Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
Applicant elected Group I and Species (ii) without traverse. Species (ii) is directed towards Figs. 13-18 illustrating an OrbitrapTM mass analyser, defined by the specifications as an electrostatic orbital mass analyser: “an electrostatic orbital mass analyser, such as an OrbitrapTM mass analyser.” Therefore, claims 8-13 will not be considered, given they are directed to a time-of-flight mass analyser.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 16 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 16 recites the limitation "the first and second ion guides" in line 2. There is insufficient antecedent basis for this limitation in the claim. The specifications of the present disclosure state “ion traps may be supplied with ions via a branched ion guide, such as a branched RF ion guide.” For the purposes of examination, the "the first and second ion guides" will be interpreted to mean the first and second ion traps.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 5, 7 and 17-18 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Alexander Alekseevich Makarov (WO 2013092923), hereinafter referred to as Makarov.
Regarding claim 1, Makarov teaches a method of operating an analytical instrument that comprises: a mass analyser (mass analyser 50);
a first ion trap coupled to the mass analyser (fragmentation cell chambers 41);
and a second ion trap coupled to the mass analyser (fragmentation cell chambers 42);
the method comprising: operating the first ion trap in a mode of operation in which the first ion trap confines ions having mass-to-charge ratios within a first m/z range, and storing first ions in the first ion trap (the first stage of mass analysis 20 ejects precursor ions. Ions of different mass to charge ratios, m/z, emerge from the first stage of mass analysis at different moments in time, or separate in time of flight downstream of the first stage of mass analysis. In either case, precursor ions of different mass to charge ratios arrive at a rastering device 30 such as an ion deflector at different times. The rastering device 30 deflects precursor ions with mass to charge ratios m-i , nri2 ... ITIN into corresponding chambers 1 , 2 ... N of a fragmentation cell 40. Each mass to charge ratio mi , .Math.τ^ ... ITIN represents a single ion species having a single mass to charge ratio, or alternatively a range of precursor ions having a commensurate range of mass to charge ratios (page 7, lines 10-20));
operating the second ion trap in a mode of operation in which the second ion trap confines ions having mass-to-charge ratios within a second different m/z range, and storing second ions in the second ion trap (the first stage of mass analysis 20 ejects precursor ions. Ions of different mass to charge ratios, m/z, emerge from the first stage of mass analysis at different moments in time, or separate in time of flight downstream of the first stage of mass analysis. In either case, precursor ions of different mass to charge ratios arrive at a rastering device 30 such as an ion deflector at different times. The rastering device 30 deflects precursor ions with mass to charge ratios m-i , nri2 ... ITIN into corresponding chambers 1 , 2 ... N of a fragmentation cell 40. Each mass to charge ratio mi , .Math.τ^ ... ITIN represents a single ion species having a single mass to charge ratio, or alternatively a range of precursor ions having a commensurate range of mass to charge ratios (page 7, lines 10-20));
ejecting the first ions from the first ion trap into the mass analyser (ions in any one of the fragmentation cell chambers can be ejected, independently of the others and without the need to pass ions through any other fragmentation cell chambers, via the fragmentation cell ion exit, to a second stage mass analyser 50 (page 13, lines 18-21));
ejecting the second ions from the second ion trap into the mass analyser (ions in any one of the fragmentation cell chambers can be ejected, independently of the others and without the need to pass ions through any other fragmentation cell chambers, via the fragmentation cell ion exit, to a second stage mass analyser 50 (page 13, lines 18-21));
and mass analysing the first ions and the second ions, wherein a combination of the first and second m/z ranges provides a wider m/z range than any one of the first and second m/z ranges alone (The second stage mass analyser 50 collects and detects the fragment ions and any remaining precursor ions which are ejected to it from the individual fragmentation cell chambers within the fragmentation cell 40 (page 13, lines 24-27)).
The fragmentation chambers each hold ions with different mass to charge ratios or a different range of mass to charge ratios, therefore the combination of first and second m/z ratios provides a wider m/z range than any one of the first and second m/z ranges alone.
