WO1995033279A1 - Tandem mass spectrometry apparatus - Google Patents

Tandem mass spectrometry apparatus Download PDF

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Publication number
WO1995033279A1
WO1995033279A1 PCT/GB1995/001252 GB9501252W WO9533279A1 WO 1995033279 A1 WO1995033279 A1 WO 1995033279A1 GB 9501252 W GB9501252 W GB 9501252W WO 9533279 A1 WO9533279 A1 WO 9533279A1
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WO
WIPO (PCT)
Prior art keywords
time
ions
mass spectrometry
ion
tandem mass
Prior art date
Application number
PCT/GB1995/001252
Other languages
French (fr)
Inventor
Peter John Derrick
David John Reynolds
Alexander Alekseevich Makarov
Original Assignee
University Of Warwick
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to GB9410864A priority Critical patent/GB9410864D0/en
Priority to GB9410864.4 priority
Application filed by University Of Warwick filed Critical University Of Warwick
Priority claimed from GB9625017A external-priority patent/GB2303962B/en
Publication of WO1995033279A1 publication Critical patent/WO1995033279A1/en

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Classifications

    • HELECTRICITY
    • H01BASIC ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/26Mass spectrometers or separator tubes
    • H01J49/34Dynamic spectrometers
    • H01J49/40Time-of-flight spectrometers
    • H01J49/405Time-of-flight spectrometers characterised by the reflectron, e.g. curved field, electrode shapes
    • HELECTRICITY
    • H01BASIC ELECTRIC ELEMENTS
    • H01JELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00Particle spectrometers or separator tubes
    • H01J49/004Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn

Abstract

Tandem mass spectrometry apparatus comprises a serial arrangement of an ion source (10), a first time-of-flight means (20, 80), a collision cell (40) to generate fragment ions and a second time-of-flight analyser (50). The second time-of-flight analyser comprises an ion mirror (51, 52) which is arranged to produce a quadratic field along or at an angle to the optical axis of the apparatus. The first time-of-flight analyser may comprise a sequential S configuration of toroidal or cylindrical electrostatic analysers (70) or may comprise two electrostatic lenses (80, 96) to either side of an ion mirror or may comprise an electrostatic lens (80). The first time-of-flight analysers thus comprise electrostatic field means for providing spatial focusing of ions in all three dimensions at or near the entrance to the ion mirror of the second time-of-flight analyser (50). The spatial focusing, concomitant with time focusing, is the essential requirement for the quadratic field mirror to give high resolution.

Description

TANDEM MASS SPECTROMETRY APPARATUS

The invention relates to tandem mass spectrometry apparatus.

The expanding areas of biotechnology and biological sciences have lead to an increased demand for sensitivity from mass spectrometry, especially as regards structural analysis of small and medium-sized biological molecules (100-100000 Da) which may be available in complex mixtures and trace amounts of, say, a picomole or less. The same requirements for structural information arise with synethetic polymers.

Traditional mass spectrometric analysis of such biological and polymeric molecules has been carried out by tandem instruments consisting of either twin sector, twin quadrupole or some hybrid combination such as sector plus quadrupole. In such a system molecules will be ionized by some technique such as fast atom bombardment (FAB) and mass/energy selected by the first mass spectrometer (MS1 ) , the selected ions will then undergo collisional activation by passing through a cell containing some neutral gas. The fragment ions thus obtained will then be analysed by the second mass analyser (MS2) . According to the invention there is provided tandem mass spectrometry apparatus comprising a serial arrangement of an ion source, a first time-of-flight analyser, means for dissociating ions from the first analyser to generate fragment ions, and a second time- of-flight analyser, the second time-of-flight analyser comprising an ion mirror which is arranged to produce an appropriately reflecting a quadratic field, the first time-of-flight analyser comprising electrostatic field means for providing spatial focusing of ions at or near the entrance to the quadratic field ion mirror.

The inventors have recognised that tandem time-of- flight mass spectrometry apparatus provides important increases specificity and in sensitivity. Nevertheless conventional time-of-flight analysers produce spatial spreads of ions so that the use of two such analysers in tandem is not practical of the level of resolution required for structural determinations. By the use of a second time-of-flight analyser comprising an ion mirror which is arranged to produce a quadratic field (along or at the same angle to the optical axis of the apparatus) and a first time-of- flight analyser comprising electrostatic field means for providing spatial focusing of ions at or near the entrance to the ion mirror, an effective ion tandem time-of-flight mass spectrometry apparatus is provided which not only provides the desired increase in sensitivity but also provides a high level of resolution.

