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 disclosure is objected to because of the following informalities:
13:8-9: “packets of ions are pulsed from the accumulator 6 into the transfer region 6” should be “transfer region 7”.
Appropriate correction is required.
The abstract of the disclosure is objected to because the disclosure exceeds the 150 words limit. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
Claim Objections
Claims 5 and 20 are objected to because of the following informalities:
Claim 5 recites “other precursor ions species,” should be “other precursor ion species”
Claim 20 recites “to generate a set or fragment or product ion species,” should be “a set of fragment or product ion species.”
Appropriate correction is required.
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.
Claims 6 and 12 are 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 6 recites “each time the sequence of steps b) and c) is performed…”, which is inconsistent with claim 1, in which step b) establishes a separation cycle and steps c) through f), rather than steps b) and c), are repeated during that separation cycle. It is therefore unclear whether claim 6 requires step b) to be repeated for every mass-filter transmission event or merely requires the mass filter of step c) to be controlled during the single separation cycle of step b).
Claim 12 recites “wherein the second physicochemical property is mass to charge ratio, … wherein the second physicochemical property is ion mobility…,” this is indefinite since mass-to-charge ratio and ion mobility are different properties and the claim does not indicate whether these limitations are intended as alternatives, cumulative requirements, or separate separation stages.
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.
Claims 1-12, 14-20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over US 2003/0213900 A1 [hereinafter Hoyes] US 2020/0152441 A1 [hereinafter Furuhashi].
Regarding Claims 1 and 15:
The specification describes the second ion accumulator as “the second ion accumulator 6 may be omitted and the fragmentation or reaction device 5 may pulse ions into the transfer region 7 instead… Alternatively, the second ion accumulator 6 and fragmentation or reaction device 5 may be two parts of the same device” (See Spec 13: 9-13). As such, in light of the specification, the claimed “second ion accumulator” is interpreted as a component configured to accumulate/trap the generated fragment/ product ions, and is not necessarily structurally separate from the fragmenting/reaction device.
Hoyes teaches a method of a mass spectrometry and a mass spectrometer (Abstract), comprising:
a first ion accumulator (Fig. 7-upstream trap 2);
an ion separator (Fig. 7-IMS 4);
a mass filter (Fig. 7- mass filter 5);
a fragmentation or reaction device; a second ion accumulator (Fig. 7 fragmentation/reaction device 6);
a TOF mass analyser (Fig. 7- TOF analyzer 11); having a time of flight region and a pusher electrode (Fig. 7- pusher electrode 8) (para. [0170]: “all the ions arriving at the pusher electrode 8 will be orthogonally accelerated into the drift region of the mass analyser 11”); and
control circuitry configured to control the mass spectrometer to:
a) accumulating precursor ions in a first ion accumulator (para. [0137]: “generates a beam of ions 1 which are trapped in an upstream ion trap 2 upstream of the ion mobility spectrometer 4”);
b) performing a separation cycle comprising pulsing a packet of the precursor ions out of the first ion accumulator and into an ion separator, and separating the precursor ions such that precursor ions having different values of a first physicochemical property elute from the ion separator at different times (para. [0141]: “The ion mobility spectrometer 4 is a device which causes ions to become temporally separated based upon their ion mobility);
c) mass filtering the precursor ions that elute from the ion separator so as to transmit a selected precursor ion species (paras. [0152, 0156]: “Downstream of the ion mobility spectrometer 4 …may be provided leading to a vacuum chamber housing a quadrupole mass filter 5…. then the mass filter 5 can be set to transmit (in conjunction with the operation of the ion mobility spectrometer 5) only those ions having a mass to charge ratio that corresponds at any particular point in time with the charge state of the ions of interest”);
d) fragmenting or reacting the selected precursor ion species so as to generate a set of fragment or product ion species therefrom (para. [0158]: “a downstream ion trap 6 is provided downstream of the ion mobility spectrometer 4 and the quadrupole mass filter 5… downstream ion trap 6 comprises a collision (or gas) cell 6. Ions may be arranged so that …they collide with gas molecules present in the gas cell 6 and fragment into daughter ions”);
