Canadian Patents Database / Patent 2672526 Summary

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(12) Patent: (11) CA 2672526
(54) English Title: MASS SPECTROMETER
(54) French Title: SPECTROMETRE DE MASSE
(51) International Patent Classification (IPC):
  • H01J 49/40 (2006.01)
(72) Inventors :
  • KENNY, DANIEL JAMES (United Kingdom)
  • WILDGOOSE, JASON LEE (United Kingdom)
  • GREEN, MARTIN (United Kingdom)
(73) Owners :
  • MICROMASS UK LIMITED (Not Available)
(71) Applicants :
  • MICROMASS UK LIMITED (United Kingdom)
(74) Agent: RIDOUT & MAYBEE LLP
(74) Associate agent:
(45) Issued: 2016-08-23
(86) PCT Filing Date: 2007-12-14
(87) Open to Public Inspection: 2008-06-19
Examination requested: 2012-08-15
(30) Availability of licence: N/A
(30) Language of filing: English

(30) Application Priority Data:
Application No. Country/Territory Date
0624993.2 United Kingdom 2006-12-14
60/884,509 United States of America 2007-01-11

English Abstract

A mass spectrometer is disclosed comprising an orthogonal acceleration Time of Flight mass analyser. A pulse or packet of ions is released either from an ion trap (7) or alternatively from a travelling wave ion guide arranged upstream of an orthogonal acceleration electrode (2) which forms part of the Time of Flight mass analyser. Ions in the pulse or packet of ions which is released become temporally dispersed and the orthogonal acceleration electrode (2) is energised multiple times prior the release of a subsequent pulse or packet of ions.


French Abstract

La présente invention concerne un spectromètre de masse comportant un analyseur de masse à temps de vol de l'accélération orthogonale. Une impulsion ou un paquets d'ions est libéré(e) soit à partir d'une piège à ions (7) soit à partir d'un guide d'ions ionique par ondes en amont d'une électrode d'accélération orthogonale (2) formant partie de l'analyseur de masse de temps de vol d'accélération orthogonale. Des ions dans l'impulsion ou le paquet d'ions qui est libéré(e) sont dispersés dans le temps et l'électrode d'accélération orthogonale (2) est excitée plusieurs fois préalablement à la libération d'une impulsion ou d'un paquet d'ions ultérieur(e).


Note: Claims are shown in the official language in which they were submitted.

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Claims
1. A mass spectrometer comprising:
an ion guide comprises a plurality of electrodes;
transient DC voltage means arranged and adapted to apply
one or more transient DC voltages or potentials or one or
more transient DC voltage or potential waveforms to at least
some of the electrodes forming said ion guide in order to
urge at least some ions along at least 5% of the axial length
of said ion guide; and
a Time of Flight mass analyser arranged downstream of
said ion guide and comprising an orthogonal acceleration
electrode and a drift region;
wherein, in use, a first pulse or packet of ions is
released from said ion guide at a first release time T1;
wherein said mass analyser further comprises a control
device which is arranged and adapted:
(i) to energise said orthogonal acceleration electrode a
first time after a first delay time .DELTA.t1-1 from said first
release time T1 and prior to the release of a second pulse or
packet of ions from said ion guide at a second release time
T2; and
(ii) to energise said orthogonal acceleration electrode
at least a second subsequent time after a second delay time
.DELTA.t1-2 from said first release time T1 and prior to the release
of the second pulse or packet of ions at the second release
time T2.
2. A mass spectrometer as claimed in claim 1, wherein said
control device is arranged and adapted to energise said
orthogonal acceleration electrode a third time after a third
delay time .DELTA.t1-3 from said first release time T1.

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3. A mass spectrometer as claimed in claim 1 or 2, wherein,
in use, the second pulse or packet of ions is released at the
second release time T2.
4. A mass spectrometer as claimed in claim 3, wherein said
control device is arranged and adapted to energise said
orthogonal acceleration electrode a first time after a first
delay time .DELTA.t2-1 from said second release time T2 and at least
a second subsequent time after a second delay time .DELTA.t2-2 from
said second release time T2 and prior to the release of a
third pulse or packet of ions at a third release time T3.
5. A mass spectrometer as claimed in claim 3 or 4,
wherein, in use, a third pulse or packet of ions is released
at a third release time T3.
6. A mass spectrometer as claimed in any one of claims 1-5,
wherein the first delay time or the second delay time is
varied, increased, decreased or progressively changed after
each release of a pulse or packet of ions.
7. A mass spectrometer as claimed in any one of claims 1-6,
wherein said Time of Flight mass analyser comprises an
orthogonal acceleration Time of Flight mass analyser.
8. A mass spectrometer as claimed in any one of claims 1-7,
wherein one or more axial potential wells or one or more
axial pseudo-potential wells are translated along the length
of said ion guide and wherein when an axial potential well or
an axial pseudo-potential well reaches an end or exit region
of the ion guide ions contained within the axial potential
well or the axial pseudo-potential well are arranged and
adapted to be released or onwardly transmitted as a pulse or
packet of ions.
9. A mass spectrometer as claimed in any one of claims 1-8,
wherein said ion guide comprises:

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(i) a multipole rod set or a segmented multipole rod
set;
(ii) an ion tunnel or ion funnel; or
(iii) a stack or array of planar, plate or mesh
electrodes.
10. A mass spectrometer as claimed in claim 9, wherein said
ion tunnel or ion funnel comprises a plurality of electrodes
or at least 5 electrodes having apertures through which ions
are transmitted in use, wherein at least 5% of said
electrodes have apertures which are of substantially the same
size or area or which have apertures which become
progressively larger or smaller in size or in area.
11. A mass spectrometer as claimed in any one of claims 1-
10, wherein said ion guide is arranged and adapted to receive
a beam of ions and the application of one or more transient
DC voltages or potentials or one or more transient DC voltage
or potential waveforms to at least some of the electrodes
forming said ion guide converts or partitions said beam of
ions such that at least 2 separate groups or packets of ions
are confined or isolated in said ion guide at any particular
time, and wherein each group or packet of ions is separately
confined or isolated in a separate axial potential well
formed in said ion guide.
12. A mass spectrometer as claimed in any one of claims 1-
11, wherein said one or more transient DC voltages or
potentials or one or more transient DC voltage or potential
waveforms are translated along the length of the ion guide so
that at least 2 separate groups or packets of ions are
confined or isolated in said ion guide at any particular time
and are axially translated along the length of said ion
guide.
13. A mass spectrometer as claimed in any one of claims 1-
12, further comprising a collision, fragmentation or reaction
device.

- 40 -
14. A mass spectrometer as claimed in claim 13, further
comprising a control system arranged and adapted to switch or
repeatedly switch the potential difference through which ions
pass prior to entering said collision, fragmentation or
reaction device between a relatively high fragmentation or
reaction mode of operation wherein ions are substantially
fragmented or reacted upon entering said collision,
fragmentation or reaction device and a relatively low
fragmentation or reaction mode of operation wherein
substantially fewer ions are fragmented or reacted or wherein
substantially no ions are fragmented or reacted upon entering
said collision, fragmentation or reaction device.
15. A method of mass analysing ions according to their Time
of Flight, comprising:
providing an ion guide comprising a plurality of
electrodes;
applying one or more transient DC voltages or potentials
or one or more transient DC voltage or potential waveforms to
at least some of the electrodes forming said ion guide in
order to urge at least some ions along at least 5% of the
axial length of said ion guide; and
providing an orthogonal acceleration electrode and a
drift region downstream of said ion guide;
releasing a first pulse or packet of ions from said ion
guide at a first release time T1;
energising said orthogonal acceleration electrode a
first time after a first delay time .DELTA.t1-1 from said first
release time T1 and prior to the release of a second pulse or
packet of ions from said ion guide at a second release time
T2; and
energising said orthogonal acceleration electrode at
least a second subsequent time after a second delay time .DELTA.t1-2
from said first release time T1 and prior to the release of
the second pulse or packet of ions at the second release time
T2.

Note: Descriptions are shown in the official language in which they were submitted.

CA 02672526 2009-06-10
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MASS SPECTROMETER
The present invention relates to a mass spectrometer and a
method of mass spectrometry. The preferred embodiment relates to
a method of enhancing the duty cycle of an orthogonal
acceleration Time of Flight mass analyser.
In a conventional orthogonal acceleration Time of Flight
mass analyser ions having approximately the same energy are
arranged to be passed through an orthogonal acceleration region.
An orthogonal acceleration electric field is periodically applied
across the orthogonal acceleration region in order to
orthogonally accelerate ions into the drift region of the Time of
Flight mass analyser. The length of the region over which the
orthogonal acceleration electric field is applied, the energy of
the ions and the frequency of the application of the orthogonal
acceleration electric field deteimine the sampling duty cycle of
the Time of Flight mass analyser. Ions which have approximately
the same energy but different mass to charge ratios will have
different velocities and hence will have different sampling duty
cycles.
The maximum ion sampling duty cycle for a conventional
orthogonal acceleration Time of Flight mass analyser when used
with a continuous ion beam is typically approximately 20-25%.
The maximum duty cycle is achieved for thOse ions which have the
maximum mass to charge ratio which are mass analysed by the mass
analyser. The ion sampling duty cycle is lower for ions having
relatively low mass to charge ratios. -
If ions having the maximum mass to charge ratio which can
be mass analysed by the mass analyser have a mass to charge ratio
mo and the sampling duty cycle for these ions is DC0 then more
generally the sampling duty cycle DC for ions having a mass to
charge ratio m is given by:
DC = DC011-111 (1)
7770
It can be shown that the average sampling duty cycle DCav is
equal to two thirds of the maximum sampling duty cycle pc,õ

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Accordingly, if the maximum sampling duty cycle is 22.5% then the
average sampling duty cycle is 15%.
It is known to attempt to improve the duty cycle just for
ions having a relatively narrow range of mass to charge ratios by
trapping and releasing ions from an ion storage device which is
arranged upstream of the Time of Flight mass analyser. An
orthogonal acceleration pulse is timed to coincide with the
arrival of ions of interest at an orthogonal acceleration region
adjacent the orthogonal acceleration electrode. If ions are
stored in an ion trap upstream of the orthogonal acceleration
Time of Flight mass analyser and are released in a series of
packets rather than allowed to flow continuously, then the
application of a pusher voltage to the orthogonal acceleration
electrode can be synchronised with respect to the release of each
packet of ions from the ion trap. According to this arrangement
ions are arranged to be released from the ion trap with
substantially constant energy. Ions having different mass to
charge ratios will therefore travel towards the orthogonal
acceleration region with different velocities. As a result, ions
having different mass to charge ratios will arrive at the
orthogonal acceleration region at different times. The time
delay between the release of a packet of ions from the ion trap
to the application of the pusher voltage to the orthogonal
acceleration electrode determines the mass to charge ratio of the
ions that are transmitted into the drift region of the orthogonal
acceleration Time of Flight mass analyser. For those ions having
a narrow range of mass to charge ratios which are transmitted
into the draft region of the orthogonal acceleration Time of
Flight mass analyser, the duty cycle can be increased to
substantially 100%. However, the majority of other ions having
other mass to charge ratios will not lie fully in the orthogonal
acceleration region at the time when the pusher voltage is
applied to the pusher electrode. Accordingly, all other ions
will have substantially lower sampling efficiencies and ions
having mass to charge ratios which are removed from those ions
which are orthogonally accelerated will have a sampling
efficiency of zero.
It is also known to attempt to increase the duty cycle of a
Time of Flight mass analyser for ions having a limited range of

