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 .
Priority
Applicant's foreign application priority to JP 2023-030220 seems to be incorrect. JP 2023-030220 is drawn to programs, methods, and electronic devices for games filed by Cygames Inc.
Additionally, the Instant Application's PG Pub 2024/0182291 claims to be a continuation of US Pat. Application 17/694,083 (now Pat. No. 11,932,531) drawn to a curved cantilever design to reduce stress in a MEMS actuator filed by Taiwan Semiconductor Manufacturing Company, Ltd. which claims priority to Provisional Application No. 63/299,081.
Response to Amendment
Applicant's amendment filed 7/20/2026 has been received and entered into the record. As a result, claims 1, 2, 4, 14, and 15 have been amended. Therefore, claims 1-18 are presented for examination.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitation(s) is/are: "a scattered light information acquirer configured to acquire" in claim 14.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Objections
Claims 14 and 15 are objected to because of the following informalities:
Claim 14 recites, "a liquid chromatography device [line 18]." The examiner suggests, "the liquid chromatography device."
Claim 15 recites, "a liquid chromatography device [line 11]." The examiner suggests, "the liquid chromatography device."
Appropriate correction is required.
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 1-7, 9-12, and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Toru et al. [JP 2019119308A Translation provided] ("Toru") in view of Tiemann et al. [US Pub. 2022/0128531] ("Tiemann").
With regard to claim 1, Toru teaches a failure detection method ("abnormality detection device [abstract]") comprising:
providing:
a light source configured to irradiate an inside of an electrospray ion source with light ("an irradiation means for irradiating the inside of the ion source spray chamber with light [par. 0015]");
a scattered light information acquisition device ("photographing means 4 are arranged in the ion source 30 [par. 0020]") configured to acquire scattered light information ("captured image of scattered light [par. 0031]") that is information of scattered light scattered by a droplet generated by electrospraying ("the light scattered by the spray droplets can be observed in the region 22 immediately below the spray nozzle 1 [par. 0031]" and "electrospray [par. 0005]"); and
a processing device [fig. 1: Spray State Monitoring Means (11)] configured for storing, in a storage unit (see [par. 0072] where various means are stored), determination reference information indicating a relationship between a parameter of a ("liquid chromatography [par. 0002]") in a normal state and the scattered light information ("from the overall control means 15 of the mass spectrometer, abnormality determination pixel information and abnormality determination conditions for determining the spray state when a predetermined sample solution is sprayed under predetermined appropriate conditions are set in advance [par. 0044]" and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068]"),
the processing device being further configured for acquiring the scattered light information from the scattered light information acquisition device ("the pixel information of the light emission detection area 34 and the pixel information of the non-light emission detection area 35 are obtained from the obtained captured image. In this case, the brightness of each pixel is expressed by, for example, 256 gradations [par. 0038]");
comparing acquired scattered light information with the determination reference information ("the information extracted from the captured image and the information stored in the preset abnormality determination pixels and the abnormality determination condition storage means 12 are compared and determined by the comparison means and the abnormality determination means 10, and if it is determined to be abnormal, it is determined [par. 0046]");
detecting a change in the scattered light relative to a value of the determination reference information based on the acquired scattered light information ("it is determined whether or not the pixel information in the light emission detection region 34 has a predetermined brightness or higher [par. 0039]"); and
determining a failure of a ("when the tone is 200 tones or less, it is determined as abnormal in the processing step S5 [sic] because the light emission is insufficient. Here, it is advisable to also present the possible reasons for the abnormality [par. 0039]" and "from the overall control means 15 of the mass spectrometer, abnormality determination pixel information and abnormality determination conditions for determining the spray state when a predetermined sample solution is sprayed under predetermined appropriate conditions are set in advance [par. 0044]" and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068]" and "ion source abnormality [par. 0019]").
wherein the parameter of the solvent or a mixing ratio of the solvent ("It is presumed that the change in the droplet diameter is caused by factors such as fluctuations in the flow rate of the supplied sample liquid, fluctuations in the ejection speed of the spray gas [par. 0041]" and "The spraying conditions of the sample solution by the spray nozzle may vary depending on the type and concentration of the sample to be measured and the type of solvent … it is necessary to change the pixel for discriminating the spray abnormality and the brightness threshold condition for discriminating according to the spraying condition and the measurement sample condition [par. 0067]" and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068]").
