Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
CA 02742437 2013-06-05
Title
Mass Spectrometer
Field
The present invention relates to a mass spectrometer,
an ion mobility separator, a method of mass spectrometry
and a method of ion mobility separation.
Background
Radio Frequency (RF) ion guides are commonly used for
confining and transporting ions. Conventionally a
plurality of electrodes are provided wherein an RE 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 RE 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 molecules. However, although
the collisions with gas molecules may cause the ions to
scatter and lose energy, the pseudo-potential well
generated by the RE ion guide acts to radially confine the
ions within the ion guide. RE 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
CA 02742437 2013-06-05
-2-
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 from 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
CA 02742437 2013-06-05
-3-
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 the 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 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 collision with a gas
molecule. A weak electric field, in 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.
Summary
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
CA 02742437 2013-06-05
-4-
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 RE'
ion guide such as a multipole rod set or a stacked ring
set. The ion guide is preferably segmented in the axial
direction so that independent transient DC potentials can
be applied to each segment. The transient DC potentials
are preferably superimposed on top of an AC or RF voltage
which acts to radially confine ions and/or 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 the ions move in the required
direction so 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
CA 02742437 2013-06-05
-5-
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%, 40%, 50%, 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 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%
or 95% of the ions having the second ion mobility are
moved along the ion mobility separator by the applied DC
voltage to a lesser degree than the ions having the first
ion mobility 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 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 higher velocity
than the ions having the second ion mobility.
According to another aspect of the present invention
there is provided a mass spectrometer comprising:
CA 02742437 2013-06-05
-6-
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.
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%, 60%, 70%,
80%, 90% or 95% of the ions having the 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%,
CA 02742437 2013-06-05
-7-
60%, 70%, 80%, 90% or 95% of the ions having the second
ion mobility 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 is; (ii) 1-
ps; (iii) 10-50 ps; (iv) 50-100 is; (v) 100-200 ps;
10 (vi) 200-300 ps; (vii) 300-400 is; (viii) 400-500 ps; (ix)
500-600 is; (x) 600-700 ps; (xi) 700-800 ps; (xii) 800-900
ps; (xiii) 900-1000 ps; (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.
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:
(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
CA 02742437 2013-06-05
-8-
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 across 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 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
not pass across the first 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
CA 02742437 2013-06-05
-9-
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 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 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%, 60%, 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 separator, wherein t
falls within a range selected from the group consisting
of: (i) < 1 ps; (ii) 1-10 ps; (iii) 10-50 ps; (iv) 50-100
ps; (v) 100-200 ps; (vi) 200-300 ps; (vii) 300-400 ps;
(viii) 400-500 ps; (ix) 500-600 ps; (x) 600-700 ps; (xi)
700-800 ps; (xii) 800-900 ps; (xiii) 900-1000 ps; (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
CA 02742437 2013-06-05
-10-
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.
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
CA 02742437 2013-06-05
-11-
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 is 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.
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 electrode is no longer
supplied with the first DC voltage so that the first
electrode is returned to the first reference potential and
CA 02742437 2013-06-05
-12-
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, 14, 15, 16, 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.
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.
CA 02742437 2013-06-05
-13-
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) less than or equal to
CA 02742437 2013-06-05
-14-
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 waveforms 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.
CA 02742437 2013-06-05
-15-
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 more 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 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 has 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 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) 5-10%; (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 are preferably
substantially zero and the second amplitude is
substantially non-zero. Preferably, the second amplitude
CA 02742437 2013-06-05
-16-
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: (i) 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 waveforms 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 or 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
CA 02742437 2013-06-05
-17-
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 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 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 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
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
wavelength, and wherein the wavelength: (i) remains
substantially constant; (ii) varies; (iii) increases; (iv)
increases then decreases; (v) decreases; or (vi) decreases
then increases.
CA 02742437 2013-06-05
-18-
Two or more transient DC voltages or two or more
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 same
direction; (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 least 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
CA 02742437 2013-06-05
-19-
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.
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%,
30%, 40%, 50%, 60%, 70%, 80%, 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;
CA 02742437 2013-06-05
-20-
(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 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%
or 95% of the electrodes forming the 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.
The ion mobility separator preferably 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) more than 150 electrodes.
The thickness of at least 10%, 20%, 30%, 40%, 50%,
60%, 70%, 80%, 90% or 95% 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) 20-25 cm;
(vi) 25-30 cm; and (vii) greater than 30 cm.
