DETAILED ACTION
Response to Arguments
Applicant's arguments filed 11/07/2025 have been fully considered but they are not persuasive.
Applicant argues that the prior art of record does not teach or disclose the limitation “measuring, for a predetermined time period, an ion detection sensitivity in a state in which an optimal voltage that maximizes an amount of ions in the sample is applied to the electrodes and the quadrupole mass filters”. Examiner disagrees as Ueda discloses measuring an ion detection sensitivity (analysis start time in step S3, see paragraph [0051], a measurement example of the ion intensity observed during a period of time T1 in step S3, see paragraph [0058]; reduction of the ion intensity cause by the charge-up, see paragraph [0051]), in a state in which an optimal voltage that maximizes an amount of ions in the sample is applied to the electrodes (controller 6 is responsible for controlling the system with data processor 5 for storing values of control, see paragraph [0041]; voltages applied to electrodes of ion guide 15, see paragraph [0039]; during measurement in the analysis start time in step S3, it is preferable that the predetermined time is a length of time in which the sending of the standard sample from the sample supply unit 2 is sufficiently stable, see paragraph [0051]; Fig. 3 depicts during time period T1 before a reduction in detection ion intensity due to contamination of the ion optical elements is observed, the voltage is interpreted to be optimal prior to contamination (i.e. ions prevented from reaching detector to reduce detected intensity due to charge-up), see paragraph [0051]).
Applicant further argues the prior art of record does not teach or disclose the limitation “storing, for the sample, a plurality of pairs of control values for the gas flow rate to be applied for the ion source and control values for the voltage to be applied to the ion source, and a normal value of the detection sensitivity of ions in the sample for the plurality of pairs”. Examiner disagrees as Ueda teaches a controller 6 is responsible for controlling the system (e.g. voltages applied to the ion source, voltages applied to the electrodes of the ion guide, detection values at the detector), with data processor 5 for storing values of control (see paragraph [0041]). Ueda further teaches a normal value of detection sensitivity is realized when a detection of a reduction of the ion intensity cause by the charge-up (see paragraph [0051]).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 recites the limitation "…the electrodes and quadrupole mass filters forming the mass spectrometry unit" (emphasis added) in lines 7-8 of the claim. There is insufficient antecedent basis for this limitation in the claim.
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 2-5 are rejected under 35 U.S.C. 103 as being unpatentable over Ueda (US PGPub 2021/0217605, hereinafter Ueda) in view of King III et al. (US PGPub 2019/0237314, hereinafter King).
Regarding claim 2, Ueda discloses a method for controlling a mass spectrometer (present invention relates to a mass spectrometer and to a technique for improving maintainability of the mass spectrometer, see paragraph [0001]) including:
an ion source that ionizes a compound in a sample (ESI probe 11 for ionizing the compounds in a liquid sample, see paragraph [0038]),
a mass spectrometry unit that separates ions based on a mass to charge ratio (ions having a specific mass to charge ratio corresponding to a voltage is allowed to pass the quadrupole mass filter 18 to reach the ion detector 19, see paragraph [0045]), and
a plurality of electrodes that form an electric field that transports ions generated by the ion source to the mass spectrometry unit (ions derived from the sample are focused by the multipole ion guide 15 and sent into the analysis chamber 104, see paragraph [0044]), the method comprising:
ionizing the sample by the ion source (ESI probe 11 for ionizing the compounds in a liquid sample, see paragraph [0038]);
detecting, based on a change in ion permeability over time, ions accumulated in the electrodes and quadrupole mass filters forming the mass spectrometry unit (ions having a specific mass to charge ratio corresponding to a voltage is allowed to pass the quadrupole mass filter 18 to reach the ion detector 19, see paragraph [0045]);
measuring, for a predetermined time period, an ion detection sensitivity in a state in which an optimal voltage that maximizes an amount of ions in the sample is applied to the electrodes and the quadrupole mass filters (ion intensity data acquisition 51 starts collecting ion intensity data, for a length of time where the analysis is sufficiently stable and the reduction of the ion intensity caused by the charge-up of the contaminated part when any of the ion optical elements is contaminated can be sufficiently observed (e.g. optimal window for ion detection sensitivity), see paragraphs [0050-0051]; controller 6 is responsible for controlling the system with data processor 5 for storing values of control of voltages applied to ion guide 15, see paragraph [0041]; data processor 5 has an ion intensity data acquisition unit 51 and a charge-up determination unit 52 for normal values of detection sensitivity, see paragraph [0041]; predetermined time for detection, for example T1, see Fig. 3 and paragraph [0058]);
calculating a change in the ion detection sensitivity over time by comparing the ion detection sensitivity at a time point immediately after the start of the measurement with the ion detection sensitivity when the predetermined time period elapses (ion intensity reduction caused by the charge-up, see paragraph [0051]; for a predetermined time from the analysis start time (usually 5 to 10 minutes) due to charge-up effects, see paragraphs [0050-0051]);
comparing the change in the ion detection sensitivity over time with a predetermined threshold to determine whether the change in the ion detection sensitivity over time is normal or abnormal (reduction in ion intensity caused by charge up, see paragraph [0051] and paragraph [0065] for comparing charge-up with a threshold value); and
determining whether any of the electrodes and the quadrupole mass filters is dirty when it is determined that the change in ion detection sensitivity over time is abnormal (charge-up determination unit 52 gives a charge-up check results showing the point that is estimated to have been contaminated, see paragraph [0062]; alternatively, the quadrupole mass spectrometer is possible to automatically and reliably estimate the point where contaminant has progressed (e.g. with the charge-up threshold value) to inform the operator, see paragraph [0064]).
