DC voltage waveforms as the one or more
transient DC voltages or the one or more transient DC
voltage waveforms are progressively applied to the
electrodes.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms are preferably such
that at least IO~, 20°s, 30%, 40~, 50o, 60$, 70%, 80~,
90$ or 950 of the ions having the second ion mobility
are moved along the ion mobility separator by the
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applied DC voltage to a lesser decree than the ions
having the first ion mobility as t:he one or more
transient DC voltages or the one or more transient DC
voltage waveforms are progressively applied to the
electrodes.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms are preferably such
that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%,
90% or 95% of the ions having the first ion mobility are
moved along the ion mobility separator with a highe r
velocity than the ions having the second ion mobility.
According to another aspect of the present
invention there is provided a mass spectrometer
comprising:
an ion mobility separator for separating ions
according to their ion mobility, the ion mobility
separator comprising a plurality o:E electrodes wherein
in use one or more transient DC vo:Ltages or one or more
transient DC voltage waveforms are progressively applied
to the electrodes so that ions are moved towards a
region of the ion mobility separator wherein at least
one electrode has a potential such that at least some
ions having a first ion mobility will pass across the
potential whereas other ions having a second different
ion mobility will not pass across the potential.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms are preferably such
that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%,
90% or 95% of the ions having the first ion mobility
pass across the potential. The one or more transient DC
voltages or the one or more transient DC voltage
waveforms are such that at least 10%, 20%, 30%, 40%,
50 0, 60%, 70%, 80%, 90 % or 95 % of the ions having the
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second ion mobility will not pass across the potential.
The at least one electrode is preferably provided with a
voltage such that a potential hill or valley,is
provided.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms are preferably such
that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%,
90% or 95% of the ions having the first ion mobility
exit the ion mobility separator substantially before
ions having the second ion mobility. The one or more
transient DC voltages or the one or more transient DC
voltage waveforms are preferably such that at least 10%,
20%, 30%, 40%, 50%, 60%, 70%, 80%, 90 % or 95 % of the
ions having the second ion mobilityy exit the ion
mobility separator substantially after ions having the
first ion mobility.
A majority of the ions having the first ion
mobility preferably exit the ion mobility separator a
time t before a majority of the ions having the second
ion mobility exit the ion mobility separator, wherein t
falls within a range selected from the group consisting
of: (i) < 1 us; (ii) 1-10 us; (iii) 10-50 us; (iv) 50-
100 us; (v) 100-200 us; (vi) 200-300 ps; (vii) 300-400
us; (viii) 400-500 us; (ix) 500-600 us; (x) 600-700 us;
{xi) 700-800 us; (xii) 800-900 us; (xiii) 900-1000 us;
(xiv) 1.0-1.1 ms (xv) 1.1-1.2 ms; (xvi) 1.2-1.3 ms;
(xvii) 1.3-1.4 ms; (xviii) 1.4-1.5 ms; (xix) 1.5-1.6 ms;
(xx) 1.6-1.7 ms; (xxi) 1.7-1.8 ms; (xxii) 1.8-1.9 ms;
(xxiii) 1.9-2.0 ms; (xxiv) 2.0-2.5 ms; (xxv) 2.5-3.0 ms;
(xxvi) 3.0-3.5 ms; (xxvii) 3.5-4.0 :ms; (xxviiij 4.0-4.5
ms; (xxix) 4.5-5.0 ms; (xxx) 5-10 ms; (xxxi) 10-15 ms;
(xxxii) 15-20 ms; (xxxiii) 20-25 ms; and (xxxiv) 25-30
ms.
CA 02433508 2003-06-25
According to another aspect o:E the present
invention there is provided a mass spectrometer
comprising:
an ion mobility separator for separating ions
according to their ion mobility, the ion mobility
separator comprising a plurality of electrodes wherein
in use one or more transient DC voltages or one or more
transient DC voltage waveforms are progressively applied
to the electrodes so that:
(i) ions are moved towards a region of the ion
mobility separator wherein at least: one electrode has a
first potential such that at least some ions having
first and second different ion mobilities will pass
across the first potential whereas other ions having a
third different ion mobility will not pass across the
first potential; and then
(ii) ions having the first and second ion
mobilities are moved towards a region of the ion
mobility separator wherein at least: one electrode has a
second potential such that at least: some ions having the
first ion mobility will pass acrosL~ the second potential
whereas other ions having the second different ion
mobility will not pass across the second. potential.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms and the first
potential are preferably such that at least 10%, 20%,
30%, 40%, 50%, 60%, 70%, 80%, 90 % or 95 % of the ions
having the first ion mobility pass across the first
potential. The one or more transient DC voltages or the
one or more transient DC voltage waveforms and the first
potential are preferably such that at least 10%, 20%,
30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of the ions
having the second ion mobility pass across the first
CA 02433508 2003-06-25
_ g _
potential. The one or more transient DC voltages or the
one or more transient DC voltage waveforms and the first
potential are preferably such that at least 10%, 20%,
30%, 40%, 50%, 60%, 70%, 80%, 90 % or 95 % of the ions
having the third ion mobility do riot pass across the
first potential.
The one or more transient DC voltages or the one or
more transient DC voltage waveform.s and the second
potential are preferably such that at least 10%, 20%,
30%, 40%, 50%, 60%, 70%, 80%, 90% or 95% of the ions
having the first ion mobility pass across the second
potential. The one or more transient DC voltages or the
one or more transient DC voltage waveforms and the
second potential are preferably such that at least 10%,
20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or 95 % of the
ions having the second ion mobility do not pass across
the second potential.
The one or more transient DC voltages or the one or
more transient DC voltage waveform:a are preferably such
that at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%,
90% or 95% of the ions having the second ion mobility
exit the ion mobility separator substantially before
ions having the first and third ion mobilities. The one
or more transient DC voltages or the one or more
transient DC voltage waveforms are preferably such that
at least 10%, 20%, 30%, 40%, 50%, fi0%, 70%, 80%, 90 % or
95% of the ions having the first and third ion
mobilities exit the ion mobility separator substantially
after ions having the second ion mobility.
