DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of species I, subspecies i in the reply filed on 12 March 2026 is acknowledged. The traversal is on the ground(s) that that the office has not demonstrated separate status in the art due to their different classification, divergent subject matter, different field of search different classes/subclasses.. This is not found persuasive because the MR-TOF MS is divergent from ion mobility in that TOF measures m/z ratio by their flight time vs the ion mobility which measures an ions mobility. As evidenced in at least Yamaguchi below no ion mobility spectrometry is suggested, nor would it appear obvious to apply the method of Yamaguchi to an IMS. Moreover, MR-TOF performs multiple reflections to separate the ions and classified in CPC symbols (H01J49/406), whereas cyclic TOF MS is classified in H01J49/408 whereas ion mobility separators are classified in G01N27/622. Moreover, the structural differences between the various MR-TOF devices disclosed requires different search strings. For instance GB2580089 has parallel ion mirrors (see for instance figure 16), whereas US9136101 has nonparallel ion mirrors. The instant specification discloses both however a reference reading on a claimed parallel arrangement would unlikely read on a claimed non-constant arrangement. Moreover, the tandem IMS/MS arrangement is separately classified in G01N27/623. Cyclic IMS would require searching both of H01J49/408 and G01N27/622.
The method of figure 7 is disclosed to be distinct from the method of figure 6. Specifically, the published specification teaches “In respect of each candidate value of N (step 72), for each peak a candidate m/z value is calculated (step 73). Thus, a list of the possible m/z values for each ion peak of interest is generated. Matching pairs of ion peaks between the two spectra are then identified to determine the accurate N for each pair of corresponding ion peaks (step 74). Finally, the unambiguous m/z of each matching pair of ion peaks is determined and assigned to each ion peak (step 75).” ([0179]).
This is divergent from figure 6 which assigns a number of passes to each peak as equation in step 62 to calculate a true m/z ratio. It is noted that as evidenced by Yamaguchi below, the elected group I (fig. 6) is anticipated by Yamaguchi, however Yamaguchi is silent with respect to candidate number of passes (fig. 7), demonstrating that group I and group II contain divergent subject matter that would require additional search strings to identify the candidate number.
It is noted that the subspecies elected (i) covers cyclic TOF. Paragraph [0114] recites “figs. 3-5 illustrate various exemplary embodiments of the cyclic analyzer 30”. Figures 3-5 are directed towards different MR-TOF mass spectrometers. Therefore, due to this oversight the elected subspecies is inclusive of figs. 3-5 (species iii-v). Therefore, claims directed towards figures 3-5 will be examined herewith.
However, the ion mobility spectrometer of sub species ii, the tandem cIMS/MS of species vi, the post deflector arrangement to the MR-TOF (fig. 8/sub species vii) and the additional of a flight tube (species viii) would require substantial search burden. Specifically, as discussed above IMS has an entirely different structure and analytical process for TOF-MS as evident from the separate CPC symbols. Additionally, placing a detector after the analyser is divergent from the detector being on the same side (see as evidence references below teaching detectors on the same side to perform multiple analysis) therefore additional search strings would be required to find references for species (vii) and (viii).
A few notes, the election will be treated to cover group I and subspecies group (i), which by oversight covers sub-species (iii)-(v). However, subspecies (ii) directed towards a separate classification (see above), subspecies vi directed towards a tandem configuration (separately classified), subspecies vii directed towards divergent subject matter (different placement of detector after analyzer) and modification (viii) would require search burden to find any potential claim requirement.
The elected claims are broad enough to read on species of group I and sub-species of group I, with the exception of claim 10. Claim 10 will be treated remains withdrawn.
The requirement is still deemed proper and is therefore made FINAL.
Claim Rejections - 35 USC § 102
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 1-2 and 11-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yamaguchi (US20060219890) as evidenced by Yamaguchi (JP2006012747) (copy of publication and machine translation submitted herewith)(herein ‘747).
