Note: Descriptions are shown in the official language in which they were submitted.
CA 02434143 2003-07-02
MASS SPECTROMETER
The present invention relates to a mass
spectrometer and. a method of mass spectrometry.
Organic molecules and biomolecules may be
identified by a technique known as MS/MS using a tandem
mass spectrometer. Parent ions of interest are
selectively transmitted by an upstream mass filter and
are then fragmented in a collision cell. The resulting
fragment ions are then analysed by a mass analyser
downstream of the collision cell.
Known tandem mass spectrometers commonly use a
collision cell in which the selected precursor or parent
ion are induced to fragment upon colliding with gas
molecules in the collision cell. The most common form
of collision cell is an enclosed chamber into which gas
is introduced. The collision gas is commonly nitrogen
or argon, although other gases such as air, helium,
xenon, methane or a mixture of gases may be used. The
gas pressure is typically in the range 10"3 mbar to 10 2
mbar.
The optimum collision energy for fragmentating ions
depends upon a number of factors including the mass,
charge, composition and internal energy of the ion to be
fragmented and the mass of the collision gas. The
optimum collision energy for collision induced
fragmentation generally increases with the mass of the
ion to be fragmented. For singly charged peptide ions
formed using a MALDI source and subsequently cooled by
collisions with the molecules of a background gas it has
been empirically determined that the optimum collision
energy (CE) voltage:
CA 02434143 2003-07-02
2 -
CE-- 0.05m
where m is the mass of the parent ion in daltons. The
kinetic energy of an ion is given by:
mv a
E= =eV
2
where E is the ion energy, m is the mass, v is the
velocity of the ion, e is electron charge and V is
Volts. Accordingly:
V, _ 2eV
m
In MKS units and where M is in daltons:
V _ 2 x 1.6x10-19 V (m/s)2
1.67x1027 m
since electron charge is 1.6 x 10-19 coulombs and 1
dalton is 1.67 x 10-27 kg. According to the empirically
determined relationship for singly charged ions the
optimum collision energy voltage is approximately equal
to the mass in daltons divided by 20 and hence:
2 2 x 1.6x10-19 1
V (M /S)2
1.67x10-27 20
thus:
CA 02434143 2003-07-02
3
v2'4107 (r/s)`
v%ts3000 mis
Hence the optimum collision conditions are
conventionally met when ions irrespective of their mass
enter a collision cell having e.g. nitrogen or argon
collision gas with a velocity of approximately 3000 m/s.
Once the ions enter a conventional collision cell then
they quickly lose their energy. The empirically
determined optimum velocity of approximately 3000 m/s is
not therefore an average velocity of the ions travelling
through the collision cell but rather corresponds with
the velocity that the ions should have upon initially
entering the collision cell.
Conventionally it is known to accelerate ions
having different masses so that the ions have
substantially the same energy prior to entering a
collision cell. However, it is not known to accelerate
ions having different masses to have substantially the
same velocity prior to entering a collision cell.
Conventional collision cell arrangements are
therefore unable to fragment a relatively large number
of ions having different masses all at substantially the
same time and all at substantially the optimum collision
energy. The collision energy must either be set at some
compromise value which will tend to be less than optimum
for some of the ions entering the collision cell or the
ions must be arranged to have a collision energy which
is progressively increased in a stepped or otherwise
scanned manner over an appropriate range of energies.
If the range of parent ion masses to be fragmented is
relatively large, for example ranging from mass 500 to
CA 02434143 2003-07-02
4 -
2500 daltons, then it is apparent that the ions will be
fragmented in a sub-optimal manner.
It is therefore desired to provide a mass
spectrometer having an improved fragmentation device.
According to an aspect of the present invention
there is provided a mass spectrometer comprising:
a fragmentation device for fragmenting ions, the
fragmentation device comprising a plurality of
electrodes wherein in use at least 50%, 60%, 70%, 80%,
90% or 95% of ions having a first mass to charge ratio
and at least 500, 60%, 70%, 80%, 90% or 95% of ions
having a second different mass to charge ratio are
arranged to be substantially simultaneously transmitted
through at least a portion of the fragmentation device
at substantially the same first velocity.
The preferred embodiment relates to an AC or RF
collision cell with a superimposed DC travelling wave
with constant wave velocity.
In use at least 50%, 60%, 70%, 80%, 90% or 95% of
ions having mass to charge ratios in between the first
mass to charge ratio and the second mass to charge ratio
are preferably also substantially simultaneously
transmitted through the fragmentation device at
substantially the same the first velocity.
The first velocity may be in the range selected
from the group consisting of: (i) 500-600 m/s; (ii) 600-
700 m/s; (iii) 700-800 m/s; (iv) 800-900 m/s; (v) 900-
1000 m/s; (vi) 1000-1100 m/s; (vii) 1100-1200 m/s;
(viii) 1200-1300 m/s; (ix) 1300-1400 m/s; and (x) 1400-
1500 m/s. The first velocity may alternatively be in
the range selected from the group consisting of: (i)
1500-1600 m/s; (ii) 1600-1700 m/s; (iii) 1700-1800 m/s;
(iv) 1800-1900 m/s; (v) 1900-2000 m/s; (vi) 2000-2100
CA 02434143 2003-07-02
- 5 -
m/s; (vii) 2100-2200 m/s; (viii) 2200-2300 m/s; (ix)
2300-2400 m/s; and (x) 2400-2500 m/s. The first
velocity may alternatively be in the range selected from
the group consisting of: (i) 2500-2600 m/s; (ii) 2600-
2700 m/s; (iii) 2700-2800 m/s; (iv) 2800-2900 m/s; (v)
2900-3000 m/s; (vi) 3000-3100 m/s; (vii) 3100-3200 m/s;
(viii) 3200-3300 m/s; (ix) 3300-3400 m/s; and (x) 3400-
3500 m/s. The first velocity may alternatively be in
the range selected from the group consisting of: (i)
3500-3600 m/s; (ii) 3600-3700 m/s; (iii) 3700-3800 m/s;
(iv) 3800-3900 m/s; (v) 3900-4000 m/s; (vi) 4000-4100
m/s; (vii) 4100-4200 m/s; (viii) 4200-4300 m/s; (ix)
4300-4400 m/s; and (x) 4400-4500 m/s. The first
velocity could also be in the range selected from the
group consisting of: (i) 4500-4600 m/s; (ii) 4600-4700
m/s; (iii) 4700-4800 m/s; (iv) 4800-4900 m/s; (v) 4900-
5000 m/s; (vi) 5000-5100 m/s; (vii) 5100-5200 m/s;
(viii) 5200-5300 m/s; (ix) 5300-5400 m/s; (x) 5400-5500
m/s; (xi) 5500-5600 m/s; (xii) 5600-5700 m/s; (xiii)
5700-5800 m/s; (xiv) 5800-5900 m/s; (xv) 5900-6000 m/s;
and (xvi) > 6000 m/s.