CA 02672526 2014-04-23
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mass to charge ratios by providing a travelling wave ion guide upstream
of a mass analyser. The orthogonal acceleration voltage is sychronised
with packets of ions released from the travelling wave ion guide. The
ion guide is arranged to partition a continuous stream of ions into a
series of packets of ions. The time delay between the release of a
packet of ions from the exit region of the travelling wave ion guide to
the application of a pusher voltage determines the mass to charge ratio
range of ions which are transmitted into the drift region of the
orthogonal acceleration Time of Flight mass analyser. For those ions
that are transmitted the duty cycle can be increased to substantially
100%. However, ions having other mass to charge ratios will not all be
present in the orthogonal acceleration region at the time when the
pusher voltage is applied to the orthogonal acceleration electrode.
Accordingly, the sampling efficiency for these ions will be lower and
may be zero.
It is desired to provide an improved mass spectrometer and method
of mass spectrometry.
According to another aspect there is provided a mass spectrometer
comprising:
an ion guide comprises a plurality of electrodes;
transient DC voltage means arranged and adapted to apply one or
more transient DC voltages or potentials or one or more transient DC
voltage or potential waveforms to at least some of
the electrodes foLming said ion guide in order to urge at least some
ions along at least 5% of the axial length of said ion guide; and
a Time of Flight mass analyser arranged downstream of said ion
guide and comprising an orthogonal acceleration electrode and a
drift region;
wherein, in use, a first pulse or packet of ions is released from
said ion guide at a first release time Tl;
wherein said mass analyser further comprisestt a control device
which is arranged and adapted:
(i) to energise said orthogonal acceleration electrode a first
time after a first delay time Ati_i from said first release time T1 and
prior to the release of a second pulse or packet of ions from said ion
guide at a second release time T2; and
(ii) to energise said orthogonal acceleration electrode at least
a second subsequent time after a second delay time 8t.1_2 from said first
release time T1 and prior to the release of the second pulse or packet
of ions at the second release time T2.
The first and/or second pulse or packet of ions may according to
one embodiment be released from an ion trap, ion trapping region or ion
gate upstream of the Time of Flight mass analyser.
According to an embodiment, second and/or third and/or fourth
and/or fifth and/or sixth and/or seventh and/or eighth

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and/or ninth and/or tenth and/or further pulses or packets of
ions are released from the ion trap, ion trapping region of ion
gate.
According to another embodiment the first and/or second
pulse or packet of ions may be released from an ion guide which
is preferably arranged upstream of the Time of Flight mass
analyser. According to this embodiment the ion guide preferably
partitions a continuous ion beam into a series of packets of
ions. Each packet of ions is preferably translated along the
length of the ion guide in an axial potential or axial pseudo-
potential well. When a particular axial potential or axial
= pseudo-potential well reaches the end of the ion guide then the
packet of ions is preferably released from the ion guide. The
ions are then preferably onwardly transmitted to the Time of
Flight mass analyser.
According to an embodiment, second and/or third and/or
fourth and/or fifth and/or sixth and/or seventh and/or eighth
= and/or ninth and/or tenth and/or further pulses or packets of
ions are released from the ion guide.
The control device is preferably arranged and adapted to
energise the orthogonal acceleration electrode a third time after
a third delay time Atl._3 from the first release time T1 and/or a
fourth time after a fourth delay time Atl_4 from the first release
time Tl and/or a fifth time after a fifth delay time it15 from
the first release time T1 and/or a sixth time after a sixth delay
time At1_6 from the first release time T1 and/or a seventh time
after a seventh delay time Lti,._7 from the first release time T1
and/or an eighth time after an eighth delay time At1_8 from the
first release time T1 and/or a ninth time after a ninth delay
time Ati_9 from the first release time T1 and/or a tenth time
after a tenth delay time t10 from the first release time T1 and
prior to the release of a second pulse or packet of ions at a
second release time T2.
'The first delay time t1 and/or the second delay time
and/or the third delay time Lt i_3 and/or the fourth delay time
8ti_.4 and/or the fifth delay time Ati_5 and/or the sixth delay time
nt1_6 and/or the seventh delay time L,t1_7 and/or the eighth delay
time Atiõ.8 and/or the ninth delay time At and/or the tenth delay

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time ,Ato are preferably predetamined delay times subsequent to
the first release time Tl.
A second pulse or packet of ions is preferably released at
a second release time T2. The control device is preferably
arranged and adapted to energise the orthogonal acceleration
electrode a first time after a first delay time At2_1 from the
second release time T2 and at least a second subsequent time
after a second delay time Lt2..2 from the second release time T2
and prior to the release of a third pulse or packet of ions at a
third release time T3.
The control device is preferably arranged and adapted to
energise the orthogonal acceleration electrode a third time after
a third delay time .6,t2_3 from the second release time T2 and/or a
fourth time after a fourth delay time At2...4 from the second
release time T2 and/or a fifth time after a fifth delay time ,At2-5
from the second release time T2 and/or a sixth time after a sixth
delay. time Lt2..6 from the second release time T2 and/or a seventh
time after a seventh delay time At2..7 from the second release time
T2 and/or an eighth time after an eighth delay time At2_8 from the
second release time T2 and/or a ninth time after a ninth delay
time L\t.2_9 from the second release time T2 and/or a tenth time
after a tenth delay time At.2...10from the second release time T2
and prior to the release of a third pulse or packet of ions at a
third release time T3.
The first delay time Lt2._1 and/or the second delay time Lt2-2
and/or the third delay time At.2_3 and/or the fourth delay time
Lt2..4 and/or the fifth delay time At2_,5 and/or the sixth delay time
8t.2.,_6 and/or the seventh delay time Lt2_7 and/or the eighth delay
time 6,t2._8 and/or the ninth delay time At.2_9 and/or the tenth delay
time ,n;t2-10 are preferably predeteimined delay times subsequent to
the second release time T2.
A third pulse or packet of ions is preferably released at a
third release time T3. The control device is preferably arranged
and adapted to energise the orthogonal acceleration electrode a
first time after a first delay time 6,t3_1 from the third release
time T3 and at least a second subsequent time after a second
delay time At3_.2 from the third release time T3 and prior to the
release of a fourth pulse or packet of ions at a fourth release
time T.

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The control device is preferably arranged and adapted to
energise the orthogonal acceleration electrode a third time after
a third delay time At3_3 from the third release time T3 and/or a
fourth time after a fourth delay time At3_4 from the third release
time T3 and/or a fifth time after a fifth delay time At3_5 from
the third release time T3 and/or a sixth time after a sixth delay
time At3_6 from the third release time T3 and/or a seventh time
after a seventh delay time At3._7 from the third release time T3
and/or an eighth time after an eighth delay time At3.8 from the
, 10 third release time T3 and/or a ninth time after a ninth delay
time Lt3._9 from the third release time T3 and/or a tenth time
after a tenth delay time Lt3.40from the third release time T3 and
prior to the release of a fourth pulse or packet of ions at a
fourth release time T4.
The first delay time At3_1 and/or the second delay time L,t3-2
and/or the third delay time At3...3 and/or the fourth delay time
At3._4 and/or the fifth delay time Lt3...5 and/or the sixth delay time
Lt3_6 and/or the seventh delay time At3_7 and/or the eighth delay
time At3_8 and/or the ninth delay time At3..9 and/or the tenth delay
time At3-10 are preferably predetelmined delay times subsequent to
the third release time T3.
A fourth pulse or packet of ions is preferablli released at
a fourth release time T4. The control device is preferably
arranged and adapted to energise the orthogonal acceleration
electrode a first time after a first delay time ,t4.4 from the
fourth release time T4 and at least a second subsequent time
after a second delay At4_2 from the fourth release time T4 and
prior to the release of a fifth pulse or packet of ions at a
fifth release time T5.
The control device is preferably arranged and adapted to
energise the orthogonal acceleration electrode a third time after
a third delay time At4...3 from the fourth release time T4 and/or a
fourth time after a fourth delay time ,Lt4..4 from the fourth
release time T4 and/or a fifth time after a fifth delay time At.4..5
from the fourth release time T4 and/or a sixth time after a sixth
delay time 6,t4_6 from the fourth release time T4 and/or a seventh
time after a seventh delay time Lt4_7 from the fourth release time
T4 and/or an eighth time after an eighth delay time At4._8 from the
fourth release time T4 and/or a ninth time after a ninth delay

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time At4_9 from the fourth release time T4 and/or a tenth time
after a tenth delay time At4_10 from the fourth release time T4
and prior to the release of a fifth pulse or packet of ions at a
fifth release time T5.
The first delay time At4_1 and/or the second delay time L.t.4_2
and/or the third delay time At4,..3 and/or the fourth delay time
At4..4 and/or the fifth delay time Lt4_5 and/or the sixth delay time
Lt4_6 and/or the seventh delay time At4_7 and/or the eighth delay
time Lt4_8 and/or the ninth delay time L,t1_9 and/or the tenth delay
time At4...10 are preferably predetermined delay times subsequent to
the fourth release time T4.
A fifth pulse or packet of ions is preferably released at a
fifth release time T5. The control device is preferably
arranged and adapted to energise the orthogonal acceleration
electrode a first time after a first delay time ,n,t5_1 from the
fifth release time T5 and at least a second subsequent time after
a second delay time At5,.2 from the fifth release time T5 and prior
to the release of a sixth pulse or packet of ions at a sixth
release time T6.
The control device is preferably arranged and adapted to
' 1
energise the orthogonal acceleration electrode a third time after
a third delay time At5_3 from the fifth release time T5
and/or a fourth time after a fourth delay time Lt5_4 from the
fifth release time T5 and/or a fifth time after a fifth delay
time At5_5 from the fifth release time T5 and/or a sixth time
after a sixth delay time Lts..6 from the fifth release time T5
and/or a seventh time after a seventh delay time At5..7 from the
fifth release time T5 and/or an eighth time after an eighth delay
time At from the fifth release time T5 and/or a ninth time
after a ninth delay time At from the fifth release time T5
and/or a tenth time after a tenth delay time Llt5_10 from the fifth
release time T5 and prior to the release of a sixth pulse or
packet of ions at a sixth release time T6.
The first delay time At and/or the second delay time ,Lt5-2
and/or the third delay time At5_3 and/or the fourth delay time
Lt5_4 and/or the fifth delay time At5_5 and/or the sixth delay time
At and/or the seventh delay time &t5...7 and/or the eighth delay
time L,t5_13 and/or the ninth delay time At5_9 and/or the tenth delay

