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 .
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, 5-7, 12-14 and 16-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hoyes (US 20090134321 A1).
Regarding claim 1, Hoyes teaches a system (fig. 44, [0408-0409]) comprising:
A first pre-separation device (ion trap 182; constitutes a “preferred ion trap” described in previous embodiments of the invention) configured to spatially separate precursor ions into a plurality of subsets of precursor ions according to mobilities of the precursor ions and sequentially emit the plurality of subsets of precursor ions from the first pre-separation device (operated as mobility separator, [0410]; the ions may be precursor ions since a fragmentation cell can be provided downstream, [0191]; the preferred ion trap accumulates ions and emits them as packets, fig 3);
A second pre-separation device (ion trap 186) positioned downstream of the first pre-separation device, the second pre-separation device configured to receive the plurality of subsets of precursor ions emitted from the first pre-separation device and, for each subset of precursor ions, sequentially emit a plurality of packets of precursor ions from the second pre-separation device based on a mass-to-charge ratio of the precursor ions (mass selective ejection from ion trap 186, [0409]; as another “preferred ion trap” it is presumed to also operate in the accumulation and extraction mode shown in fig. 3 resulting in ions being released as packets); and
A mass spectrometer (mass analyzer 188) positioned downstream of the second pre-separation device and configured to receive the plurality of packets of precursor ions from the second pre-separation device and acquire mass spectra for the plurality of packets of precursor ions;
Wherein the second pre-separation device is synchronized with the mass spectrometer such that an m/z range of the precursor ions included in each packet of precursor ions emitted from the second pre-separation device corresponds to a precursor m/z isolation window of the mass spectrometer (synchronization of ion ejection from the mass selective ion transmission stage and mass scanning of mass spectrometer, [0412]; mass to charge ratio of ejected ion from a preferred ion trap corresponds to a m/z transmission window of subsequent mass analyzer, [0304]).
Regarding claim 2, Hoyes teaches that the first pre-separation device comprises a trapped ion mobility separator (ion mobility selective ion trap, [0159]).
Regarding claim 5, Hoyes teaches that the second pre-separation device comprises a linear ion trap ([0091]) including an end electrode (exit end plate 140, [0347]) configured to sequentially emit the plurality of packets of ions through an aperture of the end electrode.
Regarding claim 6, Hoyes teaches that the end electrode is configured to selectively apply a blocking DC potential to the precursor ions to sequentially emit the plurality of packets from the end electrode ([trapping ions by biasing the end plate, 0347]).
Regarding claim 7, Hoyes teaches that the second pre-separation device is an ion accumulator (ion trap 186 is filled with ions which are then extracted, [0409]).
Regarding claim 12, Hoyes teaches that the first pre-separation device is configured to continuously transport the precursor ions through the pre-separation device to spatially separate the precursor ions into the plurality of subsets of precursor ions (ion mobility separation, [0406]; continuous ion beam, fig. 43).
Regarding claim 13, Hoyes teaches that the first pre-separation device is configured to emit the plurality of subsets of precursor ions and the second pre-separation device is configured to emit the plurality of packets of precursor ions according to a timing scheme (output of ion traps is synchronized with mass selection windows, Abstract).
Regarding claim 14, Hoyes teaches that the timing scheme includes emitting an initial subset of precursor ions from the first pre-separation device and emitting the plurality of packets of precursor ions from the second pre-separation device prior to emitting a next subset of precursor ions from the first pre-separation device (the ion trap extracts ions after the scan cycle of the downstream device, fig. 3).
Regarding claim 16, Hoyes teaches that the mass spectrometer comprises a mass filter (188) configured to filter the plurality of packets of precursor ions based on the m/z of the precursor ions being within the precursor m/z isolation window, wherein the second pre-separation device is synchronized with the mass filter such that the m/z range of the precursor ions included in each packet of precursor ions emitted from the second pre-separation device corresponds to a precursor m/z isolation window of the mass filter (transmission window of ion trap is synchronized with scanning window of mass filter, [0304]).
Regarding claim 17, Hoyes teaches that the mass spectrometer is configured to fragment the plurality of packets of precursor ions within the precursors m/z isolation window into product ions and acquire the mass spectra based on the product ions (the system may include a downstream fragmentation means for triple quadrupole mass spectrometry, [0191]).