A majority of the ions having the second ion
mobility preferably exit the ion mobility separator a
time t before a majority of the ions having the first
and third ion mobilities exit the ion mobility
CA 02433508 2003-06-25
a
g _
separator, wherein t falls within a range selected from
the group consisting of: (i) < 1 ~,s; (ii) 1-10 us; (iii)
10-50 us; (iv} 50-100 ~s; (v) 100-200 us; (vi) 200-300
us; (vii) 300-400 us; (viii) 400-500 us; (ix) 500-600
us; (x} 600-700 ~s; (xi) 700-800 us; (xii) 800-900 us;
(xiii) 900-1000 us; (xiv} 1.0-1.1 ms (xv) 1.1-1.2 ms;
(xvi) 1.2-1.3 ms; (xvii) 1.3-1.4 ms; (xviii) 1.4-1.5 ms;
(xix) 1.5-1.6 ms; (xx} 1.6-1.7 ms; (xxi) 1.7-1.8 ms;
(xxii) 1.8-1.9 ms; (xxiii) 1.9-2.0 ms; (xxiv) 2.0-2.5
ms; (xxv) 2.5-3.0 ms; (xxvi) 3.0-3.5 ms; (xxvii) 3.5-4.0
ms; (xxviii) 4.0-4.5 ms; (xxix) 4.5-5.0 ms; (xxx) 5-10
ms; (xxxi) 10-15 ms; (xxxii) 15-20 ms; (xxxiii) 20-25
ms; and (xxxiv) 25-30 ms.
The one or more transient DC voltages may create:
(i) a potential hill or barrier; (ii) a potential well;
(iii) a combination of a potential hill or barrier and a
potential well; (iv) multiple potential hills or
barriers; (v) multiple potential wells; 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 such as a
square wave.
The one or more transient DC voltage waveforms
preferably create a plurality of potential peaks or
wells separated by intermediate regions. The DC voltage
gradient in the intermediate regions is preferably non-
zero and may be either positive or negative. The DC
voltage gradient in the intermediate regions may be
linear or non-linear. For example, the DC voltage
gradient in the intermediate regions may increase or
decrease exponentially.
CA 02433508 2003-06-25
,e
~. W'
The amplitude of the potential peaks or wells may
remain substantially constant or the amplitude of the
potential peaks or wells may become progressively larger
or smaller. The amplitude of the potential peaks or
wells may increase or decrease either linearly or non-
linearly.
In use an axial DC voltage gradient is preferably
maintained along at least a portion of the length of the
ion mobility separator and wherein the axial voltage
gradient varies with time.
The ion mobility separator 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 first 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 second 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;
and at a third 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.
Preferably, at the first time t1 the second
electrode is at the second reference potential and the
third electrode is at the third reference potential; at
the second time t2 the first electrode is at the first
potential and the third electrode i.s at the third
reference potential; and at the third time t3 the first
electrode is at the first potential and the second
electrode is at the second potential.
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Alternatively, at the first time t1 the second
electrode is at the second reference potential and the
third electrode is at the third reference potential; at
the second time t2 the first elects°ode is 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: and at the third time t3 the first electrode
is at the first reference potential the second electrode
is no longer supplied with the second DC voltage so that
the second electrode is returned to the second reference
potential.
The first, second and third reference potentials
are preferably substantially the same. Preferably, the
first, second and third DC voltages are substantially
the same. Preferably, the first, second and third
potentials are substantially the same.
The ion mobility separator may comprise 3, 4, 5, 6,
7, 8, 9, 10, 11, 12, 13, I4, 15, 1f>, 17, 18, 19, 20, 21,
22, 23, 24, 25, 26, 27, 28, 29, 30 or >30 segments,
wherein each segment 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 maintained at
substantially the same DC potential.. Preferably, a
plurality of segments are maintained at substantially
the same DC potential. Preferably, each segment is
maintained at substantially the same DC potential as the
subsequent nth segment wherein n is 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 are preferably confined radially within the
ion mobility separator by an AC or RF electric field.
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Ions are preferably radially confined within the ion
mobility separator in a pseudo-potential well and are
moved axially by a real potential barrier or well.
In use one or more additional 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 mobility separator.
Such AC or RF voltage waveforms are additional to the AC
or RF voltages which radially confine ions within the
ion mobility separator.
The transit time of ions through the ion mobility
separator is preferably selected from the group
consisting of: (i) less than or equal to 20 ms; (ii)
less than or equal to 10 ms; (iii) less than or equal to
5 ms; (iv) less than or equal to 1 ms; and (v) less than
or equal to 0.5 ms.
The ion mobility separator may be 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. Preferably, the ion mobility separator 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)
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less than or equal to 0.005 mbar; (ix) less 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.
Preferably, the ion mobility separator 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 mobility separator is preferably
maintained, in use, at a pressure such that a viscous
drag is imposed upon ions passing 'through the ion
mobility separator.
In use the one or more transient DC voltages or the
one or more transient DC voltage waveforms are
preferably initially provided at a first axial position
and are then subsequently provided at second, then third
different axial positions along the ion mobility
separator.
The one or more transient DC voltages or the one or
more transient DC voltage waveforme~ preferably move from
one end of the ion mobility separator to another end of
the ion mobility separator so that at least some ions
are urged along the ion mobility separator.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms preferably have at
least 2, 3, 4, 5, 6, 7, 8, 9 or 10 different amplitudes.
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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
alternatively the amplitude of the one or more transient
DC voltages or the one or more transient DC voltage
waveforms may vary with time. For example, the
amplitude of the one or mare transient DC voltages or
the one or more transient DC voltage waveforms either:
(i) increases with time; (ii) increases then decreases
with time; (iii) decreases with time; or (iv) decreases
then increases with time.
The ion mobility separator may comprise an upstream
entrance regian, a downstream exit regian 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 has a
first amplitude; in the intermediate region the
amplitude of the one or more transs.ent DC voltages or
the one or more transient DC voltage waveforms has a
second amplitude; and in the exit region the amplitude
of the one or more transient DC voltages or the one or
more transient DC voltage waveforms has a third
amplitude.
The entrance and/or exit region preferably comprise
a proportion of the total axial length of the ion
mobility separator selected from the group consisting
of: (i) < 5%; (ii) 5-100; (iii) 10-150; (iv) 15-200; (v)
20-250; (vi) 25-30%; (vii) 30-350; (viii) 35-40~; and
(ix) 40-45%.