Regarding claim 2, Makarov teaches the method of claim 1, wherein the instrument further comprises a third ion trap coupled to the mass analyser (fragmentation cell chamber 43),
and wherein the method further comprises: operating the third ion trap in a mode of operation in which the third ion trap confines ions having mass-to-charge ratios within a third different m/z range, and storing third ions in the third ion trap (Thus, for example, ions with a first mass to charge ratio ΙΓΗ may be directed by the rastering device 30, under the control of the controller 60, to a first of the fragmentation cell chambers 41. Ions of a second mass to charge ratio nri2, arriving at the rastering device 30 at different time to the ions of mass to charge ratio ΙΓΗ, may be directed to the second fragmentation cell chamber 42, and so forth (page 12, lines 26-28));
ejecting the third ions from the third ion trap into the mass analyser (ions in any one of the fragmentation cell chambers can be ejected, independently of the others and without the need to pass ions through any other fragmentation cell chambers, via the fragmentation cell ion exit, to a second stage mass analyser 50 (page 13, lines 18-21));
and mass analysing the third ions, wherein the combination of the first, second and third m/z ranges collectively provides a wider m/z range than the combination of the first and second m/z ranges alone (The second stage mass analyser 50 collects and detects the fragment ions and any remaining precursor ions which are ejected to it from the individual fragmentation cell chambers within the fragmentation cell 40 (page 13, lines 24-27)).
The fragmentation chambers each hold ions with different mass to charge ratios or a different range of mass to charge ratios, therefore the combination of first and second m/z ratios provides a wider m/z range than any one of the first and second m/z ranges alone.
Regarding claim 3, Makarov teaches the method of claim 1, wherein the first and second m/z ranges are non- overlapping (In one embodiment, for example, the controller 60 may control the rastering device 30 to direct precursor ions of only a single ion species/mass to charge ratio into a respective separate one of the multiple fragmentation cell chambers lines (page 17, lines 18-21)).
Regarding claim 5, Makarov teaches the method of claim 1, further comprise separating ions according to their m/z before the ions are stored in the first ion trap and/or the second ion trap (The rastering device 30 deflects precursor ions with mass to charge ratios m-i , nri2 ... ITIN into corresponding chambers 1 , 2 ... N of a fragmentation cell 40. Each mass to charge ratio mi , .Math.τ^ ... ITIN represents a single ion species having a single mass to charge ratio, or alternatively a range of precursor ions having a commensurate range of mass to charge ratios (page 7, lines 10-20)).
Regarding claim 7, Makarov teaches the method of claim 1, wherein the mass analyser is an electrostatic ion trap mass analyser (The second stage (external) mass analyser 50 may, as with the arrangement of Figures 1 and 2, be a high resolution mass analyser such as an orbital electrostatic trap (page 13, lines 21-23)).
Regarding claim 17, Makarov teaches the method of claim 1, wherein the instrument further comprises: one or more first deflectors arranged downstream of the first and second ion traps (Fig. 4 as annotated below),
and one or more second deflectors arranged downstream of the one or more first deflectors (Fig. 4 as annotated below);
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wherein the one or more first deflectors are configured to cause ions ejected from the first and second ion traps to travel to the one or more second deflectors (After that, the ions are accelerated by applying a voltage between the exit aperture of a particular fragmentation cell chamber 41, 42 ... 43 and its exit deflector 91 , 92 ... 93. Ions leave the exit deflector of a particular fragmentation cell chamber where they pass across a second differentially pumped volume 95 (Figure 4) as they are directed by the exit deflector to arrive at an exit deflector 90 arranged within or adjacent to the exit aperture of the fragmentation cell 40 (page 14, lines 18-23));
and wherein the one or more second deflectors are configured to direct ions into the mass analyser and/or to direct ions along an ion path of the mass analyser (Fig. 5 as annotated below).
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Regarding claim 18, the method of claim 17, wherein the one or more second deflectors comprises a single deflector (Fig. 5 as annotated below), and wherein the method comprises applying a first voltage to the second deflector when the second deflector receives ions from the first ion trap, and applying a second different voltage to the second deflector when the second deflector receives ions from the second ion trap.