The difference between the first mass to charge
ratio and the second mass to charge ratio may be
preferably at least 50, 100, 150, 200, 250, 300, 350,
400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900,
950, 1000, 1050, 1100, 1150, 1200, 1250, 1300, 1350,
1400, 1450, 1500, 1550, 1600, 1650, 1700, 1750, 1800,
1850, 1900, 1950, 2000, 2050, 2100, 2150, 2200, 2250,
2300, 2350, 2400, 2450, 2500, 2550, 2600, 2650, 2700,
2750, 2800, 2850, 2900, 2950 or 3000 mass to charge
ratio units.
The ions having the first mass to charge ratio and
the ions having the second mass to charge ratio are
CA 02434143 2003-07-02
6 -
preferably substantially transmitted through at least
5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,
60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the axial
length of the fragmentation device at substantially the
same first velocity.
Ions having different mass to charge ratios are
preferably substantially simultaneously transmitted in
use through the fragmentation device by one or more
transient DC voltages or one or more transient DC
voltage waveforms which are progressively applied to the
electrodes so that ions are urged along the
fragmentation device.
In use an axial voltage gradient is preferably
maintained along at least a portion of the length of the
fragmentation device and wherein the axial voltage
gradient varies with time whilst ions are being
transmitted through the fragmentation device.
The fragmentation device may comprise at least 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.
CA 02434143 2003-07-02
- 7 -
According to an embodiment 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.
According to an alternative embodiment 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 the third electrode is at
the third reference potential; and at the third time t3
the second electrode is no longer supplied with the
second DC voltage so that the second electrode is
returned to the second reference potential and the first
electrode is at the first reference potential.
The first, second and third reference potentials
are preferably substantially the same. The first,
second and third DC voltages are preferably
substantially the same. The first, second and third
potentials are preferably substantially the same.
The fragmentation device 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.
CA 02434143 2003-07-02
8 -
A plurality of segments may be 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
fragmentation. device by an AC or RF electric field.
Ions are radially confined within the fragmentation
device in a pseudo-potential well and are preferably
constrained axially by a real potential barrier or well.
The transit time of ions through the fragmentation
device 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.
At least 50%, 60%, 70%, 80%, 90% or 95% of the ions
entering the fragmentation device are arranged
preferably to have, in use, an energy greater than or
equal to 10 eV for a singly charged ion or greater than
or equal to 20 eV for a doubly charged ion such that the
ions are caused to fragment.
At least 50%, 60%, 70%, 80%, 90% or 95% of the ions
entering the fragmentation device are preferably
arranged to fragment upon colliding with collision gas
within the fragmentation device.
The fragmentation device is preferably maintained
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
CA 02434143 2003-07-02
- 9 -
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 fragmentation device is
maintained at a pressure selected from the group
consisting of: (i) less than or equal to 10 mbar; (ii)
less than or equal to 5 mbar; (iii) less than or equal
to 1 mbar; (iv) less than or equal to 0.5 mbar; (v) less
than or equal to 0.1 mbar; (vi) less than or equal to
0.05 mbar; (vii) less than or equal to 0.01 mbar; (viii)
less than or equal to 0.005 mbar; (ix) less 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 fragmentation device 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 fragmentation device is preferably maintained,
in use, at a pressure such that a viscous drag is
imposed upon ions passing through the fragmentation
device.
In use one or more transient DC voltages or 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
CA 02434143 2003-07-02
-
different axial positions along the fragmentation
device.
One or more transient DC voltages or one or more
transient DC voltage waveforms are preferably arranged
5 to move in use from one end of the fragmentation device
to another end of the fragmentation device so that ions
are urged along the fragmentation device.
The one or more transient DC voltages may create:
(i) a potential hill or barrier; (ii) a potential well;
10 (iii) multiple potential hills or barriers; (iv)
multiple potential wells; (v) a combination of a
potential hill or barrier and a potential well; or (vi)
a combination of multiple potential hills or barriers
and multiple potential wells.
The one or more transient DC voltage waveforms
preferably comprise a repeating waveform such as a
square wave.
The amplitude of the. one or more transient DC
voltages or the one or more transient DC voltage
waveforms preferably remains substantially constant with
time. Alternatively, the amplitude of the one or more
transient DC voltages or the one or more transient DC
voltage waveforms may vary with time. The amplitude of
the one or more transient DC voltages or the one or more
transient DC voltage waveforms may increase with time,
increase then decrease with time, decrease with time or
decrease then increase with time.
The fragmentation device 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
CA 02434143 2003-07-02
- 11 -
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
fragmentation device 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 may be
substantially zero and.the second amplitude may be
substantially non-zero. Preferably, the second
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 fragmentation device with a second
velocity. The second velocity may remain substantially
constant, vary, increase, increase then decrease,
decrease, decrease then increase, reduce to
substantially zero, reverse direction or reduce to
substantially zero and then reverse direction.