The first and/or third amplitudes are preferably
substantially zero and the second amplitude is
substantially non-zero. Preferably,. the second
CA 02433508 2003-06-25
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amplitude is larger than the first= amplitude and/or the
second amplitude is larger than the third amplitude.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms preferably pass in
use along the ion mobility separator with a first
velocity. Preferably, the first velocity: (t) remains
substantially constant; (ii) varies; (iii) increases;
(iv) increases then decreases; (v) decreases; (vi)
decreases then increases; (vii) reduces to substantially
zero; (viii) reverses direction; or (ix) reduces to
substantially zero and then reverses direction.
The one or more transient DC voltages or the one or
more transient DC voltage waveform.s preferably cause
some ions within the ion mobility separator to pass
along the ion mobility separator with a second different
velocity. Preferably, the one or :more transient DC
voltages or the one or more transient DC voltage
waveforms causes some ions within the ion mobility
separator to pass along the ion mobility separator with
a third different velocity. Preferably, the one or more
transient DC voltages or the one o:r more transient DC
voltage waveforms causes some ions within the ion
mobility separator to pass along the ion mobility
separator with a fourth different velocity. Preferably,
the one or more transient DC voltages or the one or more
transient DC voltage waveforms causes some ions within
the ion mobility separator to pass along the ion
mobility separator with a fifth different velocity.
The difference between the first velocity and the
second and/or the third and/or the fourth and/or the
fifth velocities is preferably selected from the group
consisting of: (t) less than or equal to 50 m/s; (ii)
less than or equal to 40 m/s; (iii) less than or equal
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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 ~. m/s;
The first velocity is preferably 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; and (xii) 2750-3000 m/s. The second
10 and/or the third and/or the fourth and/or the fifth
different velocity is preferably 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
15 m/s; (ix) 2000-2250 m/s; (x) 2250-2500 m/s; (xi) 2500-
2750 m/s; and(xii) 2750-3000 m/s.
The one or more transient DC voltages or the one or .
more transient DC voltage waveforms preferably has a
frequency, and wherein the frequency: (i) remains
20 substantially constant; (ii) varies; (iii) increases;
(iv) increases then decreases; (v) decreases; or (vi)
decreases then increases.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms preferably has a
25 wavelength, and wherein the wavelength: (i) remains
substantially constant; (ii) varies; (iii) increases;
(iv) increases then decreases: (v) decreases; or (vi)
decreases then increases.
Two or more transient DC voltages or two or more
30 transient DC voltage waveforms may pass simultaneously
along the ion mobility separator. The two or more
transient DC voltages or the two or more transient DC
voltage waveforms may be arranged to move: (i) in the
CA 02433508 2003-06-25
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same directions (ii) in opposite directions; (iii)
towards each other; or (iv) away from each other.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms may pass along the
ion mobility separator and at leap>t one substantially
stationary transient DC potential voltage or voltage
waveform is provided at a position along the ion
mobility separator.
The one or more transient~DC voltages or the one or
more transient DC voltage waveforms are preferably
repeatedly generated and passed in use along the ion
mobility separator, and wherein the frequency of
generating the one or more transient DC voltages or the
one or more transient DC voltage waveforms: (i) remains
substantially constant; (ii) varies; (iii) increases:
(iv) increases then decreases; (v) decreases; or (vi)
decreases then increases.
A continuous beam of ions may be received at an
entrance to the ion mobility separator or packets of
ions may be received at an entrance to the ion mobility
separator.
Pulses of ions preferably emerge from an exit of
the ion mobility separator. The mass spectrometer
preferably further comprises an ion detector, the ion
detector being arranged to be substantially phase locked
in use with the pulses of ions emerging from the exit of
the ion mobility separator. The mass spectrometer also
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 the pulses of ions emerging from the exit of the
ion mobility separator.
CA 02433508 2003-06-25
- 18 -
The ion mobility separator is preferably selected
from the group consisting of: (i) 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; (ii) an ion tunnel comprising a plurality of
electrodes having apertures therein through which ions
are transmitted, wherein the diameter of the apertures
remains substantially constant; and (iii) a stack of
plate, ring or wire loop electrodes.
The ion mobility separator preferably comprises a
plurality of electrodes, each electrode having an
aperture through which ions are transmitted in use.
Each electrode may have a substantially circular
aperture. Each electrode may have a single aperture
through which ions are transmitted in use.
The diameter of the apertures of at least 10$, 20$,
300, 40$, 50$, 60$, 70$, 800, 90$ or 95$ of the
electrodes forming the ion mobility separator 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 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 100, 20$, 30a, 90$, 500, 60$, 700, 80$,
90$ or 95$ of the electrodes forming t:he ion mobility
separator preferably have apertures which are
substantially the same size or area.
According to a less preferred embodiment the ion
mobility separator may comprise a segmented rod set.
CA 02433508 2003-06-25
19 _
The ion mobility separator prE:ferably consists 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) mare than 150 electrodes.
The thickness of at least 10%, 20%, 300, 400, 500,
600, 70a, 80%, 90% or 950 of the electrodes is
preferably 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 mobility separator 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-
cm; (vi) 25-30 cm; and (vii) greater than 30 cm.
20 At least 100, 20%, 300, 40%, 50%, 60~, 70%, 80%,
90%, or 950 of the electrodes are preferably connected
to both a DC and an AC or RF voltage supply. According
to the preferred embodiment axially adjacent electrodes
are supplied with AC or RF voltages having a phase
25 difference of 180°.
The mass spectrometer may comprise an ion source
selected from the group consisting of: (i) Electrospray
("ESI") ion source; (ii) Atmospheric Pressure Chemical
Ionisation ("APCI") ion source; (ii:i) Atmospheric
Pressure Photo Ionisation ("APPI") .ion source; (iv)
Matrix Assisted Laser Desorption Ionisation ("MALDI")
ion source; (v) Laser Desorption Ionisation ("LDI") ion
source; (vi) Inductively Coupled Plasma ("ICP°') ion
CA 02433508 2003-06-25
- 20
source: (vii) Electron Impact ("ET) ion source; (viii)
Chemical Ionisation ("CI") ion source; (ix) a Fast Atom
Bombardment ("FAB") ion source; and (x) a Liquid
Secondary Ions Mass Spectrometry ("LSIMS") ion source.