Regarding claim 1, Yamaguchi teaches a method of operating an analytical instrument (fig. 7) that comprises an ion analyser (fig. 1, for example, however paragraph [0065] teaches the present invention can be applied to various forms of TOF MS proposed in patent document 2, see paragraph [0006] citing ‘747. Figure 12 of ‘747 is the ion analyzer relied upon for the claimed structure) configured to analyse ions by determining drift times of ions along an ion path (inherent to TOF-MS), the ion path comprising at least a first segment (Fig. 12 of ‘747 shows an electrostatic analyzer 19 as the first segment), and a cyclic segment (fig. 12 of ‘747 shows the cyclic element 2 as circular orbit A), wherein the ion path is configured such that ions make a single pass of the first segment (single pass of 19 as seen in figure 12 of ‘747) and make one or more passes of the cyclic segment (inherent to circular orbit “A” of figure 12); the method comprising:
operating the analyser in a first mode of operation (Yamaguchi, s1, paragraph [0056] teaches first mode of operation applying a voltage to reflector. Paragraph [0065] teaches “ it is possible to use a different method for changing the flight distance in place of the one described in the embodiments” by using the deflector. [0044] of ‘747 teaches the incident flight path distance is changed by changing the voltage applied to 19. Thus Yamaguchi envisioned applying the same method S1 to the analyzer of figure 12 in ‘747), wherein in the first mode of operation (i) a first electric potential is provided along the first segment of the ion path (voltage applied to 19 before change in figure 12 and [0044] of ‘747), (ii) a second electric potential is provided along the cyclic segment of the ion path (voltage applied to pass ions through orbital loop 2 in figure 12. Note paragraph [0023] of ‘747 teaches a voltage applied to electrodes achieve the circular orbit A), (iii) the first segment of the ion path has a first path length (‘747, [0044] flight distance of ions through 19 before change), and (iv) the cyclic segment of the ion path has a second path length (the path length of ions through circular orbit “A” of 2), and analysing ions by determining drift times of ions along the ion path so as to obtain a first set of ion data (Yamaguchi [0056], collect first spectrum data under first condition, see paragraph [0065] which suggests applying the method to the TOF-MS disclosed in ‘276);
operating the analyser in a second mode of operation by altering at least one of (i) the first electric potential, (iii) the first path length, (paragraph [0044] of ‘276. Note this change to flight distance is envisioned by paragraph [0065] of Yamaguchi), and analysing ions by determining drift times of ions along the ion path so as to obtain a second set of ion data (Yamaguchi [0056], collect second round of measurement data under second condition (i.e. higher voltage to reflector, however envisioned different TOF-MS, thus change of voltage to electrostatic analyzer 19 of ‘747));
comparing the first set of ion data to the second set of ion data ([0055] of Yamaguchi comprising the two flight time spectrums obtained through the first round of measurement and second round of measurement ), and identifying a first ion peak in the first set of ion data that corresponds to a second ion peak in the second set of ion data ([0057]);
determining the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks ([0059]); and
using the determined number of passes N to determine a value of a physicochemical property of the ions associated with the corresponding first and second ion peaks ([0059] with the number of turns, data processor recalculates the exact mm/z of each ion on the basis of the flight time calculated using the number of turns, wherein the number of turns is determined by the corresponds of the beams of two flight time spectrums.).
Regarding claim 2, Yamaguchi teaches wherein the ion analyser is a time-of-flight (ToF) mass analyser (abstract), and wherein the physicochemical property is mass to charge ratio (m/z) ([0059]).
Regarding claim 11, Yamaguchi teaches wherein the method comprises altering the first electric potential in the second mode of operation (as evidenced by ‘747, paragraph [0044]).
Regarding claim 12, Yamaguchi teaches wherein the instrument further comprises a flight tube arranged along at least part of the first segment of the ion path (‘747, Linb is a flight distance, see paragraph [0044]), and wherein the method comprises altering the first electric potential in the second mode of operation by altering a voltage applied to the flight tube (‘747, see paragraph [0044]).
Regarding claim 13, Yamaguchi teaches wherein the ion analyser comprises an ion injector (‘747 electrostatic analyzer) configured to accelerate ions along the ion path (via change in direction, the ions are accelerated as an acceleration is a vector), and wherein the method comprises altering the first electric potential in the second mode of operation by altering an acceleration field provided by the ion injector for accelerating ions along the ion path ([0065] of Yamaguchi teaches changing potential in any of the TOF described in ‘747. ‘747 teaches a change of potential of the electrostatic accelerator, see paragraph [0044]).
Regarding claim 14, Yamaguchi teaches wherein determining the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks comprises: measuring a drift time difference between first and second ion peaks ([0059] flight time difference); and using the measured drift time difference to estimate the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks (the flight time difference is used to approximate m/z to determine number of turns. Since the m/z value is approximate, the number of turns is an estimate).