The difference between the first (ion) velocity and
the second (travelling DC voltage wave) velocity is
preferably selected from the group consisting of: (i)
less than or equal to 50 m/s; (ii) less than or equal to
40 m/s; (iii) less than or equal to 30 m/s; (iv) less
than or equal to 20 m/s; (v) less than or equal to 10
m/s; (vi) less than or equal to 5 m/s; and (vii) less
than or equal to 1 m/s.
CA 02434143 2003-07-02
- 12 -
The second velocity is preferably selected from the
group consisting of: (i) 500-750 m/s; (ii) 750-1000 m/s;
(iii) 1000-1250 m/s; (iv) 1250-1500 m/s; (v) 1500-1750
m/s; (vi) 1750-2000 m/s; (vii) 2000-2250 m/s; (viii)
2250-2500 m/s; (ix) 2500-2750 m/s; (x) 2750-3000 m/s;
(xi) 3000-3250 m/s; (xii) 3250-3500 m/s; (xiii) 3500-
3750 m/s; (xiv) 3750-4000 m/s; (xv) 4000-4250 m/s; (xvi)
4250-4500 m/s; (xvii) 4500-4750 m/s; (xviii) 4750-5000
m/s; (xix) 5000 m/s-5250 m/s; (xx) 5250--5500 m/s; (xxi)
5500-5750 m/s; and (xxii) 5750-6000 m/s; and (xxiii) >
6000 m/s.
The second velocity is preferably substantially the
same as the first velocity.
The one or more transient DC voltages or the one or
more transient DC voltage waveforms preferably have 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 have 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.
Two or more transient DC voltages or two or more
transient DC voltage waveforms may pass simultaneously
along the fragmentation device. The two or more
transient DC voltages or the two or more transient DC
voltage waveforms may move: (i) in the same direction;
(ii) in opposite directions; (iii) towards each other;
(iv) away from each other.
CA 02434143 2003-07-02
- 13 -
The one or more transient DC voltages or the one or
more transient DC voltage waveforms may be repeatedly
generated and passed in use along the fragmentation
device, 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.
In use a continuous beam of ions may be received at
an entrance to the fragmentation device. Alternatively,
packets of ions may be received at an entrance to the
fragmentation device.
Pulses of ions preferably emerge from an exit of
the fragmentation device. 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 fragmentation device. The mass spectrometer may
comprise 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 fragmentation device.
The fragmentation device 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
CA 02434143 2003-07-02
- 14 -
remains substantially constant; and (iii) a stack of
plate, ring or wire loop electrodes.
The fragmentation device preferably comprises a
plurality of electrodes, each electrode having an
aperture through which ions are transmitted in use.
Each electrode has preferably a substantially circular
aperture. Each electrode preferably has a single
aperture through which ions are transmitted in use.
The diameter of the apertures of at least 50%, 60%,
70%, 80%, 90% or 95% of the electrodes forming the
fragmentation device is 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 50%, 60%, 70%, 80%, 90% or 95% of the
electrodes forming the fragmentation device preferably
have apertures which are substantially the same size or
area.
According to another embodiment the fragmentation
device may comprise a segmented rod set.
The fragmentation device 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.
CA 02434143 2003-07-02
- 15 -
The thickness of at least 50%, 60%, 70%, 80%, 900
or 95% of the electrodes is selected from the group
consisting of: (i) less than or equal to 3 mm; (ii) less
than or equal to 2.5 mm; (iii) less than or equal to 2.0
mm; (iv) less than or equal to 1.5 mm; (v) less than or
equal to 1.0 mm; and (vi) less than or equal to 0.5 mm.
The fragmentation device 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.
The fragmentation device preferably comprises a
housing having an upstream opening for allowing ions to
enter the fragmentation device and a downstream opening
for allowing ions to exit the fragmentation device.
The fragmentation device may further comprise an
inlet port through which a collision gas is introduced.
The collision gas may comprise air and/or one or more
inert gases and/or one or more non-inert gases.
Preferably, at least 10%, 20%, 30%, 40%, 50%, 60%,
70%, 80%, 90%, or 95% of the electrodes are connected to
both a DC and an AC or RF voltage supply. Axially
adjacent electrodes are supplied with AC or RF voltages
having a phase difference of 180 .
According to a less preferred embodiment in use one
or more AC or RF voltage waveforms may be applied to at
least some of the electrodes so that ions are urged
along at least a portion of the length of the
fragmentation device. The AC or RF voltage waveforms
are additional to the AC or RF voltages supplied to the
electrodes and which act to radially confine the ions
within the fragmentation device but which do not
substantially urge ions along the length of the device.
CA 02434143 2003-07-02
- 16 -
The mass spectrometer preferably comprises 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 ("EI) 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.
A continuous or pulsed ion source may be provided.
According to another aspect of the present
invention there is provided a mass spectrometer
comprising:
an ion source;
a mass filter;
a fragmentation device, for fragmenting ions, the
fragmentation device comprising a plurality of
electrodes wherein in use at least 50%, 60%, 70%, 80%,
90% or 95% of ions having a first mass to charge ratio
and at least 50%, 60%, 70%, 80%, 90% or 95% of ions
having a second different mass to charge ratio are
arranged to be substantially simultaneously transmitted
through at least a portion of the fragmentation device
at substantially the same first velocity; and
a mass analyser.
There is preferably further provided an ion guide
arranged upstream of the mass filter. The ion guide may
comprise a plurality of electrodes wherein at least some
of the electrodes are connected to both a DC and an AC
CA 02434143 2003-07-02
- 17 -
or RF voltage supply and wherein one or more transient
DC voltages or the one or more transient DC voltage
waveforms are passed in use along at least a portion of
the length of the ion guide to urge ions along the
portion of the length of the ion guide.