The ion source may be either a continuous or a pulsed
ion source.
According to another aspect of the present
invention, there is provided an ion mobility separator
for separating ions according to their ion mobility, the
ion mobility separator comprising a plurality of
electrodes wherein in use one or more transient DC
voltages or one or more transient :DC voltage waveforms
are progressively applied to the electrodes so that at
least some ions having a first ion mobility are
separated from other ions having a second different ion
mobility.
According' to another aspect o:f the present
invention, there is provided an ion mobility separator
for separating ions according to their ion mobility, the
ion mobility separator comprising a plurality of
electrodes wherein in use one or more transient DC
voltages or one or more transient DC voltage waveforms
are progressively applied to the electrodes so that ions
are moved towards a region of the ion mobility separator
wherein at least one electrode has a potential such that
at least some ions having a first ion mobility will pass
across the potential whereas other ions having a second
different ion mobility will not pass across the
potential.
According to another aspect of the present
invention, there is provided an ion mobility separator
for separating ions according to their ion mobility, the
ion mobility separator comprising a plurality of
CA 02433508 2003-06-25
- 21 -
electrodes wherein in use one or more transient DC
voltages or one or more transient DC voltage waveforms
are progressively applied to the electrodes so that:
(i) ions are moved towards a region of the ion
mobility separator wherein at least. one electrode has a
first potential such that at least some ions having
first and second different ion mob}_lities will pass
across the first potential whereas other ions having a
third different ion mobility will not pass across the
first potential; and then
(ii) ions having the first and second ion
mobilities are moved towards a region of the ion
mobility separator wherein at least. one electrode has a
second potential such that at least: some ions having the
first ion mobility will pass across the second potential
whereas other ions having the second different ion
mobility will not pass across the scecond potential.
According to another aspect of: the present
invention, there is provided a method of mass
spectrometry comprising:
receiving ions in an ion mobility separator
comprising a plurality of electrodes; and
progressively applying to the electrodes one or
more transient DC voltages or one or more transient DC
voltage waveforms so that at least some ions having a
first ion mobility are separated from other ions having
a second different ion mobility.
According to another aspect of the present
invention, there is provided a method of mass
spectrometry comprising:
receiving ions in an ion mobility separator
comprising a plurality of electrodes; and
CA 02433508 2003-06-25
- 22 -
progressively applying to the electrodes one or
more transient DC voltages or one or more transient DC
voltage waveforms so that ions are moved towards a
region of the ion mobility separator wherein at least
one electrode has a potential such that at least some
ions having a first ion mobility will pass across the
potential whereas other ions having a second different
ion mobility will not pass across the potential.
According to another aspect of the present
invention, there is provided a method of mass
spectrometry comprising:
receiving ions in an ion mobility separator
comprising a plurality of electrodes;
progressively applying to the electrodes one or
more transient DC voltages or one or more transient DC
voltage waveforms so that ions are moved towards a
region of the ion mobility separator wherein at least
one electrode has a first potential such that at least
some ions having a first and second different ion
mobilities will pass across the fio~st potential whereas
other ions having a third differeni~ ion mobility will
not pass across the first potentials and then
progressively applying to the electrodes one or
more transient DC voltages or one or more transient DC
voltage waveforms so that ions having the first and
second ion mobilities are moved towards a region of the
ion mobility separator wherein at least one electrode
has a second potential such that at: least some ions
having the first ion mobility will pass across the
second potential whereas other ions having the second
different ion mobility will not pa~~s across the second
potential.
CA 02433508 2003-06-25
- 23 --
According to another aspect of the present
invention, there is provided a method of ion mobility
separation comprising:
receiving ions in an ion mobility separator
comprising a plurality of electrodes: and
progressively applying to the electrodes one or
more transient DC voltages or one or more transient DC
voltage waveforms so that at least some ions having a
first ion mobility are separated from other ions having
a second different ion mobility.
According to another aspect of the present
invention, there is provided a method of ion mobility
separation comprising:
receiving ions in an ion mobility separator
comprising a plurality of electrodes; and
progressively applying to the electrodes one or
more transient DC voltages or one or more transient DC
voltage waveforms so that ions are moved towards a
region of the ion mobility separator wherein at least
one electrode has a potential such that at least some
ions having a first ion mobility will pass across the
potential whereas other ions having a second different
ion mobility will not pass across the potential.
According to another aspect of the present
invention, there is provided a method of ion mobility
separation comprising:
receiving ions in an ion mobility separator
comprising a plurality of electrodes;
progressively applying to the ~slectaodes one or
more transient DC voltages or one o:r more transient DC
voltage waveforms so that ions are moved towards a
region of the ion mobility separator wherein at least
one electrode has a first potential such that at least
CA 02433508 2003-06-25
- 24 -
some ions having a first and second different ion
mobilities will pass across the first potential whereas
other ions having a third different ion mobility will
not pass across the first potential; and then
progressively applying to the electrodes one or
more transient DC voltages or one or more transient DC
voltage waveforms so that ions having the first and
second ion mobilities are moved towards a region of the
ion mobility separator wherein at least one electrode
has a second potential such that at least some ions
having the first ion mobility will pass across the
second potential whereas other ions having the second
different ion mobility will not pass across the second
potential.
According to another aspect of the present
invention, there is provided an ion mobility separator
wherein ions separate within the ion mobility separator
according to their ion mobility and assume different
essentially static or equilibrium axial positions along
the length of the ion mobility separator.
The ion mobility separator preferably comprises a
plurality of electrodes and wherein ane or more
transient DC voltages or one or more transient DC
voltage waveforms are progressively applied to the
electrodes so as to urge at least some ions in a first
direction and wherein a DC voltage gradient acts to urge
at least some ions in a second direction, the second
direction being opposed to the first direction.
The peak amplitude of the one or more transient DC
voltages or the one or more transient DC voltage
waveforms preferably remains substantially constant or
reduces along the length of the ion mobility separator.
CA 02433508 2003-06-25
- 25 -
The DC voltage gradient preferably progressively
increases along the length of th.e ion mobility
separator.