The ion mirror may take any suitable form and may be arranged to produce a parabolic field along the optical axis of the apparatus. The ion mirror may be an appriximation to a quadratic f-ireld with allowance for effects of fringing fields at the entrance, exit and elsewhere.

The ion source may provide either a pulsed beam of ions or a continuous beam. Pulsing may be achieved by either pulsing a continuous source such as electrospray or by the use of an inherently pulsed technique such as matrix assisted laser desorption/ionization (MALDI) to provide intact molecule ions of molecules for example in the mass range 100-100000 Da. Means for compressing or bunching ions into a pulse of ions may be provided. The bunching means may compress a pulse of ions into an ion pulse of shorter duration, or may convert a continuous beam into a pulsed beam. Bunching may take place before the first mass analyser, after the first mass analyser or in both places. An ion mirror of this kind used in combination with an ion "buncher", enables a much improved mass resolving power to be achieved compared with that attained by known tandem mass spectrometry systems based on time- of-flight. Use of the ion mirror enables the whole of the mass spectrum to be detected without the need for any re-tuning, and the mass spectrum can be easily calibrated with absolute precision.

Because the flight-times of the ions through the ion mirror depend on their mass-to-charge ratios, and are entirely independent of their energies, a high degree of mass resolution can be attained, even though the ions are subject to a very substantial spreading of their energies due to the effect of the ion "buncher" on the ions and due to partitioning of energy as a part of fragmentation.

The ion "buncher" may comprise an electrostatic means defining a "buncher" space, having an entrance, by which a pulse of ions selected by the first mass analyser enters the "buncher" space, and an exit by which the pulse exits the "buncher" space. The electrostatic means operates to apply an electrostatic accelerating force to ions in a pulse that has entered the "buncher" space whereby to accelerate the ions to higher energies in proportion to their distances from the exit of the "buncher" space.

Preferably the first mass analyser comprises a time- of-flight (TOF) analysis means capable of providing focusing of an isobaric ion packet with regard to spread normal to the optical axis, spread along the optical axis of the machine, spread in the energy of the ions within the packet and focusing in time.

The first analyser preferably comprises a sequential S configuration of a plurality of toroidal or cylindrical electrostatic analysers. This device will provide a focused isobaric ion packet at a particular point in time discrete from that of ions of differing mass at a point in space focused at the dissociation cell. It also has the benefit of triple isochronous focusing.

In an alternative embodiment, the first time-of-flight means comprises an ion mirror after an electrostatic lens. Preferably, the first time-of-flight means further comprises a second electrostatic lens after the ion mirror. The ion mirror may be a gridless planar mirror with a substantially zero optical strength. In a further embodiment, the first time-of- flight means may comprise an electrostatic lens. The ion source may then include an electrostatic means to accelerate ions into the electrostatic lens. This arrangement involves few components and is relatively simple to set up. The electrostatic lens may comprise an axially symmetrical body at a raised potential. The structure described for the first time-of-flight means enables spatial focusing which gives a significant improvement in resolution. The concept of spatial focusing is a significant advance in this field.

Three embodiments of the invention will now be described by way of example and with reference to the accompanying drawings, in which:

Fig. 1 is a diagrammatic illustration of tandem mass spectrometry apparatus in accordance with the first embodiment of the invention;

Fig. 2 is a plan view in cross-section of the first mass analyser of the embodiment of Fig. 1; Fig. 3 schematically illustrates an ion "buncher" used in the tandem mass spectrometry apparatus of Fig.

1;

Fig. 4 schematically illustrates flight paths of an undissociated precursor ion and two fragment ions. The quadratic field in this arrangement is perpendicular to the XZ plane in the direction of the X axis;

Figs. 5 and 6 show a transverse, cross-sec ional view and a perspective view respectively of one type of ion mirror with a 2-dimensional quadratic field;

Fig. 7 is a diagrammatic illustration of tandem mass spectrometry apparatus in accordance with the second embodiment of the invention; and

Fig. 8 is a diagrammatic illustration of tandem mass spectrometry apparatus in accordance with the third embodiment of the invention.

Referring to Fig. 1 of the drawings, the tandem mass spectrometry system comprises a serial arrangement of a pulsed ion source or a continuous source with a "buncher" 10, a time-of-flight analyser 20, an ion lens L and deflector plates D, , an ion "buncher" 30, a cell in which ions dissociate 40, deflector plates D, and a quadratic-field ion mirror for TOF (time-of- flight) analysis.

Ions produced by the ion source 10 are admitted to the mass analyser 20 in short pulses, typically less than 300-500 ns duration.