The mass filter may comprise a quadrupole rod set
mass filter. The mass analyser preferably comprises a
Time of Flight mass analyser, a quadrupole mass
analyser, a Fourier Transform Ion Cyclotron Resonance
("FTICR") mass analyser, a 2D (linear) quadrupole ion
trap or a 3D (Paul) quadrupole ion trap.
According to another aspect of the present
invention there is provided a mass spectrometer having a
collision cell wherein ions differing in mass to charge
ratios by at least 100, 200, 300, 400, 500, 600, 700,
800, 900 or 1000 mass to charge ratio units travel
through at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%,
45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%
of the collision cell at substantially the same
velocity.
According to another aspect of the present
invention there is provided a collision cell wherein, in
use, ions having substantially different mass to charge
ratios are transmitted through the collision cell at
substantially the same velocity.
According to another aspect of the present
invention there is provided a method of mass
spectrometry comprising:
providing a fragmentation device for fragmenting
ions, the fragmentation device comprising a plurality of
electrodes; and
substantially simultaneously transmitting at least
50%, 60%, 70%, 80%, 90% or 95% of ions having a first
CA 02434143 2003-07-02
- 18 -
mass to charge ratio and at least 50%, 60%, 70%, 80%,
90% or 950 of ions having a second different mass to
charge ratio through at least a portion of the
fragmentation device at substantially the same first
velocity.
According to another aspect of the present
invention there is provided a method of mass
spectrometry comprising:
providing an ion source, a mass filter, a
fragmentation device for fragmenting ions, the
fragmentation device comprising a plurality of
electrodes and a mass analyser; and
substantially simultaneously transmitting at
substantially the same first velocity through at least a
portion of the fragmentation device at least 50%, 60%,
70%, 80%, 90% or 95% of ions having a first mass to
charge ratio and at least 50%, 60%, 70%, 80%, 90% or 95%
of ions having a second different mass to charge ratio.
According to another aspect of the present
invention there is provided a method of mass
spectrometry comprising:
providing a collision cell; and
passing ions differing in mass to charge ratios by
at least 100, 200, 300, 400, 500, 600, 700, 800, 900 or
1000 mass to charge ratio units through at least 5%,
10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%,
65%, 70%, 75%, 80%, 85%, 90%, or 95% of the collision
cell at substantially the same velocity.
According to another aspect of the present
invention there is provided a method of mass
spectrometry comprising:
providing a collision cell; and
CA 02434143 2003-07-02
- 19 -
transmitting ions having substantially different
mass to charge ratios through the collision cell at
substantially the same velocity.
According to another aspect of the present
invention there is provided a mass spectrometer
comprising:
an AC or RF ion guide; and
a fragmentation device arranged downstream of the
AC or RF ion guide;
wherein in use one or more transient DC voltages or
one or more transient DC voltage waveforms are
progressively applied to the AC or RF ion guide so that
ions having a plurality of different mass to charge
ratios are arranged to be transmitted through the ion
guide with substantially the same velocity whereupon the
ions are then arranged to enter the fragmentation device
with substantially the same velocity and are
substantially fragmented.
According to another aspect of the present
invention there is provided a method of mass
spectrometry comprising:
providing an AC or RF ion guide and a fragmentation
device downstream of the AC or RF ion guide; and
progressively applying one or more transient DC
voltages or one or more transient DC voltage waveforms
to the AC or RF ion guide so that ions having a
plurality of different mass to charge ratios are
transmitted through the ion guide with substantially the
same velocity and are then arranged to enter the
fragmentation device with substantially the same
velocity whereupon they are substantially fragmented.
CA 02434143 2003-07-02
- 20 -
Preferably, the background gas within the
fragmentation device is substantially heavier than the
background gas within the AC or RF ion guide.
Preferably, the fragmentation device is maintained
at a higher pressure than the AC or RF ion guide. For
example, the pressure in the fragmentation device may be
at least 10%, 20%, 30%, 40%, 50%, 60%, '70%, 80%, 90%,
100% greater than the pressure within the AC or RF ion
guide. According to another embodiment the pressure in
the fragmentation device may be at least x2, x5, x10,
x20, x50, x100, x200, x500, x1000, x2000, x5000, xl0000
times the pressure within the AC or RF ion guide.