Once ions have assumed essentially static or
5 equilibrium axial positions along the length of the ion
mobility separator at least some of the ions may then be
arranged to be moved towards an exit of the ion mobility
separator. At least some of the ions may be arranged to
be moved towards an exit of the ion mobility separator
by: (i) reducing or increasing an axial DC voltage
gradient; (ii) reducing or increasing the peak amplitude
of the one or more transient DC voltages or the one or
more transient DC voltage waveforms; (iii) reducing or
increasing the velocity of the one or more transient DC
voltages or the one or more transient DC voltage
waveforms; or (iv) reducing or increasing the pressure
within the ion mobility separator.
According to another aspect of the present
invention, there is provided a mass spectrometer
20 comprising an ion mobility separator as described above.
According to another aspect of the present
invention, there is provided a method of ion mobility
separation comprising causing ions to separate within an
ion mobility separator and assume different essentially
25 static or equilibrium axial positions along the length
of the ion mobility separator.
The ion mobility separator may comprise a plurality
of electrodes and wherein one or more transient AC
voltages or one or more transient I>C voltage waveforms
30 are progressively applied to the electrodes so as to
urge at least some ions in a first direction and wherein
a DC voltage gradient acts to urge at least some ions in
CA 02433508 2003-06-25
- 26 -
a second direction, the second direction being opposed
to the first direction.
According to another aspect of the present
invention, there is provided a method of mass
spectrometry comprising:
providing an ion mobility separator for separating
ions according to their ion mobility, the ion mobility
separator comprising a plurality of electrodes wherein
in use one or more transient DC voltages or one or more
transient DC voltage waveforms are progressively applied
to the electrodes so that at least some ions having a
first ion mobility are separated from other ions having
a second different ion mobility;
separating ions according to their ion mobility in
the ion mobility separator;
providing a quadrupole mass filter downstream of
the ion mobility separator; and
scanning the quadrupole mass filter in a stepped
manner in synchronisation with the ion mobility
separator so as to onwardly transmit ions having a
desired charge state.
According to another aspect of the present
invention, there is provided a
mass spectrometer comprising:
an ion mobility separator for separating ions
according to their ion mobility, the ion mobility
separator comprising a plurality of electrodes wherein
in use one or more transient DC voltages or one or more
transient DC voltage waveforms are progressively applied
to the electrodes so that at least some ions having a
first ion mobility are separated from other ions having
a second different ion mobility; anal
CA 02433508 2003-06-25
- 27
a quadrupole mass filter downstream of the ion
mobility separator;
wherein the quadrupole mass filter is scanned in
use in a stepped manner in synchronisation with the ion
mobility separator so as to onwardly transmit ions
having a desired charge state.
Various embodiment 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 equilibrium in a preferred ion
mobility separator together with the voltage profile
along the length of the ion mobility separator;
Fig. 2 shows ions within an ion mobility separator
as a travelling DC voltage begins at one end of the
preferred ion mobility separator together with the
voltage profile along the length of the ion mobility
separator;
Fig. 3 shows the effect as a travelling DC voltage
wave sweeps high mobility ions towards one end of the
preferred ion mobility separator together with the
voltage profile along the length of the ion mobility
separator;
Fig. 4 shows an embodiment wherein all high
mobility ions have been swept towards one end of the
preferred ion mobility separator and the ions are then
ejected from the preferred ion mobility separator
together with the voltage profile along the ion mobility
separator;
Fig. 5 shows at equilibrium another embodiment
wherein the preferred ion mobility separator is divided
into two regions separated by a potential hill together
with the voltage profile along the length of the ion
mobility separator;
.._.._. .___~m_~~" ~..--.~;~,.,,~.~~ ~~.w M ..~~ ~._~.~,..w~,..r~.~x.,~.r
.."~",.e,e~._u.~___._._.. ___..,."~..~.__.___.. ..__
CA 02433508 2003-06-25
28 -
Fig. 6 shows an embodiment wherein higher mobility
ions have been swept into a second region of the ion
mobility separator and wherein a travelling DC voltage
wave reverses in direction together with the voltage
profile along the length of the ion mobility separator;
Fig. 7 shows a bandpass mode of operation
embodiment wherein ions having an intermediate ion
mobility are left in a second stage of the preferred ion
mobility separator together with the voltage profile
along the length of the ion mobility separator;
Fig. 8 shows a predetermined separation of two
samples;
Fig. 9A shows a preferred travelling DC voltage
waveform, Fig. 9B shows another travelling DC voltage
waveform and Fig. 9C shows a further travelling DC
voltage waveform; and
Fig. 10A shows the transit time recorded for
Gramacidin-S (m/z 572) through a preferred ion mobility
separator and Fig. 10B shows the transit time recorded
for Leucine Enkephalin (m/z 556) through a preferred ion
mobility separator.
Fig. 1 shows a preferred ion mobility separator 1
comprising a plurality of electrodes 3 each having an
aperture through which ions may be transmitted.
Adjacent electrodes 3 are preferably connected to
opposite phases of an AC or RF voltage supply. The ion
mobility separator 1 is preferably held at a pressure
such that ions traversing its length undergo many
collisions with gas molecules. The ion mobility
separator 1 may according to one embodiment receive ions
generated by an Electrospray or a MALDI ion source. One
or more end plates 2a,2b of the ion mobility separator 1
may be maintained at a slight positive voltage relative
CA 02433508 2003-06-25
29 _
to the other electrodes 3 so that ions once entering the
ion mobility separator 1 are effectively trapped within
the ion mobility separator 1 and are unable to surmount
the potential barrier at one or both ends. After a
certain period of time equilibrium may be reached within
the ion mobility separator 1 so that ions of all masses
and mobilities are substantially equally distributed
along the length of the ion mobility separator 1. As
shown in Fig. 2, according to one embodiment a voltage
30 pulse Vg may be applied to the first electrode of the
ion guide adjacent to one of the end plates 2a so that
some ions will be pushed by the applied voltage pulse Vg
along the ion mobility separator 1. The local field
variation is given by:
TT~,~ -_ KE(x~
where Varift is the drift velocity of an ion, K is the
mobility of the ion and E(x) is the electric field
caused by the applied voltage. The' electric field
caused by the applied voltage decays rapidly to a
negligible value within a few electrode spacings.