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time ,6,t5_10 are preferably predeteimined delay times subsequent to
the fifth release time T5.
According to an embodiment: (i) the first delay time Ati_i
from the fIrst release time T1 and/or the first delay time At2-1.
from the second release time T2 and/or the first delay time At3.A.
from the third release time T3 and/or the first delay time Lt4-3.
from the fourth release time T4 and/or the first delay time Lt5.4
from the fifth release time T5 are substantially the same; and/or
(ii) the second delay time Ati._2 from the first release time T1
and/or the second delay time At2..2 from the second release time T2
and/or the second delay time nt3_2 from the third release time T3
and/or the second delay time At4_2 from the fourth release time T4
and/or the second delay time At5_2 from the fifth release time T5
are substantially the same; and/or (iii) the third delay time
At1_3 from the first release time Tl and/or the third delay time
,Lt2_3 from the second release time T2 and/or the third delay time
LVt3._3 from the third release time T3 and/or the third delay time
Lt4_3 from the fourth release time T4 and/or the third delay time
At5_3 from the fifth release time T5 are substantially the same;
and/or (iv) the fourth delay time ,Lt1..4 from the first release
time T1 and/or the fourth delay time At2..4 from the second release
time T2 and/or the fourth delay time At3.õ1 from the third release
time T3 and/or the fourth delay time L),t4_4 from the fourth release
time T4 and/or the fourth delay time At5..4 from the fifth release
time T5 are substantially the same; and/or (v) the fifth delay
time At1...5 from the first release time T1 and/or the fifth delay
time Lt2..5 from the second release time T2 and/or the fifth delay
time At3_5 from the third release time T3 and/or the fifth delay
time 6,4.5 from the fourth release time T4 and/or the fifth delay
time Ats_s from the fifth release time T5 are substantially the
same.
According to another embodiment: (i) the first delay time
Ati_i from the first release time T1 and/or the first delay time
Lt2..1 from the second release time T2 and/or the first delay time
At3_1 from the third release time T3 and/or the first delay time
6,t4.4 from the fourth release time T4 and/or the first delay time
.6,t5...1 from the fifth release time T5 are substantially different;
and/or (ii) the second delay time At1..2 from the first release
time T1 and/or the second delay time nt2_2 from the second release

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time T2 and/or the second delay time ,8t3._2 from the third release
time T3 and/or the second delay time At4.2 from the fourth release
time T4 and/or the second delay time Lt5...2 from the fifth release
time T5 are substantially different; and/or (iii) the third delay
time Lt,...3 from the first release time T1 and/or the third delay
time Z,t2._3 from the second release time T2 and/or the third delay
time At3_3 from the third release time T3 and/or the third delay
time Lt4_3 from the fourth release time T4 and/or the third delay
time At5_3 from the fifth release time T5 are substantially
different; and/or (iv) the fourth delay time At1..4 from the first
release time Tl and/or the fourth delay time Lt2..4 from the second
release time T2 and/or the fourth delay time At3_4 from the third
release time T3 and/or the fourth delay time At4.4 from the fourth
release time T4 and/or the fourth delay time Lt5..4 from the fifth
release time T5 are substantially different; and/or (v) the fifth
delay time At from the first release time T1 and/or the fifth
delay time At2_5 from the second release time T2 and/or the fifth
delay time At3.5 from the third release time T3 and/or the fifth
delay time At4_5 from the fourth release time T4 and/or the fifth
delay time At5_5 from the fifth release time T5 are substantially
different.
According to an embodiment the first delay time Ati_l from
the first release time T1 and/or the first delay time At2_1 from
the second release time T2 and/or the first delay time At3_1 from
the third release time T3 and/or the first delay time 6,t4..1 from
the fourth release time T4 and/or the first delay time Lt5.1 from
the fifth release time T5 are preferably selected from the group
consisting of: (i) < 1 4s; (ii) 1-2 ps; (iii) 2-3 4s; (iv) 3-4
ps; (v) 4-5 ps; (vi) 5-6 ps; (vii) 6-7 4s; (viii) 7-8 4s; (ix) 8-
9 4s; (x) 9-10 ps; (xi) 10-11 IS; (xii) 11-12 4s; (xiii) 12-13
4s; (xiv) 13-14 ps; (xv) 14-15 4s; (xvi) 15-16 4s; (xvii) 16-17
4s; (xviii) 17-18 4s; (xix) 18-19 ps; (xx) 19-20 ps; (xxi) 20-25
4s; (xxii) 25-30 ps; (xxiii) 30-35 ps; (xxiv) 35-40 45;; (xxv)
40-45 ps; (xxvi) 45-50 4s; (xxvii) 50-55 4s; (xxviii) 55-60 uS;
(xxix) 60-65 4s; (xxx) 65-70 4s; (xxxi) 70-75 4s; (xxxii) 75-80
4s; (xxxiii) 80-85 4s; (xxxiv) 85-90 ps; (xxxv) 90-95 4s; (xxxvi)
95-100 4s; (xxxvii) 100-120 ps; (xxxviii) 120-140 ps; (xxxix)
140-160 4s; (xl) 160-180 4s; (xli) 180-200 4s; and (xlii) > 200
4s.

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According to an embodiment the second delay time Ati..2 from
the first release time T1 and/or the second delay time At2_2 from
the second release time T2 and/or the Second delay time .6t3_2 from
the third release time T3 and/or the second delay time 6,4_2 from
the fourth release time T4 and/or the second delay time .6t2 from
the fifth release time T5 are preferably selected from the group
consisting of: (i) < 1 ps;,(ii) 1-2 ps; (iii) 2-3 ps; (iv) 3-4
ps; (v) 4-5 ps; (vi) 5-6 ps; (vii) 6-7 ps; (viii) 7-8 ps; (ix) 8-
9 ps; (x) 9-10 ps; (xi) 10-11 ps; (xii) 11-12 ps; (xiii) 12-13
ps; (xiv) 13-14 ps; (xv) 14-15 ps; (xvi) 15-16 ps; (xvii) 16-17
ps; (xviii) 17-18 ps; (xix) 18-19 ps; (xx) 19-20 ps; (xxi) 20-25
ps; (xxii) 25-30 ps; (xxiii) 30-35 ps; (xxiv) 35-40 ps;; (xxv
40-45 ps; (xxvi) 45-50 ps; (xxvii) 50-55 ps; (xxviii) 55-60 ps;
(xxix) 60-65 ps; (xxx) 65-70 ps; (xxxi) 70-75 ps; (xxxii) 75-80
ps; (xxxiii) 80-85 ps; (xxxiv) 85-90 ps; (xxxv) 90-95 ps; (xxxvi)
95-100 ps; (xxxvii) 100-120 ps; (xxxviii) 120-140 ps; (xxxix)
140-160 ps; (xl) 160-180 ps; (xli) 180-200 ps; and (xlii) > 200_
ps.
According to an embodiment the third delay time At1_3 from
the first release time T1 and/or the third delay time 4t.2._3 from
the second release time T2 and/or the third delay time At3._3 from
the third release time T3 and/or the third delay time At.4õ3 from
the fourth release time T4 and/or the third delay time At5_3 from
the fifth release time T5 are substantially different are
preferably selected from the group consisting of: (i) < 1 ps;
(ii) 1-2 ps; (iii) 2-3 ps; (iv) 3-4 ps; (v) 4-5 ps; (vi) 5-6 ps;
(vii) 6-7 ps; (viii) 7-8 ps; (ix) 8-9 ps; (x) 9-10 ps; (xi) 10-11
ps; (xìì) 11-12 ps; (xiii) 12-13 ps; (xiv) 13-14 ps; (xv) 14-15
ps; (xvi) 15-16 ps; (xvii) 16-17 ps; (xviii) 17-18 ps; (xix) 18-
19 ps; (xx) 19-20 ps; (xxi) 20-25 ps; (xxii) 25-30 ps; (xxiii)
30-35 ps; (xxiv) 35-40 ps;; (xxv) 40-45 ps; (xxvi) 45-50 ps;
(xxvii) 50-55 ps; (xxviii) 55-60 ps; (xxix) 60-65 ps; (xxx) 65-70
ps; (xxxi) 70-75 ps; (xxxii) 75-80 ps; (xxxiii) 80-85 ps; (xxxiv)
85-90 ps; (xxxv) 90-95 ps; (xxxvi) 95-100 ps; (xxxvii) 100-120
ps; (xxxviii) 120-140 ps; (xxxix) 140-160 ps; (xl) 160-180 ps;
(xli) 180-200 ps; and (xlii) > 200 ps.
According to an embodiment the fourth delay time Lti_4 from
the first release time T1 and/or the fourth delay time Lt2,4 from
the second release time T2 and/or the fourth delay time Llt3.õ1 from