Ueda fails to disclose detecting a change in ionization efficiency of the ion source based on a change in an amount of ions with respect to a gas flow rate for the ion source or a voltage of the ion source.
King discloses continuously monitoring the performance of an ionization system (see abstract). King further teaches the continuous monitoring may be used in real time to make adjustments to the parameters associated with the ionization system, such as current, voltage, flow rate, to ensure the process is run under uniform and stable conditions (see paragraph [0087]).
King modifies Ueda by suggesting a continuous monitoring of the ionization system to make real time adjustments associated with the ionization system.
Since both inventions are drawn to ionization sources, it would have been obvious to the ordinary artisan before the effective filing date to modify Ueda by continuously monitoring of the ionization system to make adjustments, such as a gas flow rate of the ion source and an optimal voltage for maximizing ion generation of the ionization system, for the purpose of ensuring the processes for the ionization system is run under uniform and optimal stable conditions as taught by King.
Regarding claim 3, Ueda discloses specifying one of the electrodes and one of the quadrupole mass filters in such a manner that the specified electrode and the specified quadrupole mass filter are to be subjected to determination of whether a change in the ion detection sensitivity over time is normal or abnormal (ion intensity data acquisition 51 starts collecting ion intensity data, for a length of time where the analysis is sufficiently stable and the reduction of the ion intensity caused by the charge-up of the contaminated part when any of the ion optical elements is contaminated can be sufficiently observed (e.g. optimal window for ion detection sensitivity), see paragraphs [0050-0051]; the quadrupole mass spectrometer is possible to automatically and reliably estimate the point where contaminant has progressed (e.g. with the charge-up threshold value) to inform the operator, see paragraph [0064]);
sequentially specifying one of the electrodes and one of the quadrupole mass filters as polarity reversal electrodes (after the ion intensity gradually decreases due to charge-up is observed, a voltage having polarity reversed is temporarily applied in order from the heated capillary 12, see paragraph [0058]);
measuring, after a voltage that is at a reverse potential of the optimal voltage is applied to the specified polarity reversal electrodes for a fixed time period, the ion detection sensitivity for the predetermined time period while applying the optimal voltage (after the voltage applied to the ion optical element is reversed, the ion intensity has remarkably increased before and after the change, see paragraphs [0059-0060];
obtaining a change in the ion detection sensitivity over time by comparing the ion detection sensitivity at a time point immediately after the start of the measurement with the ion detection sensitivity when the predetermined time period elapses (the ion intensity has remarkably increased before and after the change, see paragraph [0060]);
comparing the change in the ion detection sensitivity over time with a predetermined threshold to determine whether the change in the ion detection sensitivity over time is normal or abnormal (reduction in ion intensity caused by charge up, see paragraph [0051] and paragraph [0065] for comparing charge-up with a threshold value); and
determining that ions are accumulated in the polarity reversal electrodes, when it is not determined that a change in the ion detection sensitivity over time is abnormal in the specified polarity reversal electrodes (reduction in ion intensity caused by charge up, see paragraph [0051] and paragraph [0065] for comparing charge-up with a threshold value).