Note: claim is presented in the alternative.
While Toru teaches determining a relationship between a parameter and failure of the spray system [par. 0041] and where the parameter includes a flow rate of the solvent or a mixing ratio of the solvent [par. 0041 and 0067], Toru does not explicitly teach a channel system and a plurality of solvents.
In an analogous art (liquid chromatography), Tiemann teaches determining a relationship between a parameter of a channel system and determining a failure of a channel system ("identifying the differences in flow conditions related to systematic flow delays in any of the one or more of the multiple fluidic streams compared to the other fluidic stream or streams caused by a valve condition, e.g., a valve wear or a valve defect … caused by an LC column condition, e.g., an LC column aging or an LC column defect … caused by a clogging, e.g., by an LC column clogging or by a valve clogging … caused by a loosely connected LC column or capillary, a leakage in an LC column or capillaries and/or in a valve or other connecting elements … caused by incorrect fitting of one or more LC columns … resulting from manufacturing tolerances in one or more components of the LC system [par. 0062]"), and
a plurality of solvents ("the comparing step can include flowing the LC eluate (i.e., the liquid emerging from the LC column that can comprise at least one analyte of interest and a solvent or a mixture of solvents) to the ionization source for further ionization and subsequent detection in the MS [par. 0052]").
Because Toru teaches, "it is necessary to stably ionize a liquid sample, and for that purpose, it is important to form stable microdroplets with an atmospheric pressure spray [par. 0003]" and Tiemann teaches, "the streams of a multiple-stream LC-MS systems may be subjected to variances. For instance, LC columns, capillary dimension, valves, etc. may differ between streams which ultimately can affect, e.g., the total and dead volumes. Other reasons may include clogging in different elements along a flow path of a fluidic stream, manufacturer tolerances in capillary dimensions or other constituting elements of the apparatus as well as many other reasons [par. 0004]" and " liquid chromatography-mass spectrometry (LC-MS) apparatuses based on multiple fluidic streams instead of commonly used LC-MS devices comprising only a single stream have recently attracted much attention in the context of minimizing an injection-to-injection cycle time between subsequent samples and providing high-throughput of the apparatus [par. 0003]" it would have been obvious to one having ordinary skill in the art at the time of filing the invention to have included Tiemann's teachings of determining failures of a channel system with a plurality of solvents, with the teachings of Toru, for the benefit of determining and correcting an issue in the channel system with multiple streams to stably ionize liquid samples.
Although Toru teaches the relationship between the parameter of the system of the liquid chromatography device and the scattered light [par. 0044, 0068], Toru does not explicitly teach a trend of the relationship.
Tiemann teaches a trend of a relationship between the parameter of the channel system and the ionization current ("identifying differences in the flow conditions of the present techniques can include comparing a profile of the monitored ionization current (e.g., a time series of the profile of the monitored ionization current) of the one or more of the multiple fluidic streams with a reference profile of an ionization current (e.g., with a time series of the reference profile of the ionization current) [par. 0059]" and "identifying differences in the flow conditions can involve assessing a profile shift or a profile change of the monitored ionization current. In one example, the assessing step can include comparing a profile shift or a profile change of the monitored ionization current of one of the multiple fluidic streams with respect to a time series of the monitored ionization current of the same stream measured during a previous connection of this stream to the ionization source [par. 0060]" and [fig. 3]).
Tiemann further teaches, "Such differences can, for example, be reflected in the measured shape of the monitored ionization current and/or in a position in time of one or more characteristic features of a profile of the monitored ionization current. These differences can be identified by the controller 60 [par. 0044]."
It would have been obvious to one of ordinary skill in the art at the time of filing the invention to have modified Toru's teachings of comparing a reference image data with measured image data, to include Tiemann's teachings of determining a trend of relationship data over time, for the benefit of more accurately identifying differences between the data.
With regard to claim 2, the combination above teaches the failure detection method according to claim 1. Toru in the combination further teaches wherein the processing device acquires the scattered light information when the mixing ratio of the plurality of solvents introduced into the electrospray ion source changes ("The spraying conditions of the sample solution by the spray nozzle may vary depending on the type and concentration of the sample to be measured and the type of solvent … it is necessary to change the pixel for discriminating the spray abnormality and the brightness threshold condition for discriminating according to the spraying condition and the measurement sample condition [par. 0067]" and "from the overall control means 15 of the mass spectrometer, abnormality determination pixel information and abnormality determination conditions for determining the spray state when a predetermined sample solution is sprayed under predetermined appropriate conditions are set in advance [par. 0044];" where Tiemann in the combination teaches the plurality of solvents and "switching between the multiple fluidic streams 11, 12, 13 at a constant pace [par. 0048]").