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the third release time T3 and/or the fourth delay time At4._4 from
the fourth release time T4 and/or the fourth delay time At5_4 from
the fifth release time T5 are substantially different are
preferably selected from the group consisting of: (i) < 1 ps;
(ii) 1-2 ps; (iii) 2-3 ps; (iv) 3-4 ps; (v) 4-5 ps; (vi) 5-6 Ps;
(vii) 6-7 ps; (viii) 7-8 ps; (ix) 8-9 ps; (x) 9-10 ps; (xi) 10-11
ps; (xii) 11-12 ps; (xiii) 12-13 ps; (xiv) 13-14 ps; (xv) 14-15
ps; (xvi) 15-16 ps; (xvii) 16-17 ps; (xviii) 17-18 ps; (xix) 18-
19 ps; (xx) 19-20 ps; (xxi) 20-25 ps; (xxii) 25-30 ps; (xxiii)
30-35 ps; (xxiv) 35-40 ps;; (xxv) 40-45 ps; (xxvi) 45-50 ps;
(xxvii) 50-55 ps; (xxviii) 55-60 ps; (xxix) 60-65 ps; (xxx) 65-70
ps; (xxxi) 70-75 ps; (xxxii) 75-80 ps; (xxxiii) 80-85 ps; (xxxiv)
85-90 ps; (xxxv) 90-95 ps; (xxxvi) 95-100 ps; (xxxvii) 100-120
ps; (xxxviii) 120-140 ps; (xxxix) 140-160 ps; (xl) 160-180 ps;
(xli) 180-200 ps; and (xlii) > 200 ps.
According to an embodiment the fifth delay time ,n,t1_5 from
the first release time T1 and/or the fifth delay time At2_5 from
the second release time T2 and/or the fifth delay time At3_5 from
the third release time T3 and/or the fifth delay time 8t4_5 from
the fourth release time T4 and/or the fifth delay time At5_5 from
the fifth release time T5 are preferably selected from the group
consisting of: (i) < 1 ps; (ii) 1-2 ps; (iii) 2-3 ps; (iv) 3-4
ps; (v) 4-5 ps; (vi) 5-6 ps; (Vii) 6-7 ps; (viii) 7-8 ps; (ix) 8-
9 ps; (x) 9-10 ps; (xi) 10-11 ps; (xii) 11-12 ps; (xiii) 12-13
ps; (xiv) 13-14 ps; (xv) 14-15 ps; (xvi) 15-16 ps; (xvii) 16-17
ps; (xviii) 17-18 ps; (xix) 18-19 ps; (xx) 19-20 ps; (xxi) 20-25
ps; (xxii) 25-30 ps; (xxiii) 30-35 ps; (xxiv) 35-40 ps;; (xxv)
40-45 ps; (xxvi) 45-50 ps; (xxvii) 50-55 ps; (xxviii) 55-60 ps;
(xxix) 60-65 ps; (xxx) 65-70 ps; (xxxi) 70-75 ps; (xxxii) 75-80
ps; (xxxiii) 80-85 ps; (xxxiv) 85-90 ps; (xxxv) 90-95 ps; (xxxvi)
95-100 ps; (xxxvii) 100-120 ps; (xxxviii) 120-140 ps; (xxxix)
140-160 ps; (xl) 160-180 ps; (xli) 180-200 ps; and (xlii) > 200
ps.
The control device is preferably arranged and adapted to
energise the orthogonal acceleration electrode x times prior to
the release of a subsequent pulse or packet of ions, wherein x is
selected from the group consisting of: (i) 2; (ii) 3; (iii) 4;
(iv) 5; (v) 6; (vd) 7; (vii) 8; (viii) 9; (ix) 10; (x). 11; (xi)

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12; (xii) 13; (xiii) 14; (xiv) 15; (xv) 16; (xvi) 17; (xvii) 18;
(xviii) 19; (xix) 20; and (xx) > 20.
The first delay time is preferably varied, increased,
decreased or progressively changed after each release of a pulse
or packet of ions.
The second delay time is preferably varied, increased,
decreased or progressively changed after each release of a pulse
or packet of ions.
The third delay time is preferably varied, increased,
decreased or progressively changed after each release of a pulse
or packet of ions.
The fourth delay time is preferably varied, increased,
decreased or progressively changed after each release of a pulse
or packet of ions.
The fifth delay time is preferably varied, increased,
decreased or progressively changed after each release of a pulse
or packet of ions.
According to an embodiment after the release of a pulse or
packet of ions at a n-th release time Tn there is a constant,
increasing, decreasing, linear, non-linear, quadratic,
exponential, polynomial or other predeteLmined relationship
between the first delay time Ltn_1 and/or the second delay time
Lt.,2 and/or the third delay time Atn_3 and/or the fourth delay
time Lt4 and/or the fifth delay time it and/or the sixth: delay
time At,6 and/or the seventh delay time At,, and/or the eighth
delay time Atn_8 and/or the ninth delay time At,9 and/or the tenth
delay time &t10 from the n-th release time Tn and prior to the
release of a subsequent pulse of ions at a later release time
Tn+1, wherein n is selected from one or more of the following:
(i) 1; (ii) 2; (iii) 3; (iv) 4; (v) 5; (vi) 6; (vii) 7; (viii) 8;
(ix) 9; and (x) 10. According to an embodiment, n may be in the
range 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, 90-
100, 100-110, 110-120, 120-130, 130-140, 140-150, 150-160, 160-
170, 170-180, 180-190, 190-200, 200-250, 250-300, 300-350, 350-
400, 400-450, 450-500 and > 500.
According to an embodiment there may be a constant,
increasing, decreasing, linear, non-linear, quadratic,
exponential, polynomial or other predeteLmined relationship
between the releae times Tn at which a pulse or packet of ions

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is released. An exponential relationship is particularly
preferred. Also, cycles of operation may be performed in various
different orders and the mass spectral data may then be
interleaved or assembled into a composite set of mass spectral
data.
The Time of Flight mass analyser preferably comprises an
orthogonal acceleration Time of Flight mass analyser.
The Time of Flight mass analyser preferably further
comprises a reflectron and an ion detector, wherein in use at
least some ions are orthogonally accelerated by energisation of
the orthogonal acceleration electrode into the drift region and
wherein the ions which are orthogonally accelerated are then
reflected by the reflectron and are directed so as to impinge
upon the ion detector.
According to an embodiment the mass spectrometer may
comprise an ion trap, ion trapping region or ion gate arranged
preferably upstream of the Time of Flight mass analyser. The ion
trap, ion trapping region or ion gate is preferably arranged and
adapted to periodically release or transmit a pulse or packet of
ions. In a cycle of operation the ion trap, ion trapping region
or ion gate is preferably arranged to onwardly transmit or pass
ions from the ion trap, ion trapping region or ion gate towards
an orthogonal acceleration region arranged adjacent the
orthogonal acceleration electrode during a time period xl and
substantially to prevent the onward transmission or passing of
ions from the ion trap, ion trapping region or ion gate towards
the orthogonal acceleration region arranged adjacent the
orthogonal acceleration electrode during a time period x2.
Preferably, x2 > xl.
Preferably, xl and/or x2 are selected from the group
consisting of: (i) < 1 is; (ii) 1-2 ps; (iii) 2-3 ps; (iv) 3-4
ps; (v) 4-5 ps; (vi) 5-6 ps; (vii) 6-7 ps; (viii) 7-8 ps; (ix) 8-
9 ps; (x) 9-10 ps; (xi) 10-11 ps; (xii) 11-12 ps; (xiii) 12-13
ps; (xiv) 13-14 ps; (xv) 14-15 ps; (xvi) 15-16 ps; (xvii) 16-17
ps; (xviii) 17-18 ps; (xix) 18-19 ps; (xx) 19-20 ps; (xxi) 20-25
ps; (xxii) 25-30 ps; (xxiii) 30-35 ps; (xxiv) 35-40 ps;; (xxv)

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40-45 ps; (xxvi) 45-50 ps; (xxvii) 50-55 ps; (xxviii) 55-60 ps;
(xxix) 60-65 ps; (xxx) 65-70 us; (xxxi) 70-75 ps; (xxxii) 75-80
ps; (xxxiii) 80-85 ps; (xxxiv) 85-90 ps; (xxxv) 90-95 ps; (xxxvi)
95-100 ps; (xxxvii) 100-120 ps; (xxxviii) 120-140 ps; (xxxix)
140-160 ps; (xl) 160-180 ps; (xli) 180-200 ps; and (xlii) > 200
ps.
The ratio x2/x1 is preferably selected from the group
consisting of: (i) 1-5; (ii) 5-10; (iii) 10-15; (iv) 15-20; (v)
20-25; (vi) 25-30; (vii) 30-35; (viii) 35-40; (ix) 40-45; (x) 45-
50; (xi) 50-55; (xii) 55-60; (xiii) 60-65; (xiv) 65-70; (xv) 70-
75; (xvi) 75-80; (xvii) 80-85; (xviii) 85-90; (xix) 90-95; (xx)
95-100; (xxi) 100-120; (xxii) 120-140; (xxiii) 140-160; (xxiv)
160-180; (xxv) 180-200; and (xxvi) > 200.
The first pulse or packet of ions is preferably released or
onwardly transmitted from the ion trap, ion trapping region or
ion gate at the first release time T1 and/or wherein the second
pulse or packet of ions is preferably released or onwardly
transmitted from the ion trap, ion trapping region or ion gate at
the second release time T2 and/or wherein the third pulse or
packet of ions is preferably released or onwardly transmitted
from the ion trap, ion trapping region or ion gate at the third
release time T3 and/or wherein the fourth pulse or packet of ions
is preferably released or onwardly transmitted from the ion trap,
ion trapping region or ion gate at the fourth release time T4
and/or wherein the fifth pulse or packet of ions is preferably
released or onwardly transmitted from the ion trap, ion trapping
region or ion gate at the fifth release time T5.
The ion trap, ion trapping region or ion gate preferably
comprises a plurality of electrodes arranged upstream of the Time
of Flight mass analyser. The ion trap, ion trapping region or
ion gate preferably comprises: (i) a multipole rod set or a
segmented multipole rod set; (ii) an ion tunnel or ion funnel; or
(iii) a stack or array of planar, plate or mesh electrodes.
The mass spectrometer comprises an ion guide arranged
preferably upstream of the mass analyser. According to the
preferred embodiment one or more axial potential wells or one or
more axial pseudo-potential wells are preferably translated along
the length of the ion guide and wherein when an axial potential
well or an axial pseudo-potential

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well reaches the end or exit region of the ion guide ions
contained within the axial potential well or the axial pseudo-
potential well are preferably caused to be released. The ions
are preferably onwardly transmitted as a pulse or packet of ions.
The first pulse or packet of ions is preferably released or
onwardly transmitted from the ion guide at the first release time
T1 and/or wherein the second pulse or packet of ions is
preferably released or onwardly transmitted from the ion guide at
the second release time T2 and/or wherein the third pulse or
packet of ions is preferably released or onwardly transmitted
from the ion guide at the third release time T3 and/or wherein
the fourth pulse or packet of ions is preferably released or
onwardly transmitted from the ion guide at the fourth release
time T4 and/or wherein the fifth pulse or packet of ions is
preferably released or onwardly transmitted from the ion guide at
the fifth release time T5.
Various embodiments have been described above in detail
wherein up to five pulses or packets of ions are released either
from an ion trap, ion trapping region or ion gate or
alternatively from an ion guide (preferably a travelling wave ion
guide). However, further embodiments are contemplated wherein at
least 5-10, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-
90, 90-100, 100-110, 110-120, 120-130, 130-140, 140-150, 150-160,
160-170, 170-180, 180-190, 190-200, 200-250, 250-300, 300-350,
350-400, 400-450, 450-500 or > 500 pulses or packets of ions are
released in an experimental run.
The ion guide comprises a plurality of electrodes arranged
upstream of the Time of Flight mass analyser. The ion guide
preferably comprises: (i) a multipole rod set or a segmented
multipole rod set; (ii) an ion tunnel or ion funnel; or (iii) a
stack or array of planar, plate or mesh electrodes.
The multipole rod set preferably comprises a quadrupole rod
set, a hexapole rod set, an octapole rod set or a rod set
comprising more than eight rods.
The ion tunnel or ion funnel preferably comprises a
plurality of electrodes or at least 2, 5, 10, 20, 30, 40, 50, 60,
70, 80, 90 or 100 electrodes having apertures through which ions
are transmitted in use, wherein at least 5%, 10%, 15%, 20%, 25%,
30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,