At least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%,
or 95% of the electrodes are preferably connected to both
CA 02742437 2013-06-05
-21-
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 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; (iii) 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 source; (vii)
Electron Impact ("El) 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 of the present invention,
there is provided an ion mobility separator for separating
ions according to their ion mobility, the ion mobility
CA 02742437 2013-06-05
-22-
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 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 across the second potential whereas other ions having
the second different ion mobility will not pass across the
second potential.
CA 02742437 2013-06-05
-23-
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
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
CA 02742437 2013-06-05
-24-
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 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 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:
CA 02742437 2013-06-05
-25-
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 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 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
CA 02742437 2013-06-05
-26-
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 one 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.
The DC voltage gradient preferably progressively
increases along the length of the ion mobility separator.
Once ions have assumed essentially static or
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;
CA 02742437 2013-06-05
-27-
(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 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 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 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.
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
CA 02742437 2013-06-05
-28-
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; and
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.
CA 02742437 2013-06-05
-29-
Brief Description of the Drawings
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;
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
CA 02742437 2013-06-05
-30-
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.
Description
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 I may according to
one embodiment receive ions generated by an Electrospray
CA 02742437 2013-06-05
-31-
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 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 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:
Vdr = KE(x)
o
where Vdrlft 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
CA 02742437 2013-06-05
-32-
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 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 I 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
mobilities remain substantially trapped within the ion
mobility separator 1.
The sweep time Tsweep 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. It will be
CA 02742437 2013-06-05
-33-
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 (i.e. reduction in sweep
time or increase in the voltage of the voltage pulse)
between the adjacent sweeps the greater the 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 than 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 6 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
CA 02742437 2013-06-05
-34-
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 separators and the
relationship between the drift tube length and the applied
axial voltage drop is given by:
1X1 0.173
L 11F7
where mod X is the spatial spread due to diffusion, L
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 time. Diffusion was
introduced into the model as a random scattering component
over the time of residence of the voltage on an element.
CA 02742437 2013-06-05
-35-
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 mobility 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 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 100% as it can be arranged to eject
CA 02742437 2013-06-05
-36-
only ions having a desired ion mobility whilst storing 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 lost.
An embodiment is contemplated wherein a quadrupole
mass filter is provided downstream of a preferred ion
mobility separator 1 and set to a discrete mass to charge
ratio transmission window so as to match the desired
mobility range ejected by the preferred ion mobility
separator 1. This means that the desired ions 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
CA 02742437 2013-06-05
-37-
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 potential or pulse Vg is translated along the length of
the ion mobility separator 1, according to 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 surf on 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 drift region. The ion
guide may comprise either a stack of plates or a segmented
CA 02742437 2013-06-05
-38-
multipole rod set. An ion trapping region upstream of the
drift region may be 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. 93 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 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.
CA 02742437 2013-06-05
-39-
These ions may be transmitted in a band-pass operation.
The mode of operation using a voltage waveform as shown in
Fig. 90 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 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
CA 02742437 2013-06-05
-40-
of the ion mobility separator 1 by reducing the velocity
of the travelling DC voltage wave or by reducing the gas
pressure. Ions 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
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
CA 02742437 2013-06-05
-41-
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 for 11 ms and then released over a 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 RE' voltage applied to the rods so that
is it was acting as an ion guide and not as a mass filter.
CA 02742437 2013-06-05
-42-
The ions exiting the quadrupole rod set ion guide then
entered an ion mobility separator 1 according to the
preferred embodiment.
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 RE' voltage was applied between neighbouring rings
to radially confine the ions within the ion mobility
separator 1. The pressure in the ion 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 k 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 X. was equivalent to the
length of 9 electrodes or 13.5 mm and the total ion
mobility separator was equivalent to approximately 13.5 X.
The travelling DC voltage wave was generated by applying
approximately 0.65V to each ring electrode for 5 ns before
moving the applied voltage to the next (adjacent) ring
CA 02742437 2013-06-05
-43-
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 1 the ions
passed through a second quadrupole rod set. This was
operated in an RE' and DC mode (i.e. mass 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 protonated ions of Gramacidin-S (m/z 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 Enkephalin is shown in
Fig. 103 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
Gramacidin-S was about 940 ns less than that for Leucine
CA 02742437 2013-06-05
-44-
Enkephalin. This is in spite of the fact that the m/z
value for Gramacidin-S (572) is slightly greater than that
for Leucine Enkephalin (556) and that the Gramacidin-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 force 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)2/3 which is approximately 1.6.
Hence the Gramacidin-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, Gramacidin-S
ions are more strongly affected by the travelling DC
voltage waveform than Leucine Enkephalin ions. As a
result, the transit time for Gramacidin-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 Gramacidin-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
CA 02742437 2015-09-30
-45-
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.