The voltage pulse Vg is then preferably rapidly
switched to the next adjacent electrode. An ion which
has had enough time to drift at least one electrode
spacing will therefore experience the same force and
will again move along the length of the ion mobility
separator 1 in the direction in which the voltage pulse
Vg is heading. However, ions having a lower ion
mobility may not have had sufficient time to drift far
enough to see the influence of the voltage when it
switched to the adjacent electrode. Accordingly, these
CA 02433508 2003-06-25
30 -
lower mobility ions will be effectively left behind by
the travelling voltage pulse Vg or voltage waveform.
The voltage pulse Vg preferably travels along the
ion mobility separator 1 from electrode to electrode
sweeping those ions with a sufficiently high ion
mobility with it. As shown in Figs. 3 and 4 the ion
mobility separator 1 may therefore in one embodiment act
as a high pass ion mobility filter such that ions having
ion mobilities greater than a certain value are
preferably ejected from the ion mobility separator 1
whereas ions having lower ion mobi.lities remain
substantially trapped within the ion mobility separator
1.
The sweep time TaWeep of the ion mobility separator 1
may then be reduced to select a slightly lower
(intermediate) ion mobility so that those ions having an
intermediate ion mobility may then be subsequently
ejected from the ion mobility separator 1. By gradually
further reducing the sweep time a complete mobility scan
may be built up until the ion mobility separator 1 is
substantially empty of ions.
According to another mode of operation the voltage
of the voltage pulse Vg may be progressively increased
with each sweep thereby collecting ions having
progressively decreasing ion mobilities in the same way.
Tt will be appreciated from consideration of the above
equation that doubling the voltage will double the
velocity of an ion.
The resolution of the ion mobility separator 1 will
in part be determined by the sweep time Tsweep Or Voltage
increment. The smaller the step fi..e, reduction in
sweep time or increase in the voltage of the voltage
pulse) between the adjacent sweeps the greater the
CA 02433508 2003-06-25
- 31 -
resolution of the ion mobility separator 1. Fig. 4
shows ions at the end of a voltage sweep being ejected
from the ion mobility separator 1.
The mode of operation described above may build up
a mobility spectrum by a series of high pass further
steps. However, isolation of a particular range of ion
mobilities i.e. bandpass operation may also be achieved
by employing a two stage device. As shown in Fig. 5,
ions with an ion mobility greater i~han a certain value
may be arranged to pass along a portion of the ion
mobility separator 1 by the operation of a voltage pulse
Vg passing along the ion mobility separator 1. The ions
then pass from a first region 4 to an electrode which is
maintained at a certain potential 0 and into a second
region 5 which is preferably substantially empty of
ions. As shown in Fig. 6, once some ions have been
swept into the second region 5 the travelling voltage
pulse Vg may then be reversed so as to sweep some ions
from the second region 5 past the same (or another
electrode) which is maintained at a preferably lower
potential 6' back into the first region 4_ The reverse
sweep may be faster and/or have a higher voltage than
the forward sweep so that as shown in Fig. 7 ions having
ion mobilities within a desired range may remain trapped
in the second region 5.
The resolution of the ion mobility separator 1 has
been modelled to include the effect of diffusion of
ions. Diffusion effects are known to degrade the
resolution of conventional drift tube ion mobility
30 separators and the relationship between the drift tube
length and the applied axial voltage drop is given by;
_~~'I ' 0.173
L .,(y
CA 02433508 2003-06-25
-~ 32 -
where mod X is the spatial spread due to diffusion,
Z is the length of the drift tube and V the applied
axial voltage drop.
To increase the resolving power of a conventional
mobility spectrometer longer drift tubes and higher
voltages may be employed. However,. an advantage of the
preferred ion mobility separator 1 is that the voltage
required can be a relatively low e.g. 10V at a pressure
of 2 mbar. Furthermore, the low (10V) voltage only
needs to be applied to a single electrode at any one
point in time. The preferred ion mobility separator 1
can therefore achieve ion mobility separation using a
low voltage source whereas a conventional drift tube
type ion mobility spectrometer would require
approximately 1000V to achieve comparable ion mobility
separation.
The ion mobility separator 1 has been modelled as a
series of electrodes with a voltagE=_ resident on each
electrode for a certain period of lime. Diffusion was
introduced into the model as a random scattering
component over the time of residence of the voltage on
an element. The result of this simulation is shown in
Fig. 8 and predicts the complete separation of
Gramacidin S (m/z 572) and Leucine Enkephalin (m/z 556).
The model was based on an ion mobi=Lity separator 1
having 100 electrodes and wherein a voltage of 7V was
progressively applied along the length of the ion
mobility separator 1. This result is comparable with
the performance which may be expected from a
conventional drift tube ion mobility separator of
similar dimensions.
Further improvements in resolution may be achieved
by sweeping the ions backwards and forwards through the
-.._., , . awAN aulom" 4Yy,~7AA0 rc~.P"-.'ssH.sXa> wm,..,... _ ,.mmax
3~, ~&'g<':a~.sr.x..,.~aew~m.~..---..._..r. ,~,.....«,m,.".-~_ .._ . . . .
CA 02433508 2003-06-25
- 33 -
same volume a number of times. This has the effect of
increasing the effective length of the ion mobility
separator 1 without actually increasing its physical
dimensions. A more compact ion mobility separator than
a conventional ion mobility spectrometer may therefore
be provided according to a preferred embodiment. As
will be appreciated, a greater number of passes through
the ion mobility separator 1 allows for greater
isolation of the desired species of ions.
Ions may be purged from the swept volume after the
passage of the travelling voltage wave by switching the
AC or RF voltage OFF and allowing ions to diffuse out of
that portion of the ion mobility separator 1. After a
desired number of passes of the same volume the ions may
be allowed out of the ion mobility separator 1 for
subsequent mass analysis.
The ion mobility separator 1 according to the
preferred embodiment can advantageously operate at duty
cycles approaching 1000 as it can be arranged to eject
only ions having a desired ion mobility whilst staring
the other ions for further analysis;. This is in
contrast to a Field Asymmetric Ion Mobility Spectrometer
(FAIMS) which is a scanning device whereby ions that are
not transmitted are lost to the walls of the device.
A charge state separation device wherein a
quadrupole is scanned in synchronisation with the output
of a drift tube is the subject of a. pending application.