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95% or 100% of the electrodes have apertures which are of
substantially the same size or area or which have apertures which
become progressively larger and/or smaller in size or in area.
At least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,
60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the electrodes
preferably have internal diameters or dimensions selected from
the group consisting of: (i) 1.0 mm; (ii) 2.0 mm; (iii) 3.0
mm; (iv) 4.0 mm; (v) 5.0 mm; (vi) 6.0 mm; (vii) 7.0 mm;
(viii) 8.0 mm; (ix) 9.0 mm; (x) 10.0 mm; and (xi) > 10.0
mm.
The stack or array of planar, plate or mesh electrodes
preferably comprises a plurality or at least 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 planar, plate or
mesh electrodes wherein at least 5%, 10%, 15%, 20%, 25%, 30%,
35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%
or 100% of the planar, plate or mesh electrodes are arranged
generally in the plane in which ions travel in use. At least
some or at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%,
55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the
planar, plate or mesh electrodes are preferably supplied with an
AC or RF voltage and wherein adjacent planar, plate or mesh
electrodes are supplied with opposite phases of the AC or RF
voltage.
The ion guide preferably comprises a plurality of axial
segments or at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55,
60, 65, 70, 75, 80, 85, 90, 95 or 100 axial segments.
The ion guide preferably has an axial length selected from
the group consisting of: (i) < 20 mm; (ii) 20-40 mm; (iii) 40-60
mm; (iv) 60-80 mm; (v) 80-100 mm; (vi) 100-120 mm; (vii) 120-140
mm; (viii) 140-160 mm; (ix) 160-180 mm; (x) 180-200 mm; (xi) 200-
220 mm; (xii) 220-240 mm; (xiii) 240-260 mm; (xiv) 260-280 mm;
(xv) 280-300 mm; and (xvi) > 300 mm.

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The mass spectrometer preferably further comprises
transient DC voltage means arranged and adapted to apply one or
more transient DC voltages or potentials or one or more transient
DC voltage or potential waveforms to at least some of the
electrodes forming the ion guide in order to urge at least some
ions along at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%,
55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the axial
length of the ion guide. The ion guide is preferably arranged
and adapted to receive a continuous or pseudo-continuous beam of
ions. The application of one or more transient DC voltages or
potentials or one or more transient DC voltage or potential
wavefo/ms to at least some of the electrodes forming the ion
guide preferably converts or partitions the beam of ions such
that at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,
16, 17, 18, 19 or 20 separate groups or packets of ions are
confined and/or isolated in the ion guide at any particular time.
Each group or packet of ions is preferably separately confined
and/or isolated in a separate axial potential well formed in the
ion guide.
The one or more transient DC voltages or potentials or one
or more transient DC voltage or potential waveforms are
preferably translated along the length of the ion guide so that
at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,
17, 18, 19 or 20 separate groups or packets of ions are confined
and/or isolated in the ion guide at any particular time and are
preferably axially translated along the length of the ion guide.
The mass spectrometer preferably further comprises AC or RF
voltage means arranged and adapted to apply two or more phase-
shifted AC or RF voltages to electrodes forming the ion guide in
order to urge at least some ions along at least 5%, 10%, 15%,
20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%,
85%, 90%, 95% or 100% of the axial length of the ion guide.
The mass spectrometer preferably further comprises means
for applying a single phase AC or RF voltage across at least a
portion of the length of the ion guide in order to generate an
axial pseudo-potential. The axial pseudo-potential is preferably
arranged to urge at least some ions along at least 5%, 10%, 15%,

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20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%,
85%, 90%, 95% or 100% of the axial length of the ion guide.
The mass spectrometer preferably further comprises a
further mass filter or mass analyser which is preferably arranged
upstream of the Time of Flight mass analyser. The further mass
filter or mass analyser is preferably selected from the group
consisting of: (i) a quadrupole rod set mass filter; (ii) a Time
of Flight mass filter or mass analyser; (iii) a Wein filter; and
(iv) a magnetic sector mass filter or mass analyser.
The mass spectrometer preferably further comprises a
collision, fragmentation or reaction device. The collision,
fragmentation or reaction device is preferably arranged and
adapted to fragment ions by Collision Induced Dissociation
("CID"). Alternatively, the collision, fragmentation or reaction
device may be selected from the group consisting of: (i) a
Surface Induced Dissociation ("SID") fragmentation device; (ii)
an Electron Transfer Dissociation fragmentation device; (iii) an
Electron Capture Dissociation fragmentation device; (iv) an
Electron Collision or Impact Dissociation fragmentation device;
(v) a Photo Induced Dissociation ("PID") fragmentation device;
(vi) a Laser Induced Dissociation fragmentation device; (vii) an
infrared radiation induced dissociation device; (viii) an
ultraviolet radiation induced dissociation device; (ix) a nozzle-
skimmer interface fragmentation device; (x) an in-source
fragmentation device; (xi) an ion-source Collision Induced
Dissociation fragmentation device; (xii) a thermal or temperature
source fragmentation device; (xiii) an electric field induced
fragmentation device; (xiv) a magnetic field induced
fragmentation device; (xv) an enzyme digestion or enzyme
degradation fragmentation device; (xvi) an ion-ion reaction
fragmentation device; (xvii) an ion-molecule reaction
-fragmentation-deVio'ei cxviii) an ion-atom reaction fragmentation
device; (xix) an ion-metastable ion reaction fragmentation
device; (xx) an ion-metastable molecule reaction fragmentation
device; (xxi) an ion-metastable atom reaction fragmentation
device; (xxii) an ion-ion reaction device for reacting ions to
form adduct or product ions; (xxiii) an ion-molecule reaction
device for reacting ions to foim adduct or product ions; (xxiv)
an ion-atom reaction device for reacting ions to foim adduct or

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=
product ions; (xxv) an ion-metastable ion reaction device for
reacting ions to form adduct or product ions; (xxvi) an ion-
metastable molecule reaction device for reacting ions to faun
adduct or product ions; and (xxvii) an ion-metastable atom
reaction device for reacting ions to faun adduct or product ions.
According to an embodiment the mass spectrometer may
further comprise acceleration means arranged and adapted to
accelerate ions into the collision, fragmentation or reaction
device wherein in a mode of operation at least 5%, 10%, 15%, 20%,
25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,
90%, 95% or 100% of the ions are caused to fragment or react upon
entering the collision, fragmentation or reaction device.
The mass spectroMeter preferably further comprises a
control system arranged and adapted to switch or repeatedly
switch the potential difference through which ions pass prior to
entering the collision, fragmentation or reaction device between
a relatively high fragmentation or reaction mode of operation
wherein ions are substantially fragmented or reacted upon
entering the collision, fragmentation or reaction device and a
relatively low fragmentation or reaction mode of operation
wherein substantially fewer ions are fragmented or reacted or
wherein substantially no ions are fragmented or reacted upon
entering the collision, fragmentation or reaction device. In the
relatively high fragmentation or reaction mode of operation ions
entering the collision, fragmentation or reaction device are
preferably accelerated through a potential difference selected
from the group consisting of: (i) ->= 10 V; (ii) 20 V; (iii) 30
V; (iv) >- 40 V; (v) 50 V; (vi) 60 V; (vii) 70 V;
(viii)
80 V; (ix) 90 V; (x) 100 V; (xi) 110 V; (xii) 120 V;
(xiii) 130 V; (xiv) 140 V; (xv) 150 V; (xvi) 160 V;
(xvii) 170 V; (xviii) 180 V; (xix) 190 V; and (xx)
200 V.
-In-the relativeiyinefita-tion UL reaction mode of operation
ions entering the collision, fragmentation or reaction device are
preferably accelerated through a potential difference selected
from the group consisting of: (i) 20 V; (ii) 15 V; (iii) 10
V; (iv) 5V; and (v) 1V.
The control system is preferably arranged and adapted to
switch the collision, fragmentation or reaction device between
the relatively high fragmentation or reaction mode of operation

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and the relatively low fragmentation or reaction mode of
operation at least once every 1 ms, 5 ms, 10 ms, 15 ms, 20 ms, 25
ms, 30 ms, 35 ms, 40 ms, 45 ms, 50 ms, 55 ms, 60 ms, 65 ms, 70
ms, 75 ms, 80 ms, 85 ms, 90 ms, 95 ms, 100 ms, 200 ms, 300 ms,
400 ms, 500 ms, 600 ms, 700 ms, 800 ms, 900 ms, 1 s, 2 s, 3 s, 4
s, 5 s, 6 s, 7 s, 8 s, 9 s or 10 s.
The collision, fragmentation or reaction device is
preferably arranged and adapted to receive a beam of ions and to
convert or partition the beam of ions such that at least 1, 2, 3,
4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20
separate groups or packets of ions are confined and/or isolated
in the collision, fragmentation or reaction device at any
particular time, and wherein each group or packet of ions is
separately confined and/or isolated in a separate axial potential
well folmed in the collision, fragmentation or reaction device.
The mass spectrometer preferably further comprises an ion
source. The ion source is preferably selected from the group
consisting of: (i) an Electrospray ionisation ("ESI") ion source;
(ii) an Atmospheric Pressure Photo Ionisation ("APPI") ion
source; (iii) an Atmospheric Pressure Chemical Ionisation
("APCI") ion source; (iv) a Matrix Assisted Laser Desorption
Ionisation ("MALDI") ion source; (v) a Laser Desorption
Ionisation ("LDI") ion source; (vi) an Atmospheric Pressure
Ionisation ("API") ion source; (vii) a Desorption Ionisation on
Silicon ("DIOS") ion source; (viii) an Electron Impact ("EI") ion
source; (ix) a Chemical Ionisation ("CI") ion source; (x) a Field
Ionisation ("FI") ion source; (xi) a Field Desorption ("FD") ion
source; (xii) an Inductively Coupled Plasma ("ICP") ion source;
(xiii) a Fast Atom Bombardment ("FAB") ion source; (xiv) a Liquid
Secondary Ion Mass Spectrometry ("LSIMS") ion source; (xv) a
Desorption Electrospray Ionisation ("DESI") ion source; (xvi) a
Nickel-63 radioactive ion source; (xvii) a Thermospray ion
source; (xviii) a Particle Beam ("PB") ion source; and (xix) a
Flow Fast Atom Bombardment ("Flow FAB") ion source.
The mass spectrometer preferably further comprises a
continuous or pulsed ion source.
According to another aspect of the present invention there
is provided a method of mass analysing ions according to their
Time of Flight, comprising:

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providing an ion guide comprising a plurality of
electrodes;
applying one or more transient DC voltages or potentials or
one or more transient DC voltage or potential waveforms to at
least some of the electrodes forming said ion guide in order to
urge at least some ions along at least 5% of the axial length of
said ion guide; and
providing an orthogonal acceleration electrode and a drift
region downstream of said ion guide;
releasing a first pulse or packet of ions from said ion
guide at a first release time Tl;
energising said orthogonal acceleration electrode a first
time after a first delay time Lti_l from said first release time
T1 and prior to the release of a second pulse or packet of ions
from said ion guide at a second release time T2; and
energising said orthogonal acceleration electrode at least
a second subsequent time after a second delay time At12 from said
first release time T1 and prior to the release of the second
pulse or packet of ions at the second release time T2.
25
35

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According to an embodiment one or more packets of ions are
preferably released from an ion trap or other device which is
preferably arranged upstream of an orthogonal acceleration Time
of Flight mass analyser. The ions in each packet preferably have
a variety or range of different mass to charge ratios.
The Time of Flight mass analyser preferably comprises an
orthogonal acceleration electrode or a pusher and/or puller
electrode. An orthogonal acceleration voltage is preferably
applied to the orthogonal acceleration electrode or pusher and/or
puller electrode at two or more separate or different delay times
after the release of a packet of ions from the ion trap or other
device and prior to a release of a subsequent packet of ions from
the ion trap or other device.
The orthogonal acceleration voltage is preferably applied
to the orthogonal acceleration in synchronism with the release of
each packet of ions. According to the preferred embodiment an
orthogonal acceleration voltage is preferably applied at two or
more pre-determined delay times after the release of each packet
of ions and prior to the release of a following or subsequent
packet of ions.
According to an embodiment the orthogonal acceleration
voltage is applied in synchronism with the release of each packet
30

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of ions and is applied at two or more pre-detaLmined delay times
after the release of a first packet of ions and is then applied
again at two or more different pre-determined delay times after
the release of a second subsequent packet of ions.
The preferred embodiment advantageously enables the duty
cycle of an orthogonal acceleration Time of Flight mass analyser
to be increased or enhanced across a wide mass to charge ratio
range compared to the known method of enhancing the duty cycle
which is only effective across a narrow mass to charge ratio
range.
Another advantage of the preferred embodiment is that the
increase or enhancement in duty cycle is also preferably
substantially constant across a wide mass to charge ratio range.
A further advantage of the preferred embodiment is that the
duty cycle of a limited number of ions of interest may be
increased to substantially 100% giving a significant overall duty
cycle improvement over arrangements which utilise one orthogonal
acceleration pulse per packet of ions released.
The mass spectrometer preferably comprises an ion source.
The ion source may comprise a pulsed ion source such as a Laser
Desorption Ionisation ("LDI") ion source, a Matrix Assisted Laser
Desorption Ionisation ("MALDI") ion source or a Desorption
Ionisation on Silicon ("DIOS") ion source.
Alternatively, and more preferably, the mass spectrometer
may comprise a continuous ion source. A means for converting a
continuous ion beam into a discontinuous ion beam may be
provided. For example, an RF ion trap may be provided which may
be arranged to store ions and/or periodically release ions.
According to an embodiment a travelling wave RF ion guide
may be provided. The RF ion guide preferably comprises a
plurality of electrodes. According to this embodiment a
"ccmtItiuous ion-bearri is preferably partitioned or fractionated
into a series of packets of ions. Each packet of ions is
preferably contained or confined within a separate axial
potential well which is preferably translated along the length of
the ion guide. One or more transient DC voltages or potentials
or one or more transient DC voltage or potential wavefolias are
preferably applied to the electrodes. One or more axial

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potential wells are preferably created or generated which are
then preferably translated along the length of the ion guide.
According to an embodiment a continuous ion source may be
provided. The ion source may, for example, comprise an
Electrospray Ionisation ("ESI") ion source, an Atmospheric
Pressure Chemical Ionisation ("APCI") ion source, an Electron
Impact ("El") ion source, an Atmospheric Pressure Photon
Ionisation ("APPI") ion source, a Chemical Ionisation ("CI") ion
source, a Fast Atom Bombardment ("FAB") ion source, a Liquid
Secondary Ion Mass Spectrometry ("LSIMS") ion source, a Field
Ionisation ("FI") ion source or a Field Desorption ("FD") ion
source. Other continuous or pseudo-continuous ion sources may
also be used.
The mass spectrometer may comprise a mass filter which may
be arranged downstream of the ion source. The mass filter is
preferably arranged upstream of the orthogonal acceleration Time
of Flight mass analyser. The mass filter may also be arranged
upstream of any means for converting a continuous ion beam into a
discontinuous ion beam.
According to an embodiment the mass filter may be operated
in a mass filtering mode of operation wherein the mass filter is
arranged to transmit ions having a single or specific mass to
charge ratio or a relatively narrow range of mass to charge
ratios.
= The mass filter preferably comprises either a quadrupole
rod set mass filter. However, according to other embodiments the
mass filter may comprise a Time of Flight mass analyser, a Wein
filter or a magnetic sector mass analyser.
The mass spectrometer may include a collision or
fragmentation cell. According to an embodiment the collision or
fragmentation cell is preferably arranged upstream of any means
for converting a-continuous ion beam into a discontinuous ion
beam. In one mode of operation at least some ions entering the
collision or fragmentation cell are preferably caused to fragment
into a plurality of fragment or daughter ions.
Various embodiments of the present invention together with
an arrangement given for illustrative purposes only will now be
described, by way of example only, and with reference to the
accompanying drawings in which:

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Fig. lA shows a conventional orthogonal acceleration Time
of Flight mass analyser wherein a continuous ion beam is
periodically sampled by energising an orthogonal acceleration
electrode and Fig. 1B shows the duty cycle as a function of mass
to charge ratio for a conventional orthogonal acceleration Time
of Flight mass analyser and a plot of an enhanced duty cycle as a
function of mass to charge ratio which may be obtained according
to a known method of enhancing the duty cycle of a Time of Flight
mass analyser;
Fig. 2A shows an orthogonal acceleration Time of Flight
mass analyser according an embodiment of the present invention
wherein ions are initially trapped in an ion trap, Fig. 2B shows
a first packet of ions which has been released from the ion trap
and which becomes spatially dispersed, Fig. 2C shows an
orthogonal acceleration electrode being energised for a first
time so that a first group of ions are orthogonally accelerated
into the drift region of the Time of Flight mass analyser, Fig.
2D shows other ions continuing to arrive at an orthogonal
acceleration region adjacent the orthogonal acceleration
electrode, and Fig. 2E shows the orthogonal acceleration
electrode being energised for a second time prior to a second
packet of ions being released from the ion trap;
Fig. 3 illustrates the enhancement in duty cycle which may
obtained according to an embodiment of the present invention by
energising the orthogonal acceleration electrode of a Time of
Flight mass analyser at three different delays times after the
release of a first packet of ions from an ion trap and prior to
the release of a second packet of ions from the ion trap;
Fig. 4A is a plot of the duty cycle according to an
embodiment wherein two cycles are performed and the orthogonal
acceleration electrode is energised at three different delay
-times in¨e-afeh-Cardle-and wherein the delay times are increased
from one cycle to the next, Fig. 4B is a plot of the duty cycle
according to an embodiment wherein three cycles are perfolmed and
the orthogonal acceleration electrode is energised at three
different delay times in each cycle and Wherein the delay times
are increased from one cycle to the next, Fig. 4C is a plot of
the duty cycle according to an embodiment wherein four cycles are
perfolmed and the orthogonal acceleration electrode is energised

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at three different delay times in each cycle and wherein the
delay times are increased from one cycle to the next, Fig. 4D is
a plot of the duty cycle according to an embodiment wherein ten
cycles ate perfolmed and the orthogonal acceleration electrode is
energised at three different delay times in each cycle and
wherein the delay times are increased from one cycle to the next,
Fig. 4E illustrates the resulting duty cycle corresponding to the
embodiment shown in Fig. 4A wherein two cycles were perfoimed,
Fig. 4F illustrates the resulting duty cycle corresponding to the
embodiment shown in Fig. 4B wherein three cycles were perfoLmed,
Fig. 4G illustrates the resulting duty cycle corresponding to the
embodiment shOwn in Fig. 4C wherein four cycles were performed
and Fig. 4H illustrates the resulting duty cycle corresponding to
the embodiment shown in Fig. 4D wherein ten cycles were
perfoLmed;
Fig. 5 shows: (i) the duty cycle of an orthogonal
acceleration Time of Flight mass spectrometer operated in a
conventional manner wherein a continuous ion beam is periodically
sampled; (ii) a duty cycle according to an embodiment of the
present invention which was theoretically predicted; (iii) and a
duty cycle according to an embodiment of the present invention as
was obtained experimentally; and
Fig. 6A shows a mass spectrum obtained by operating an
orthogonal acceleration Time of Flight mass analyser in a
conventional manner wherein a continuous ion beam was
periodically sampled and Fig. 6B shows a mass spectrum obtained
according to an embodiment of the present invention wherein the
duty cycle was enhanced across a large proportion of the mass
spectrum.
A known orthogonal acceleration Time of Flight mass
analyser is shown in Fig. 1A. The orthogonal acceleration Time
of-Frighf-ffia-g- arialysei: comiorises an orthogonal acceleration
electrode 2, a reflectron 5 and an ion detector 6. A continuous
beam of ions is transmitted to the mass analyser and the mass
analyser is arranged to sample the continuous beam of ions by
periodically accelerating ions out from an acceleration region
which is arranged adjacent to the orthogonal acceleration
electrode 2. The ions which are orthogonally accelerated pass
into a drift region of the mass analyser. According to the known

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arrangement a fraction or proportion 3 of the continuous ion beam
is sampled or orthogonally accelerated into the drift region of
the mass analyser when the orthogonal acceleration or pusher
electrode 2 is energised. The ions 4 which are orthogonally
accelerated into the drift region are then reflected by a
reflectron 5 and are directed back towards the ion detector 6.
The ions follow a trajectory as indicated by arrow 4.
Once a packet of ions has been orthogonally accelerated
into the drift region of the mass analyser an orthogonal
acceleration voltage is not applied again to the orthogonal
acceleration electrode 2 until the last of ions which have been
orthogonally accelerated into the drift region arrive at the ion
detector 6 and are detected. The last ions to arrive at the ion
detector 6 are those having the highest mass to charge ratio.
The requirement of waiting until the last ions have arrived at
the ion detector 6 before energising the orthogonal acceleration
electrode 2 again is necessary in order to prevent ions having a
relatively high mass to charge ratio which were orthogonally
accelerated by a first pulse and which have not yet reached the
ion detector 6 from being overtaken by ions having a relatively
low mass to charge ratio which were orthogonally,accelerated by a
second subsequent pulse. The maximum sampling duty cycle DC of
ions having a particular mass to charge ratio is determined by
the geometry of the Time of Flight mass analyser and is typically
between 10% and 25%. The duty cycle can be calculated using the
following relation:
miz
DC = ____________________
L (m/z).
(2)
wherein_w is _length of the _orthogonal -acceleration or pusher-
region adjacent the orthogonal acceleration electrode, L is the
separation between the centre of the orthogonal acceleration or
pusher electrode and the centre of the ion detector and (m/z)õ,,õ
is the maximum mass to charge ratio of ions of interest.
The duty cycle is therefore lowest at relatively low mass
to charge ratios and is highest at relatively high mass to charge
ratios. This is demonstrated by the unbroken line shown in Fig.