A sample under investigation could be ionised by using either a laser beam or an ion beam, both of which can be generated in a pulsed mode. The pulses forming the ionising beam may be of relatively short duration, the resulting ions being extracted from the source, for admittance to the time-of-flight analyser 20, using a static extraction field. Alternatively, longer ionising pulses might be used, in which case the extraction field would be pulsed. The analyser 20 is tuned to select only those ions having a chosen mass- to-charge ratio.

In the example of a laser pulse, the pulse will ionize and volatilize the target material and start the timing for the first time-of-flight stage 20. The first time-of-flight mass analyser 20 comprises an "S" configuration of four toroidal electrostatic analysers feeding one to the next in an undulating path as shown in Fig. 2. A deflector D, will refocus the beam on the first detector, an ion multiplier at the end of the first mass analyser 20 and prior to the collision cell 40. A preliminary time-of-flight spectrum will then be recorded. The timing from this preliminary experiment will be used to time the deactivation of the deflector D, allowing the ion packet of desired mass to enter the dissociation cell 40. Alternatively all ions of all masses will be allowed to enter the dissociation cell. After collisional activation the fragment ions will proceed to the second time-of- flight mass spectrometer 50 for subsequent mass separation and detection on the channel plate or other detector assembly.

The two sets of electrostatic deflector plates D, and D. are used to control angles of incidence at the entrance of the ion mirror 50, with the aim of optimising sensitivity. It is known that the optimum mass revolving power R of a TOF mass analyser is related to the duration or time-width, Δ T, of the ion pulses and to the flight time, T, of the ions through the analyser by the following expression:

2 Δ T

Accordingly, the mass resolving power R can be improved if the time width Δ T of the ion pulses is as short as possible. For example, ions entering the flight path of the TOF mass analyser 50 may typically have energies of the order of 10 keV and if the flight path is 1m, a resolution of 5000 at mass 5000 can only be achieved if the pulse width Δ T is of the order of 14 ns or less.

If an ion buncher is used in the initial stage then a mass selected ion packet would be compressed by using the preliminary time-of-flight spectrum to time a ramping pulse across the buncher 10 which would have the effect of compressing the ion spread in space or time at a focus within the dissociation cell 40.

Alternatively all (parent and product) ions' times of flight may be timed from the source. In this case the deflector D, would not be used. After a satisfactory spectrum had been obtained, the kinetic energy imparted to the parent ions would be changed by a small amount for another time-of-flight experiment.

In this second experiment the parent ions flight time would be shifted by a time related to the energy shift, however the fragment ions' times of flight would remain fixed in relation to their respective parent ions. This would allow all parent ion fragmentations to be analysed simultaneously since sets of fragments relating to individual parent ions would be distinguishable.

An ion buncher 30 may be provided between the ion lens L and the TOF mass analyser 50 in order to compress the ion pulses produced by source 10 into pulses of much shorter duration.

As shown in Fig. 3, the ion "buncher" 30 comprises a pair of electrodes P, , P: which are normally maintained at ground potential. In order to compress a pulse of the mass-selected parent ions into a much shorter pulse, the electrode P, , that is to say the electrode nearer the mass analyser 20, is ramped up rapidly to a positive voltage V, (for positive ions) when the pulse lies wholly within the "buncher" space S, between the electrodes.

This voltage subjects each ion in the pulse to an electrostatic accelerating force in the direction of the ion mirror 50, and accelerates the ion to a higher energy by an amount proportional to its separation from the grounded electrode P2. The ions in the pulse which entered the buncher space first and are closer to electrode P2, spend less time in the accelerating field than do the ions which entered the "buncher" space later. Accordingly, the "later ions" tend to catch up with the "earlier ions". The distance s separating the two electrode plates, the distance d separating the downstream plate and the entrance to the TOF mass analyser 50, and the voltage V, applied to electrode plate P, are chosen so that the ions in a pulse all arrive at the entrance to the TOF mass analyser at substantially the same time.

The significant consequence of subjecting the mass- selected ions in each pulse to the accelerating voltage V8 is to introduce a significant spreading of their energies. If, for example, the ion pulses produced by ion source 10 are spread out in space over 50mm so that they just span the electrodes P, , P. of the ion buncher, the energies of parent ions arriving at the ion mirror 50 would range from 10 keV (if this were the energy of the leading ion in the pulse which receives no energy from the accelerating field) and 14 keV (the energy of the trailing ion in the pulse which receives the maximum energy of 4 keV from the accelerating field) .

