DETAILED ACTION
Specification
The disclosure (specification) is objected to because it is unclear. Going forward with examination, the following specification paragraphs are interpreted to be (Note that in applicant’s response, where a change is requested in the specification, an entire paragraph of the specification containing the change will be needed):
--[0002] A mobile phase solvent used in dissolved in the mobile phase solvent as the time elapses, and possibly becomes a foreign substance contaminating the mobile phase solvent. When the mobile phase solvent is contaminated by a foreign substance, a phenomenon that ionization of a measurement object substance dissolved in the mobile phase intrinsically desired to be ionized is suppressed (ion suppression) occurs, and the measurement sensitivity of the liquid chromatograph mass spectrometer (LC/MS) for the measurement object substance deteriorates.--
--[0003] In Patent Literature 1 described below, measurement is performed by adding an internal standard substance to a mobile phase solvent, and when the intensity of the internal standard substance becomes less than a reference, it is determined that the ion suppression has occurred (refer to the abstract).--
--[0015] FIG. 2 is a graph illustrating a measurement result of a chromatogram signal. Here, it is assumed that each of the first mobile phase solvent and the second mobile phase solvent is a mixed liquid of [[the]] a liquid A (deionized water) and [[the]] a liquid B (methanol). When a ratio of the liquid B changes over time as the upper stage of FIG. 2, [[the]] a blank sample of each of the first mobile phase solvent and the second mobile phase solvent is to be measured by a gradient elution method using the mass spectrometer 5. The horizontal axis of FIG. 2 shows the elapsed time from the start of elution. The vertical axis of the lower stage of FIG. 2 shows the ion signal intensity acquired by measuring the blank sample of each of the first mobile phase solvent and the second mobile phase solvent in which the ratio of the liquid B within the mobile phase changes over time .--
--[0016] First, the mass spectrometer 5 measures the ion signal intensity using the first mobile phase solvent. The first mobile phase solvent is a mobile phase solvent known not contaminated. Followings for example can be used as the first mobile phase solvent: (a) a mobile phase solvent not long after preparation; (b) a mobile phase solvent having been stored under a condition where the temperature and the humidity were managed after preparation until the time of use (refrigerator and the like). With the time point of starting elution using the first mobile phase solvent being made the time point 0, the mass spectrometer 5 measures the ion signal intensity I1, t1 at the time point t1 and the ion signal intensity I.1, t2 at the time point t2 respectively. The time point t1 and the time point t2 are made the ratio of the liquid B mobile phase solvent changes over tine so as to be different from each other. The mass spectrometer 5 calculates the ratio R1 of each ion signal intensity of the first mobile phase solvent as follows: I1, t2/I1, t1=R1.--
--[0017] Next, the mass spectrometer 5 measures the ion signal intensity using the second mobile phase solvent. The second mobile phase solvent is a determination object for determining whether or not there is contamination in the second mobile phase solvent. The second mobile phase solvent is a mobile phase solvent that is not the first mobile phase solvent and is subjected to time elapses after being arranged in the mass spectrometer 5. With the time point of starting elution using the second mobile phase solvent being made the time point 0, the mass spectrometer 5 measures respectively the ion signal intensity I2, t1 and I2, t2 at the time t1 and t2 which are same to those for the first mobile phase solvent. The mass spectrometer 5 calculates the ratio R2 of each ion signal intensity as follows: I2, t2/I2, t1 = R2.--
--[0018] When the second mobile phase solvent is contaminated and contains much foreign substance associated with the second mobile phase solvent rises more than that of the non-contaminated first mobile phase solvent accompanying by an effect of a rise of the ratio of the liquid B within the mobile phase solvent. Utilizing the effect, by comparison of R1 and R2, it is possible to determine whether or not the second mobile phase solvent is contaminated. In concrete terms, when R2/R1 or R2-R1 is a threshold or more (namely when the both deviate from each other largely and the absolute difference of the both is a threshold or more), it is determined that the second mobile phase solvent used in measurement of R2 is contaminated.--
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception relating to an abstract idea without significantly more. The claims recite a method for controlling a liquid chromatograph mass spectrometer. The method comprising plural steps that appear to be merely a mental process practiced mentally and not integrated into any of the physical statutory patentable categories: process, machine, manufacture, or composition of matter. One cannot physically practice claims 1-14 (See MPEP 2106).