With regard to claim 3, the combination above teaches the failure detection method according to claim 2. Toru in the combination further teaches wherein the processing device acquires information with respect to a continuous change in the scattered light information when the mixing ratio of the plurality of solvents continuously changes ("The spraying conditions of the sample solution by the spray nozzle may vary depending on the type and concentration of the sample to be measured and the type of solvent … it is necessary to change the pixel for discriminating the spray abnormality and the brightness threshold condition for discriminating according to the spraying condition and the measurement sample condition [par. 0067]" and "is variable adjusted so that the spray state becomes appropriate. It can also be used for feedback control [par. 0057];" where Tiemann in combination teaches the ionization source continuously changing: "switching between the multiple fluidic streams 11, 12, 13 at a constant pace [par. 0048]").
With regard to claim 4, the combination above teaches the failure detection method according to claim 1. Toru in the combination further teaches wherein the processing device acquires the scattered light information when the flow rate of the solvent of the plurality of solvents is introduced into the electrospray ion source changes ("The spraying conditions of the sample solution by the spray nozzle may vary depending on the type and concentration of the sample to be measured and the type of solvent … it is necessary to change the pixel for discriminating the spray abnormality and the brightness threshold condition for discriminating according to the spraying condition and the measurement sample condition [par. 0067] and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068]" and "is variable adjusted so that the spray state becomes appropriate. It can also be used for feedback control [par. 0057]").
With regard to claim 5, the combination above teaches the failure detection method according to claim 1. Toru in the combination further teaches wherein the scattered light information is intensity of the scattered light ("the pixel information of the light emission detection area 34 and the pixel information of the non-light emission detection area 35 are obtained from the obtained captured image. In this case, the brightness of each pixel is expressed by, for example, 256 gradations [par. 0038]").
With regard to claim 6, the combination above teaches the failure detection method according to claim 1. Toru in the combination further teaches wherein a liquid chromatography mass spectrometer including the electrospray ion source switches at least two modes;
the at least two modes includes
an analysis mode during ion measurement ("when a predetermined sample solution is sprayed under predetermined appropriate conditions are set in advance [par. 0044]" and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068]") and
a monitoring mode during state monitoring ("The mass spectrometer control means 15 transmits a spray observation signal 26 for confirming the spray state to the spray state monitoring means 11 after starting the spray operation by the spray control means 16 for moving the ion source 30. [par. 0045]"), and
in the monitoring mode, at least one of a flow rate and a temperature in the monitoring mode is lowered relative to one in the analysis mode ("to detect a change in the spray state from the change in the non-light emitting region and the light emitting region even from the limited observation image in the ion source 30 of the mass spectrometer … fluctuations in the ejection speed of the spray gas, and fluctuations in the temperature of the heating gas [par. 0041];" where the rate and temperature can be higher or lower).
With regard to claim 7, the combination above teaches the failure detection method according to claim 1. Toru in the combination further teaches wherein a variation in the scattered light information caused by a droplet generated by electrospraying is used as an evaluation index for determining the failure ("when the tone is 200 tones or less, it is determined as abnormal in the processing step S5 [sic] because the light emission is insufficient. Here, it is advisable to also present the possible reasons for the abnormality [par. 0039]").
With regard to claim 9, the combination above teaches the failure detection method according to claim 7. Toru in the combination further teaches wherein the scattered light information is intensity of the scattered light ("the pixel information of the light emission detection area 34 and the pixel information of the non-light emission detection area 35 are obtained from the obtained captured image. In this case, the brightness of each pixel is expressed by, for example, 256 gradations [par. 0038]"), and when the intensity decreases not in a pulsed manner, the processing device determines that liquid feeding is unstable due to a failure of a pump that feeds a solvent flowing through the channel system ("when the tone is 200 tones or less, it is determined as abnormal in the processing step S5 [sic] because the light emission is insufficient. Here, it is advisable to also present the possible reasons for the abnormality [par. 0039]" and "It is presumed that the change in the droplet diameter is caused by factors such as fluctuations in the flow rate of the supplied sample liquid, fluctuations in the ejection speed of the spray gas, and fluctuations [par. 0041]" and Tiemann: "The total volume of a fluidic stream may also include a dwell volume and/or a gradient delay volume associated with the pumping systems. [par.0035]" and "a difference in flow conditions can be caused by changes in the flow conditions developed during operation of the LC-MS apparatus (e.g., due to wear of components) [par. 0044]").