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1B which illustrates the duty cycle for the Case where w/L =
0.22.
As previously mentioned, it is known to attempt to maximise
the duty cycle for ions having a relatively narrow range of mass
to charge ratios. The known method of duty cycle enhancement
involves trapping ions in an ion trap which is arranged upstream
of the Time of Flight mass analyser. Ions are released in a
pulse from the ion trap and an orthogonal acceleration pulse is
applied to the orthogonal acceleration electrode 2 after a
predeteimined delay. The delay time is set so as to correspond
with the arrival of particular ions of interest at the orthogonal
acceleration region adjacent which is immediately adjacent the
orthogonal acceleration or pusher electrode 2.
Another method of duty cycle enhancement is known wherein a
travelling wave ion guide is provided upstream of an orthogonal
acceleration Time of Flight mass analyser. The travelling wave
ion guide is used to partition a continuous stream of ions which
is received at the entrance to the travelling wave ion guide.
Packets of ions are periodically released from the exit region of
the ion guide as an axial potential well reaches the end of the
ion guide. The energisation of the orthogonal acceleration
electrode is synchronised with each packet of ions which is
released or ejected from the travelling wave ion guide. The
dashed line in Fig. IB shows how the Duty Cycle may be enhanced
when an orthogonal acceleration pulse is synchronised to
correspond with the arrival of ions having a mass to charge ratio
of 500 Da at the orthogonal acceleration region of the Time of
Flight mass analyser.
The operation of a mass spectrometer according to a
preferred embodiment of the present invention will now be
described with reference to Figs. 2A-2E. The mass spectrometer
-compri-ses -an-orthogoriaa dbd-dlerafion-TiM6--of Flight mass analyser
and an ion storage device or an ion partitioning device 7 which
is preferably arranged upstream of the Time of Flight mass
analyser as shown in Fig. 2A. The ion storage or ion
partitioning device 7 may comprise according to an embodiment
either an ion trap or alternatively a travelling wave ion guide.
The orthogonal acceleration Time of Flight mass analyser
preferably comprises an orthogonal acceleration region which is

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preferably located adjacent an orthogonal acceleration electrode
or a pusher and/or puller electrode 2. The Time of Flight mass
analyser preferably further comprises a reflectron 5 and an ion
detector 6. An arrow 4 indicates the approximate path that ions
follow once they have been accelerated into the drift region of
the orthogonal acceleration Time of Flight mass analyser.
A packet of ions is preferably released from the ion guide
or the ion trap 7 arranged upstream of the orthogonal
acceleration Time of Flight mass analyser. The ions which are
released preferably travel towards the orthogonal acceleration
region of the Time of Flight mass analyser. The ions preferably
become spatially and/or temporally dispersed by the time that at
least some ions arrive at or approach the orthogonal acceleration
region adjacent the orthogonal acceleration or pusher and/or
puller electrode 2. This is illustrated in Fig. 2B. Ions having
a relatively low mass to charge ratio M1 will reach the
orthogonal acceleration or pusher and/or puller electrode 2 prior
to other ions which have a relatively high mass to charge ratio.
As shown in Fig. 2C, the orthogonal acceleration or pusher
and/or puller electrode 2 is preferably energised a first time so
as to orthogonally accelerate some ions into the drift or time of
flight region of the Time of Flight mass analyser. The ions are
orthogonally accelerated at a predetermined time t2 after ions
, were first released from the upstream ion guide or ion trap 7.
The arrival time of an ion at the orthogonal acceleration region
adjacent the orthogonal acceleration or pusher and/or puller
electrode 2 is preferably dependent upon the mass to charge ratio
of the ion. If an appropriate time delay is set between the
release of ions from the ion guide or ion trap 7 and the
subsequent energisation of the orthogonal acceleration or pusher
and/or puller electrode 2 then substantially 100% of ions having
a-particuiar masb
t heratio (M2) will be orthogonally
accelerated into the drift region of the Time of Flight mass
analyser.
A proportion of other ions having mass to charge ratios
(M1,M3) which are close to the mass to charge ratio of the ion of
interest (M2) will also be present in the orthogonal acceleration
region or adjacent the orthogonal acceleration electrode or
pusher and/or puller electrode 2 when the orthogonal acceleration

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electrode or pusher and/or puller electrode 2 is energised.
Accordingly, ions having mass to charge ratios (M1,M3) which are
close to the mass to charge ratio (M2) of the ions of interest
will also exhibit an improvement in duty cycle but the duty cycle
will be less than 100%.
According to an important aspect of the preferred
embodiment the orthogonal acceleration electrode or pusher and/or
puller electrode 2 is preferably energised at least a second time
before a second or subsequent packet of ions is released from the
ion guide or ion trap 7. This is in contrast to the known Time
of Flight mass spectrometer wherein the orthogonal acceleration
electrode is only energised once per release of ions from an ion
trap arranged upstream of the Time of Flight mass analyser.
According to the preferred embodiment after a first pulse
of ions has been orthogonally accelerated by the first
energisation of the orthogonal acceleration electrode or pusher
and/or puller electrode 2 the voltage applied to the orthogonal
acceleration electrode or pusher and/or puller electrode 2 is
preferably reset to zero. Further ions preferably continue to
approach the orthogonal acceleration region adjacent the
orthogonal acceleration electrode or pusher and/or puller
electrode 2. Once the orthogonal acceleration region has
refilled with or admitted ions having relatively higher mass to
charge ratios (as shown in Fig. 2D) then the orthogonal
acceleration electrode or pusher and/or puller electrode 2 is
preferably energised a second time at a time t4 shown in Fig. 2E.
Fig. 2E shows how substantially all ions having a mass to charge
ratio of M6 and some ions having a mass to charge ratio of either
M5 or M7 are orthogonally accelerated into the drift region of
the Time of Flight mass analyser according to the preferred
embodiment wherein M7 > M6 > M5.
The process of energising the orthogonal acceleration
electrode or pusher and/or puller electrode 2 may be repeated a
third and subsequent times prior to releasing.a second or
subsequent pulse of ions from the ion guide or ion trap 7. The
orthogonal acceleration electrode or pusher and/or puller
electrode 2 is preferably repeatedly re-energised until ions
having the highest mass to charge ratio of interest which were
contained in the original or first packet of ions which was

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released from the ion guide or ion trap 7 has passed to the
orthogonal acceleration region adjacent the orthogonal
acceleration or pusher and/or puller electrode 2.
According to an embodiment the number of repeat pulses or
energisations of the orthogonal acceleration electrode or pusher
and/or puller electrode 2 per release of a packet of ions from
the ion guide or ion trap 7 may be partly dependent upon how
quickly the acceleration voltage can be reset to zero after a
group of ions has exited the orthogonal acceleration region. It
may also be dependent upon the mass to charge ratio range of ions
released in the initial packet of ions from the ion trap 7.
Fig. 3 shows a plot of the theoretical duty cycle as a
function of mass to charge ratio which may be achieved according
to an embodiment of the present invention by energising the
orthogonal acceleration electrode or pusher and/or puller
electrode 2 three times after each release of an ion packet from
an upstream ion trap 7 and prior to the release of subsequent
packet of ions from the ion trap 7. The timing of the
energisation of the orthogonal acceleration electrode or pusher
and/or puller electrode 2 was set so that ions having mass to
charge ratios of 50, 270 and 1454 Da were optimised to be.
orthogonally accelerated into the drift region of the Time of
Flight mass analyser. The full width at half maximum (FWHM) of
an enhanced duty cycle window at a mass to charge ratio (m/z) for
each selected ion is governed by the following relation which is
relevant to the apparatus used for these experiments:
,m1111=inlz
(8)
2.2
It is apparent that the mass to charge ratio range over
which a duty cycle gain is achieved is relatively narrow at
relatively low mass to charge ratios but is relatively wide at
relatively high mass to charge ratios.
The range of mass to charge ratios over which a duty cycle
gain is achieved may be widened but at the expense of the maximum
duty cycle that can be obtained.

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The time delay between the release of a packet of ions from
an upstream ion trap 7 or alternatively from a travelling wave
ion guide to the energisation of the orthogonal acceleration
electrode or pusher and/or puller electrode 2 may.be varied from
release to release. According to an embodiment the various delay
times may be incremented by pre-determined amounts for a pre-
determined number of releases of packets of ions. This enables
'multiple enhanced duty cycle windows to be interleaved to give an
overall averaged duty cycle. The number of enhanced duty cycle
windows that may be averaged in this manner may vary from two to
any number.
The time delay between orthogonal pushes or energisations
of the orthogonal acceleration or pusher and/or puller electrode
2 may be varied in different ways which may have the effect of
altering the final averaged duty cycle distribution. For
example, it may be varied linearly with mass or mass to charge
ratio or it may be varied linearly with time. Other embodiments
are contemplated wherein the time delay may be varied or
exponentially with mass or mass to charge ratio or exponentially
with time during a cycle. For example, ions may according to an
embodiment be orthogonally accelerated after time delays of 2.5
ps, 5 ps, 10 ps and 20 ps.
Fig. 4A shows the duty cycle for two interleaved enhanced
duty cycle windows. According to this embodiment, in a first
cycle a first pulse or packet of ions was released from an ion
trap and then the orthogonal acceleration electrode was energised
three times. In a second cycle a second pulse or packet of ions
was released from the ion trap and the orthogonal acceleration
electrode was then energised a further three times. The delay
times at which the orthogonal acceleration electrode was
energised in the second cycle were arranged to be different from
the-delay times in-the-first cycle.
Fig. 4B shows the duty cycle for three interleaved enhanced
duty cycle windows. According to this embodiment, in a first
cycle a first pulse or packet of ions was released from an ion
trap and then the orthogonal acceleration electrode was energised
three times. In a second cycle a second pulse or packet of ions
was released from the ion trap and the orthogonal acceleration
electrode was then energised a further three times. In a third

