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 .
Status of Claims
A Preliminary Amendment was filed on 11/8/2024 that cancelled claim 21. Accordingly, an Office Action on the merits of claims 1-20 is as follows:
Specification
The original disclosure is objected to because of the following informalities:
[0059] recites the phrase “includes a volatile memory 150”, which reuses the previously mentioned “150” that referred to “at least one processing element”. Based on Figure 1B, it appears this should be “includes a volatile memory 155”.
[0100] recites the phrase “the slope of the calibration curve becomes negative as shown in FIG. 2 (Region C)”. However, Figure 6 shows this calibration curve. Figure 2 is a schematic diagram of an example methodology for determining sensitivity of droplet volume to droplet dispenser driving parameters.
[0111] recites the phrase “reference standard pump 425”, which reuses the previously mentioned “425” that referred to “the processing element“. Based on Figure 5 and [0093], it appears this should be “reference standard pump 505”.
[0152] recites “incurred with the VS”, [0153] recites “the volume standard (VS)”, [0156] recites “the volume standard”. The earliest mention of VS should be described as the “volume standard”, as opposed to the current wording.
[0153] recites the phrase “[v]olumes of samples…can be determined from the analyte peak area of its ratio to the volume standard”. It is unclear what is being performed to determine the volume of the sample in this clause. Please reevaluate this wording to properly and clearly indicate how the ratio, the peak and the volume standard are used to determine the volume of the samples.
Appropriate correction is required.
Drawings
Figure 1B (Figure 1B in US 20210121905 A1), Figures 6-7 (Figures 2-3 in WO 2020157736 A1), Figure 8 (Figure 14 in WO 2020157736 A1) and Figures 12-17 (Figures 7-12 in US 20210121905 A1), should be designated by a legend such as --Prior Art-- because only that which is old is illustrated. See MPEP § 608.02(g). Corrected drawings in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. The replacement sheet(s) should be labeled “Replacement Sheet” in the page header (as per 37 CFR 1.84(c)) so as not to obstruct any portion of the drawing figures. If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 1, 4-9 and 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Covey et al. (US 2021/0121905 A1) in view of Reichel et al. (US 2004/0120855 A1).
Considering claim 1, Covey discloses a method of calibrating a droplet dispenser for mass spectrometry, the method comprising:
- providing a liquid sample including a calibrant ([0026-27]; [0145]);
- providing the liquid sample to a well at a liquid level ([0009]; [0063]; [0076]);
- over a range of different droplet dispenser parameters, using a droplet dispenser to dispense droplets from a well into a flowing transport fluid ([0015-16]; [0072-74]; [0078]; [0152]);
- measuring a calibrant mass of calibrant ions generated from the flowing transport fluid using a mass spectrometer ([0117-119]; [0126]); and
- determining volumes of the droplets from the calibrant mass ([0117]).
The invention by Covey teaches varying acoustic ejector parameters over a single well with fluctuating volume ([0074]; [0085-90]) to calibrate volume dispensing, but Covey fails to explicitly disclose repeating the process on sets of wells, where each set has a plurality of wells with the same liquid level.
However, Reichel teaches preparing multiple wells with the same liquid level and varying ejection input power to create ejector profiles at that level ([0188-189]).
The invention by Covey teaches varying ejector profiles over a series of depths. The invention by Reichel teaches that for a given depth, the ejector profile is varied. Using the technique of Reichel, in the invention by Covey, would have arrived at repeated measurements at each level, using a plurality of wells for each level. One of ordinary skill in the art could have applied the known technique of repeated calculations at a given depth, as taught by Reichel, in the invention by Covey as it moved through various depth levels, and the results of the combination would have been predictable and repeatable. Furthermore, as suggested by Covey, it was known that multiple measurements may be averaged to provide a measurement. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize a plurality of wells for each of a plurality of well depths, based on the teachings of Reichel, in combination with Covey.
Considering claim 4, Covey discloses adjusting a parameter of the droplet dispenser based on a determined volume of a droplet ([0027]; [0126]; [0134]; [0152]).
Considering claim 5, Covey discloses introducing a reference standard of predetermined reference concentration into the flowing transport fluid; and obtaining a reference signal from ions of the reference standard generated from the flowing transport fluid using a mass spectrometer ([0029]; [0150]).