Regarding claim 15, Yamaguchi teaches a non-transitory computer readable storage medium storing computer software code which when executed on a processor performs the method of claim 1 (figure 2, data processor 7, see paragraph [0057]-[0059]).
Regarding claim 16, Yamaguchi teaches A control system for an analytical instrument, the control system configured to cause the analytical instrument to perform the method of claim 1 (data processor 7 and controller 8, applied to the distance controller of ‘747, see paragraph [0065]).
Claim 17 is a combination of claims 1 and 16 and is anticipated as discussed herein above.
Claim Rejections - 35 USC § 103
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.
Claims 1-7 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Wildgoose (US pgPub 2024/0339314) in view of Yamaguchi as evidenced by ‘747.
Regarding claim 1, Wildgose teaches a method of operating an analytical instrument (inherent to the apparatus of figure 3) that comprises an ion analyser (inherent) configured to analyse ions by determining drift times of ions along an ion path ([0088]), the ion path comprising at least a first segment (14), and a cyclic segment (ion mirrors 10), wherein the ion path is configured such that ions make a single pass of the first segment (14 is an accelerator) and make one or more passes of the cyclic segment ([0088]); the method comprising:
operating the analyser in a first mode of operation, wherein in the first mode of operation ([0088] detecting at detector 16 when 22 is deactivated) (i) a first electric potential is provided along the first segment of the ion path (potential applied to accelerator 14 to pulse packets ([0087]), paragraph [0065] describes this as a first/second mode), (ii) a second electric potential is provided along the cyclic segment of the ion path (voltages applied to ion mirrors), (iii) the first segment of the ion path has a first path length (inherent to accelerator), and (iv) the cyclic segment of the ion path has a second path length (from first end of mirror to second end of mirror and returning to ion detector 16 [0087]-[0087]), and analysing ions by determining drift times of ions along the ion path so as to obtain a first set of ion data (inherent to TOF MS);
operating the analyser in a second mode of operation (activating reflector 20 so as to reflect ions back towards the second end of mass analzyer 8, see paragraph [0088]) by altering at least one of the second path length (activating reflector 20 to increase the flight path see paragraph [0088]), and analysing ions by determining drift times of ions along the ion path so as to obtain a second set of ion data (by deactivating deflector 20 to detect data).
Wildgoose fails to disclose comparing the first set of ion data to the second set of ion data, and identifying a first ion peak in the first set of ion data that corresponds to a second ion peak in the second set of ion data; determining the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks; and using the determined number of passes N to determine a value of a physicochemical property of the ions associated with the corresponding first and second ion peaks.
However, Yamaguchi teaches comparing the first set of ion data to the second set of ion data ([0055] of Yamaguchi comparing the two flight time spectra obtained through the first round of measurement and second round of measurement ), and identifying a first ion peak in the first set of ion data that corresponds to a second ion peak in the second set of ion data ([0057]);
determining the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks ([0059]); and
using the determined number of passes N to determine a value of a physicochemical property of the ions associated with the corresponding first and second ion peaks ([0059] with the number of turns, data processor recalculates the exact mm/z of each ion on the basis of the flight time calculated using the number of turns, wherein the number of turns is determined by the corresponds of the beams of two flight time spectrums.).
Yamaguchi modifies Wildgoose by suggesting the use of the data from two different modes of operation with different flight paths (abstract, [0065]) to improve identify all peaks even in situations of samples containing may components.
Since both inventions are directed towards TOF-MS and operating in two modes (note Wildgoose describes the operation of paragraph [0088] as a first and second mode see paragraph [0065]), it would have been obvious to one of ordinary skill in the art to use the data analysis suggested in Yamaguchi in the method of Wildgoose because it would improve identification of all peaks in situations of samples containing many components (abstract). Note, Yamaguchi suggested the method is applicable to any changes in flight distance ([0065]), thus suitable for the device of Wildgoose.
Regarding claim 2, Wildgoose teaches wherein the ion analyser is a time-of-flight (ToF) mass analyser, and wherein the physicochemical property is mass to charge ratio (m/z) ([0086]).