e) accumulating the set of fragment or product ion species in a second ion accumulator (paras. [0034, 0036, 0175-0176]: “…instead of releasing fragment or product ions from the first ion trap and sending the ions directly downstream to the TOF mass analyser (which would result in a low duty cycle), the fragment or productions are instead sent back upstream of the first ion trap…. The fragment or product ions are then preferably trapped in a second ion trap upstream of the first device,” e.g., the upstream IMS);
f) releasing the set of fragment or product ion species from the second ion accumulator into a TOF mass analyser (paras. [0179-0180]: releasing the accumulated product ions from the second ion accumulator (ion trap 2b) for subsequent introducing into the TOF mass analyser, wherein the product ions are released from ion trap 2b, pass through the IMS, are accumulated in ion trap 6, and are periodically released toward the TOF),
wherein operation of the TOF mass analyser is synchronised with the release of ions from the second ion accumulator (paras. [0076, 0109]: “a mass analyser comprising an electrode for orthogonally accelerating ions …the ion trap is arranged to release fragment or productions in synchronisation with the operation of an electrode for Orthogonally accelerating ions”); and
g) repeating steps c) to f) at least once during said separation cycle, wherein said selected precursor ion species is different each time steps c) to f) are performed (para. [0023]:in one processing cycle, precursor ions having higher average m/z subsequently exit the ion mobility spectrometer and mass filter, are released from the ion trap in another pulse with an increased pusher delay, and by repeating this process, a number of times a duty cycle approaching 100% is achieved across the whole mass range).
However, Hoyes does not specially note by synchronizing the release of ions from the second ion accumulator, multiple different species of the set of fragment or product ion species are simultaneously pulsed into a time of flight region of the TOF mass analyser by a pusher electrode.
Furuhashi teaches a method of mass spectrometry (Fig. 1- Q-TOF mass spectrometer) comprising:
c) mass filtering the precursor ions that elute from the ion separator so as to transmit a selected precursor ion species (Fig. 1 and para. [0063]: “The various ions derived from the sample are introduced into the quadrupole mass filter 12. Only an ion having a specific mass-to -charge ratio corresponding to the voltage applied to the quadrupole mass filter 12 is allowed to pass through the same filter 12”);
d) fragmenting or reacting the selected precursor ion species so as to generate a set of fragment or product ion species therefrom (Fig. 1 and para. [0063]: the selected precursor ion species “is introduced into the collision cell 13 as the precursor ion… [which] undergoes dissociation, generating various product ions”);
e) accumulating the set of fragment or product ion species in a second ion accumulator (Fig. 1 and para. [0064]: “The ion guide 30, in combination with an entrance lens electrode 131 and exit lens electrode 132, functions as a type of linear ion trap. The generated product ions are temporarily accumulated by the ion guide”);
f) releasing the set of fragment or product ion species from the second ion accumulator into a TOF mass analyser (Fig. 1 and paras. [0064-0065]: “at a pre-determined timing, the accumulated ions are discharged from the collision cell 13,” and introduced into the fly region 17 of the TOF analyser by the orthogonal accelerator 16);
wherein operation of the TOF mass analyser is synchronised with the release of ions from the second ion accumulator such that multiple different species of the set of fragment or product ion species are simultaneously pulsed into a time of flight region of the TOF mass analyser by a pusher electrode (paras. [0035-0036, 0076-0078]: “ions which have been located near the exit end of the ion guide, most of which have large mass-to-charge ratios, are discharged earlier.” “Since ions having smaller mass-to-charge ratios move faster… [low mass ions] will catch up with, or at least close their distance to, the ions which have large mass-to-charge ratios and have departed at earlier points in time, before the ions reach the orthogonal accelerator.” “When a predetermined length of delay time has elapsed since the point in time of the initiation of the ion-discharging operation, a predetermined acceleration voltage is applied from the acceleration voltage generator to the orthogonal accelerator. In the conventional case, only the ions having large mass-to-charge ratios are thereby accelerated. By comparison, in the case of the present invention, ions having small mass-to-charge ratios are also accelerated along with the ions having large mass-to-charge ratios”); and
g) repeating steps c) to f) at least once during said separation cycle, wherein said selected precursor ion species is different each time steps c) to f) are performed (para. [0034]: “a measurement for ions originating from various components contained in a sample continuously introduced into an ion source of the mass spectrometer is repeatedly performed with a predetermined period”).