Various embodiments of the present invention will
now be described, by way of example only, and with
reference to the accompanying drawings in which:
Fig. 1 shows a preferred collision cell;
Fig. 2A shows a single potential hill travelling DC
voltage, Fig. 2B shows a single potential well
travelling DC voltage, Fig. 2C shows a combination of a
potential hill and potential well travelling DC voltage
waveform, Fig. 2D shows a repeating DC voltage waveform
and Fig. 2E shows a yet further repeating DC voltage
waveform;
Fig. 3A shows a mass spectrum obtained when
Verapamil parent ions having a mass to charge ratio of
455 entered a collision cell having a 150 m/s travelling
DC potential waveform with a collision energy of 9 eV,
Fig. 3B shows a mass spectrum obtained when Verapamil
parent ions entered a collision cell having a 150 m/s
travelling DC potential waveform with a collision energy
of 20 eV, Fig. 3C shows a mass spectrum obtained when
Verapamil parent ions entered a collision cell having a
150 m/s travelling DC potential waveform. with a
CA 02434143 2003-07-02
-- 21 -
collision energy of 26 eV, Fig. 3D shows a mass spectrum
obtained when Verapamil parent ions entered a collision
cell having a 150 m/s travelling potential waveform with
a collision energy of 29 eV, Fig. 3E shows a mass
spectrum obtained when Verapamil parent ions entered a
collision cell having a 150 m/s travelling DC potential
waveform with a collision energy of 39 eV, Fig. 3F shows
a mass spectrum obtained when Verapamil parent ions
entered a collision cell having a 1500 m/s travelling DC
potential waveform according to the preferred embodiment
with a collision energy of 2 eV and Fig.. 3G shows a mass
spectrum obtained when Verapamil parent ions entered a
collision cell having a 1500 m/s travelling DC potential
waveform according to the preferred embodiment with a
collision energy of 10 eV;
Fig. 4A shows a mass spectrum obtained when
diphenhydramine parent ions having a mass to charge
ratio of 256 entered a collision cell having a 150 m/s
travelling DC potential waveform with a collision energy
of 9 eV, Fig. 4B shows a mass spectrum obtained when
diphenhydramine parent ions entered a collision cell
having a 150 m/s travelling DC potential waveform with a
collision energy of 20 eV, Fig. 4C shows a mass spectrum
obtained when diphenhydramine parent ions entered a
collision cell having a 150 m/s travelling DC potential
waveform with a collision energy of 26 eV, Fig. 4D shows
a mass spectrum obtained when diphenhydramine parent
ions entered a collision cell having a 150 m/s
travelling DC potential waveform with a collision energy
of 29 eV, Fig. 4E shows a mass spectrum obtained when
diphenhydramine parent ions entered a collision cell
having a 150 m/s travelling DC potential waveform with a
collision energy of 39 eV, Fig. 4F shows a mass spectrum
CA 02434143 2003-07-02
22 -
obtained when diphenhydramine parent ions entered a
collision cell having a 1500 m/s travelling DC potential
waveform according to the preferred embodiment with a
collision energy of 2 eV and Fig. 4G shows a mass
spectrum obtained when diphenhydramine parent ions
entered a collision cell having a 1500 m/s travelling DC
potential waveform according to the preferred embodiment
with a collision energy of 10 eV;
Fig. 5A shows a mass spectrum obtained when
terfenadine parent ions having a mass to charge ratio of
472 entered a collision cell having a 150 m/s travelling
DC potential waveform with a collision energy of 9 eV,
Fig. 5B shows a mass spectrum obtained when terfenadine
parent ions entered a collision cell having a 150 m/s
travelling DC potential waveform with a collision energy
of 20 eV, Fig. 5C shows a mass spectrum obtained when
terfenadine parent ions entered a collision cell having
a 150 m/s travelling DC potential waveform with a
collision energy of 26 eV, Fig. 5D shows a mass spectrum
obtained when terfenadine parent ions entered a
collision cell having a 150 m/s travelling DC potential
waveform with a collision energy of 29 eV, Fig. 5E shows
a mass spectrum obtained when terfenadine parent ions
entered a collision cell having a 150 m/s travelling DC
potential waveform with a collision energy of 39 eV,
Fig. 5F shows a mass spectrum obtained when terfenadine
parent ions entered a collision cell having a 1500 m/s
travelling DC potential waveform according to the
preferred embodiment with a collision energy of 2 eV and
Fig. 5G shows a mass spectrum obtained when terfenadine
parent ions entered a collision cell having a 1500 m/s
travelling DC potential waveform according to the
preferred embodiment with a collision energy of 10 eV;
CA 02434143 2003-07-02
- 23 -
Fig. 6A shows a mass spectrum obtained when
sulfadimethoxine parent ions having a mass to charge
ratio of 311 entered a collision cell having a 150 m/s
travelling DC potential waveform with a collision energy
of 9 eV, Fig. 6B shows a mass spectrum obtained when
sulfadimethoxine parent ions entered a collision cell
having a 150 m/s travelling DC potential. waveform with a
collision energy of 20 eV, Fig. 6C shows a mass spectrum
obtained when sulfadimethoxine parent ions entered a
collision cell having a 150 m/s travelling DC potential
with a collision energy of 26 eV, Fig. 6D shows a mass
spectrum obtained when sulfadimethoxine parent ions
entered a collision cell having a 150 m/s travelling DC
potential waveform with a collision energy of 29 eV,
Fig. 6E shows a mass spectrum obtained when
sulfadimethoxine parent ions entered a collision cell
having a 150 m/s travelling DC potential waveform with a
collision energy of 39 eV, Fig. 6F shows a mass spectrum
obtained when sulfadimethoxine parent ions entered a
collision cell having a 1500 m/s travelling DC potential
waveform according to the preferred embodiment with a
collision energy of 2 eV and Fig. 6G shows a mass
spectrum obtained when sulfadimethoxine parent ions
entered a collision cell having a 1500 m/s travelling DC
potential waveform according to the preferred embodiment
with a collision energy of 10 eV;
Fig. 7A shows a mass spectrum obtained when
reserpine parent ions having a mass to charge ratio of
609 entered a conventional collision cell with a
collision energy of 9 eV, Fig. 7B shows a mass spectrum
obtained when reserpine parent ions entered a collision
cell having a 150 m/s travelling DC potential waveform
with a collision energy of 20 eV, Fig. 7C shows a mass
CA 02434143 2003-07-02
- 24 -
spectrum obtained when reserpine parent ions entered a
collision cell having a 150 m/s travelling DC potential
waveform with a collision energy of 26 eV, Fig. 7D shows
a mass spectrum obtained when reserpine parent ions
entered a collision cell having a 150 m/s travelling DC
potential waveform with a collision energy of 29 eV,
Fig. 7E shows a mass spectrum obtained when reserpine
parent ions entered a collision cell having a 150 m/s
travelling DC potential waveform with a collision energy
of 39 eV, - Fig. 7F shows a mass spectrum obtained when
reserpine parent ions entered a collision cell having a
1500 m/s travelling DC potential waveform according to
the preferred embodiment with a collision energy of 2 eV
and Fig. 7G shows a mass spectrum obtained when
reserpine parent ions entered a collision cell having a
1500 m/s travelling DC potential waveform according to
the preferred embodiment with a collision energy of 10
eV; and
Fig. 8 shows the variation of optimum gas velocity
with gas cell pressure for a gas cell length of 185 mm.
