DETAILED ACTION
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 .
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The disclosure is objected to because of the following informalities: Page 18, Lls. 26-28: “sample cone 12” and “skimmer cone 13” should be “sample cone 13” and “skimmer cone 14”
Appropriate correction is required.
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 1-2, 6-7, 15, and 18-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by DE 202012007249U1 [hereinafter Thermo].
Regarding Claim 1:
Thermo teaches an ion guide assembly for a mass spectrometer (annotated Fig. 1 below and para. [0001]: “a method and analyzer for mass analysis of ions”), comprising:
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a collision/reaction cell, CRC (Fig. 1 – HCD cell 16), comprising an enclosure having a first multipole RF ion guide enclosed radially therein (para. [0041]: “HCD cell 16 comprising RF multipole rods”) and a set of gas inlets, including a first gas inlet, therethrough (paras. [0041, 0048]: the “gas-filled” HCD cell “was equipped with a dedicated gas line that allowed the switching between the standard nitrogen burst gas and xenon”); and
a first ion energy filter (Fig. 1- ion gate 10 and FR multipole 12) disposed upstream of the CRC, to prevent ions having an ion energy below a first predetermined threshold from entering the CRC (paras. [0013-0015, 0019-0020]: “filtering the ions through…an energy filter…by a voltage barrier…which acts a as a filter for …low energies”, “a high-pressure surge dissociation (HCD) cell, downstream of the one or both filters”);
wherein the first ion energy filter comprises a second multipole RF ion guide (para. [0015]: the energy filter includes “one or more electrodes for applying a barrier voltage thereto to act as a filter…for low energies…The electrodes may comprise the rods of a multipole acting as an ion guide, in particular an RF multipole).
Regarding Claim 2:
Thermo teaches the ion guide assembly of claim 1. Thermo further teaches wherein the second multipole RF ion guide has a set of DC electrodes interspersed between RF rods thereof (para. [0015]: the emerging filter includes “one or more electrodes for applying a barrier voltage thereto to act as a filter…for low energies…The electrodes may comprise the rods of a multipole acting as an ion guide, in particular an RF multipole) or wherein the first ion energy filter comprises an einzel lens including the second multipole RF ion guide.
Regarding Claim 6:
Thermo teaches the ion guide assembly of claim 1. Thermo further teaches the ion guide assembly comprising an entrance ion guide (Fig.1 – flatapole 6/8) disposed upstream of the first ion energy filter for radially confining ions into the first ion energy filter (Fig. 1 and para. [0041]: “ions from the electro-sprayer pass through an injection flatapole 6 and a curved flatapole 8… [then pass] ion gate 10 in the form of a fast split lens controls the entry of the ions into the RF only transport multipole 12.. From the transport multipole… the ions may be directed into a gas-filled, electrodeless HCD cell 16”).
Regarding Claim 7:
Thermo teaches the ion guide assembly of claim 6. Thermo further teaches wherein the entrance ion guide comprises a fourth multipole RF ion guide (Flatapole is generally a RF multiple ion guide).
Regarding Claim 15:
Thermo teaches the ion guide assembly of claim 1. Thermo further teaches wherein the first ion energy filter and the first multipole RF ion guide of the CRC are coaxial (Fig.1 shows the RF multipole 12 of the upstream ion energy filtering arrangement and the RF multipole ion guide within HCD cell 16 arranged along a common ion optical axis).
Regarding Claim 18:
Thermo teaches the ion guide assembly of claim 1. Thermo further teaches the ion guide assembly comprising a mass filter disposed upstream of the CRC (paras. [0014, 0020]: “providing a mass charge ratio filter … Accordingly, the ions are preferably filtered based on their mass-to-charge ratio.” “a high-pressure surge dissociation (HCD) cell, downstream of the one or both filters”).
Regarding Claim 19:
Thermo teaches a mass spectrometer comprising an ion guide assembly according to claim 1 (Fig. 1 shows a mass spectrometer layout including ion source 2, mass analyzer 20, and the ion guide assembly according to claim 1).
Regarding Claim 20:
Thermo teaches a method of controlling interferences in a mass spectrometer comprising a collision /reaction cell, CRC (para. [0005]: “a method for mass analysis of multiply charged ions”), the method comprising:
preventing ions having an ion energy below a first predetermined threshold from entering the CRC (paras. [0014-0015]: “The filtering of the ions is preferably done by a voltage barrier upstream of the electrostatic mass analyser which acts as a filter for … for low energies”);
using a multipole RF ion guide disposed upstream of the CRC (both the energy filter and entrance ion guide upstream HDC include multipole RF ion guide).
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 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Thermo.
Regarding Claim 8:
Thermo teaches the ion guide assembly of claim 6. Although Thermo does not expressly teach wherein a field radius of the entrance ion guide is greater than a field radius of the CRC, Thermo teaches that, after the ions pass the injection flatapole 6 and a curved flatapole 8 (“entrance ion guide”), ions are filtered by a mass filter and/or an energy filter before they reach the collision cell.