Regarding claim 3, Wildgoose teaches wherein the time-of-flight mass analyser is a multi-reflection time-of-flight (MR-ToF) mass analyser (fig. 3) comprising:
two ion mirrors (10) spaced apart and opposing each other in a first direction X (fig. 3, 10 spaced apart in the x direction), each mirror elongated generally along a drift direction Y between a first end and a second end (fig. 3, shows mirrors 10 elongated along a drift direction), the drift direction Y being orthogonal to the first direction X (x (between mirrors) is orthogonal to y direction along mirrors);
an ion injector (accelerator 14) for injecting ions into a space between the ion mirrors (as seen in figure 3), the ion injector located in proximity with the first end of the ion mirrors (located in proximity to the left end of mirrors best seen in figure 3); and a detector (16) for detecting ions after they have completed a plurality of reflections between the ion mirrors (as seen in figure 3), the detector located in proximity with the first end of the ion mirrors (16 is in proximity with the same left side of mirrors 10).
Regarding claim 4, Wildgoose teaches wherein the analyser is configured to analyse ions by:
(i) injecting ions from the ion injector into the space between the ion mirrors (via accelerator 14), wherein the ions complete a first cycle in which the ions follow a zigzag ion path (from 14 to 22, see paragraph [0087]) between the ion mirrors in the direction X whilst (reflection between mirror 10 thus x direction):
(a) drifting along the drift direction Y towards the second end of the ion mirrors (drifting from 20 to 22 as seen in figure 3),
(b) reversing drift direction velocity in proximity with the second end of the ion mirrors (reversing by reversing deflector 22 back to first end see paragraph [0087], since the direction is reversed, the direction velocity is reversed),
and (c) drifting back along the drift direction Y towards the first end of the ion mirrors ([0087])
(ii) reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors (fig. 3, 20 via activating reflector 20 ions are reflected back towards the second end of mass analyzer 8 ([0088]), which comprises to ion mirrors 10) such that the ions are caused to complete a further cycle in which the ions follow a zigzag ion path having plural K reflections between the ion mirrors in the direction X (fig. 3 shows zigzag ion path, [0088], x direction interpreted to be between ion mirrors 10) whilst: (a) drifting along the drift direction Y towards the second end of the ion mirrors (y direction is from 20 to 22 see paragraph [0088] for reflection between mirrors in the above described mirror, paragraph [0087] teaches reflecting between mirrors as they drift in the z direction (i.e. equivalent to the claimed y direction)), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors ([0088] repeating the manner disclosed in paragraph [0087], which requires in part ions are reflected at the second end of the mass analyzer by the second reflector back towards the first end. That is, requiring reversing the drift direction velocity because velocity is a vector, thus any reversal of direction is a reversal of velocity), and (c) drifting back along the drift direction Y towards the first end of the ion mirrors (reversal drift the same manner as in the first direction, see paragraph [0087]-[0088]);(iii) repeating step (ii) one or more times ([0088] suggests either deactivate detector to allow detection or maintain in active state for additional cycle); and then (iv) causing the ions to travel to the detector for detection ([0088]).
Claim 5 further requires the use of a deflector in proximity with the first end of the ion mirrors to perform the claimed reversal to complete additional cycles. Wildgoose suggests using a deflector (reflector 20) in proximity with the first end (left side of mirrors 10 in figure 3) for additional cycles as discussed above in claim 4.
Regarding claim 6, Wildgoose teaches wherein the method comprises altering the second path length in the second mode of operation by altering the number K of reflections that ions make between the ion mirrors when following the zigzag ion path ([0088] which teaches either detecting ions when they return to 16 (first mode) by deactivating reflector 20 or continue back towards 22 for additional flight distance by oscillations between mirrors 10, thus altering the number of reflections between ion mirrors).
Regarding claim 7, Wildgoose teaches wherein the number K of reflections that ions make between the ion mirrors when following the zigzag ion path is altered by altering a voltage applied to the deflector ([0088], activating or deactivating reflector. Paragraph [0089] teach voltages are applied to reflectors 20/22).
Regarding claim 16, Wildgoose in view of Yamaguchi teaches a control system for an analytical instrument, the control system configured to cause the analytical instrument to perform the method of claim 1 (Wildgoose teaches control circuitry to control the activation of reflector 20/22 as modified by Yamaguchi control system claim 16 above).
Claim 17 is a combination of claims 1 and 16 and is obvious as discussed herein above.
Regarding claim 18, Wildgoose teaches wherein the ion analyser is a time-of-flight (ToF) mass analyser, and wherein the physicochemical property is mass to charge ratio (m/z) ([0086], inherent to TOF).
Claim 19 is a combination of claims 3 and 4 and is taught as in the citations herein above.