The compressed ion pulse (which may typically have a time width of 10 ns or less) passes through the cell 40 positioned at the entrance to the TOF mass analyser 50. One possibility is to fragment ions by gas collision. An alternative is to use a laser pulse to dissociate the mass-selected parent ions forming the compressed pulse. Since the compressed ion pulse is well defined in both time and space, the laser pulse can be synchronised to coincide with the arrival of each ion pulse at the time focal point.

The fragment ions, produced by dissociation of the mass-selected parent ions, continue on the same trajectory as the parent ions, with very nearly the same velocity, and so little time-spread is introduced prior to entering the ion mirror 50. Undissociated precursor ions and fragment ions introduced into the ion mirror 50 will have a substantial energy spread for two reasons. Ions of the same mass have a large energy spread due to the action of the ion buncher, as described hereinbefore. Ions of different masses have different energies (each fragment ion of mass Mp, say, will have a fraction M,/M, of the energy of the precursor ion (mass MP) from which it is derived).

The quadratic field E of the ion mirror 50 enables a high mass resolving power to be attained even though the ions introduced into the flight path of the analyser have different energies. An ion is subjected to an electrostatic reflecting force F which increased linearly as a function of the depth of penetration of the ion into the field region. This force acts in the X-direction (Fig. 4) and has a magnitude directly proportional to the separation x of the ion from the Z-axis.

The electrostatic reflecting force F can be expressed as

F « - kqx where k is a constant and q is charge.

The equation of motion of the ion in the field region is analogous to that associated with damped simple harmonic motion, and it can be shown that the time interval t during an ion mass m travels from the point of entry 1 to the point of reflection 2 is given by the expression τι m 1 i t = - ( - . - ) 2 q k Thus, the ion occupies the field region for a total time interval t' given by m 1 i f = 2t - t { - . - ) q k As this result shows, the ion occupies the field region E for the time interval which depends only on its mass-to-charge ration (m/q), and this enables ions to be distinguished from one another as a function of their mass-to-charge rations, even if, as in the present case, they have different energies.

It has been found that the flight times of ions through the ion mirror are independent of angular deviation in the X-Y plane over a relatively large angular range as measured by a flat detector in the YZ plane.

Fig. 4 shows, by way of example, the flight paths followed by undissociated precursor ions I, and by two daughter ions IB(1), I- (2) having masses M0(1), M-(2) respectively, wherein M„( 1 ) > M-(2) - it will be assumed, in this example, that the ions all have the same charge. Fig. 4 shows, by way of example, the flight paths followed by undissociated precursor ions I- and by two daughter ions I-(1), Is(2) having masses MD(1), MB(2) respectively, wherein MB(1) > M- (2) - it will be assumed, in this example, that the ions all have the same charge.

The undissociated precursor ions Ip, being the heaviest, have the longest flight time through the field region and they move along the outermost path, whereas the light daughter ions ID(2) have the shortest flight time and because they have lower energy they follow the innermost path.

Ions having different masses exit the field region at different positions. The ions may be detected using, for example, a multichannel plate detector mounted in the time-focus plane.

As explained hereinbefore, the two sets of deflector plates D, , D, may be used to control the angles of incidence « of the ions entering the TOF mass analyser. The particular function of the second set of deflector plates D, may be to reduce the spatial spread of ions at the detector, enabling all ions to be detected. To that end, the deflector plates D, subject all the ions to an electrostatic deflecting ions received at the detector. In principle, it is possible to collect all the undissociated precursor ions and the fragment ions that constitute the entire mass spectrum.

A feature of this form of energy-independent ion mirror is that the dissociation cell 40 can be maintained at ground potential, obviating the need for retardation and consequent spatial defocusing of the ion beam and obviating the need for any energy- dependent extraction optics.

In a further embodiment, the quadratic field may have rotational symmetry about an axis, the X axis say. Such a field may be generated by an electrode structure comprising one electrode having a conical electrode surface and a second electrode having a hyperbolic or spherical electrode surface facing the conical electrode surface. The second electrode would be maintained at a retarding potential with respect to the first electrode.

A tandem mass spectrometry system as described finds particular application in the structural analysis of large molecules, for example biological and polymer samples. Because the flight-times of ions through the ion mirror depend on their mass-to-charge ratios, and are entirely independent of their energies, a high mass-resolution can be attained even though the ions are subject to a substantial spreading of their energies due to the effect of the ion buncher on the precursor ions.

A second embodiment of the invention will now be described which is similar to the first embodiment. Only the differences from the first embodiment will be described and the same reference numerals will be used for equivalent features.