Considering claim 6, Covey discloses using the reference signal to correct a measured calibrant mass (Figure 11; [0031]; [0126]; [0149-151]).
Considering claim 7, Covey discloses that the parameters include droplet dispenser transducer voltage and burst number ([0072]; [0078]).
Considering claim 8, Covey discloses that the droplet dispenser comprises an acoustic droplet dispenser ([0130]; [0144]).
Considering claim 9, Covey discloses a device for calibrating a droplet dispenser for mass spectrometry, the device comprising:
- a droplet dispenser (Fig 2; [0130]);
- a sample delivery system positioned to receive droplets dispensed by the droplet dispenser (Fig 2; [0131]); and
- a controller 130 connected to the droplet dispenser, the controller configured to control the droplet dispenser to dispense droplets of a liquid sample from a set of wells into the sample delivery system using a range of different droplet dispenser parameters, wherein a set of wells have a different level of the liquid sample ([0015-16]; [0072-74]; [0078]; [0134], controlling communication link from computing element to sample dispensing device; [0152]), wherein the liquid sample includes a calibrant ([0026-27]; [0145]);
- the controller further configured to measure a calibrant mass of the calibrant from ions generated from the liquid sample and detected by an ion detector ([0117-119]; [0126]); and
- the controller further configured to determine volumes of the droplets from the calibrant mass for each well ([0117]).
The invention by Covey teaches varying acoustic ejector parameters over a single well with fluctuating volume ([0074]; [0085-90]) to calibrate volume dispensing, but Covey fails to explicitly disclose repeating the process on sets of wells, where each set has a plurality of wells with the same liquid level.
However, Reichel teaches preparing multiple wells with the same liquid level and varying ejection input power to create ejector profiles at that level ([0188-189]).
The invention by Covey teaches varying ejector profiles over a series of depths. The invention by Reichel teaches that for a given depth, the ejector profile is varied. Using the technique of Reichel, in the invention by Covey, would have arrived at repeated measurements at each level, using a plurality of wells for each level. One of ordinary skill in the art could have applied the known technique of repeated calculations at a given depth, as taught by Reichel, in the invention by Covey as it moved through various depth levels, and the results of the combination would have been predictable and repeatable. Furthermore, as suggested by Covey, it was known that multiple measurements may be averaged to provide a measurement. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize a plurality of wells for each of a plurality of well depths, based on the teachings of Reichel, in combination with Covey.
Considering claim 12, Covey discloses that the controller is further configured to adjust a parameter of the droplet dispenser based on a determined volume of a droplet ([0027]; [0126]; [0134]; [0152]).
Considering claim 13, Covey discloses that the controller is further configured to obtain a reference signal from ions of a reference standard detected by the ion detector, wherein the reference standard is pumped into the sample delivery system at a predetermined reference concentration ([0029]; [0150]; [0131]).
Considering claim 14, Covey discloses that the controller is further configured to use the reference signal to correct a measured calibrant mass (Figure 11; [0031]; [0129]; [0149-151]).
Considering claim 15, Covey discloses that the parameters include droplet dispenser transducer voltage and burst number ([0072]; [0078]).
Considering claim 16, Covey discloses that the droplet dispenser comprises an acoustic droplet dispenser ([0130]; [0144]).
Claims 2-3 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Covey et al. (US 2021/0121905 A1) in view of Reichel et al. (US 2004/0120855 A1), as applied to claims 1 and 9, respectively, above, and further in view of Forbush et al. (US 2019/0232275 A1).
Considering claim 2, Covey, as modified by Reichel, fails to disclose assigning the range of different liquid levels and range of different droplet dispenser parameters to a droplet dispenser profile, and associating the droplet dispenser profile to an intended droplet volume for the liquid sample.
However, Forbush disclose a calibration file/profile for each droplet volume containing voltage, burst and focus entries for 36 liquid levels ([0038-39]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to create a droplet dispense profile from each of the different liquid levels and range of parameters, as taught by Forbush, in the invention by Covey, as modified by Reichel. The motivation for doing so is to quickly determine the appropriate settings for a desired volume, based on the correlation between the stored data entries, as would have been understood in the art.