Regarding claim 20, Wildgoose teaches a deflector located in proximity with the first end of the ion mirrors and wherein reversing the drift direction velocity of the ions includes using the deflector to reverse the drift velocity of the ion ([0088]-[0099])
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Yamaguchi as evidenced by ‘747 in view of Grinfeld (USPN 9,136,101) or Stewart (GB2580089) (copy of publication submitted herewith) or Wildgoose (US pgPub 2024/0339314)
Regarding claim 3, while Yamaguchi as evidence by ‘747teaches a large number of TOF-MS, including orbiting (fig. 12 of ‘747) and reciprocal between two reflectors (figures 6 and 13 of ‘747). Yamaguchi fails to expressly suggest, herein the time-of-flight mass analyser is a multi-reflection 30 time-of-flight (MR-ToF) mass analyser comprising: two ion mirrors spaced apart and opposing each other in a first direction X, each mirror elongated generally along a drift direction Y between a first end and a second end, the drift direction Y being orthogonal to the first direction X; an ion injector for injecting ions into a space between the ion mirrors, the ion injector located in proximity with the first end of the ion mirrors; and a detector for detecting ions after they have completed a plurality of reflections between the ion mirrors, the detector located in proximity with the first end of the ion mirrors.
However, Grinfeld et al. teach wherein the time-of-flight mass analyser is a multi-reflection time-of-flight (MR-ToF) mass analyser (fig. 11a-11b) comprising:
two ion mirrors (71 and 72) spaced apart and opposing each other in a first direction X (fig. 11a, 71 and 72 spaced apart and opposing each other in the x direction), each mirror elongated generally along a drift direction Y between a first end and a second end (fig. 11a, 7/72 elongated in a drift y direction), the drift direction Y being orthogonal to the first direction X (x is orthogonal to y as seen in figure 11a);
an ion injector (injection via 111 and 114) for injecting ions into a space between the ion mirrors (as seen in figure 11), the ion injector located in proximity with the first end of the ion mirrors (located in proximity to the left end of mirrors best seen in figure 11b or figure 9, which fig. 11 is a detailed view); and a detector (117) for detecting ions after they have completed a plurality of reflections between the ion mirrors (as seen in figures 11a-11b or figure 9), the detector located in proximity with the first end of the ion mirrors (117 is in proximity with the same left side of mirrors 71 and 72).
Grinfeld modifies Yamaguchi by suggesting another type of TOF-MS that increases flight length.
Since both inventions are directed towards increasing the flight path via multiple reflections or orbits in a TOF mass spectrometer, it would have been obvious to one of ordinary skill in the art to apply the conditional change method of Yamaguchi to the MR-TOF of Grinfeld because determining the number of turns of each ion that forms a peak in the flight time spectrum allows the determining the m/z of each ion even if the sample to be analyzed contains many components. That is, Yamaguchi already envisioned apply the method towards a large number of various orbiting and multi-reflecting TOF analyzers (see as evidence ‘747, figures 6, 12 and 13), therefore applying the method to an MR-TOF as claimed and known to the art would predictably achieved similar advantages in such a system, as evidenced by the method being envisioned by Yamaguchi to be used in multi reflection type systems (figure 6 or 13 of ‘247). Lastly, the structure of the reciprocal multi reflecting system of ‘747 cited in Yamaguichi, is not disclosed, therefore adopting the structure suggested by Grinfeld would resolve the problem as to how to construct a reciprocal system for the purposes of achieving the method disclosed in Yamaguchi.
Alternatively, Stewart teaches wherein the time-of-flight mass analyser is a multi-reflection time-of-flight (MR-ToF) mass analyser (fig. 16) comprising:
two ion mirrors (6 and 8) spaced apart and opposing each other in a first direction X (fig. 16, x direction interpreted to be between 6 and 8), each mirror elongated generally along a drift direction Y between a first end and a second end (fig. 16, y direction along elongated mirrors 6 and 8), the drift direction Y being orthogonal to the first direction X (x (between mirrors ) is orthogonal to y direction along mirrors);
an ion injector (204, 205, 206) for injecting ions into a space between the ion mirrors (as seen in figure 16), the ion injector located in proximity with the first end of the ion mirrors (located in proximity to the left end of mirrors best seen in figure 16); and a detector (210) for detecting ions after they have completed a plurality of reflections between the ion mirrors (as seen in figure 16), the detector located in proximity with the first end of the ion mirrors (210 is in proximity with the same left side of mirrors 8 and 6).