Going forward with examination, claims 1-14 are interpreted to be:
--1. A method for controlling a liquid chromatograph mass spectrometer, the control method comprising:
using a controller of the liquid chromatograph mass spectrometer to calculate a first ratio of chromatogram signal intensities at two different time points, the chromatogram signal intensities being obtained by the liquid chromatograph mass spectrometer measuring a blank sample with a gradient elution method by using a first mobile phase solvent having a specific composition and solvent ratio and having a known degree of contamination less than a reference value;
using the controller to calculate a second ratio of chromatogram signal intensities at the liquid chromatograph mass spectrometer measuring a blank sample with the gradient elution method by using a second mobile phase solvent having the same composition and solvent ratio as those of the first mobile phase solvent; and
using the controller to determine whether or not the second mobile phase solvent is contaminated by using the first ratio and the second ratio,
wherein
the first ratio is a ratio between a chromatogram signal intensity at a first time point at which a first time elapses from start of elution using the first mobile phase solvent and a chromatogram signal intensity at a second time point at which a solvent ratio in the first mobile phase solvent is different from that in the first mobile phase solvent of the first time point
the second ratio is a ratio between a chromatogram signal intensity at a first time point at which [[the]] a first time elapses from start of elution using the second mobile phase solvent and a chromatogram signal intensity at a second time point at which a solvent ratio in the second mobile phase solvent is different from that in the second mobile phase solvent of the first time point ,
the time span between the first time point and the second time point with respect to the second ratio is substantially equal to the time span between the first time point and the second time point with respect to the first ratio; and
the controller determines that the second mobile phase solvent is contaminated when an absolute difference between the first ratio and the second ratio is equal to or greater than a threshold value.--
--2. The control method according to claim 1, wherein each of the respective first time points and the second time points is set to be different from a time point at which an elution time of a target substance to be measured by the liquid chromatograph mass spectrometer using the solvent ratio at each of the first time points and the second time points is scheduled to elapse.--
--3. The control method according to claim 1, further comprising:
the controller notifying, when it is determined in the determining step that the second mobile phase solvent is contaminated, a user of the result; and
the liquid chromatograph mass spectrometer starting, when the controller determines that the second mobile phase solvent is not contaminated, measurement of a target substance to be measured by the liquid chromatograph mass spectrometer.--
--4. The control method according to claim 1, further comprising:
the liquid chromatograph mass spectrometer switching the second mobile phase solvent to another mobile phase solvent when the controller determines that the second mobile phase solvent is contaminated; and
the liquid chromatograph mass spectrometer starting, when the controller determines that the second mobile phase solvent is not contaminated, measurement of a target substance to be measured by the liquid chromatograph mass spectrometer.--
--5. The control method according to claim 4, wherein
the liquid chromatograph mass spectrometer includes a container containing a third mobile phase solvent having the same composition as the second mobile phase solvent, and
the liquid chromatograph mass spectrometer switches to the another mobile phase solvent
--6. The control method according to claim 4, wherein
the liquid chromatograph mass spectrometer includes a mechanism configured to replace the second mobile phase solvent in a container containing the second mobile phase solvent with the second mobile phase solvent that is not contaminated, and
when the liquid chromatograph mass spectrometer switches to the another mobile phase solvent, the second mobile phase solvent is switched to the another mobile phase solvent by replacing, using the mechanism, the second mobile phase solvent in the container containing the second mobile phase solvent with the second mobile phase solvent that is not contaminated.--
--7. The control method according to claim 4, wherein after the liquid chromatograph mass spectrometer switches to the another mobile phase solvent, the controller calculates the second ratio and determines whether or not the second mobile phase solvent is contaminated again.--
--8. The control method according to claim 4, further comprising:
the controller recalculating the first ratio using the another mobile phase solvent after the liquid chromatograph mass spectrometer switching to the another mobile phase solvent.--
--9. The control method according to claim 1, further comprising:
the liquid chromatograph mass spectrometer switching measuring only an ion signal of specific m/z, wherein
when the controller calculating the first ratio and the step of calculating the second ratio, the controller calculating each of the first ratio and the second ratio by the liquid chromatograph mass spectrometer measuring only the ion signal of the specific m/z.--
--10. The control method according to claim 1, further comprising:
the liquid chromatograph mass spectrometer measuring an ion signal of m/z included in a specific range by scanning within the range, wherein
when the controller calculating the first ratio and the controller calculating each of the first ratio and the second ratio by the liquid chromatograph mass spectrometer measuring the ion signal by the scanning.--
--11. The control method according to claim 10, further comprising:
the controller estimating a foreign substance in the second mobile phase solvent and an amount of the foreign substance by using a mass spectrum obtained by the liquid chromatograph mass spectrometer measuring the ion signal by the scanning.--