With regard to claim 10, the combination above teaches the failure detection method according to claim 1. Toru in the combination further teaches wherein parameters of the channel system are set by a plurality of values, and the scattered light information acquisition device acquires the scattered light information at each of the plurality of values ("when a predetermined sample solution is sprayed under predetermined appropriate conditions are set in advance [par. 0044]" and "it is necessary to change the pixel for discriminating the spray abnormality and the brightness threshold condition for discriminating according to the spraying condition and the measurement sample condition [par. 0067]" and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068];" where Tiemann in the combination teaches the channel system).
With regard to claim 11, the combination above teaches the failure detection method according to claim 1. Toru in the combination further teaches wherein the determination reference information stores at least information about ("it is necessary to change the pixel for discriminating the spray abnormality and the brightness threshold condition for discriminating according to the spraying condition and the measurement sample condition [par. 0068]")
a relationship between a flow rate of a solvent flowing through the channel system and the scattered light information ("the sample or sample solvent condition to be measured, the spray gas
pressure, and the sample liquid flow rate can be stored [par. 0068]"),
a relationship between a mixing ratio of the solvent in the channel system and the scattered light information ("the spray nozzle may vary depending on the type and concentration of the sample to be measured and the type of solvent [par. 0067]"), and
a variation in information of the scattered light when no failure occurs in the channel system ("if it is 200 tones or more, it is determined to be normal in the processing [par. 0039]" and "if it is 50 tones or less, it is determined to be normal in [par. 0040]").
With regard to claim 12, the combination above teaches the failure detection method according to claim 1. Tiemann in the combination further teaches wherein a plurality of the channel systems are provided in which each of the channel systems includes a separation column ("components (LC columns, capillaries, channels, and/or valves) [par. 0044]"),
the parameter for each of the plurality of channel systems is sequentially changed ("This can involve a modification of the one or more fluidic streams to ensure that the eluates of interest from the respective streams arrive in the respective detection time window (e.g., a detection time window of a fixed duration if the streams are switched at a constant pace). [par. 0063]"), and
the light irradiates from the channel system to the droplet generated in the electrospray ion source in which the parameter has been changed in the channel system (Toru: "an irradiation means for irradiating the inside of the ion source spray chamber with light [par. 0015]").
With regard to claim 14, Toru teaches a failure detection system ("abnormality detection device [abstract]") comprising:
a light source configured to irradiate an inside of an electrospray ion source with light ("an irradiation means for irradiating the inside of the ion source spray chamber with light [par. 0015]");
a scattered light information acquisition device ("photographing means 4 are arranged in the ion source 30 [par. 0020]") configured to acquire scattered light information ("captured image of scattered light [par. 0031]") that is information of scattered light scattered by a droplet generated by electrospraying ("the light scattered by the spray droplets can be observed in the region 22 immediately below the spray nozzle 1 [par. 0031]" and "electrospray [par. 0005]"); and
a processing device [fig. 1: Spray State Monitoring Means (11)] that stores, in a storage unit (see [par. 0072] where various means are stored), determination reference information indicating a relationship between a parameter of a ("liquid chromatography [par. 0002]") in a normal state and the scattered light information ("from the overall control means 15 of the mass spectrometer, abnormality determination pixel information and abnormality determination conditions for determining the spray state when a predetermined sample solution is sprayed under predetermined appropriate conditions are set in advance [par. 0044]" and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068]"),
wherein the processing device further comprises:
a scattered light information acquirer configured to acquire the scattered light information from the scattered light information acquisition device ("the pixel information of the light emission detection area 34 and the pixel information of the non-light emission detection area 35 are obtained from the obtained captured image. In this case, the brightness of each pixel is expressed by, for example, 256 gradations [par. 0038]"); and
a determination processor configured to determine a failure of a ("it is determined whether or not the pixel information in the light emission detection region 34 has a predetermined brightness or higher … when the tone is 200 tones or less, it is determined as abnormal in the processing step S5 [sic] because the light emission is insufficient. Here, it is advisable to also present the possible reasons for the abnormality [par. 0039]" and "from the overall control means 15 of the mass spectrometer, abnormality determination pixel information and abnormality determination conditions for determining the spray state when a predetermined sample solution is sprayed under predetermined appropriate conditions are set in advance [par. 0044]" and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068]" and "ion source abnormality [par. 0019]"), wherein the parameter of the solvent or a mixing ratio of the solvent ("It is presumed that the change in the droplet diameter is caused by factors such as fluctuations in the flow rate of the supplied sample liquid, fluctuations in the ejection speed of the spray gas [par. 0041]" and "The spraying conditions of the sample solution by the spray nozzle may vary depending on the type and concentration of the sample to be measured and the type of solvent … it is necessary to change the pixel for discriminating the spray abnormality and the brightness threshold condition for discriminating according to the spraying condition and the measurement sample condition [par. 0067]" and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068]").