Both Hoyes and Furuhashi teach analyzing mass filtered and fragmented product ions using TOF. Hoyes recognizes that directly sending fragment ions from the fragmentation cell to the TOF results in a low duty cycle and therefore temporarily accumulates the fragment ions before TOF analysis. However, Hoyes still requires repeated TOF measurements with progressively increasing pusher delays in order to analyze fragment ions across abroad m/z. Furuhashi teaches an improved ion release control technique in which accumulated product ions are discharged from the ion accumulator in accordance with their m/z so that product ions having different m/z arrive at the orthogonal accelerator together and are simultaneously injected into the TOF. Therefore, it would have been obvious to an ordinary skilled person in the art, before the effective time of filing, to modify Hoyes with the ion release control technique of Furuhashi, to improve TOF utilization, reduce the number of required pusher events, and increase measurement throughput and duty cycle.
Regarding Claim 2:
Hoyes in view of Furuhashi teach the mass spectrometer of claim 1. Hoyes further teaches wherein the ion separator is an ion mobility separator and the physicochemical property is ion mobility (para. [0141]: “The ion mobility spectrometer 4 is a device which causes ions to become temporally separated based upon their ion mobility”).
Regarding Claim 3:
Hoyes in view of Furuhashi teach the mass spectrometer of claim 1. Furuhashi further teaches wherein the fragment or product ion species are urged into the second ion accumulator such that: (i) fragment or product ion species that are derived from the same precursor ion species arrive at the second ion accumulator over substantially the same time period and are accumulated in the second ion accumulator during at least part of this time period (paras. [0063-0064, 0074]: one precursor m/z is selected in quadrupole 12, dissociates that precursor to generate various product ions, and temporarily accumulates those products together in ion guide 30); and/or (ii) fragment or product ion species that are derived from precursor species that are transmitted by the mass filter at different times arrive at the second ion accumulator over different respective time periods.
Regarding Claim 4:
Hoyes in view of Furuhashi teach the mass spectrometer of claim 1. Furuhashi further teaches wherein each time the sequence of steps c) to e) is performed, fragment or product ion species are accumulated in the second ion accumulator over a time period that is the same as, or correlated to, the time period during which their precursor ion species is transmitted by the mass filter (paras. [0063-0065]: the precursor selected by quadrupole mass filter 12 is introduced into collision cell 13 and dissociated to generate product ions, which are temporarily accumulated in ion guide 30 during an accumulation period before being discharged at time t1; thus, the duration over which the products are generated and accumulated corresponding to the duration over which the selected precursor is supplied to the collision cell).
Regarding Claim 5:
Hoyes in view of Furuhashi teach the mass spectrometer of claim 1. Furuhashi further teaches wherein each time the sequence of steps c) to e) is performed, only fragment or product ion species derived from the selected precursor ion species, and optionally some ions of the selected precursor ion species itself, are accumulated in the second ion accumulator; whereas other precursor ions species and fragment or product ions derived therefrom are not accumulated in the second ion accumulator (paras. [0063-0064]: quadrupole 12 permits only the precursor ion having the selected m/z to pass into collision cell13. The selected precursor is associated, and the resulting products are accumulated in ion guide 30. Because other precursor species are blocked by the quadrupole, their products are not generated or accumulated in the collision cell).