The second embodiment is again the same as the first embodiment except that the first time-of-flight analyser takes a further different form. The same reference numerals will be used for equivalent features. The first part of the first time-of-flight mass analyser of the second embodiment compromises an electrostatic lens 80 after which a planar ion mirror is provided which has zero optical strength. This takes the form of two parallel planar charged grids 92 provided one above the other. The elements 94 of each grid are provided at a small angle to the perpendicular to the optical path of the ions from the electrostatic lens 80. The ions are reflected by the mirror 93 to pass through a further electrostatic lens 96 which is identical to the first electrostatic lens 80. The ions are then directed into the dissociation cell 40. The electrostatic lenses 80 and 96 serve to achieve the required spatial focusing.

The third embodiment is the same as the first embodiment except that the first tandem mass analyser 20 is not in the form of four toroidal electrostatic analysers but instead comprises a single electrostatic lens 80. The lens is in the form of a cylindrical tube which is at a raised potential of some kV and which has a surrounding tubular shroud or shield 82 which is connected to earth. In use, a laser pulse of about brief duration is focused through a lens 86 and directed against the target material 88. A portion of the target material 88 on the surface is volatilised. Two closely spaced apertured plates 90 adjacent the laser focus point on the target material 88 are maintained together with the target material at potentials which are ramped serially such that the emitted "cloud" of target material ions is directed to the electrostatic lens 80 and to the remainder of the apparatus.

The first time-of-flight mass analyser in each of the embodiments enables spatial focusing at or near the entrance to the second mass analyser 50. Time focus is also provided and these features enable the apparatus of the three embodiments to provide a significantly improved resolution over existing apparatus.

The spatial focusing, concomitant with tiem focusing, is the essential requirement for the quadratic field mirror to give high resolution.

Claims

1. Tandem mass spectrometry apparatus comprising a serial arrangement of an ion source, a first time-of-flight means, means for dissociating ions from the first ime-of-flight means to generate fragment ions and a second time-of-flight means, the second time-of-flight means comprising an ion mirror which is arranged to produce a reflecting, substantially quadratic field along the optical axis of the apparatus, the first time-of-flight means comprising electrostatic field means for providing spatial focusing of ions at or near the entrance to the ion mirror.
2. Tandem mass spectrometry apparatus as claimed in claim 1 , wherein the ion mirror is arranged to produce a parabolic field along the optical axis of the apparatus.
3. Tandem mass spectrometry apparatus as claimed in claim 1 or claim 2, wherein the ion source is arranged to emit a pulsed beam of ions.
4. Tandem mass spectrometry apparatus as claimed in claim 1, 2 or 3 , wherein the apparatus includes means for compressing or bunching ions into a pulse of ions.
5. Tandem mass spectrometry apparatus as claimed in claim 4, wherein the ion bunching means comprises electrostatic means defining a buncher space having an entrance by which a pulse of ions selected by the first time-of-flight means enters the buncher space and an exit by which the pulse exits the buncher space, the electrostatic means being operable to apply an electrostatic accelerating or decelerating force to ions in a pulse as it enters the buncher space whereby to accelerate or decelerate the ions to higher or lower energies in proportion to their separation from the exit of the buncher space.
6. Tandem mass spectrometry apparatus as claimed in claim 5, wherein the electrostatic means of the ion bunching means comprises respective electroplates at the entrance to and the exit from the buncher space.
7. Tandem mass spectrometry apparatus as claimed in any preceding claim, wherein the first time-of-flight means is arranged to provide focusing of an isobaric ion packet with regard to spread normal to the optical axis spread along the optical axis of the machine, spread in the energy of the ions within the packet and focusing in time.
8. Tandem mass spectrometry apparatus as claimed in any preceding claim, wherein the first time-of-flight means comprises a sequential S configuration of a plurality of toroidal or cylindrical electrostatic devices.
9. Tandem mass spectrometry apparatus as claimed in claim S, wherein the first time-of-flight means comprises two, three or four of said electrostatic devices.
10. Tandem mass spectrometry apparatus as claimed in any of claims 1 to 7, wherein the first time-of-flight means comprises an electrostatic lens.
11. Tandem mass spectrometry apparatus as claimed in claim 10, wherein the ion source includes an electrostatic means to accelerate ions into the electrostatic lens.
12. Tandem mass spectrometry apparatus as claimed in claim 10 or claim 11, wherein the electrostatic lens comprises an axially symmetrical body at a raised potential.
13. Tandem mass spectrometry apparatus as claimed in claim 10, 11 or 12, wherein the first time- of-flight means further comprises an ion mirror after the electrostatic lens.
14. Tandem mass spectrometry apparatus as claimed in claim 13, wherein the first time-of-flight means further comprises a second electrostatic lens after the ion mirror.
15. Tandem mass spectrometry apparatus as claimed in claim 13 or claim 14, wherein the ion mirror is a gridless planar mirror with substantially zero optical strength.
PCT/GB1995/001252 1993-12-01 1995-05-31 Tandem mass spectrometry apparatus WO1995033279A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
GB9410864A GB9410864D0 (en) 1993-12-01 1994-05-31 Tandem mass spectrometry system
GB9410864.4 1994-05-31