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cycle a third pulse or packet of ions was released from the ion
trap and the orthogonal acceleration electrode was then energised
a further three times. The delay times at which the orthogonal
acceleration electrode were energised in the first, second and
third cycles were arranged to be different.
Fig. 4C shows the duty cycle for four interleaved enhanced
duty cycle windows. According to this embodiment, in a first
cycle a first pulse or packet of ions was released from an ion
trap and then the orthogonal acceleration electrode was energised
three times. In a second cycle a second pulse or packet of ions
was released from the ion trap and the orthogonal acceleration
electrode was then energised a further three times. In a third
cycle a third pulse or packet of ions was released from the ion
trap and the orthogonal acceleration electrode was then energised
a further three times. In a fourth cycle a fourth pulse or
packet of ions was released from the ion trap and the orthogonal
acceleration electrode was then energised a further three times.
The delay times at which the orthogonal acceleration electrode
were energised in the first, second, third and fourth cycles were
arranged to be different.
Fig. 4D shows the duty cycle for ten interleaved enhanced
duty cycle windows. According to this embodiment, in a first
cycle a first pulse or packet of ions was released from an ion
trap and then the orthogonal acceleration electrode was energised
three times. In a second cycle a second pulse or packet of ions
was released from the ion trap and the orthogonal acceleration
electrode was then energised a further three times. In a third
cycle a third pulse or packet of ions was released from the ion
trap and the orthogonal acceleration electrode was then energised
a further three times. In a fourth cycle a fourth pulse or
packet of ions was released from the ion trap and the orthogonal
acceleration electtode was then energised a further three times.
In a fifth cycle a fifth pulse or packet of ions was released
from the ion trap and the orthogonal acceleration electrode was
then energised a further three times. In a sixth cycle a sixth
pulse or packet of ions was released from the ion trap and the
orthogonal acceleration electrode was then energised a further
three times. In a seventh cycle a seventh pulse or packet of
ions was released from the ion trap and the orthogonal

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acceleration electrode was then energised a further three times.
In an eighth cycle an eighth pulse or packet of ions was released
from the ion trap and the orthogonal acceleration electrode was
then energised a further three times. In a ninth cycle a ninth
pulse or packet of ions was released from the ion trap and the
orthogonal acceleration electrode was then energised a further
three times. In a tenth cycle a tenth pulse or packet of ions
was released from the ion trap and the orthogonal acceleration
electrode was then energised a further three times. The delay
times at which the orthogonal acceleration electrode was
energised in the first, second, third, fourth, fifth, sixth,
seventh, eighth, ninth and tenth cycles were arranged to be
different.
In Figs. 4A-4D the continuous line shows the duty cycle due
to energising the orthogonal acceleration electrode a first time
and at different delay times in each cycle. The short dashed
line shows the duty cycle due to energising the orthogonal
acceleration electrode a second time and at different delay times
in each= cycle. The long dashed line shows the duty cycle due to
energising the orthogonal acceleration electrode a third time and
at different delay times.
Fig. 4E shows the total averaged duty cycle when the
contributions from two cycles of three pushes per cycle were
combined. Fig. 4F shows the total averaged duty cycle when the
contributions from three cycles of three pushes per cycle were
combined. Fig. 4G shows the total averaged duty cycle when the
contributions from four cycles of three pushes per cycle were
combined. Fig. 4H shows the total averaged duty cycle when the
contributions from ten cycles of three pushes per cycle were
combined.
In these examples the first push has been interleaved
between-50-and 270 Da, the "second push has been interleaved
between 270 and 1450 Da and the third Push has been interleaved
between 1450 and 7800 Da. Increasing the number of pushes has
the effect of smoothing out the duty cycle distribution. It can
be seen from Fig. 4H that interleaving ten cycles gives a
constant 30% duty cycle from approximately 50 Da upwards.
Fig. 5 illustrates the noimal duty cycle of an orthogonal
= acceleration Time of Flight mass analyser when sampling a

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continuous ion beam in a conventional manner. Fig. 5 also shows
the theoretical enhancement in duty cycle which may be obtained
according to an embodiment of the present invention together with
an experimentally obtained enhancement in duty cycle. The
theoretical and experimental enhancements in duty cycle relate to
an embodiment wherein three orthogonal acceleration pulses were
applied to the orthogonal acceleration electrode or pusher and/or
puller electrode 2 after each packet of ions was released from
the ion trap 7. Four different enhanced duty cycle windows were
interleaved. Fig. 5 also shows preliminary experimental data
which confilms that an improvement in duty cycle to a
substantially constant value may be achieved over a wide mass to
charge ratio range.
Fig. 6A shows a mass spectrum obtained by operating an
orthogonal acceleration Time of Flight mass spectrometer in a
conventional manner. Fig. 6B shows a corresponding mass spectrum
obtained according to a preferred embodiment by energising the
pusher electrode 2 of a Time of Flight mass analyser multiple
times after each release of ions from an ion trap 7 arranged
upstream of the Time of Flight mass analyser. The enhanced duty
cycle windows were interleaved. The two mass spectra are plotted
with the same vertical or intensity scale. The significant
improvement in duty cycle particularly at relatively low mass to
charge ratio has the effect of significantly increasing the
intensity of the ion signal for these ions without sacrificing
sensitivity for ions having relatively high mass to charge
ratios.
Further embodiments are contemplated wherein the pusher
electrode 2 may be energised whilst ions from a preceding push
are still travelling towards the ion detector 6. The ions in a
preceding push are predominantly lower in mass to charge ratio
than-those-in-the-sUbSeqUeht push dnd hence the ions from the
subsequent push will not overtake the ions having relatively
lower mass to charge ratios from the preceding push. Therefore,
spectral overlap will not occur. Since a first Time of Flight
measurement is still underway whilst a second Time of Flight
measurement begins, two or more Time to Digital Converters
("TDCs") may be used. Alternatively, a single Time to Digital
Converter may be used wherein a flag may be placed at a time

CA 02672526 2014-04-23
- 36 -
which corresponds with the second pusher pulse. In this way the
single Time to Digital Convertor may record both Time of Flight
measurements.
With reference to Fig. 4H, although according to the
preferred embodiment the delay times at which points the
orthogonal acceleration electrode is energised after the release
of pulses or packets of ions may be varied in, for example, ten
subsequent cycles of operation so that a substantially constant
overall duty cycle of approximately 30% may be obtained across
substantially the whole of the mass to charge ratio of interest,
other embodiments are contemplated wherein only ions having
certain mass to charge to ratios may be of interest. According
to this embodiment the delay times may not be varied from one
cycle to the next. For example, with reference to Fig. 3, ions
having a mass to charge ratio of 50, 270 and 1454 may be
orthogonally accelerated with a duty cycle of 100%.
Alternatively, the Time of Flight mass analyser may be operated
in a mode wherein there are only two different delay times in
subsequent cycles of operation. According to this embodiment the
overall duty cycle would be similar to that shown in Fig. 4E.
According to this embodiment five species of ions could, for
example, be orthogonally accelerated with a duty cycle of 50%.
Similarly, according to the embodiment described above with
reference to Fig. 4F seven species of ions could be orthogonally
accelerated with a duty cycle of approximately 40%. It will be
apparent that other variations are possible.
Embodiments of the present invention are contemplated
wherein the Time of Flight mass analyser may be operated in a
first mode of operation wherein a plurality of species of ions
may be orthogonally accelerated with a high duty cycle (50-100%)
and in a second mode of operation wherein substantially all ions
above a low-mass cut-off are orthogonally accelerated with a
substantially constant and relatively high duty cycle of
approximately 30%.

A single figure which represents the drawing illustrating the invention.

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Admin Status

Title Date
Forecasted Issue Date 2016-08-23
(86) PCT Filing Date 2007-12-14
(87) PCT Publication Date 2008-06-19
(85) National Entry 2009-06-10
Examination Requested 2012-08-15
(45) Issued 2016-08-23

Abandonment History

There is no abandonment history.

Maintenance Fee

Description Date Amount
Last Payment 2019-11-20 $250.00
Next Payment if small entity fee 2020-12-14 $125.00
Next Payment if standard fee 2020-12-14 $250.00

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Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Filing $400.00 2009-06-10
Maintenance Fee - Application - New Act 2 2009-12-14 $100.00 2009-12-14
Maintenance Fee - Application - New Act 3 2010-12-14 $100.00 2010-11-18
Maintenance Fee - Application - New Act 4 2011-12-14 $100.00 2011-11-24
Request for Examination $800.00 2012-08-15
Maintenance Fee - Application - New Act 5 2012-12-14 $200.00 2012-11-23
Maintenance Fee - Application - New Act 6 2013-12-16 $200.00 2013-11-19
Maintenance Fee - Application - New Act 7 2014-12-15 $200.00 2014-11-20
Maintenance Fee - Application - New Act 8 2015-12-14 $200.00 2015-11-20
Final Fee $300.00 2016-06-27
Maintenance Fee - Patent - New Act 9 2016-12-14 $200.00 2016-12-12
Maintenance Fee - Patent - New Act 10 2017-12-14 $250.00 2017-12-11
Maintenance Fee - Patent - New Act 11 2018-12-14 $250.00 2018-11-23
Maintenance Fee - Patent - New Act 12 2019-12-16 $250.00 2019-11-20
Current owners on record shown in alphabetical order.
Current Owners on Record
MICROMASS UK LIMITED
Past owners on record shown in alphabetical order.
Past Owners on Record
GREEN, MARTIN
KENNY, DANIEL JAMES
WILDGOOSE, JASON LEE
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.

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Representative Drawing 2009-09-10 1 6
Cover Page 2009-09-21 1 36
Abstract 2009-06-10 1 63
Claims 2009-06-10 24 1,101
Drawings 2009-06-10 10 127
Description 2009-06-10 36 2,190
Claims 2009-10-02 5 174
Description 2014-04-23 36 2,020
Claims 2014-04-23 4 149
Claims 2015-09-09 4 148
Cover Page 2016-07-14 1 36
Fees 2009-12-14 1 34
Prosecution-Amendment 2009-10-02 7 226
PCT 2009-06-10 2 60
Assignment 2009-06-10 5 133
Fees 2010-11-18 1 35
Prosecution-Amendment 2012-08-15 1 35
Assignment 2014-04-02 7 191
Prosecution-Amendment 2013-10-25 5 308
Prosecution-Amendment 2014-04-23 29 1,326
Prosecution-Amendment 2015-03-17 3 189
Prosecution-Amendment 2015-09-09 3 105
Correspondence 2016-06-27 1 50