Note: claim is presented in the alternative.
While Toru teaches determining a relationship between a parameter and failure of the spray system [par. 0041] and where the parameter includes a flow rate of the solvent or a mixing ratio of the solvent [par. 0041 and 0067], Toru does not explicitly teach a channel system and a plurality of solvents.
In an analogous art (liquid chromatography), Tiemann teaches determining a relationship between a parameter of a channel system and determining a failure of a channel system ("identifying the differences in flow conditions related to systematic flow delays in any of the one or more of the multiple fluidic streams compared to the other fluidic stream or streams caused by a valve condition, e.g., a valve wear or a valve defect … caused by an LC column condition, e.g., an LC column aging or an LC column defect … caused by a clogging, e.g., by an LC column clogging or by a valve clogging … caused by a loosely connected LC column or capillary, a leakage in an LC column or capillaries and/or in a valve or other connecting elements … caused by incorrect fitting of one or more LC columns … resulting from manufacturing tolerances in one or more components of the LC system [par. 0062]"), and
a plurality of solvents ("the comparing step can include flowing the LC eluate (i.e., the liquid emerging from the LC column that can comprise at least one analyte of interest and a solvent or a mixture of solvents) to the ionization source for further ionization and subsequent detection in the MS [par. 0052]").
Because Toru teaches, "it is necessary to stably ionize a liquid sample, and for that purpose, it is important to form stable microdroplets with an atmospheric pressure spray [par. 0003]" and Tiemann teaches, "the streams of a multiple-stream LC-MS systems may be subjected to variances. For instance, LC columns, capillary dimension, valves, etc. may differ between streams which ultimately can affect, e.g., the total and dead volumes. Other reasons may include clogging in different elements along a flow path of a fluidic stream, manufacturer tolerances in capillary dimensions or other constituting elements of the apparatus as well as many other reasons [par. 0004]" and " liquid chromatography-mass spectrometry (LC-MS) apparatuses based on multiple fluidic streams instead of commonly used LC-MS devices comprising only a single stream have recently attracted much attention in the context of minimizing an injection-to-injection cycle time between subsequent samples and providing high-throughput of the apparatus [par. 0003]" it would have been obvious to one having ordinary skill in the art at the time of filing the invention to have included Tiemann's teachings of determining failures of a channel system with a plurality of solvents, with the teachings of Toru, for the benefit of determining and correcting an issue in the channel system with multiple streams to stably ionize liquid samples.
Although Toru teaches the relationship between the parameter of the system of the liquid chromatography device and the scattered light [par. 0044, 0068], Toru does not explicitly teach a trend of the relationship.
Tiemann teaches a trend of a relationship between the parameter of the channel system and the ionization current ("identifying differences in the flow conditions of the present techniques can include comparing a profile of the monitored ionization current (e.g., a time series of the profile of the monitored ionization current) of the one or more of the multiple fluidic streams with a reference profile of an ionization current (e.g., with a time series of the reference profile of the ionization current) [par. 0059]" and [fig. 3]).
Tiemann further teaches, "Such differences can, for example, be reflected in the measured shape of the monitored ionization current and/or in a position in time of one or more characteristic features of a profile of the monitored ionization current. These differences can be identified by the controller 60 [par. 0044]."