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP50052396A JPH10501095A (en) 1994-05-31 1995-05-31 Tandem mass spectrometry
GB9625017A GB2303962B (en) 1994-05-31 1995-05-31 Tandem mass spectrometry apparatus
AU26221/95A AU2622195A (en) 1994-05-31 1995-05-31 Tandem mass spectrometry apparatus

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WO1995033279A1 true WO1995033279A1 (en) 1995-12-07

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AU (1) AU2622195A (en)
WO (1) WO1995033279A1 (en)

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2305539A (en) * 1995-09-19 1997-04-09 Bruker Franzen Analytik Gmbh Time-of-flight mass spectrometers
GB2308491A (en) * 1995-09-19 1997-06-25 Bruker Franzen Analytik Gmbh Time-of-flight mass spectrometry
GB2308492A (en) * 1995-12-21 1997-06-25 Bruker Franzen Analytik Gmbh Time-of-flight mass spectrometry
US5742049A (en) * 1995-12-21 1998-04-21 Bruker-Franzen Analytik Gmbh Method of improving mass resolution in time-of-flight mass spectrometry
WO1999027560A2 (en) * 1997-11-24 1999-06-03 The Johns-Hopkins University Method and apparatus for correction of initial ion velocity in a reflectron time-of-flight mass spectrometer
WO2001069648A2 (en) * 2000-03-13 2001-09-20 University Of Warwick Time of flight mass spectrometry apparatus
WO2001078106A2 (en) * 2000-04-10 2001-10-18 Perseptive Biosystems, Inc. Preparation of ion pulse for time-of-flight and for tandem time-of-flight mass analysis
WO2002017349A1 (en) * 2000-08-24 2002-02-28 Unisearch Limited Two-dimensional tofms for desorption ion sources
WO2003107387A1 (en) * 2002-05-30 2003-12-24 The Johns Hopkins University Non-linear time-of-flight mass spectrometer
WO2004077488A3 (en) * 2003-02-21 2005-10-06 Univ Johns Hopkins Tandem time-of-flight mass spectrometer
GB2454767A (en) * 2007-10-10 2009-05-20 Bruker Daltonik Gmbh Producing cleaned daughter ion spectra from a MALDI ionisation TOF mass spectrometer
WO2011068654A1 (en) * 2009-12-03 2011-06-09 Quest Diagnostics Investments Incorporated Vitamin d detection by mass spectrometry with laser diode thermal desorption
US7972867B2 (en) 2005-04-06 2011-07-05 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites by mass spectrometry
US7977117B2 (en) 2009-12-03 2011-07-12 Quest Diagnostics Investments Incorprated Vitamin D metabolite determination utilizing mass spectrometry following derivatization
US8034627B2 (en) 2009-12-03 2011-10-11 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
US8101427B2 (en) 2005-04-06 2012-01-24 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites by mass spectrometry
US8173442B2 (en) 2007-11-28 2012-05-08 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
US9034653B2 (en) 2009-12-11 2015-05-19 Quest Diagnostics Investments Inc. Mass spectrometry of steroidal compounds in multiplexed patient samples
US9136100B2 (en) 2011-10-21 2015-09-15 Shimadzu Corporation ToF mass analyser with improved resolving power
GB2536776A (en) * 2015-02-04 2016-09-28 Bruker Daltonik Gmbh Method for measurement of fragment ion mass spectra with tandem time-of-flight mass spectrometers
EP3306640A1 (en) * 2010-12-20 2018-04-11 Shimadzu Corporation Time-of-flight mass spectrometer
US10147591B2 (en) 2015-02-03 2018-12-04 Auckland Uniservices Limited Ion mirror, an ion mirror assembly and an ion trap