Regarding claim 4, Ueda discloses a method for controlling a mass spectrometer (present invention relates to a mass spectrometer and to a technique for improving maintainability of the mass spectrometer, see paragraph [0001]) including:
an ion source that ionizes a compound in a sample (ESI probe 11 for ionizing the compounds in a liquid sample, see paragraph [0038]),
a mass spectrometry unit that separates ions based on a mass to charge ratio (ions having a specific mass to charge ratio corresponding to a voltage is allowed to pass the quadrupole mass filter 18 to reach the ion detector 19, see paragraph [0045]), and
a plurality of electrodes that form an electric field that transports ions generated by the ion source to the mass spectrometry unit (ions derived from the sample are focused by the multipole ion guide 15 and sent into the analysis chamber 104, see paragraph [0044]), the method comprising:
ionizing the sample by the ion source (ESI probe 11 for ionizing the compounds in a liquid sample, see paragraph [0038]);
detecting, based on a change in ion permeability over time, ions accumulated in the electrodes and quadrupole mass filters forming the mass spectrometry unit (ions having a specific mass to charge ratio corresponding to a voltage is allowed to pass the quadrupole mass filter 18 to reach the ion detector 19, see paragraph [0045]);
storing, for the sample, a plurality of pairs of control values for the gas flow rate to be applied for the ion source and control values for the voltage to be applied to the ion source, and a normal value of the detection sensitivity of ions in the sample for the plurality of pairs (charge-up check controller 41 opens the valve 22 of the sample supply unit 2 to introduce gas to the sample reservoir 23, see paragraph [0049]; sample liquid is given electric charges at the tip of the probe 11 to form a fine charged droplets, see paragraph [0044]; controller 6 is responsible for controlling the system with data processor 5 for storing values of control, see paragraph [0041]; data processor 5 has an ion intensity data acquisition unit 51 and a charge-up determination unit 52 for normal values of detection sensitivity, see paragraph [0041]); and
sequentially applying the control values for the plurality of pairs and measuring the detection sensitivity of ions in the sample for each of the pairs to measure a characteristic of the ion source of the gas flow rate and the voltage (controller 6 is responsible for controlling the system with data processor 5 for storing values of control, see paragraph [0041]; data processor 5 has an ion intensity data acquisition unit 51 and a charge-up determination unit 52 for normal values of detection sensitivity, see paragraph [0041]).
Ueda fails to disclose detecting a change in ionization efficiency of the ion source based on a change in an amount of ions with respect to a gas flow rate for the ion source or a voltage of the ion source.
King discloses continuously monitoring the performance of an ionization system (see abstract). King further teaches the continuous monitoring may be used in real time to make adjustments to the parameters associated with the ionization system, such as current, voltage, flow rate, to ensure the process is run under uniform and stable conditions (see paragraph [0087]).
King modifies Ueda by suggesting a continuous monitoring of the ionization system.
Since both inventions are drawn to ionization sources, it would have been obvious to the ordinary artisan before the effective filing date to modify Ueda by continuously monitoring of the ionization system, such as a flow rate of the ion source, for the purpose of ensuring the processes for the ionization system is run under uniform and stable conditions as taught by King.
Regarding claim 5, Ueda discloses comparing the measured ion detection sensitivity for the gas flow rate and the voltage with the previously stored normal value of the ion detection sensitivity (controller 6 is responsible for controlling the system with data processor 5 for storing values of control, see paragraph [0041]; data processor 5 has an ion intensity data acquisition unit 51 and a charge-up determination unit 52 for normal values of detection sensitivity, see paragraph [0041]; ion intensity reduction caused by the charge-up, see paragraph [0051]; for a predetermined time from the analysis start time (usually 5 to 10 minutes) due to charge-up effects, see paragraphs [0050-0051]); and
determining that an abnormality is present in the ion source when it is determined that the measured ion detection sensitivity is abnormal (reduction in ion intensity caused by charge up, see paragraph [0051] and paragraph [0065] for comparing charge-up with a threshold value; controller 6 is responsible for controlling the system with data processor 5 for storing values of control, see paragraph [0041]; data processor 5 has an ion intensity data acquisition unit 51 and a charge-up determination unit 52 for normal values of detection sensitivity, see paragraph [0041]).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANWAY CHANG whose telephone number is (571)270-5766. The examiner can normally be reached Monday - Friday 7:30 AM - 4:00 PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Kim can be reached at (571)272-2293. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Hanway Chang
/HC/Examiner, Art Unit 2881
/MICHAEL J LOGIE/ Primary Examiner, Art Unit 2881