However, losses in ion transmission. may occur as ions
that enter the quadrupole with a stable trajectory may
find themselves unstable part way through the quadrupole
and so be last.
An embodiment is contemplated wherein a quadrupole
mass filter is provided downstream of a preferred .ion
CA 02433508 2003-06-25
- 34 -
mobility separator 1 and set to a discrete mass to
charge ratio transmission window so as to match the
desired mobility range ejected by t:he preferred ion
mobility separator 1. This means that the desired fans
are stable in the quadrupole mass filter all through the
device. The equivalent to a scanning experiment can
therefore be performed in a stepped manner with no loss
in duty cycle as unejected ions are still stored by the
ion mobility separator 1.
A conventional drift tube type of ion mobility
spectrometer requires the use of a trapping stage in
order to obtain a high duty cycle when using a
continuous ion source. Ions may be admitted to the
conventional drift tube ion mobility spectrometer using
gate pulses which are narrow compared to drift times of
ions. An ion mobility spectrometer that disperses ions
on the millisecond timescale therefore requires a gate
pulse of the order of microseconds in order to achieve
the best resolution. The use of such gate pulses
results in ion mobility discrimination at the entrance
to the ion mobility spectrometer which results in
reduced sensitivity and skewed spectra. In contrast,
the ion mobility separator according to the preferred
embodiment has no need for a narrow gate pulse as the
ion mobility separator can be filled with a longer pulse
of ions and so does not suffer from. such problems which
are inherent with conventional arrangements. An ion
trap or other device for periodically releasing a pulse
of ions into the ion mobility spectrometer 1 may
nonetheless preferably be provided.
In addition to embodiments wherein a single
transient DC patential or pulse Vg is translated along
the length of the ion mobility separator 1, according to
CA 02433508 2003-06-25
- 35 -
other embodiments a travelling DC 'voltage wave having a
repeating waveform may be used to .separate ions
according to their ion mobilities, The amplitude and
velocity of the one or more DC voltage waveforms may be
arranged such that ions do not sur:E an a single voltage
pulse along the drift region but instead roll over the
top of subsequent pulses thereby receiving a succession
of nudges leading to an overall drift in the wave
direction. The transit time of an ion through the ion
mobility separator 1 will therefore be dependent upon
its ion mobility.
According to this embodiment a travelling wave ion
guide may be used to provide the dx:ift region. The ion
guide may comprise either a stack of plates or a
segmented multipole rod set. An ion trapping region
upstream of the drift region may beg provided with an ion
gate to periodically pulse bunches of ions from the ion
trap into the drift region.
Fig. 9A shows a travelling DC voltage wave form
having a periodic pulse of constant. amplitude and
velocity. Fig. 9B shows another DC potential waveform
wherein a reverse DC gradient is superimposed on the
travelling DC voltage waveform so that the field acts
between pulses to move ions back towards the upstream
ion gate or the entrance of the ion mobility separator
1. Such a DC voltage waveform may enhance the
separation characteristics of the ion mobility separator
1 and may be used to prevent ions having an ion mobility
less than a certain value from travelling with the
travelling DC voltage wave and exiting the ion mobility
separator 1. Fig. 9C shows a further DC potential
waveform wherein the height of the voltage pulses
reduces along the drift region as the potential due to
CA 02433508 2003-06-25
-- 36 -
an axial DC voltage gradient increases. Such a waveform
may also enhance separation.
With the DC voltage waveform ;shown in Fig. 9C ions
having a certain ion mobility may find balance points
along the length of the drift region where the movement
caused by the travelling DC voltage wave is counteracted
by the reverse axial DC voltage gradient. Ions of
different mobility may therefore find different balance
points along the length of the ion mobility separator 1.
A static mobility separation may therefore be produced
and ions of similar mobility may collect in specific
regions. These ions may be transmitted in a band-pass
operation. The mode of operation using a voltage
waveform as shown in Fig. 9C does not necessarily
require an ion gate since it may operate with a
continuous ion beam. Furthermore, the DC axial field
may be constant or variable with position. This may be
achieved by applying potentials to the electrodes
forming the ion guide which increase linearly or non-
linearly. Alternatively, the amplitude of the
travelling DC voltage wave may decrease linearly or non-
linearly as it progresses from the entrance to the exit
of the ion mobility separator 1. The DC axial field and
amplitude of the travelling wave may change with
position. In one particular embodiment the DC axial
field may continuously increase from the entrance to the
exit of the ion mobility separator whilst the amplitude
of the travelling DC voltage wave remains substantially
constant.
The DC axial voltage gradient, the amplitude of the
travelling wave and the velocity of the travelling DC
voltage wave may also change with time. Hence, ions of
differing mobility may first be separated spatially
CA 02433508 2003-06-25
37 -
along the length of the ion guide and may then be moved
along the ion mobility separator 1 to one end or the
other. Ions may therefore be caused to exit the ion.
mobility separator 1 in increasing or decreasing order
of their mobility.
Ions that have been separated according to their
ion mobility may be caused to move to the exit of the
ion mobility separator 1 by either reducing the DC
potential gradient or by increasing the amplitude of the
travelling DC voltage wave. These ions may also be
moved to the exit of the ion mobil_Lty separator 1 by
reducing the velocity of the travelling DC voltage wave
or by reducing the gas pressure. 7:ons may also be
caused to move by changing a combination of these
controls. According to an embodiment ions may be caused
to leave the ion mobility separator 1 in order of their
ion mobility, starting with ions of: highest mobility.
According to another embodiment the separated ions
may be caused to move to the entrance of the ion
mobility separator either by increasing the DC potential
gradient and/or by reducing the amplitude of the
travelling DC voltage wave and/or by increasing the
velocity of the DC voltage wave and./or by increasing the
gas pressure. According to this embodiment ions may be
caused to be emitted from the ion mobility separator 1
via what was initially the entrance of the ion mobility
separator 1 in order of their mobility starting with
ions having the lowest ion mobility.
According to an embodiment the pulse amplitude,
wave velocity, pressure and axial gradient may be varied
during operation so as to enhance the separation.
Although the ion mobility separator 1 as described
above may be used in isolation for the analysis of a
CA 02433508 2003-06-25
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substance by means of measurement of the mobility of its
component parts, it may also be used for separation,
collection and storage of components of a substance.