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2340150C (en) * 2000-06-09 2005-11-22 Micromass Limited Methods and apparatus for mass spectrometry
GB0021902D0 (en) * 2000-09-06 2000-10-25 Kratos Analytical Ltd Ion optics system for TOF mass spectrometer
US20020115056A1 (en) 2000-12-26 2002-08-22 Goodlett David R. Rapid and quantitative proteome analysis and related methods
GB0305796D0 (en) 2002-07-24 2003-04-16 Micromass Ltd Method of mass spectrometry and a mass spectrometer

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2045338A1 (en) * 1969-09-15 1971-03-18 Shell Int Research
EP0403965A2 (en) * 1989-06-23 1990-12-27 Bruker-Franzen Analytik GmbH MS-MS-flight time mass spectrometer
EP0408288A1 (en) * 1989-07-12 1991-01-16 Kratos Analytical Limited An ion mirror for a time-of-flight mass spectrometer
EP0456517A2 (en) * 1990-05-11 1991-11-13 Kratos Analytical Limited Time-of-flight mass spectrometer
DE4134905A1 (en) * 1990-10-18 1992-04-23 Unisearch Ltd Tandem mass spectrometer based on flight time analysis

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2045338A1 (en) * 1969-09-15 1971-03-18 Shell Int Research
EP0403965A2 (en) * 1989-06-23 1990-12-27 Bruker-Franzen Analytik GmbH MS-MS-flight time mass spectrometer
EP0408288A1 (en) * 1989-07-12 1991-01-16 Kratos Analytical Limited An ion mirror for a time-of-flight mass spectrometer
EP0456517A2 (en) * 1990-05-11 1991-11-13 Kratos Analytical Limited Time-of-flight mass spectrometer
DE4134905A1 (en) * 1990-10-18 1992-04-23 Unisearch Ltd Tandem mass spectrometer based on flight time analysis

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KUTSCHER R ET AL: "A TRANSVERSALLY AND LONGITUDINALLY FOCUSING TIME-OF-FLIGHT MASS SPECTROMETER", INTERNATIONAL JOURNAL OF MASS SPECTROMETRY AND ION PROCESSES, vol. 103, no. 2 / 03, 1 January 1991 (1991-01-01), pages 117 - 128, XP000172837 *