It would have been obvious to one of ordinary skill in the art at the time of filing the invention to have modified Toru's teachings of comparing a reference image data with measured image data, to include Tiemann's teachings of determining a trend of relationship data over time, for the benefit of more accurately identifying differences between the data.
What regard to claim 15, Toru teaches an electrospray ion source ("ion source spray chamber [par. 0015]") comprising,
in a housing [fig. 2: ion source spray chamber (2)]:
a light source installation portion wherein a light source irradiates an inside of the electrospray ion source with light is installed ("an irradiation means for irradiating the inside of the ion source spray chamber with light [par. 0015]" and "the lighting means 3 and the photographing means 4 are arranged in the ion source 30 [par. 0020]"); and
a scattered light information acquisition device installation portion ("photographing means 4 are arranged in the ion source 30 [par. 0020]") wherein a scattered light information acquisition device acquires scattered light information ("captured image of scattered light [par. 0031]") that is information of scattered light scattered by a droplet generated by electrospraying is installed ("the light scattered by the spray droplets can be observed in the region 22 immediately below the spray nozzle 1 [par. 0031]" and "electrospray [par. 0005]");
a processing device installation portion [fig. 1: Spray State Monitoring Means (11)] wherein a processing device stores, in a storage unit (see [par. 0072] where various means are stored), determination reference information indicating a relationship between a parameter of a ("liquid chromatography [par. 0002]") in a normal state and the scattered light information ("from the overall control means 15 of the mass spectrometer, abnormality determination pixel information and abnormality determination conditions for determining the spray state when a predetermined sample solution is sprayed under predetermined appropriate conditions are set in advance [par. 0044]" and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068]"), and
wherein the parameter of the solvent or a mixing ratio of the solvent ("It is presumed that the change in the droplet diameter is caused by factors such as fluctuations in the flow rate of the supplied sample liquid, fluctuations in the ejection speed of the spray gas [par. 0041]" and "The spraying conditions of the sample solution by the spray nozzle may vary depending on the type and concentration of the sample to be measured and the type of solvent … it is necessary to change the pixel for discriminating the spray abnormality and the brightness threshold condition for discriminating according to the spraying condition and the measurement sample condition [par. 0067]" and "a plurality of spray state determination conditions can be stored, and the sample or sample solvent condition to be measured, the spray gas pressure, and the sample liquid flow rate can be stored [par. 0068]").
Note: claim is presented in the alternative.
While Toru teaches where the parameter includes a flow rate of the solvent or a mixing ratio of the solvent [par. 0041 and 0067], Toru does not explicitly teach a channel system and a plurality of solvents.
In an analogous art (liquid chromatography), Tiemann teaches determining a relationship between a parameter of a channel system and determining a failure of a channel system ("identifying the differences in flow conditions related to systematic flow delays in any of the one or more of the multiple fluidic streams compared to the other fluidic stream or streams caused by a valve condition, e.g., a valve wear or a valve defect … caused by an LC column condition, e.g., an LC column aging or an LC column defect … caused by a clogging, e.g., by an LC column clogging or by a valve clogging … caused by a loosely connected LC column or capillary, a leakage in an LC column or capillaries and/or in a valve or other connecting elements … caused by incorrect fitting of one or more LC columns … resulting from manufacturing tolerances in one or more components of the LC system [par. 0062]"), and
a plurality of solvents ("the comparing step can include flowing the LC eluate (i.e., the liquid emerging from the LC column that can comprise at least one analyte of interest and a solvent or a mixture of solvents) to the ionization source for further ionization and subsequent detection in the MS [par. 0052]").
Because Toru teaches, "it is necessary to stably ionize a liquid sample, and for that purpose, it is important to form stable microdroplets with an atmospheric pressure spray [par. 0003]" and Tiemann teaches, "the streams of a multiple-stream LC-MS systems may be subjected to variances. For instance, LC columns, capillary dimension, valves, etc. may differ between streams which ultimately can affect, e.g., the total and dead volumes. Other reasons may include clogging in different elements along a flow path of a fluidic stream, manufacturer tolerances in capillary dimensions or other constituting elements of the apparatus as well as many other reasons [par. 0004]" and " liquid chromatography-mass spectrometry (LC-MS) apparatuses based on multiple fluidic streams instead of commonly used LC-MS devices comprising only a single stream have recently attracted much attention in the context of minimizing an injection-to-injection cycle time between subsequent samples and providing high-throughput of the apparatus [par. 0003]" it would have been obvious to one having ordinary skill in the art at the time of filing the invention to have included Tiemann's teachings of determining failures of a channel system with a plurality of solvents, with the teachings of Toru, for the benefit of determining and correcting an issue in the channel system with multiple streams to stably ionize liquid samples.
