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 § 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. Claim s 1 -3 , 10, 12-14 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Stults (US 20050072915 A1) in view of Van Berkel (US 20060273808 A1). Regarding claim 1 , Stults teaches a system comprising: One or more processors ( CPU, fig. 3 ); and Memory (fig. 3) storing executable instructions (algorithm for the optimization process, [0006]) that, when executed by the one or more processors, cause a computing device to perform a process comprising: Obtaining image data representative of one or more images that depict an inlet of a mass spectrometer (entrance 16 to MS, fig. 1) and an emitter (microfluidic chip 10, which is an electrospray assembly, [0019]) positioned near the inlet (imaging using CCD camera 18, [0020]) ; and Adjusting a position of the emitter relative to the inlet to an optimum position that is at or near a reference position relative to the inlet ( controlling position of ESI chip to predetermined position based on optimal electrospray properties, [00 19 ] ) . Stults does not teach that the position adjustment is based on the image data. Van Berkel teaches adjusting the position of a mass spectrometry probe based on image data ( Abstract ) . It would have been obvious to one of ordinary skill in the art at the time of the invention t o use the image data from the CCD camera of Stults to perform the position adjustment of the electrospray emitter using image analysis , as Van Berkel teaches that this is a method of precisely controlling the relative position of parts of a mass spectrometry system, which can be applied using the camera and processor of Stults by one of ordinary skill in the art. Regarding claim 2, Stults teaches that the process is an iterative optimization process comprising a plurality of iterations (optimization process with feedback loop, [0021]) , wherein each iteration comprises: Acquiring a portion of the data (image data in the combination with Van Berkel , above) when the emitter is positioned in a current position; Determining, based on an emitter positioning algorithm and the p ortion of the data (image data in the combination above) acquired while the emitter is positioned at the current position, an update position for the emitter (optimization based on optimization algorithm, [0022]) ; and Directing an automated position system (XYZ positioner 15 controlled by I/O controller, [0020]) to move the emitter to the updated position. Regarding claim 3, Stults teaches that each iteration further comprises determining whether a stop criterion is satisfied ( i.e. whether the emitter is at the predetermined position, [0019]); and terminating the iterative optimization process in response to a determination that the stop criterion is sat isfied. Regarding claim 10 , Stults teaches an imaging system configured to generate image data (CCD camera 18) . Regarding claim 1 2 , Stults teaches a non-transitory computer-readable medium (m emory fig. 3) storing instructions (algorithm for the optimization process, [0006]) that, when executed, cause a computing device to perform a process comprising: Obtaining image data representative of one or more images that depict an inlet of a mass spectrometer (entrance 16 to MS, fig. 1) and an emitter (microfluidic chip 10, which is an electrospray assembly, [0019]) positioned near the inlet (imaging using CCD camera 18, [0020]); and Adjusting a position of the emitter relative to the inlet to an optimum position that is at or near a reference position relative to the inlet (controlling position of ESI chip to predetermined position based on optimal electrospray properties, [0019]). Stults does not explicitly teach that the position adjustment is based on the image data. Van Berkel teaches adjusting the position of a mass spectrometry probe based on image data ( Abstract ). It would have been obvious to one of ordinary skill in the art at the time of the invention to use the image data from the CCD camera of Stults to perform the position adjustment of the electrospray emitter using image analysis, as Van Berkel teaches that this is a method of precisely controlling the relative position of parts of a mass spectrometry system, which can be applied using the camera and processor of Stults by one of ordinary skill in the art. Regarding claim 13 , Stults teaches that the process is an iterative optimization process comprising a plurality of iterations (optimization process with feedback loop, [0021]), wherein each iteration comprises: Acquiring a portion of the data (image data in the combination with Van Berkel , above) when the emitter is positioned in a current position; Determining, based on an emitter positioning algorithm and the portion of the image data acquired while the emitter is positioned at the current position, an update position for the emitter (optimization based on optimization algorithm, [0022]); and Directing an automated position system (XYZ controller 15) to move the emitter to the updated position. Regarding claim 14 , Stults teaches that each iteration further comprises determining whether a stop criterion is satisfied ( whether emitter is at a predetermined position, [0019]); and terminating the iterative optimization process in response to a determination that the stop criterion is satisfied. Regarding claim 19 , Stults teaches a system comprising: An automated positioning system (XYZ stage 15, controlled by I/O controller, [0020]) configured to hold an ionization emitter (microfluidic chip 10, which is an electrospray assembly [0019]) near an inlet of a mass spectrometer (16, fig. 1) and adjust a position of the ionization emitter relative to the inlet of the mass spectrometer (controlling position of ESI chip to predetermined position based on optimal electrospray properties, [0019]); An imaging system (CCD camera 18) configured to capture images of the ionization emitter and the inlet of the mass spectrometer ([0020] ); And a position control system (XYZ positioner 15) configured to perform a process comprising: Obtaining, from the imaging system, image data representative of one or more images that depict the inlet of the mass spectrometer and the ionization emitter positioned near the inlet (CCD camera implicitly images emitter and inlet) ; and Directing the automated positioning system to adjust a position of the emitter relative to the inlet to an optimum position that is at or near a reference position relative to the inlet (controlling position of ESI chip to predetermined position based on optimal electrospray properties, [0019]). Stults does not explicitly teach that the position adjustment