The ion mobility separator 1 may form part of a mass
spectrometer or a tandem mass spectrometer. The
combination with a mass spectrometer provides a means of
analysis with greater specificity. It also provides a
means of separation, collection and storage of component
fractions of a substance and therefore provides a means
by which more components of a substance may be
subsequently analysed in a mass spectrometer in greater
detail.
A reversed axial voltage gradient may be used to
enhance separation by constantly returning ions which
have not been carried along by the travelling DC voltage
wave to the entrance of the separation region.
Experimental data will now be presented. Ions were
initially collected in an ion tunnel ion trap consisting
of a stack of 90 ring electrodes each 0.5 mm thick and
spaced apart by 1.0 mm. The central aperture of each
ring was 5.0 mm diameter and the total length of the ion
tunnel ion trap was 134 mm. A 2.1 MHz RF voltage was
applied between neighbouring rings to radially confine
the ion beam within the ion trap. Ions were retained in
the ion tunnel ion trap by raising the DC potential at
each end of the ion trap by approximately 5V. The
pressure in the ion tunnel ion trap was about 10-3 mbar.
Ions were continuously generated using an
Electrospray ion source and were continuously directed
into the ion tunnel ion trap. The DC potential at the
exit end of the ion trap was periodically reduced to
allow ions to exit the ion trap. Ions were repeatedly
collected and stored fox 11 ms and then released over a
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period of 26 ns. Ions leaving the ion trap were
accelerated through a 3 V potential difference and were
then passed through a quadrupole rod set ion guide. The
quadrupole was operating with only RF voltage applied to
the rods so that is it was acting as an ion guide and
not as a mass filter. Tho ions exiting the quadrupole
rod set ion guide then entered an .ion mobility separator
1 according to the preferred embod_Lment.
The ion mobility separator 1 consisted of a similar
ion tunnel arrangement to that used for initially
collecting and storing ions emitted from the ion source.
The ion mobility separator 1 consisted of a stack of 122
ring electrodes, each 0.5 mm thick and spaced apart by
1.0 mm. The central aperture within each ring was 5.0
mm diameter and the total length of: ring stack was 182
mm. A 2.4 MHz RF voltage was applied between
neighbouring rings to radially confine the ions within
the ion mobility separator 1. The pressure in the i.on
mobility separator 1 was approximately 2 x 10-2 mbar. A
travelling DC voltage wave was applied to the ion
mobility separator 1 and consisted of a regular periodic
pulse of constant amplitude and velocity.
The travelling DC voltage wave was generated by
applying a DC voltage to a single ring electrode and
every subsequent ring displaced by nine rings along the
ring stack. Hence, one wavelength ~, of the DC voltage
waveform consisted of one electrode with a raised DC
potential followed by eight electrodes held at a lower
(reference) potential. Thus the wavelength ~. was
equivalent to the length of 9 electrodes or 13.5 mm and
the total ion mobility separator was equivalent to
approximately 13.5 ~,. The travelling DC voltage wave
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was generated by applying approximately 0.65V to each
ring electrode for 5 ns before moving the applied
voltage to the next (adjacent) ring electrode. Thus the
wave period or cycle time t was 45 ns. This was
repeated uniformly along the length of the ion mobility
separator 1. Thus the DC voltage wave velocity was
equal to a constant 300 m/s.
At the exit of the ion mobility separator I the
ions passed through a second quadrupole rod set. This
was operated in an RF and DC mode (i.e. rnass filtering
mode) and was arranged to transmit ions having a
particular mass to charge ratio. The ions were detected
using an ion detector positioned downstream of the
second quadrupole rod set.
A mixture of Gramacidin-S (mol wt 1142 daltons) and
Leucine Enkephalin (mol wt 555 daltons) were
continuously introduced into an Electrospray ion source.
Singly charged protonated ions of Leucine Enkephalin
(m/z 556) and doubly charged protor.~ated ions of
Gramacidin-S (m/2 572) were collected and stored in the
upstream ion trap. These ions were periodically
released and their transit times to the ion detector
were recorded and are shown in Figs, 10A and 10B. For
each measurement the second quadrupole mass filter was
tuned to just transmit either m/z 556 for Leucine
Enkephalin or m/z 572 for Gramacidin-S.
The trace for Gramacidin-S is shown in Fig. 10A and
shows that the peak arrival time for ions was about 2.2
ms after release from the upstream ion trap. The
corresponding trace for Leucine Enk:ephalin is shown in
Fig. 10B and shows the corresponding peak arrival time
was about 3.1 ms after release from the upstream ion
trap. Timing cursors showed that the transit time for
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Gramicidin-S was about 940 ns less than that for Leucine
Enkephalin. This is in spite of the fact that the m/z
value for Gramicidin-S (572) is slightly greater than
that for Leucine Enkephalin (556} and that the
Gramicidin-S molecule (mol wt 1142 daltons) is also
larger than the Leucine Enkephalin molecule (mol wt 555
daltons}. However, shorter transit. time for Gramacidin-
S may be expected since the m/z 572 ion is doubly
charged and experiences twice the j:orce due to the
electric field of the travelling wave than that
experienced by the singly charged Leucine Enkephalin ion
having m/z 556.
Although the doubly charged Gramicidin-S ion
experienced twice the force it did not experience twice
the viscous drag since its cross sectional area is not
twice that of Leucine Enkephalin. It may be estimated
that their relative cross sectional. areas are in the
ratio approximately (1144/556)23 which is approximately
1.6. Hence the Gramicidin-S ion is more mobile than the
Leucine Enkephalin ion in the presence of the same
electric field and same high gas pressure. As a result,
Gramicidin-5 ions are more strongly affected by the
travelling DC voltage waveform than Leucine Enkephalin
ions. As a result, the transit time for Gramicidin-S
ions through the ion mobility separator 1 was found to
be less than that for Leucine Enkephalin. In fact the
overall transit time for Gramicidin-S ions is less than
that for Leucine Enkephalin despite the fact that the
Leucine Enkephalin ions having lower mass to charge
ratios will travel slightly faster through the two
quadrupoles.
This experiment also demonstrates how two ions with
substantially similar mass to charge ratios but having
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different charge states (z values) may be separated by
the travelling wave ion mobility separator according to
the preferred embodiment.
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.