With regard to claim 16, the combination above teaches the electrospray ion source according to claim 15. Taru in the combination further teaches wherein the scattered light information acquisition device installation portion includes a transparent member ("Glass was arranged in these windows 5 and 6, and the lighting means 3 and the photographing means 4 were arranged outside the ion source spray chamber 2 [par. 0028]").
With regard to claim 17, the combination aboveteaches the electrospray ion source according to claim 15. Taru in the combination further teaches wherein the scattered light information acquisition device installation portion is provided in a position facing a pore of a mass spectrometer ("the introduction port to the mass spectrometer is located on the back side of the paper surface near the center of the cylinder of the cylindrical ion source spray chamber 2 … Since the photographing means 4 is arranged on the side surface of the cylinder, it is easy to detect the spray bending on the side toward the introduction port to the mass spectrometer [par. 0053]").
With regard to claim 18, the combination above teaches the electrospray ion source according to claim 15. Taru in the combination further teaches wherein the scattered light information acquisition device installation portion is provided in a direction orthogonal to a direction of a pore of a mass spectrometer ("the introduction port to the mass spectrometer is located on the back side of the paper surface near the center of the cylinder of the cylindrical ion source spray chamber 2 … Since the photographing means 4 is arranged on the side surface of the cylinder, it is easy to detect the spray bending on the side toward the introduction port to the mass spectrometer, that is, the direction perpendicular to the paper surface [par. 0053]").
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Toru in view of Tiemann further in view of Potta et al. [US Pub. 2017/0216199] ("Potta").
With regard to claim 13, the combination of Toru and Tiemann teaches the failure detection method according to claim 1. The combination does not explicitly teach wherein the light is a laser sheet.
In the same field of endeavor (spray illumination), Potta teaches wherein a light is a laser sheet ("The spay pattern is measured by shining a laser sheet perpendicular to the spray at a specific distance from the orifice [par. 0130]").
It would have been obvious to one having ordinary skill in the art at the time of filing the invention to have substituted the light taught by Toru, for the laser sheet as taught by Potta, since it is known in the art that a laser sheet operates to light an area and one of ordinary skill in the art could have substituted the light for the laser by known methods and the combination would predictably use prior art elements according to their established functions to yield the predictable result of lighting the area.
Allowable Subject Matter
Claim 8 is objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
While the prior art of record teaches detecting intensity of the scattered light to determine various abnormalities, the prior art of record fails to teach or suggest, alone or in combination, when the intensity decreases in a pulsed manner, the processing device determines that air bubbles are contaminated in a solvent flowing through the channel system as recited in claim 8, in combination with the limitations as set forth in intervening claim 7 and independent claim 1.
Response to Arguments
Applicant’s arguments with respect to claims 1, 14 and 15 have been considered but are moot in light of the new grounds of rejection necessitated by Applicant's amendment. Specifically, Tiemann et al. is now relied upon to teach aspects of the newly added limitations.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Valaskovic et al. [US Pub. 2002/0190203] teaches a feedback control system for an electrospray nozzle using optical system for monitoring and controlling dynamic or static morphology of the fluid exiting the electrospray nozzle.
Quint et al. [US Pub. 2021/0063361] teaches monitoring a state of an analyzer including a mass spectrometer (MS) with an electrospray ionization (ESI) source coupled to a liquid chromatography (LC) stream, including monitoring an electrospray ionization current of the ESI source and identifying a condition of multiple conditions of the analyzer based on the monitored ionization current of the ESI source, one of the conditions being a presence of a dead volume in a liquid chromatography stream of the analyzer downstream of an LC column of the LC stream.
Oberhauser [US Pat. 6,190,550] teaches verifying changes in solution composition by monitoring time-varying output of a column which provides an indication of band-spreading due to mixing of adjacent volumes of different solvents.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/VINCENT WEN-LIANG CHANG/
Examiner
Art Unit 2119
/MOHAMMAD ALI/Supervisory Patent Examiner, Art Unit 2119
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