Cited By (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2305539A (en) * 1995-09-19 1997-04-09 Bruker Franzen Analytik Gmbh Time-of-flight mass spectrometers
GB2308491A (en) * 1995-09-19 1997-06-25 Bruker Franzen Analytik Gmbh Time-of-flight mass spectrometry
GB2305539B (en) * 1995-09-19 2000-03-01 Bruker Franzen Analytik Gmbh Improved mass resolution in time-of-flight mass spectrometers with reflectors
GB2308491B (en) * 1995-09-19 2000-08-16 Bruker Franzen Analytik Gmbh Time-of-flight mass spectrometry with improved mass resolution
GB2308492A (en) * 1995-12-21 1997-06-25 Bruker Franzen Analytik Gmbh Time-of-flight mass spectrometry
US5742049A (en) * 1995-12-21 1998-04-21 Bruker-Franzen Analytik Gmbh Method of improving mass resolution in time-of-flight mass spectrometry
WO1999027560A2 (en) * 1997-11-24 1999-06-03 The Johns-Hopkins University Method and apparatus for correction of initial ion velocity in a reflectron time-of-flight mass spectrometer
WO1999027560A3 (en) * 1997-11-24 1999-07-29 Univ Johns Hopkins Method and apparatus for correction of initial ion velocity in a reflectron time-of-flight mass spectrometer
US6365892B1 (en) 1997-11-24 2002-04-02 Robert J. Cotter Method and apparatus for correction of initial ion velocity in a reflectron time-of-flight mass spectrometer
WO2001069648A3 (en) * 2000-03-13 2001-12-20 Alexander William Colburn Time of flight mass spectrometry apparatus
WO2001069648A2 (en) * 2000-03-13 2001-09-20 University Of Warwick Time of flight mass spectrometry apparatus
WO2001078106A2 (en) * 2000-04-10 2001-10-18 Perseptive Biosystems, Inc. Preparation of ion pulse for time-of-flight and for tandem time-of-flight mass analysis
WO2001078106A3 (en) * 2000-04-10 2003-02-06 Perseptive Biosystems Inc Preparation of ion pulse for time-of-flight and for tandem time-of-flight mass analysis
WO2002017349A1 (en) * 2000-08-24 2002-02-28 Unisearch Limited Two-dimensional tofms for desorption ion sources
WO2003107387A1 (en) * 2002-05-30 2003-12-24 The Johns Hopkins University Non-linear time-of-flight mass spectrometer
US20050230613A1 (en) * 2002-05-30 2005-10-20 The John Hopkins University Non-linear time-of-flight mass spectrometer
US7381945B2 (en) 2002-05-30 2008-06-03 The Johns Hopkins Univeristy Non-linear time-of-flight mass spectrometer
WO2004077488A3 (en) * 2003-02-21 2005-10-06 Univ Johns Hopkins Tandem time-of-flight mass spectrometer
US7825374B2 (en) 2003-02-21 2010-11-02 The Johns Hopkins University Tandem time-of-flight mass spectrometer
US8936943B2 (en) 2005-04-06 2015-01-20 Quest Diagnostics Investments, Inc. Methods for detecting vitamin D metabolites by mass spectrometry
US9529004B2 (en) 2005-04-06 2016-12-27 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites by mass spectrometry
US7972867B2 (en) 2005-04-06 2011-07-05 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites by mass spectrometry
US9244084B2 (en) 2005-04-06 2016-01-26 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites by mass spectrometry
US8101427B2 (en) 2005-04-06 2012-01-24 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites by mass spectrometry
US9880180B2 (en) 2005-04-06 2018-01-30 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites by mass spectrometry
US8431411B2 (en) 2005-04-06 2013-04-30 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites by mass spectrometry
US10267810B2 (en) 2005-04-06 2019-04-23 Quest Diagnostics Investments Incorporated Methods for detecting vitamin D metabolites by mass spectrometry
US7989759B2 (en) 2007-10-10 2011-08-02 Bruker Daltonik Gmbh Cleaned daughter ion spectra from maldi ionization
GB2454767B (en) * 2007-10-10 2012-05-23 Bruker Daltonik Gmbh Method and apparatus for producing cleaned daughter ion spectra from MALDI ionization
GB2454767A (en) * 2007-10-10 2009-05-20 Bruker Daltonik Gmbh Producing cleaned daughter ion spectra from a MALDI ionisation TOF mass spectrometer
US8173442B2 (en) 2007-11-28 2012-05-08 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
US8389292B2 (en) 2007-11-28 2013-03-05 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
US8852951B2 (en) 2007-11-28 2014-10-07 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
WO2011068654A1 (en) * 2009-12-03 2011-06-09 Quest Diagnostics Investments Incorporated Vitamin d detection by mass spectrometry with laser diode thermal desorption
US8293540B2 (en) 2009-12-03 2012-10-23 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
US8084269B2 (en) 2009-12-03 2011-12-27 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
US8076157B2 (en) 2009-12-03 2011-12-13 Quest Diagnostics Investments Incorporated Vitamin D metabolite determination utilizing mass spectrometry following derivatization
US7977117B2 (en) 2009-12-03 2011-07-12 Quest Diagnostics Investments Incorprated Vitamin D metabolite determination utilizing mass spectrometry following derivatization
US9625477B2 (en) 2009-12-03 2017-04-18 Quest Diagnostics Invstments Incorporated Vitamin D metabolite determination utilizing mass spectrometry following derivatization
US9535077B2 (en) 2009-12-03 2017-01-03 Quest Diagnostics Investments Incorporated Vitamin D metabolite determination utilizing mass spectrometry following derivatization
US8034627B2 (en) 2009-12-03 2011-10-11 Quest Diagnostics Investments Incorporated Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
US10429398B2 (en) 2009-12-03 2019-10-01 Quest Diagnostics Investments Incorporated Vitamin D metabolite determination utilizing mass spectrometry following derivatization
US9506937B2 (en) 2009-12-11 2016-11-29 Quest Diagnostics Investments Incorporated Mass spectrometry of steroidal compounds in multiplexed patient samples
US9034653B2 (en) 2009-12-11 2015-05-19 Quest Diagnostics Investments Inc. Mass spectrometry of steroidal compounds in multiplexed patient samples
EP3306640A1 (en) * 2010-12-20 2018-04-11 Shimadzu Corporation Time-of-flight mass spectrometer
US9136100B2 (en) 2011-10-21 2015-09-15 Shimadzu Corporation ToF mass analyser with improved resolving power
US10147591B2 (en) 2015-02-03 2018-12-04 Auckland Uniservices Limited Ion mirror, an ion mirror assembly and an ion trap
US9761430B2 (en) 2015-02-04 2017-09-12 Bruker Daltonik Gmbh Fragment ion mass spectra measured with tandem time-of-flight mass spectrometers
GB2536776A (en) * 2015-02-04 2016-09-28 Bruker Daltonik Gmbh Method for measurement of fragment ion mass spectra with tandem time-of-flight mass spectrometers

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