Stewart modifies Yamaguchi by suggesting another type of TOF-MS that increases flight length.
Since both inventions are directed towards increasing the flight path via multiple reflections or orbits in a TOF mass spectrometer, it would have been obvious to one of ordinary skill in the art to apply the conditional change method of Yamaguchi to the MR-TOF of Stewart because determining the number of turns of each ion that forms a peak in the flight time spectrum allows the determining the m/z of each ion even if the sample to be analyzed contains many components (abstract). Moreover, the device of Stewart reduces the TOF aberration across the width of the ion beam (page 47, first full paragraph).
Alternatively, Wildgoose teaches wherein the time-of-flight mass analyser is a multi-reflection time-of-flight (MR-ToF) mass analyser (fig. 3) comprising:
two ion mirrors (10) spaced apart and opposing each other in a first direction X (fig. 3, 10 spaced apart in the x direction), each mirror elongated generally along a drift direction Y between a first end and a second end (fig. 3, shows mirrors 10 elongated along a drift direction), the drift direction Y being orthogonal to the first direction X (x (between mirrors) is orthogonal to y direction along mirrors);
an ion injector (accelerator 14) for injecting ions into a space between the ion mirrors (as seen in figure 3), the ion injector located in proximity with the first end of the ion mirrors (located in proximity to the left end of mirrors best seen in figure 3); and a detector (16) for detecting ions after they have completed a plurality of reflections between the ion mirrors (as seen in figure 3), the detector located in proximity with the first end of the ion mirrors (16 is in proximity with the same left side of mirrors 10).
Wildgoose modifies Yamaguchi by suggesting ways of changing the flight distance by use of a deflector in an MR-TOF.
Since Yamaguchi is directed towards a method of operating the TOF in two modes to change the flight distance and Wildgoose teaches a reflector 20 to facilitate a change in flight distance ([0088]), it would have been obvious to one of ordinary skill in the art to apply the method of Yamaguchi to the device of Wildgoose because it would achieve the same advantages disclosed in Yamaguchi (abstract and discussed above) in the MR-TOF of Wildgoose. That is, because Yamaguchi envisioned the device to operate in a variety of orbital or reciprocating TOF devices as evidenced by ‘747 and paragraph [0065] of Yamaguchi, since Wildgoose envisioned.
Claim 4-5 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Yamaguchi as evidenced by ‘747 in view of Stewart (GB2580089) (copy of publication submitted herewith) and further in view of Wildgoose (US pgPub 2024/0339314).
Regarding claim 4, Yamaguchi in view of Stewart teach wherein the analyser is configured to analyse ions by:
(i) injecting ions from the ion injector into the space between the ion mirrors (Stewart, via 204), wherein the ions complete a first cycle in which the ions follow a zigzag ion path (best seen in figure 16 of Stewart) having plural K reflections (each reflection from 6 and 8) between the ion mirrors in the direction X whilst (reflection along x direction as seen in figure 16):
(a) drifting along the drift direction Y towards the second end of the ion mirrors (page 47, lines 4-7),
(b) reversing drift direction velocity in proximity with the second end of the ion mirrors (reversing via reversing deflector 208 at distal end of mirrors 6/8, see page 47, lines 4-8),
and (c) drifting back along the drift direction Y towards the first end of the ion mirrors (page 47, lines 8-11).
While Stewart suggests a deflector at the proximal end (i.e. injector end), Yamaguchi in view of Stewart suggest activating the deflector to reverse the drift direction a second time. Therefore, the combination fails to disclose (ii) reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors such that the ions are caused to complete a further cycle in which the ions follow a zigzag ion path having plural K reflections between the ion mirrors in the direction X whilst: (a) drifting along the drift direction Y towards the second end of the ion mirrors, (b) reversing drift direction velocity in proximity with the second end of the ion mirrors, and (c) drifting back along the drift direction Y towards the first end of the ion mirrors;(iii) repeating step (ii) one or more times; and then (iv) causing the ions to travel to the detector for detection.