Regarding Claim 6:
Hoyes in view of Furuhashi teach the mass spectrometer of claim 1. Hoyes further teaches wherein each time the sequence of steps b) and c) is performed, the mass filter is controlled so as to transmit the precursor ion species of interest only over a time period that is the same as, correlated to, or shorter than the time period during which that precursor ion species elutes from the ion separator (paras. [0039, 0156, 0167]: quadrupole 5 is synchronizes with IMS 4 so that, at each time during the IMS cycle, the quadrupole transmits the m/z corresponding to the desired ions then eluting. The quadrupole transmission window is therefore temporarily correlated with the period during which the corresponding ions emerge from the IMS).
Regarding Claims 7 and 16:
Hoyes in view of Furuhashi teach the method of claim 1 and the mass spectrometer of claim 15, respectively. Furuhashi further teaches wherein step f) comprises releasing the fragment or product ion species from the second ion accumulator in reverse order of mass to charge ratio, starting with ions of relatively high mass to charge ratio and progressively releasing ions of progressively lower mass to charge ratios, such that different ones of the fragment or product ion species simultaneously arrive at the pusher and are simultaneously pulsed into the time of flight region of the TOF mass analyser by the pusher electrode (paras. [0035-0037 and 0074-0078]: high m/z products are concentrated near exist electrode 132 while lower m/z. products are displaced farther upstream. When the barrier is removed, high m/z ions exit first and lower m/z ions exist later. Lower m/z ions travel faster and close the distance to the high m/z ions, and then the pusher fires when the ion population are mixed at the accelerator).
Regarding Claims 8 and 17:
Hoyes in view of Furuhashi teach the method of claim 7 and the mass spectrometer of claim 16, respectively. Furuhashi further teaches wherein a transfer region is provided between the second ion accumulator and the TOF mass analyser, and wherein the pressure in the transfer region and the energies with which ions are released from second ion accumulator are such that fragment or product ions having relatively low mass to charge ratios catch up with fragment or product ions having a higher mass to charge ratio so that the ions simultaneously arrive at the pusher and are simultaneously pulsed into the time of flight region of the TOF mass analyser by the pusher electrode (paras. [0005, 0064-0065, 0076-0078]: CID gas cools product ions so ions of different m/z have approximately equal kinetic energies. Lower m/z ions therefore travel faster and “will catch up with, or at least close their distance to, the ions which have large mass-to-charge ratios and have departed at earlier points in time, before the ions reach the orthogonal accelerator”).
Regarding Claim 9:
Hoyes in view of Furuhashi teach the mass spectrometer of claim 7. Furuhashi further teaches wherein substantially all of the fragment or product ion species released from the second ion accumulator, each time step f) is performed, arrive at the pusher at substantially the same time and are simultaneously pulsed into the time of flight region of the TOF mass analyser by the pusher electrode (para. [0078]: “by appropriately determining the delay time Tdelay, it is possible to accelerate and eject ions passing through the space between the push-out electrode 161 and the extraction electrodes 162 at the timing when the ions having high mass-to- charge ratios are mixed with the ions having low mass-to-charge ratios which have been discharged with a delay. As a result, the ions which have been accumulated within the collision cell 13 to increase their amounts can be subjected to mass spectrometry over a wide range of mass-to-charge ratios which is not unevenly distributed on either the high mass-to-charge -ratio side or low mass -to - charge - ratio side”).
Regarding Claims 10 and 18:
Hoyes in view of Furuhashi teach the method of claim 1 and the mass spectrometer of claim 15, respectively. Furuhashi further teaches wherein step f) comprises
releasing all of the fragment or product ion species from the second ion accumulator at substantially the same time (para. [0010]: “…ions are temporarily accumulated within the collision cell 13, the ions in the form of a mass (bunch) are discharged into the orthogonal accelerator 16 in a synchronized fashion with the ion-ejecting pulse in the orthogonal accelerator 16”);
wherein a transfer region is provided between the second ion accumulator and the TOF mass analyser (the travel region between the collision cell and the accelerator),
wherein ions are separated in the transfer region according to a second physicochemical property such that fragment or product ion species arrive at the TOF mass analyser at times that depend on their second physicochemical property value (para. [0012]: “the ions which have been almost simultaneously discharged from the collision cell 13, and are dispersed in the travelling direction according to their mass-to-charge ratios during their travel to the orthogonal accelerator 16”);
wherein the operation of the TOF mass analyser is synchronised with the release of ions from the second ion accumulator such that fragment or product ion species having a selected range of values of the second physicochemical property value are simultaneously pulsed into the time of flight region of the TOF mass analyser by the pusher electrode (para. [0012]: “at the timing of the acceleration by the orthogonal accelerator 16, the ions are distributed in an elongated form along their travelling direction according to their mass-to - charge ratios, and only the ions falling within a specific mass-to-charge-ratio range will be ejected toward the flight space”).