--12. The control method according to claim 1, further comprising:
the liquid chromatograph mass spectrometer measuring only an ion signal of specific m/z, wherein
when the controller calculating the first ratio and the controller calculating each of the first ratio and the second ratio chromatogram signal obtained by the liquid chromatograph mass spectrometer measuring only the ion signal of the specific m/z, and
the method further comprises:
the liquid chromatograph mass spectrometer measuring, when the controller determines that the second mobile phase solvent is contaminated, an ion signal of m/z included in a specific range by scanning within the range; and
the controller estimating a foreign substance in the second mobile phase solvent and an amount of the foreign substance by using a mass spectrum obtained by the liquid chromatograph mass spectrometer measuring the ion signal by the scanning.--
--13. The control method according to claim 1, wherein the controller calculates the second ratio and determines whether or not the second mobile phase solvent is contaminated in a vacant time during which a target substance to be measured by the liquid chromatograph mass spectrometer using the solvent ratio at each of the first time point and the second time point is not measured.--
--14. A liquid chromatograph apparatus, comprising[[:]] a liquid chromatograph mass spectrometer with a controller, wherein the apparatus is configured to perform the method according to claim 1.--
Allowable Subject Matter
Claims 1-14 would be allowed if the 101 rejections were overcome. The following would be an examiner’s statement of reasons for allowance:
With respect to the sole independent claim 1, prior art of record doesn’t teach, suggest, or render obvious the total combination of the recited features, including the following allowable subject matter:
“using a controller of the liquid chromatograph mass spectrometer to calculate a first ratio of chromatogram signal intensities at two different time points, the chromatogram signal intensities being obtained by the liquid chromatograph mass spectrometer measuring a blank sample with a gradient elution method by using a first mobile phase solvent having a specific composition and solvent ratio and having a known degree of contamination less than a reference value;
using the controller to calculate a second ratio of chromatogram signal intensities at two different time points, the chromatogram signal intensities being obtained by the liquid chromatograph mass spectrometer measuring a blank sample with the gradient elution method by using a second mobile phase solvent having the same composition and solvent ratio as those of the first mobile phase solvent; and
using the controller to determine whether or not the second mobile phase solvent is contaminated by using the first ratio and the second ratio,
wherein
the first ratio is a ratio between a chromatogram signal intensity at a first time point at which a first time elapses from start of elution using the first mobile phase solvent and a chromatogram signal intensity at a second time point at which a solvent ratio in the first mobile phase solvent is different from that in the first mobile phase solvent of the first time point,
the second ratio is a ratio between a chromatogram signal intensity at a first time point at which a first time elapses from start of elution using the second mobile phase solvent and a chromatogram signal intensity at a second time point at which a solvent ratio in the second mobile phase solvent is different from that in the second mobile phase solvent of the first time point,
the time span between the first time point and the second time point with respect to the second ratio is substantially equal to the time span between the first time point and the second time point with respect to the first ratio; and
the controller determines that the second mobile phase solvent is contaminated when an absolute difference between the first ratio and the second ratio is equal to or greater than a threshold value.”
Conclusion
The prior art made of record below and not relied upon is considered pertinent to applicant’s disclosure/invention.
WO 2014132387 A1 to Matsumoto et al. discloses a method for controlling a liquid chromatograph mass spectrometer. As shown in fig. 3 (reproduced and annotated below), the method basically includes using the spectrometer to measure a first spectrum of a mobile phase solvent that is free of a target component. The first spectrum likely contains a spectrum associated with any contamination in the mobile phase solvent. The spectrometer stores the first spectrum in a memory. The spectrometer measures a second spectrum of the same mobile phase solvent containing the target component to be detected. The spectrometer then subtracts the first spectrum from the second spectrum to obtain a third spectrum of the mobile phase solvent containing the target component and as if the mobile phase solvent were free of contamination. As a result, the spectrometer can better detect the target component in the mobile phase solvent.
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WO 2009/123297 A1 to Hirabayashi et al. (mentioned in the specification of the present disclosure and cited in an IDS filed on March 12, 2024) discloses a method for controlling a liquid chromatograph mass spectrometer. Aligning with the present disclosure, the method basically includes using a controller of the spectrometer to determine whether a mobile phase solvent is contaminated beforehand, so as to avoid using the mobile phase solvent if it is contaminated. The method, however, applies steps that are completely different from those disclosed by the present disclosure.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nguyen (Wyn) Q. Ha whose telephone number is (571) 272-2863, email: nguyenq.ha@uspto.gov. The examiner can normally be reached Monday - Friday 8 am - 4:30 pm (Eastern Time).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Stephen Meier can be reached at (571) 272-2149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Nguyen Q. Ha/Primary Examiner, Art Unit 2853 February 24, 2026