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Ion traps 41 and 42 house ions of different mass to charge ratios. Applying a different voltage to deflector 90 in order to guide ions of different mass to charge ratios to the mass analyser 50 is inherent to Makarov. Without adjusting the voltage of deflector 90, directing ions to mass analyser 50 could not be achieved.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Makarov, and in further view of Dirk Nolting (US 20200294784), hereinafter referred to as Nolting.
Regarding claim 4, Makarov teaches the method of claim 1, wherein: operating the first ion trap in the mode of operation in which the first ion trap confines ions having mass to charge ratios within the first m/z range (Thus, for example, ions with a first mass to charge ratio ΙΓΗ may be directed by the rastering device 30, under the control of the controller 60, to a first of the fragmentation cell chambers 41. Ions of a second mass to charge ratio nri2, arriving at the rastering device 30 at different time to the ions of mass to charge ratio ΙΓΗ, may be directed to the second fragmentation cell chamber 42, and so forth (page 12, lines 26-28)) comprises applying to the first ion trap a first RF voltage having a first amplitude and a first frequency (Each of the fragmentation cell chambers 41 ... 43 is preferably formed of an RF- only multipole filled with collision gas).;
And operating the second ion trap in the mode of operation in which the second ion trap confines ions having mass to charge ratios within the second different m/z range comprises applying to the second ion trap a second RF voltage having a second amplitude and a second frequency (Each of the fragmentation cell chambers 41 ... 43 is preferably formed of an RF- only multipole filled with collision gas);
Makarov fails to explicitly teach wherein the second amplitude is different to the first amplitude; and/or wherein the second frequency is different to the first frequency.
However, Nolting teaches teach wherein the second amplitude is different to the first amplitude; and/or wherein the second frequency is different to the first frequency (applying a first RF trapping amplitude to the ion trapping assembly, so as to trap introduced ions which have m/z ratios within a first range of m/z … (e) trapping, at the second, lower RF trapping amplitude, introduced ions having m/z ratios within a second range of m/z ratios (para. [0011])).
Both Makarov and Nolting teach trapping ion with different m/z ranges. Nolting teaches trapping ions of different m/z ranges by using two different RF amplitudes. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Nolting into Makarov by changing the amplitude of the RF voltage in order to trap ions of different m/z ranges. Different amplitudes of the RF voltage allow for the trapping of different species of ions.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Makarov, and in further view of Viatcheslav V. Kovtoun (US 20150287585), hereinafter referred to as Kovtoun, and Zheng Ouyang (US 6838666), hereinafter referred to as Ouyang.
Regarding claim 6, Makarov teaches the method of claim 1, wherein:
each ion trap has a trap axis (Fig. 4 as annotated below),
a trap axis of the first trap is aligned with a trap axis of the second trap (Fig. 4 as annotated below);
[AltContent: arrow][AltContent: arrow][AltContent: textbox (a trap axis of the first trap is aligned with a trap axis of the second trap (axis are parallel))]
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and then cooling the first ions in the first ion trap, and cooling the second ions in the second ion trap (Each of the fragmentation cell chambers 41 ... 43 is preferably formed of an RF- only multipole filled with collision gas. The chambers function not only to fragment ions, but also to ensure collisional cooling of the fragments (Page 9, para. [25-27]));
Makarov fails to teach and wherein ions stored in each ion trap are ejected into the mass analyser in an extraction direction orthogonal to the trap axis; an extraction direction of the first trap is parallel to an extraction direction of the second trap; and the instrument further comprises an array of trapping regions upstream of the first and second ion traps, and wherein the method comprises: storing the first ions in a first trapping region of the array of trapping regions, and storing the second ions in a second trapping region of the array of trapping regions; transferring the first ions from the first trapping region to the first ion trap, and transferring the second ions from the second trapping region to the second ion trap;
However, Ouyang teaches wherein ions stored in each ion trap are ejected into the mass analyser in an extraction direction orthogonal to the trap axis (Fig. 21 as annotated below);
an extraction direction of the first trap is parallel to an extraction direction of the second trap (Fig. 21 as annotated below);
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It would have been obvious to one of ordinary skill in the art to modify the device described in Makarov to include the teachings of Ouyang so as to allow the ions stored in each ion trap to be extracted in a direction orthogonal to the trap axis such that the extraction direction of the first trap is parallel to the extraction direction of the second trap. When the extraction direction is orthogonal to the trap axis, traps can be aligned in both series of parallel or a combination thereof while still achieving ion transfer between the traps (Ouyang; col. 2, lines 57-63).