A preferred embodiment of the present invention
will now be described in relation to Fig. 1. A
segmented collision cell 1 is provided comprising a
plurality of electrodes 2 which may be grouped together
into a plurality of segments. Ions are received at an
entrance 3 and exit via exit 4. According to one
embodiment one or more DC potential barriers/valleys may
be translated along the length of the collision cell 1
and a repeating pattern of DC electrical potentials may
be superimposed along the length of a segmented
collision cell 1 so that a periodic DC voltage waveform
is formed. The DC voltage waveform travels along at
least part of the collision cell 1 in the direction in
CA 02434143 2003-07-02
- 25 -
which it is required to move the ions at constant
velocity.
In the presence of gas at a suitable pressure the
ion motion will be dampened by the viscous drag of the
gas. The ions will therefore drift forwards with
substantially the same velocity as that of the
travelling DC waveform which is effectively being
translated along the length of the collision cell 1.
The ions will therefore travel through the collision
cell 1 with approximately the same velocity irrespective
of their mass. As will be appreciated, if the ions
being transmitted through the collision cell 1 have
substantially the same velocity then their kinetic
energy will vary in proportion to their mass. Since it
has been empirically determined that the optimum
collision energy of an ion is also proportional to the
mass of the ion then if the travelling wave is set
sufficiently fast then the kinetic energy of all the
ions may be such that the ions fragment in an optimal
manner upon colliding with gas molecules.
It has been found that according to the preferred
embodiment when a travelling DC voltage is applied to
the collision cell 1 the velocity of the travelling wave
necessary to induce fragmentation may be lower than the
value of approximately 3000 m/s which applies to
conventional collision cells. It has been found, for
example, that travelling wave velocities less than 1500
m/s are sufficient to induce fragmentation. It is
believed that reason for this is that with collision
cell 1 according to the preferred embodiment the ions
are maintained at a desired velocity whilst passing
through preferably the whole of the length of the
collision cell 1 whereas with a conventional collision
CA 02434143 2003-07-02
- 26 -
cell the ions quickly lose kinetic energy upon entering
the collision cell.
According to a less preferred embodiment an AC or
RF ion guide may be provided upstream of a collision
cell which may be a conventional collision cell or a
collision cell 1 according to the preferred embodiment
wherein a DC voltage or voltage waveform is applied to
the collision cell in order to urge ions along the
length of the collision cell 1. The AC or RF ion guide
is provided with a travelling DC voltage or voltage
waveform such that the velocity of the travelling DC
voltage waveform in the AC or RF ion guide is set
preferably just below the velocity required to induce
fragmentation with the particular gas molecules in the
ion guide. However, the ions which are emitted from the
AC or RF ion guide and which have substantially the same
velocity are then arranged to enter the collision cell,
which may according to one embodiment be maintained at a
relatively higher pressure than the AC or RF ion guide,
wherein the ions are then subject to collision induced
decomposition within the collision cell. The energy of
each ion entering the gas collision cell will be
approximately proportional to its mass and hence the
collision energy can be optimised for all ions,
simultaneously, irrespective of their mass since it is
known that the optimal collision energy is also
proportional to the mass of the ion. The collision cell
may also or alternatively contain a heavier gas than the
AC or RF ion guide so that even if the pressure of the
collision cell is substantially similar to that of the
AC or RF ion guide, the heavier gas molecules in the
collision cell are sufficient to induce fragmentation at
CA 02434143 2003-07-02
- 27 -
the velocities that the ions enter the collision cell
at.
The fragmentation device or collision cell 1
according an embodiment may comprise a segmented
multipole rod set or more preferably a stacked ring set
("ion tunnel"). The fragmentation device 1 is
preferably segmented in the axial direction so that
independent transient DC potentials or DC voltage
waveforms may be applied to individual segments. The
transient DC potential(s) or DC voltage waveforms are
preferably superimposed on top of an AC or RF voltage
applied to the electrodes which acts to radially confine
ions within the collision cell 1. The transient DC
potential(s) or voltage waveforms are also preferably
superimposed on top of any constant axial DC offset
voltage applied to the electrodes 2 which form a
constant axial DC voltage gradient. The DC potentials
applied to the electrodes 2 may be changed temporally to
generate a travelling DC voltage wave in the axial
direction.
At any instant in time a voltage gradient is
generated between electrodes 2 or segments of the
collision cell 1 which has the effect of pushing or
pulling ions in a certain direction. As the voltage
gradient moves in the required direction so do the ions.
The individual DC voltages applied to each of the
electrodes 2 or segments is preferably programmed to
create a desired DC voltage or DC voltage waveform.
Furthermore, the individual DC voltages on each of the
electrodes 2 or segments is also preferably programmed
to change in synchronism such that the voltage or
voltage waveform is preferably maintained but shifted in
the direction in which it is required to move the ions.
CA 02434143 2003-07-02
28 -
No static axial DC voltage gradient is required
although the travelling DC voltage wave may, less
preferably, be provided in conjunction with a constant
axial DC voltage gradient. The transient DC voltage or
voltage waveform applied to each segment or electrode 2
may be above and/or below that of the constant DC
voltage offset to cause movement of the ions in the
axial direction.
Figs. 2A-E show five different examples of DC
transient voltages or voltage waveforms which may be
superimposed on the electrodes 2. Fig. 2A shows a
transient DC voltage having a single potential hill or
barrier, Fig. 2B shows a transient DC voltage having a
single potential well, Fig. 2C shows a transient DC
voltage waveform having a single potential well followed
by a potential hill or barrier, Fig. 2D shows a
transient DC voltage waveform having a repeating
potential hill or barrier and Fig. 2E shows a transient
DC voltage waveform having periodic pulses.
The DC voltages or voltage waveforms applied to
each electrode 2 or segment may be programmed to change
continuously or in a series of steps. The sequence of
DC voltages applied to each electrode 2 or segment may
repeat at regular intervals or at intervals which
progressively increase or decrease.