Note Furuhashi describes the method of paragraphs [0010-0012] as a conventional ion-releasing control technique in which accumulated product ions are discharged substantially simultaneously, become temporally dispersed during transfer according to their m/z, and are pulsed into the TOF when ions with a selected m/z range are presented in the orthogonal accelerator. Although Furuhashi explains that repeated measurements with different delay times may be required when a mass spectrum covering a wide m/z range is desired, claim 10 only requires simultaneously TOF analysis of product ions within a selected range. Accordingly, the conventional technique recognized by Furuhashi is directly applicable to the more limited selected-range analysis recited in claim 10.
Regarding Claim 11:
Hoyes in view of Furuhashi teach the method of claim 10. Furuhashi further teaches receiving an input signal, at a mass spectrometer performing the method, that is representative of said selected range of values of the second physicochemical property, and wherein said operation of the TOF mass analyser is synchronised with the release of ions from the second ion accumulator such that fragment or product ion species having said selected range of values of the second physicochemical property value are simultaneously pulsed into the time of flight region of the TOF mass analyser by the pusher electrode (paras. [0068, 0084]: The delay time is chosen based on the m/z range to be observed. For example, use about 50 µs for a range up to m/z 1000 and use about 100 µs for a range up to m/z 4000. Controller 40 controlling the exit electrode and the orthogonal accelerator. Receiving an input signal may be inherent in an electronically controlled instrument, such as controller 40).
Regarding Claim 19:
Hoyes in view of Furuhashi teach the mass spectrometer of claim 18, respectively. Furuhashi further teaches a user interface configured for inputting a selected range of values of the second physicochemical property; wherein the spectrometer is configured such that the control circuitry controls the operation of the TOF mass analyser, based on the selected range of values, to synchronise the operation of the TOF mass analyser with the release of ions from the second ion accumulator such that fragment or product ion species having said selected range of values of the second physicochemical property value are simultaneously pulsed into the time of flight region of the TOF mass analyser by the pusher electrode ( claim 19 having substantially same elements as claim 18, and a control device like controller 40 in Furuhashi would inherently receive user inputs via a user interface).
Regarding Claim 12:
Hoyes in view of Furuhashi teach the mass spectrometer of claim 1.
Furuhashi teaches the combined references teaches wherein the second physicochemical property is mass to charge ratio, such that ions are separated in the transfer region according to mass to charge ratio (para. [0012]: products having different m/z values separate during transfer and arrive at different times),
Hoyes teaches wherein the second physicochemical property is ion mobility, such that ions are separated in the transfer region according to ion mobility (paras. [0179-0180]: products are released from trap 2b and temporally separated in IMS 4 according to mobility before being retrapped and TOF-analyzed).
Regarding Claim 14:
Hoyes in view of Furuhashi teach the mass spectrometer of claim 1. Hoyes further teaches wherein steps a) to g) are repeated during a single experimental run (paras. [0181-0182]: operating the instrument through four modes and returning to the first mode so the whole cycle may be repeated. It also accumulates ions continuously while other experiments re performed, preventing ion loss).