Finally, Kovtoun teaches and the instrument further comprises an array of trapping regions upstream of the first and second ion traps (Fig. 3 as annotated below),
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and wherein the method comprises: storing the first ions in a first trapping region of the array of trapping regions, and storing the second ions in a second trapping region of the array of trapping regions (Each different ion group, which occupies a 20-40 Th wide approximate m/z window, is depicted at a location within the ion separator 104 that is adjacent to one of the N storage cells of ion storage array 106. The electric field in the separator 104 is switched off at this point, and an orthogonal electric field is established to drive the different ion groups out of the separator 104 and into a respective one of the N storage cells of the ion storage array 106 (para. [0037]));
Ions are separated into groups depending on their m/z value and then distributed to respective storage cells.
transferring the first ions from the first trapping region to the first ion trap, and transferring the second ions from the second trapping region to the second ion trap (Referring still to FIG. 3, ions that are released from the 1.sup.st-N.sup.th storage cells of the ion storage array 106 are received by the first ion transport device 308. … After passing through the vacuum interface 310, each different ion group is directed to predetermined ion trap 314 of the ion trap array 114 (para. [0041]));
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Makarov to include the teachings of Kovtoun by having the first and second ions enter respective storage cells 106, as taught by Kovtoun, before transferring the first ions to the first trapping region and the second ions to the second trapping regions (Makarov; fragmentation cell chambers 41 and 42). Storage cell arrays 106 allow ions to accumulate to a desired number before being transferred to the next trap or to the mass analyser.
Claims 14 is rejected under 35 U.S.C. 103 as being unpatentable over Makarov, and in further view of Ouyang.
Regarding claim 14, Makarov teaches the method of claim 1, wherein: each ion trap has a trap axis each ion trap has a trap axis (Fig. 4 as annotated below),
a trap axis of the first trap is parallel to a trap axis of the second trap (Fig. 4 as annotated below);
an extraction direction of the first trap is aligned with an extraction direction of the second trap (Fig. 4 as annotated below);
[AltContent: textbox (a trap axis of the first trap is parallel to a trap axis of the second trap;
an extraction direction of the first trap is aligned with an extraction direction of the second trap)][AltContent: arrow][AltContent: arrow][AltContent: arrow][AltContent: arrow][AltContent: arrow]
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and the first ion trap and the second ion trap are coupled to the mass analyser via the same set of one or more ion optical devices (Once ions from the fragmentation cell chamber 41 have entered the curved linear trap 70, they are stored along a curved axis and pulsed out into the mass analyser 50. The process is described in WO-A-05/124,821. After that, the DC offset on the rods 61 is raised, for example, to 10 volts, and the DC offset on the rods 62 is lowered, for example, to ground potential. The DC offset on the rods 63 ... is kept high (for example, 20-30 volts), so that ions from the fragmentation cell chamber 42 are then forced into the fragmentation cell chamber 41 by the resulting transverse electric field created by the potential difference. This sequence is repeated across the entire parallel array of ion traps constituted by the N fragmentation cell chambers 41 ... 43 (page 11; lines 6-16)) (Fig. 2b as annotated below).