The time over which the complete sequence of
voltages is applied over one wavelength of a particular
segment is the cycle time T. The inverse of the cycle
time is the wave frequency f. The distance along the
collision cell 1 over which the voltage waveform repeats
itself is the wavelength A. The wavelength divided by
the cycle time is the velocity of the travelling DC
voltage wave. Hence, the wave velocity Vwave:
CA 02434143 2003-07-02
29
V wave r
Under correct operation the velocity v of the ions
will be equal to that of the travelling DC voltage or
voltage waveform velocity vwave. For a given wavelength
the wave velocity may be controlled by selection of the
cycle time. The preferred velocity of the travelling DC
voltage wave may be dependent upon a number of factors
including the range of ion masses to be analysed, the
pressure and composition of the collision gas and the
minimum collision energy required for fragmentation.
The travelling wave collision cell 1 may preferably
be used at intermediate pressures between 0.0001 and 100
mbar, more preferably between 0.001 and 10 mbar, further
preferably between 0.001 and 0.1 mbar. At such gas
densities a viscous drag is imposed on the ions. The
gas at these pressures will therefore appear as a
viscous medium to the ions and will act to slow the
ions. The viscous drag resulting from frequent
collisions with gas molecules will prevent the ions from
building up excessive velocity. Consequently, the ions
will tend to ride on or with the travelling DC voltage
wave rather than running ahead of the travelling DC
voltage wave and executing excessive oscillations within
the travelling potential wells.
The presence of the collision gas imposes a maximum
velocity at which the ions will travel through the gas
for a given field strength. The higher the gas pressure
the more frequent the ion-molecule collisions will be
and the slower the ions will travel for a given field
CA 02434143 2003-07-02
- 30 -
strength. The energy of the ions will be dependent upon
their mass and the square of their velocity.
It is desirable for the collision energy of singly
charged ions in a collision cell to be greater for
higher mass ions. Conventionally, if it is required to
fragment a number of different precursor ions, each
having a different mass at the same time, then it is not
possible to set just a single collision energy that is
the optimum collision energy for all the different
precursor ions having widely varying masses. However,
with the collision cell 1 according to the preferred
embodiment ions having a wide range of masses can all be
arranged to have substantially the same velocity whilst
being transmitted through the collision cell 1. If all
the ions have approximately the same velocity,
irrespective of their mass, then the ion collision
energy of the ions will be proportional to its mass.
Since it is known empirically that the optimum collision
energy is proportional to the mass of the ion then the
collision energy can be simultaneously optimised for all
ions irrespective of their mass.
The mass spectra shown in Figs. 3-7 were all
obtained using a collision cell 1 comprised of a stack
of 122 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 ring stack was
,182 mm. A 2.75 MHz RF voltage was applied between
neighbouring rings to radially confine the ion beam
within the collision cell 1. The pressure in the
collision cell 1 was approximately 3.4 x 10-3 mbar. The
travelling DC voltage waveform which was applied
comprised a regular periodic pulse of constant amplitude
and velocity. The travelling DC voltage waveform was
CA 02434143 2003-07-02
- 31 -
generated by applying a transient DC voltage to a pair
of ring electrodes and every subsequent ring pair
displaced by seven ring pairs along the ring stack. In
each ring pair one electrode was maintained at a
positive phase of the RF voltage and the other the
negative. One wavelength of the DC voltage waveform
therefore consisted of two rings with a raised
(transient) DC potential followed by twelve rings held
at lower (normal) potentials. Thus, the wavelength ?
was equivalent to 14 rings (21 mm) and. the collision
cell 1 therefore had a length equivalent to
approximately 5.8 X.
The travelling DC potential waveform was generated
by applying a transient 10 V voltage to each pair of
ring electrodes for a given time t before moving the
applied voltage to the next pair of ring electrodes.
This sequence was repeated uniformly along the length of
the collision cell 1. Thus the wave velocity vwave= V/t
was equal to 3mm/t where t is the time that the
transient DC voltage was applied to an electrode.
Figs. 3-7 show CID MS/MS data for a number of
compounds at different collision energies with a
travelling DC voltage waveform at different travelling
wave velocities. The data shows that at relatively low
wave travelling wave velocities (e.g. 150 m/s) the
collision energy determines the nature of the MS/MS
spectrum and optimises at different collision energies
for different parent ion masses. However, at higher
travelling wave velocities (e.g. 1500 m/s) high
collision energy is not required and only one wave
velocity is required to induce fragmentation
irrespective of parent ion mass.
CA 02434143 2003-07-02
- 32 -
Figs. 3A-3G show fragmentation spectra obtained
from Verapamil (m/z 455) using different collision
energies and two different travelling wave velocities.
The travelling wave velocity was 150 m/s for the mass
spectra shown in Figs. 3A-3E and 1500 m/s for the mass
spectra shown in Figs. 3F and 3G. The pulse voltage was
10V and the gas cell pressure was 3.4 x 10-3 mbar. The
collision energy was 9 eV for the mass spectrum shown in
Fig. 3A, 20 eV for the mass spectrum shown in Fig. 3B,
26 eV for the mass spectrum shown in Fig. 3C, 29 eV for
the mass spectrum shown in Fig. 3D, 39 eV for the mass
spectrum shown in Fig. 3E, 2 eV for the mass spectrum
shown in Fig. 3F and 10 eV for the mass spectrum shown
in Fig. 3G.
Figs. 4A-4G show fragmentation spectra obtained
from diphenhydramine (m/z 256) using different collision
energies and two different travelling wave velocities.
The travelling wave velocity was 150 m/s for the mass
spectra shown in Figs. 4A-4E and 1500 m/s for the mass
spectra shown in Fig. 4F and 4G. The pulse voltage was
by and the gas cell pressure 3.4 x 10-3 mbar.