Regarding Claims 20 and 22:
Hoyes teaches a method of mass spectrometry and a mass spectrometer, comprising:
a first ion accumulator; an ion separator; a mass filter; a fragmentation or reaction device; a TOF mass analyser having a time of flight region and a pusher electrode (as discussed in claim 15); and
control circuitry configured to control the mass spectrometer to perform a) accumulating precursor ions in a first ion accumulator; b) performing a separation cycle comprising pulsing a packet of the precursor ions out of the first ion accumulator and into an ion separator, and separating the precursor ions such that precursor ions having different values of a first physicochemical property elute from the ion separator at different times; c) switching a mass filter that mass filters the precursor ions that elute from the ion separator so as to begin transmitting a selected precursor ion species; d) fragmenting or reacting the selected precursor ion species so as to generate a set or fragment or product ion species therefrom (as discussed in claims 1& 15).
However, Hoyes does not expressly teach a transfer region between the fragmentation or reaction device and the TOF mass analyser; and performing e) transferring the set of fragment or product ion species through a transfer region to a TOF mass analyser having a pusher electrode and a time of flight region, wherein ions are separated in the transfer region according to a second physicochemical property such that fragment or product ion species arrive at the TOF mass analyser at times that depend on their second physicochemical property values, and wherein the operation of the TOF mass analyser is synchronised with the time that the mass filter is switched so as to begin transmitting said selected precursor ion species such that fragment or product ion species having a selected range of values of the second physicochemical property that arrive at the pusher electrode substantially simultaneously are simultaneously pulsed into the time of flight region of the TOF mass analyser by the pusher electrode; and f) repeating steps c) to e) at least once during said separation cycle, wherein said selected precursor ion species is different each time steps c) to e) are performed.
Furuhashi teaches:
a transfer region between the fragmentation or reaction device and the TOF mass analyser (the travel region between the collision cell and the accelerator),
e) transferring the set of fragment or product ion species through a transfer region to a TOF mass analyser having a pusher electrode and a time of flight region (paras. [0010-0012]: the product ions travel from the collision cell through a transfer path to OA-TOF),
wherein ions are separated in the transfer region according to a second physicochemical property such that fragment or product ion species arrive at the TOF mass analyser at times that depend on their second physicochemical property values (paras. [0010-0012]: “the ions which have been almost simultaneously discharged from the collision cell 13 are dispersed in the travelling direction according to their mass-to-charge ratios during their travel to the orthogonal accelerator 16”), and
wherein the operation of the TOF mass analyser is synchronised with the time that the mass filter is switched so as to begin transmitting said selected precursor ion species (since resulting product ions travel directly through a transfer region and are pulsed into the TOF without intermediate accumulating/trapping, the mass filter switching event provides the timing reference from which the expected product-ion arrival time and corresponding TOF-pulser operation are determined)
such that fragment or product ion species having a selected range of values of the second physicochemical property that arrive at the pusher electrode substantially simultaneously are simultaneously pulsed into the time of flight region of the TOF mass analyser by the pusher electrode (para. [0012]: “at the timing of the acceleration by the orthogonal accelerator 16, the ions are distributed in an elongated form along their travelling direction according to their mass-to-charge ratios, and only the ions falling within a specific mass-to-charge -ratio range will be ejected toward the flight space. Consequently, the ions falling within the specific mass-to-charge -ratio range are detected with a high level of sensitivity”); and
f) repeating steps c) to e) at least once during said separation cycle, wherein said selected precursor ion species is different each time steps c) to e) are performed (para. [0034]: “a measurement for ions originating from various components contained in a sample continuously introduced into an ion source of the mass spectrometer is repeatedly performed with a predetermined period”).
Therefore, it would have been obvious to an ordinary skilled person in the art, before the effective time of filing, to modify Hoyes to omit the downstream product-ion accumulation step and instead transfer the generated product ions directly through a transfer region to the TOF mass analyser, as recognized by Furuhashi, and to synchronize operation of the TOF with the precursor -selection timing so that product ions within a selected mass-to-charge-ratio range are present at the orthogonal accelerator when the pusher is operated. Such a modification would have provided a simpler ion transfer and control arrangement while still permitting high-sensitivity analysis of a desired product ion mass range, particularly where acquisition of the entire product-ion mass spectrum is not required.
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
/MICHAEL J LOGIE/ Primary Examiner, Art Unit 2881
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