Regarding claim 18, Hoyes teaches a system comprising:
A first pre-separation device (ion trap 182, fig. 44, [0408]) configured to spatially separate precursor ions into a plurality of subsets of precursor ions according to mobilities of the precursor ions and sequentially emit the plurality of subsets of precursor ions from the first pre-separation device (operated as mobility separator, [0410]; the ions may be precursor ions since a fragmentation cell can be provided downstream, [0191]);
A second pre-separation device (ion trap 186) positioned downstream of the first pre-separation device, the second pre-separation device configured to receive the plurality of subsets of precursor ions emitted from the first pre-separation device and, for each subset of precursor ions, sequentially emit a plurality of packets of precursor ions from the second pre-separation device based on a mass-to-charge ratio of the precursor ions (mass selective ejection from ion trap 186, [0409]); and
A mass spectrometer (mass analyzer 188) positioned downstream of the second pre-separation device and configured to receive the plurality of packets of precursor ions from the second pre-separation device and acquire mass spectra for the plurality of packets of precursor ions, the mass spectrometer comprising a mass filter synchronized with the second pre-separation device such that an m/z range of the precursor ions included in each packet of precursor ions emitted from the second pre-separation device corresponds to a precursor m/z isolation window of the mass spectrometer (synchronization of ion ejection from the mass selective ion transmission stage and mass scanning of mass spectrometer, [0412]).
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 3, 15, 19 and 22-25 are rejected under 35 U.S.C. 103 as being unpatentable over Hoyes in view of Wang (US 20170299550 A1).
Regarding claim 3, Hoyes teaches all the limitations of claim 1 as described above. Hoyes does not teach that the first pre-separation device comprises a drift ion mobility separator.
Wang teaches a drift ion mobility separator coupled to a mass spectrometer ([0046]).
It would have been obvious to one of ordinary skill in the art on or before the effective filing date of the invention to modify the system of Hoyes by making the mobility separator a drift-type mobility separator as taught by Wang, as a matter of selecting a known equivalent type of ion mobility separator which can perform separation of ions for a downstream mass filter, in order to perform ion separation using two unrelated techniques (IMS and MS) which assists in detecting ions from complex samples (Wang, [0004]).
Regarding claim 15, Hoyes teaches all the limitations of claim 1 as described above. Hoyes does not teach that the timing scheme includes emitting an initial subset of precursor ions from the first pre-separation device and emitting the plurality of packets of ions from the second pre-separation device based on the initial subset of sprecursor ions while a next subset of precursor ions is emitted from the first pre-separation device.
Wang teaches a system in which ions are emitted from a pre-separation device (ion mobility separator) while a second separation device (mass spectrometer) is operated to emit ions ([0080]).
It would have been obvious to one of ordinary skill in the art on or before the effective filing date of the invention to modify the duty cycle of the system of Hoyes so that the ion mobility spectrometer emits ions at the same time as the mass spectrometer is operating, in order to perform a faster analysis with no delay between cycles.
Regarding claim 19, Hoyes teaches a system comprising:
One or more processors (computer [0292]) which are configured to:
Direct a first pre-separation device (ion trap 182, fig. 44, [0408]) to spatially separate precursor ions into a plurality of subsets of precursor ions according to mobilities of the precursor ions;
Direct the first pre-separation device to sequentially emit the plurality of subsets of precursor ions according to the mobilities of the precursor ions (operated as mobility separator, [0410]; the ions may be precursor ions since a fragmentation cell can be provided downstream, [0191]);
Direct the first pre-separation device to sequentially emit the plurality of subsets of precursor ions to a second pre-separation device (ion trap 186);
Direct the second pre-separation device (ion trap 186) to sequentially emit, for each subset of precursor ions, a plurality of packets of precursor ions to a mass spectrometer based on a mass-to-charge ratio of the precursor ions (mass selective ejection from ion trap 186, [0409]); and
Direct the mass spectrometer (mass analyzer 188) to acquire mass spectra for the plurality of packets of precursor ions;
Wherein the second pre-separation device is synchronized with the mass spectrometer such that an m/z range of precursor ions included in each packet of precursor ions emitted from the second pre-separation device corresponds to a precursor m/z isolation window of the mass spectrometer (synchronization of ion ejection from the mass selective ion transmission stage and mass scanning of mass spectrometer, [0412]).
Hoyes does not teach memory storing executable instructions to cause the computing device to perform the method.
Wang teaches a mass spectrometer system having a memory storing executable instructions ([0015-0017]).
It would have been obvious to one of ordinary skill in the art on or before the effective filing date of the invention to implement the method of Hoyes using instructions stored in memory as taught by Wang, in order to perform repeatable software-based control of the mass spectrometry system with no unexpected result.
Regarding claim 22, Hoyes teaches that directing the first pre-separation device to sequentially emit the plurality of subsets of precursor ions includes directing the first pre-separation device to continuously transport the precursor ions through the pre-separation device to spatially separate the precursor ions into the plurality of subsets of precursor ions (ion mobility separation, [0406]; continuous ion beam, fig. 43).