Therefore, it would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to provide the entrance ion guide with a field radius feather than the field radius of the CRC, because the entrance ion guide receives ions before the mass/energy filtering and therefore benefits from a larger acceptance radius to collect and confine a broader incoming ion beam. After the ions pass through the upstream filtering/conditioning region, the beam may be directed into a smaller CRC field radius to maintain efficient confinement and collisions/colling performance within cell.
Regarding Claim 9:
Thermo teaches the ion guide assembly of claim 8. Although Thermo does not expressly teach wherein the field radius of the entrance ion guide is similar to, or the same as, a field radius of the first ion energy filter, Thermo teaches that the entrance ion guide is upstream of the mass/energy filter, which is upstream the collision cell. Therefore, it would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to have a field radius similar to, or the same as, the field radius of the first ion energy filter, because the entrance ion guide directly feeds ions into the energy filter. Matching the field radii of adjacent ion-guide/filter regions would help the ion beams pass smoothly from one guide to the next without losing ions at the interface, and reduce field discontinuities and ion loss during transfer.
Claims 3-5, 10, 12-13, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Thermo in view of US 2009/0065692 A1 [hereinafter Javahery].
Regarding Claim 3:
Although claim 3 recites the transfer ion guide as being “between” the first ion energy filter and the CRC, claim 5 further requires that this arrangement includes a transfer ion guide radially enclosed in the CRC enclosure. Thus, consistent with Fig. 3 of the present application, claim 3 is interpreted as not requiring the transfer ion guide to be outside the CRC enclosure.
Thermo teaches the ion guide assembly of claim 1. Thermo does not specifically teach that a transfer ion guide disposed between the first ion energy filter and the CRC, for transferring ions downstream towards the CRC. Javahery teaches a transfer ion guide disposed between the first ion energy filter and the CRC, for transferring ions downstream towards the CRC (Figs. 3 and 4, paras. [0074, 0081]: as shown in figs. 3 and 4, “Inner housing 36 of high pressure collision cell 40 may include an additional ion directing means such as ion guide 49,” which is also downstream of filter 14, “ion guide 49 is a multipole ion guide…to aid in transporting ions”).
It would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to modify ion guide assembly of Thermo to include Javahery’s transfer ion guide. As Javahery explains, ion guides are advantageous for transferring ions into and out of a collision cell, while accommodating the pressure differential between the high pressure collision region and the lower pressure region, therefore using the transfer guide would have improved ion transmission from the upstream filtering region into the collision cell and reduced ion loss during transfer.
Regarding Claim 4:
Thermo in view of Javahery teaches the ion guide assembly of claim 3. Javahery further teaches wherein the transfer ion guide comprises a third multipole RF ion guide (paras. [0074, 0081]: “ion guide 49 is a multipole ion guide”, “ion guide 49 including electrodes 50 and 52 to which RF potentials of opposite phase are applied to neighboring electrodes”).
Regarding Claim 5:
Thermo in view of Javahery teaches the ion guide assembly of claim 3. Javahery further teaches wherein the transfer ion guide is radially enclosed in the enclosure of the CRC (Figs.3/4 and para. [0081]: ion guide 49 enclosed in the inner housing of collision cell 40).
Regarding Claim 10:
Thermo teaches the ion guide assembly of claim 9. Thermo does not specifically teach an ion funnel disposed between the first ion energy filter and the CRC, for funnelling ions downstream towards the CRC. Javahery teaches an ion funnel disposed between the first ion energy filter and the CRC, for funnelling ions downstream towards the CRC (Figs. 3 and 4, paras. [0074, 0081]: “ion guide 49 is may also be… an ion funnel”, which is downstream of the mass filter 14 and enclosed in the inner housing of collision cell 40).
It would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to modify ion guide assembly of Thermo to include Javahery’s ion funnel, because ion funnels were known ion-optical structures for collecting ions from a larger upstream region and directing them toward a downstream ion guide or collision cell, and using an ion funnel would reduce ion loss a6 the transition into the collision cell region.
Regarding Claim 12:
Thermo in view of Javahery teaches the ion guide assembly of claim 10. Javahery further teaches wherein the ion funnel is radially enclosed in the enclosure of the CRC (Figs.3/4 and para. [0081]: ion funnel/ion guide 40 enclosed in the inner housing of collision cell 4).
Regarding Claim 13:
Thermo teaches the ion guide assembly of claim 1. Thermo does not specifically teach an exit ion guide disposed downstream of the CRC. Javahery teaches an exit ion guide (Fig. 6- ion guide 168), disposed downstream of the CRC (Fig. 6 and para. [0094]: “collision cell 160 which includes an outer housing 162 having two short ion guides 166 and 168 located in the entrance and exit of the walls of outer housing 162… for transferring ions into and out of the collision cell 160”).