is based on the image data. Van Berkel teaches adjusting the position of a mass spectrometry probe based on image data ( Abstract ). It would have been obvious to one of ordinary skill in the art at the time of the invention to use the image data from the CCD camera of Stults to perform the position adjustment of the electrospray emitter using image analysis, as Van Berkel teaches that this is a method of precisely controlling the relative position of parts of a mass spectrometry system, which can be applied using the camera and processor of Stults by one of ordinary skill in the art. Claim s 6 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Stults in view of Van Berkel and in further view of Prentice (US 20140319042 A1). Regarding claim s 6 and 17 , Stults and Van Berkel teach all the limitations of claim s 1 and 12 as described above. Stults and V an Berkel do not teach that the emitter is included in an emitter cartridge having an on-board memory, and the process further comprises storing, in the on-board memory of the emitter cartridge, the optimum position of the emitter. Prentice teaches an emitter cartridge (microfluidic cartridge 16) having an on-board memory (IC device 272, may be memory, [0097]) . It would have been obvious to one of ordinary skill in the art at the time of the invention to use the emitter cartridge of Prentice in the system of Stults, as a matter of selecting a known microfluidic ESI interface which can perform HPLC with low solvent consumption and improved detection sensitivity ([0012]) . It would further be obvious to store the optimum emitter position in the on-board memory, as Stults teaches storing the emitter position in local or external memory ([0022]) and one of ordinary skill in the art would under stand that using the on-board memory is functionally equivalent to using the memory in the processor of Stults . Claim s 7 , 9 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Stults in view of Van Berkel and in further view of Greving (US 9,082,600 B1). Regarding claim s 7 and 18 , Stults and Van Berkel teach all the limitat i ons of claim s 1 and 12 as described above. V an Berkel teaches identifying in the image data, the inlet and the emitter, and Stults teaches determining the optimum position of the emitter (based on the inlet and emitter images in the combination with Van Berkel above). Stults and V an Berkel do not teach identifying a reference point on the emitter and determining the optimum position based on the reference point. Greving teaches a mass spectrometry system using reference points to determine the position of elements ( determining relative position of any object in mass spectrometer using fiducial marks, col.15 lines 50-52 ). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the system of Stults and V an Berkel to have fiducial markers for assisting in locating the probe and inlet relative to each other, as this is a known common means of determining relative positions of two parts of a mass spectrometer system. Regarding claim 9 , Greving teaches that the reference point is a fiducial marker. Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Stults in view of V an Berkel and Greving and in further view of Ueda (US 20190108991 A1) Regarding claim 8 , Stults, V an Berkel and Greving teach all the limitations of claim 7 as described above. Stults, Van Berkel , and Greving do not teach that the reference point comprises a distal end of the external coating on the emitter. Ueda teaches an emitter (89) having an external coating (892) with a distal end on the emitter . It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the capillary of Stults to have the coating of Ueda , in order to prevent deformation of the capillary during injection of the sample (Ueda, Abstract) . It would further be obvious to use the end of the coating as a reference point, as the end of the coating is an easily visible marker and Greving teaches that any marker can be used as a reference point in adjusting the positions of parts of a mass spectrometry system (“a fiducial mark may be any fixed and detectable mark or feature”, col. 15 lines 50-52) . Claim s 11 , 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Stults in view of V an Berkel and in further view of Dong (CN 209132210 U). Regarding claim s 11 and 20 , Stults and V an Berkel teach all the limitations of claim 1 and 19 as described above. Stults and V an Berkel do not teach that the imaging system comprises a first camera and a second camera positioned so that optical axes of the first camera and the second camera are substantially orthogonal. Dong teaches an imaging system for positioning an emitter (Abstract) having first and second orthogonal cameras ( vertical camera 6, p. 3 paragraph 1; horizontal camera p. 4 paragraph 2 ). It would have been obvious to one of ordinary skill in the art at the time of the invention to modify the system of Stults to have multiple cameras along orthogonal axes as taught by Dong , in order to ensure that the emitter is properly aligned in two dimensions with no unexpected result. Regarding claim 2 1 , Stults teaches that the process is an iterative optimization process comprising a plurality of iterations (optimization process with feedback loop, [0021]), wherein each iteration comprises: Acquiring a portion of the data (image data in the combination with Van Berkel , above) when the emitter is positioned in a current position; Determining, based on an emitter positioning algorithm and the portion of the image data acquired while the emitter is positioned at the current position, an update position for the emitter (optimization based on optimization algorithm, [0022]); and Directing the automated positioning system to move the emitter to the updated position. Allowable Subject Matter Claim s 4-5, 15-16 and 22 are 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: the prior art does not disclose or make obvious an electrospray emitter position optimization system which stops when the probability of a forward step is within a tolerance range of the probability of a backward step, or a process which determines an instrument image setup based on image data and selects an emitter positioning algorithm based on the setup. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT DAVID E SMITH whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-7096 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M to F 8:30 AM-5:00 PM . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Robert Kim can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 22293 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. 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