Regarding claim 23, Hoyes teaches that directing the first pre-separation device to sequentially emit the plurality of subsets of precursor ions includes directing the first pre-separation device to emit the plurality of packets of precursor ions according to a timing scheme (output of ion traps is synchronized with mass selection windows, Abstract).
Regarding claim 24, Hoyes teaches that the timing scheme includes emitting an initial subset of precursor ions from the first pre-separation device and emitting the plurality of packets of precursor ions from the second pre-separation device prior to emitting a next subset of precursor ions from the first pre-separation device (the ion trap extracts ions after the scan cycle of the downstream device, fig. 3).
Regarding claim 25, Hoyes does not teach that the timing scheme includes emitting an initial subset of precursor ions from the first pre-separation device and emitting the plurality of packets of ions from the second pre-separation device based on the initial subset of precursor ions while a next subset of precursor ions is emitted from the first pre-separation device.
Wang teaches a system in which ions are emitted from a pre-separation device (ion mobility separator) while a second separation device (mass spectrometer) is operated to emit ions ([0080]).
It would have been obvious to one of ordinary skill in the art on or before the effective filing date of the invention to modify the duty cycle of the system of Hoyes so that the ion mobility spectrometer emits ions at the same time as the mass spectrometer is operating, in order to perform a faster analysis with no delay between cycles.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Hoyes in view of Prasad (US 20210247359 A1).
Regarding claim 4, Hoyes teaches all the limitations of claim 1 as described above. Hoyes does not teach that the first pre-separation device comprises a differential ion mobility separator.
Prasad teaches a differential ion mobility separator coupled to a mass spectrometer ([0034]).
It would have been obvious to one of ordinary skill in the art on or before the effective filing date of the invention to modify the system of Hoyes by making the mobility separator a differential mobility separator as taught by Prasad, as a matter of selecting a known equivalent type of ion mobility separator which can perform separation of ions for a downstream mass filter with no unexpected result.
Claims 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Hoyes in view of Ugarov (US 20220365026 A1).
Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Hoyes in view of Wang and in further view of Ugarov.
Regarding claim 8, Hoyes teaches all the limitations of claim 1 as described above. Hoyes does not teach a collector funnel positioned between the first pre-separation device and the second pre-separation device configured to guide the plurality of subsets of precursor ions from the first pre-separation device to the second pre-separation device.
Ugarov teaches a multi-stage mass spectrometry system having an ion funnel (155) for transferring ions from an ion mobility separator to a subsequent stage of the device ([0027]).
It would have been obvious to one of ordinary skill in the art on or before the effective filing date of the invention to modify the system of Hoyes to have the funnel for transferring ions between stages of the device taught by Ugarov, in order to assist in focusing ions emitted by the ion mobility device into a subsequent stage of the mass spectrometer.
Regarding claim 9, Hoyes teaches all the limitations of claim 1 as described above.
Regarding claim 20, Hoyes and Wang teaches all the limitations of claim 19 as described above.
Hoyes does not teach that the first pre-separation device comprises a plurality of channels configured to store the plurality of subsets of precursor ions within the plurality of channels, wherein the first pre-separation device is configured to sequentially emit the plurality of subsets of precursor ions from the plurality of channels.
Ugarov teaches an ion mobility separation device (125) comprising a plurality of channels (305, fig. 3) configured to store a plurality of subsets of precursor ions within the plurality of channels (each channel stores ions of like mobilities, [0034]), wherein the first pre-separation device is configured to sequentially emit the plurality of subsets of precursor ions from the plurality of channels (ions are scanned out channel-by-channel, [0036]).
It would have been obvious to one of ordinary skill in the art on or before the effective filing date of the invention to modify the system of Hoyes to have the channel structure taught by Ugarov, in order to ensure that ions remain separated into discrete mobility ranges and allow sequential releasing of the ions based on their mobility to a downstream device.
Regarding claim 10, Ugarov teaches that each channel of the plurality of channels is configured to store a distinct subset of precursor ions (each channel stores ions of like mobilities, [0034]; precursor ions in the combination with Hoyes) included in the plurality of subsets of precursor ions.
Regarding claim 11, Ugarov teaches that the first pre-separation device is configured to sequentially emit each distinct subset of precursor ions from the plurality of channels.
Regarding claim 21, Ugarov teaches that each channel of the plurality of channels is configured to store a distinct subset of precursor ions ([0034]) included in the plurality of subsets of precursor ions, wherein directing the first precursor ions includes sequentially emitting each distinct subset of precursor ions from the plurality of channels.
Conclusion
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/DAVID E SMITH/ Examiner, Art Unit 2881