However, Wildgoose teaches (ii) reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors (fig. 3, 20 via activating reflector 20 ions are reflected back towards the second end of mass analyzer 8 ([0088]), which comprises to ion mirrors 10) such that the ions are caused to complete a further cycle in which the ions follow a zigzag ion path having plural K reflections between the ion mirrors in the direction X (fig. 3 shows zigzag ion path, [0088], x direction interpreted to be between ion mirrors 10) whilst: (a) drifting along the drift direction Y towards the second end of the ion mirrors (y direction is from 20 to 22 see paragraph [0088] for reflection between mirrors in the above described mirror, paragraph [0087] teaches reflecting between mirrors as they drift in the z direction (i.e. equivalent to the claimed y direction)), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors ([0088] repeating the manner disclosed in paragraph [0087], which requires in part ions are reflected at the second end of the mass analyzer by the second reflector back towards the first end. That is, requiring reversing the drift direction velocity because velocity is a vector, thus any reversal of direction is a reversal of velocity), and (c) drifting back along the drift direction Y towards the first end of the ion mirrors (reversal drift the same manner as in the first direction, see paragraph [0087]-[0088]);(iii) repeating step (ii) one or more times ([0088] suggests either deactivate detector to allow detection or maintain in active state for additional cycle); and then (iv) causing the ions to travel to the detector for detection ([0088]).
Wildgoose modifies the combined device by suggesting operating the deflector of Yamaguchi in view of Stewart such that multiple cycles may be completed.
Since both inventions are directed towards MR-TOF, it would have been obvious to one of ordinary skill in the art before the effective filing date to have the multiple cycles suggested in Wildgoose in the combined device because it would allow for a longer drift pass to obtain a higher mass resolution measurement ([0087]).
Regarding claim 5, the combined device teaches the limitations are required by claim 4. Claim 5 further requires the use of a deflector in proximity with the first end of the ion mirrors to perform the claimed reversal to complete additional cycles. As discussed above Yamaguchi as modified by Stewart teaches a deflector proximal the first end (fig. 16, 206 proximal the same end of detector and injector), Wildgoose suggests using a deflector (reflector 20) for additional cycles as discussed above in claim 4.
Regarding claim 9, Yamaguchi in view of Stewart teaches wherein the deflector is a first deflector (Stewart, fig. 16, 206), and the analyser comprises a second deflector (Stewart, fig. 16, 208) located in proximity with the second end of the ion mirrors (208 second end), wherein the second deflector is configured to cause the ions to reverse their drift direction velocity in proximity with the second end of the ion mirrors and drift back along the drift direction towards the deflector (Stewart, page 47, lines 4-11).
Claims 8 is rejected under 35 U.S.C. 103 as being unpatentable over Wildgoose (US pgPub 2024/0339314) in view of Yamaguchi and further in view of Grinfled (USPN 9,136,101).
Regarding claim 8, Wildgoose in view of Yamaguchi fails to disclose wherein the ion mirrors are a non-constant distance from each other in the X direction along at least a portion of their lengths in the drift direction Y, wherein the drift direction velocity of ions towards the second end of the ion mirrors is opposed by an electric field resulting from the non-constant distance of the two mirrors from each other, and wherein the electric field causes the ions to reverse their drift direction velocity in proximity with the second end of the ion mirrors and drift back along the drift direction towards the deflector.
However, Grinfeld teaches wherein the ion mirrors (fig. 3, 31/32) are a non-constant distance from each other in the X direction along at least a portion of their lengths in the drift direction Y (see separation distances between 31/32 in x direction along the y direction), wherein the drift direction velocity of ions towards the second end of the ion mirrors is opposed by an electric field resulting from the non-constant distance of the two mirrors from each other (col. 23, lines 42-47 teaches field causes ion to reverse their direction and travel back toward injector thus field opposes drift direction velocity), and wherein the electric field causes the ions to reverse their drift direction velocity in proximity with the second end of the ion mirrors and drift back along the drift direction towards the deflector (col. 23, lines 42-47 and figure 3 shows ions reversing near the second end of the ion mirrors). Note: alternatively see non-constant distances between ion mirrors in figures 7a-7b and 9
Grinfeld modifies the combined device by suggesting a non-constant separation distance between ion mirrors.
Since both inventions are directed towards MR-TOF, it would have been obvious to one of ordinary skill in the art to adopt the non-constant separation distance between mirrors suggested in Grinfeld in the combined device because it would facilitate both an extended flight path and spatial focusing without additional components (col. 24, lines 17-20), therefore simplifying the device of Grinfeld by removing the need for additional periodic lenses 12 to achieve spatial focusing, thus simplifying the device.
Conclusion
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/MICHAEL J LOGIE/Primary Examiner, Art Unit 2881