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Makarov fails to teach and wherein ions stored in each ion trap are ejected into the mass analyser in an extraction direction orthogonal to the trap axis;
However, Ouyang teaches wherein ions stored in each ion trap are ejected into the mass analyser in an extraction direction orthogonal to the trap axis (Fig. 23 as annotated below);
an extraction direction of the first trap is aligned with an extraction direction of the second trap (Fig. 23 as annotated below);
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To be clear Ouyang teaches ion traps for ion transfer between traps in the x, y or z direction. The benefit of such traps is they can be “arranged in series or parallel or a combination thereof (col. 2, lines 60-61)” It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Makarov to include the teachings of Ouyang such that the first and second ion traps allow for extraction in the x, y or z direction such that the ions are extracted in a direction orthogonal to the trap axis to be ejected into the mass analyser.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Makarov and Ouyang, as applied to claim 14 above, and in further view of Bruce B. Reinhold (US6483109), hereinafter referred to as Reinhold.
Regarding claim 15, Reinhold teaches the method of claim 14, wherein the instrument comprises a lens arranged between the first ion trap and the second ion trap (Fig. 4B as annotated below).
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It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Makarov to include the teachings of Reinhold by placing a lens between the first and second ion trap. Doing so facilitates the transfer of ions from one trap to the other.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Makarov, Ouyang, and Reinhold, as applied to claim 15 above, and in further view of Kovtoun.
Regarding claim 16, Makarov fails to teach the method of claim 14, wherein the instrument further comprises a branched ion guide configured to supply the first and second ion guides with ions.
However, Kovtoun teaches wherein the instrument further comprises a branched ion guide configured to supply the first and second ion guides with ions (Branched radio frequency multipole system 100).
In Makarov, the ions are directed to the first and second ion trap using rastering device 30. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Makarov to include the teachings of Kovtoun by replacing the rastering device 30 with the branched radio frequency multipole system 100. Branched ion guides are known to one of ordinary skill in the art to improve transmission efficiency.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Makarov, as applied to claim 1 above, and in further view of John Lawrence Campbell (US 20140264009), hereinafter referred to as Campbell.
Regarding claim 19, Makarov teaches the method of claim 1, wherein the mass analyser is an electrostatic ion trap mass analyser (The second stage (external) mass analyser 50 may, as with the arrangement of Figures 1 and 2, be a high resolution mass analyser such as an orbital electrostatic trap (page 13, lines 21-23)),
Makarov fails to teach and wherein the ion trap mass analyser comprises: a first entrance aperture, and a second entrance aperture; a first entrance deflector arranged adjacent to the first entrance aperture, and a second entrance deflector arranged adjacent to the second entrance aperture;
wherein the first entrance deflector is configured to direct ions from the first ion trap into the ion trap mass analyser via the first entrance aperture; and wherein the second entrance deflector is configured to direct ions from the second ion trap into the ion trap mass analyser via the second entrance aperture.
However, Campbell teaches wherein the ion trap mass analyser comprises: a first entrance aperture, and a second entrance aperture (Fig. 1 as annotated below);
a first entrance deflector arranged adjacent to the first entrance aperture, and a second entrance deflector arranged adjacent to the second entrance aperture (Fig. 1 as annotated below);
wherein the first entrance deflector is configured to direct ions from the first ion trap into the ion trap mass analyser via the first entrance aperture; and wherein the second entrance deflector is configured to direct ions from the second ion trap into the ion trap mass analyser via the second entrance aperture (The sample ions pass through a first ion inlet 26 and a second ion inlet 28).
Inlets 26 and 28, taught by Campbell are configured to receive different ion species. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Makarov to incorporate the teachings of Campbell by replacing the deflector 90 and the inlet to the mass analyser 50, with the first and second entrance apertures 26 and 28, and their respective deflectors 18, such that the first entrance deflector directs ions from the first ion trap into the ion trap mass analyser via the first entrance aperture, and the second entrance deflector directs ions from the second ion trap into the ion trap mass analyser via the second entrance aperture. With two apertures and two separate deflectors, and when only two ion species are being analysed, the voltage on the deflectors does not need to be adjusted for a new species.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICA J. EINHORN whose telephone number is (571)272-4641. The examiner can normally be reached Mon-Fri. 7:30am-5pm.
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/MICA JILLIAN EINHORN/Examiner, Art Unit 2881
/WYATT A STOFFA/Primary Examiner, Art Unit 2881