Diphenhydramine is unusual in that it fragments
exceptionally easily. It is sometimes used as a test
compound to show how gentle a source is. The collision
energy was 9 eV for the mass spectrum shown in Fig. 4A,
20 eV for the mass spectrum shown in Fig. 4B, 26 eV for
the mass spectrum shown in Fig. 4C, 29 eV for the mass
spectrum shown in Fig. 4D, 39 eV for the mass spectrum
shown in Fig. 4E, 2 eV for the mass spectrum shown in
Fig. 4F and 10 eV for the mass spectrum shown in Fig.
4G.
Figs. 5A-5G shows fragmentation spectra obtained
from terfenadine (m/z 472) using different collision
CA 02434143 2003-07-02
- 33 -
energies and two different travelling wave velocities.
The travelling wave velocity was 150 m/s for the mass
spectra shown in Figs. 5A-5E and 1500 m/s for the mass
spectra shown in Figs. 5F and 5G. The pulse voltage was
10V and the gas cell pressure 3.4 x 10-3 mbar. The
collision energy was 9 eV for the mass spectrum shown in
Fig. 5A, 20 eV for the mass spectrum shown in Fig. 5B,
26 eV for the mass spectrum shown in Fig. 5C, 29 eV for
the mass spectrum shown in Fig. 5D, 39 eV for the mass
spectrum shown in Fig. 5E, 2 eV for the mass spectrum
shown in Fig. 5F and 10 eV for the mass spectrum shown
in Fig. 5G.
Figs. 6A-6G shows fragmentation spectra obtained
from sulfadimethoxine (m/z 311) using different
collision energies and two different travelling wave
velocities. The travelling wave velocity was 150 m/s
for the mass spectra shown in Figs. 6A-6E and 1500 m/s
for the mass spectra shown in Figs 6F and 6G. The pulse
voltage was 10V and the gas cell pressure 3.4 x 10-3
mbar. The collision energy was 9 eV for the mass
spectrum shown in Fig. 6A, 20 eV for the mass spectrum
shown in Fig. 6B, 26 eV for the mass spectrum shown in
Fig. 6C, 29 eV for the mass spectrum shown in Fig. 6D,
39 eV for the mass spectrum shown in Fig. 6E, 2 eV for
the mass spectrum shown in Fig. 6F and 10 eV for the
mass spectrum shown in Fig. 6G.
Finally, Figs. 7A-7G shows fragmentation spectra
obtained from reserpine (m/z 609) using different
collision energies and two different travelling wave
velocities. The travelling wave velocity was 150 m/s
for the mass spectra shown in Figs. 7A-7E and 1500 m/s
for the mass spectra shown in Fig. 7F and 7G. The pulse
voltage was 10V and the gas cell pressure 3.4 x 10-3
CA 02434143 2003-07-02
- 34 -
mbar. The collision energy was 9 eV for the mass
spectrum shown in Fig. 7A, 20 eV for the mass spectrum
shown in Fig. 7B, 26 eV for the mass spectrum shown in
Fig. 7C, 29 eV for the mass spectrum shown in Fig. 7D,
39 eV for the mass spectrum shown in Fig. 7E, 2 eV for
the mass spectrum shown in Fig. 7F and 10 eV for the
mass spectrum shown in Fig. 7G.
A series of experiments were then carried out using
a similar collision cell to the one used to obtain the
data shown in Figs. 3-7 to determine the optimum
velocity of the travelling DC voltage waveform to give
the best degree of fragmentation. Measurements were
carried out for several singly and doubly charged ions
with mass to charge ratios in the range 200 to 700. The
gas collision cell was 185 mm long and the collision gas
was Argon. It was observed that the optimum wave
velocity was approximately the same for all the ions
considered. However, the optimum wave velocity was less
than the conventional optimum velocity of 3000 m/s.
Furthermore, it was observed that the optimum wave
velocity was dependent upon gas pressure and reduced as
the pressure increased. Fig. 8 shows the optimum DC
voltage travelling waveform velocity for pressures over
the range 0.001 to 0.011 mbar. The optimum wave
velocity was about 1900 m/s at 0.001 mbar, about 1500
m/s at 0.003 mbar and about 950 m/s at 0.01 mbar.
The conventional empirical rule wherein the
collision energy (in Volts) is set to m/20, where m is
the mass of the ion, has been found to work quite
satisfactorily. The collision energy refers to the
energy of the ions as they enter a conventional gas
collision cell. In a conventional collision cell the
ions undergo multiple collisions and the velocity of the
CA 02434143 2003-07-02
- 35 -
ions will decay approximately exponentially. Hence, the
average ion-molecule collision velocity, or collision
energy, will be less than that of their initial
velocity.
In the case of the preferred collision cell 1
incorporating a travelling DC potential wave the ions
will be re-accelerated after losing energy through
collisions with gas molecules.
The higher the pressure in the collision cell the
shorter the mean free path between ion molecule
collisions and therefore the greater the number of
collisions. Hence, where a travelling DC voltage
waveform exists according to the preferred embodiment to
maintain the ion-molecule collision energy, the product
of average ion-molecule collision energy and number of
collisions will increase as the pressure increases. In
such a system, in order to induce optimum fragmentation,
it may be expected that the optimum ion-molecule
collision velocity will reduce if more collisions take
place. In this way the product of average ion-molecule
collision energy and number of collisions will remain
more constant. Hence, it may be expected that the
optimum wave velocity reduces as the pressure increases.
The results shown in Fig. 8 support this reasoning.
This is in contrast to a conventional gas cell
where no travelling DC voltage waveform exists to
maintain the velocity of the ions. Accordingly, ion
velocities will. decay to an insignificant level after a
certain number of collisions and provided the gas
pressure and gas cell length is adequate to get to this
point the product of average ion-molecule collision
velocity and number of collisions will remain fairly
constant. Hence, in this situation it may be expected
CA 02434143 2011-09-02
- 36 -
that the optimum collision energy is not so dependent upon
the gas pressure.