Considering claim 3, Covey already discloses that the calibration files store sample-plate material and dimensions, including well-bottom thickness and composition ([0020-21]), and therefore, the combination already discloses assigning the droplet dispenser profile to a type of well to which the set of wells belongs.
Considering claim 10, Covey, as modified by Reichel, fails to disclose that the controller is further configured to assign the different liquid levels and range of different droplet dispenser parameters to a droplet dispenser profile, and associate the droplet dispenser profile to an intended droplet volume for the liquid sample.
However, Forbush disclose a calibration file/profile for each droplet volume containing voltage, burst and focus entries for 36 liquid levels ([0038-39]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to create a droplet dispense profile from each of the different liquid levels and range of parameters, as taught by Forbush, in the invention by Covey, as modified by Reichel. The motivation for doing so is to quickly determine the appropriate settings for a desired volume, based on the correlation between the stored data entries, as would have been understood in the art.
Considering claim 3, Covey already discloses that the calibration files store sample-plate material and dimensions, including well-bottom thickness and composition ([0020-21]), and therefore, the combination already discloses that the controller is further configured to assign each droplet dispenser profile to a type of well to which a set of wells belongs.
Claims 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Forbush et al. (US 2019/0232275 A1) in view of Covey et al. (US 2021/0121905 A1).
Considering claim 17, Forbush discloses a method of operating a droplet dispenser for mass spectrometry, the method comprising:
- determining an intended volume of droplet to dispense (Figure 10; [0056]);
- determining a liquid level of a sample in a sample well (Figure 10; [0057]);
- selecting a droplet dispenser profile from a plurality of droplet dispenser profiles based on the intended volume of the droplet ([0057]);
- dispensing droplets according to parameters in the droplet dispenser profile associated with the liquid level of the sample in the sample well ([0057]).
The invention by Forbush fails to disclose dispensing the droplets into a flow of transport fluid.
However, Covey teaches dispensing droplets into flowing transport fluid (Figure 2; [0129-131]; [0144]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to dispense droplets into flowing transport fluid, as taught by Covey, in the invention by Forbush. The motivation for doing so is to provide access to mass spectrometry of the combined fluid, as taught by Covey ([0134]).
Considering claim 18, Forbush discloses that the profiles are calibrated for specific solutions and the properties of the source solution affect the usable droplet-volume range ([0038]; [0049]), but fails to explicitly disclose determining a type of the sample; and selecting the droplet dispenser profile further based on the type of the sample.
However, Covey teaches the use of different calibration/dispensing profiles based on different liquids having different viscosities ([0014]), different solvent proportions, different combinations of alcohols and water ([0019]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine the type of sample and then pick a profile based on that sample, as taught by Covey, in the invention by Forbush. The motivation for doing so, as taught by Covey, is that different liquids have different properties that affect the ability of a dispenser to dispense a specified droplet volume ([0014]), so knowing the sample allows an accurate profile to be selected.
Considering claim 19, Forbush fails to disclose determining a type of the sample well and selecting the droplet dispenser profile further based on the type of the sample well.
However, Covey teaches determining a type of the sample well and selecting the droplet dispenser profile further based on the type of the sample well ([0020-21]; [0087]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to determine the type of sample well and then pick a profile based on that sample well, as taught by Covey, in the invention by Forbush. The motivation for doing so, as taught by Covey, is that different well shapes and materials required different calibrations ([0020]).
Considering claim 20, Forbush already discloses that the droplet dispenser profile comprises selecting the droplet dispenser profile from a library of droplet dispenser profiles, wherein each droplet dispenser profile in the library associates a burst number and a transducer voltage to sample liquid level ([0038-39]).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Jhutty et al. (US 7661289 B1) discloses a method of calibrating an acoustic droplet dispensing apparatus that includes creating calibration profiles.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan M Dunlap whose telephone number is (571)270-1335. The examiner can normally be reached Mon-Fri 10AM - 7PM.
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, Peter Macchiarolo can be reached at 571-272-2375. 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. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JONATHAN M DUNLAP/Primary Examiner, Art Unit 2855 September 23, 2026