It would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to modify ion guide assembly of Thermo to include Javahery’s downstream exit ion guide, to transfer ions into and out of a collision cell, and thereby improving radial confinement and downstream transmission of ions exiting the collision cell towards the next mass analysis stage and reducing ion loss after collision/cooling.
Regarding Claim 17:
Thermo teaches the ion guide assembly of claim 1. Thermo does not specifically teach that an electron source disposed upstream of the CRC. Javahery teaches an electron source disposed upstream of the CRC (Fig. 6 and para. [0095]: “collision cell 160…may be configured to include low energy electron emitter filaments 510 for ECD. Electron emitter filament 510 may be positioned in such a way as to emit low energy electrons on axis of ion guide 166 or 168”).
It would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to modify the ion guide assembly of Thermo to include Javahery’s electron source, such as providing an electron emitter filament in the collision cell and ion guide region to emit electrons for electron capture dissociation, to add known electron based ion processing/fragmentation capability the collision cell assembly, thereby expanding the type of ion reactions/fragmentation that can be performed in the mass spectrometer.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Thermo in view of Javahery, further in view of US 2010/0301210A1 [hereinafter Bertsch].
Regarding Claim 11:
Thermo in view of Javahery teaches the ion guide assembly of claim 10. Javahery further teaches wherein the ion funnel comprises a fifth multipole RF ion guide, wherein the fifth multipole RF ion guide comprises and/or is a multipole RF ion guide (paras. [0074, 0077, 0081]: ion funnel /ion guide 49 includes multipole RF ion guide, e.g., octupole).
However, Javahery does not specifically note the multipole RF guide is frustoconical. Bertsch teaches a frustoconical multipole RF ion guide (para. [0041]: “the rods 201 are tapered along their length, again with a greater diameter at respective first ends 203 than at respective second ends. The degree of the taper can be selected and the rods 201 may have a conical shape”).
It would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to modify the multipole RF guide of the ion funnel as taught in Thermo-Javahery to include the frustoconical multipole RF ion guide taught by Bertsch, so that the converging/tapered multipole ion guide can shape and compress an ion beam from a larger input radius toward a smaller output radius, therefore would have improved ion capture from the upstream ion optics and focused the ions into the smaller downstream collision cell region, thereby reducing ion loss and improve transmission into the CRC.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Thermo in view of Javahery, further in view of US 7189967B1 [hereinafter Whitehouse].
Regarding Claim 14:
Thermo in view of Javahery teaches the ion guide assembly of claim 13. The combined references do not specifically teach that wherein the exit ion guide comprises a sixth multipole RF ion guide. Whitehouse teaches wherein the exit ion guide comprises a sixth multipole RF ion guide (Fig. 7 and Lls. 52-55: “when it is desirable to operate ion guide 704 as a collision cell, a third multipole ion guide 714 is positioned in vacuum stage 711 to efficiently transfer ions from multipole ion guide 704 into pulsing region 712”).
It would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to configure the downstream exit ion guide in the ion guide assembly of Thermo- Javahery as a multiple ion guide, as taught in Whitehouse, since using an RF multipole exit ion guide would have improved radial confinement and ion transmission from the collision cell to the downstream mass analyzer, thereby reducing ion loss after collision/cooling.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Thermo in view of US 2019/0287776A1 [hereinafter Yamada].
Regarding Claim 16:
Thermo teaches the ion guide assembly of claim 1. Thermo does not specifically teach a second ion energy filter disposed between the first ion energy filter and the CRC, to prevent ions having an ion energy below a second predetermined threshold from exiting the CRC.
Yamada teaches an ion energy filter disposed at the entrance of CRC, to prevent ions having an ion energy below a second predetermined threshold from exiting the CRC (Fig. 3 and paras. [0061 and 0068]: “The ion guide 246 is configured for operation in a collision/reaction cell assembly.” “DC potential DC3 applied to the cell entrance lens 222 … creates a DC potential barrier effective to prevent ions from entering or exiting the ion guide 246 through the cell entrance lens 222”). As such, in a modified ion guide assembly, the energy barrier taught in Yamada can be incorporated into between the first energy filter and the collision cell taught by Thermo, to prevent ions having an ion energy below a second predetermined threshold from exiting the CRC, as claimed.
It would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to modify the ion guide assembly of Thermo to include an additional DC potential barrier/ion energy barrier at or near the CRC entrance, as taught by Yamada, to prevent confined analyte ions from existing through the collision/reaction cell entrance while also preventing interfering ions from entering through the entrance. The modification would have improved ion confinement in the CRC after collision/reaction cooling and reduced loos of analyte ions back toward the upstream ion optics.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JING WANG whose telephone number is (571)272-2504. The examiner can normally be reached M-F 7:30-17:00.
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/JING WANG/Examiner, Art Unit 2881
/WYATT A STOFFA/Primary Examiner, Art Unit 2881
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