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 .
Preliminary Remarks
The amendment filed on 07/02/2026 has been entered. Claims 2-17 have been amended, no claims have been canceled, and claims 18-19 have bene added. Therefore, claims 1-19 remain pending in the application.
Claim Objections
Claims 2-17 have been amended to overcome the previously cited claim objection of said claims in the Office Action mailed on 04/02/2026.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-8 and 10-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gaitas (US 2018/0238498A1; hereinafter “Gaitas”).
Regarding claim 1, Gaitas discloses system for removal of surrounding cells from a biological sample (AFM probe on a microfluidic chip—remove the cell from its environment and surrounding cells for analysis, para. [0052], lines 20-21) the system comprising: a pipette (pipette 102, para. [0047], line 4; same probe functions as a nanoscale pipette allowing the extraction of biomolecular contents of individual nucleus or other organelles of a cell and their subsequent manipulation, para. [0052], lines 9-12) including (i) a proximal section and (ii) a distal section (pipette 102 is shown in Fig. 1A, having a proximal section and a distal section, which is typical of pipettes) with an opening (opening of pipette 102 is shown in Fig. 1A having contact with a biological sample (cell embryos 103, para. [0047], line 3, Fig.1A); configured to contact the biological sample (Gaitas discloses the probe functions as a nanoscale pipette allowing the extraction of biomolecular contents of individual nucleus or other organelles of a cell, para. [0052], lines 9-11), wherein a suction channel, ending at the opening, is defined through the proximal and distal sections (a suction channel—the tube formed in pipette 102, which ends at the opening of pipette 102, and is defined through the proximal and distal sections of pipette 102, shown in Fig. 1A);
Gaitas discloses a suction source fluidly coupled with the pipette and configured to create a negative pressure within the suction channel (a precision suction pump 111 is also used, para. [0047], line 10, Fig. 1A; further, Gaitas discloses suction is applied via a pump connected via a tube to the apparatus's main body (also referred to as substrate or chip; the tip is brought in contact with an item to be attached via suction (negative pressure, para. [0075], lines 2-5);
Gaitas discloses a piezo actuator mechanically coupled with the pipette and configured to drive piezo vibration of the pipette to remove ones of the surrounding cells (specialized micromanipulators—manual or motorized or piezoelectric or other or a combination of the aforementioned, are used to move the apparatus, para. [0075], lines 10-12).
Regarding claim 2, Gaitas discloses a pipette positioning system configured to position an end of the distal section of the pipette at a point that is offset relative to a horizontal plane passing through a volumetric center of the biological sample (specialized micromanipulators—manual or motorized or piezoelectric or other or a combination of the aforementioned, are used to move the apparatus, para. [0075], lines 10-12; additionally, Gaitas discloses the probe can be controlled with a AFM XYZ piezo 331 for probe movement, para. [0052], lines 30-31).
Regarding claim 3, Gaitas discloses wherein the pipette positioning system is configured to position the opening below the horizontal plane passing through the volumetric center of the biological sample (specialized micromanipulators—manual or motorized or piezoelectric or other or a combination of the aforementioned, are used to move the apparatus, para. [0075], lines 10-12; additionally, Gaitas discloses the probe can be controlled with a AFM XYZ piezo 331 for probe movement, para. [0052], lines 30-31).
Regarding claim 4, Gaitas discloses wherein the pipette positioning system includes a robotic pipetting arm (the device that includes a tip with an opening 120 and a microarm 121, para. [0049], lines 2-3).
Regarding claim 5, Gaitas discloses wherein the pipette positioning system is configured to position the distal section of the pipette at a non-zero angle with respect to a horizontal plane on which the biological sample is supported (specialized micromanipulators—manual or motorized or piezoelectric or other or a combination of the aforementioned, are used to move the apparatus, para. [0075], lines 10-12; additionally, Gaitas discloses the probe can be controlled with a AFM XYZ piezo 331 for probe movement, para. [0052], lines 30-31).
Regarding claim 6, Gaitas discloses wherein the proximal section and the distal section of the pipette are collinear (pipette 102, shown in Fig. 1A, is a pipette having a proximal and distal section being on the same plane).
Regarding claim 7, Gaitas discloses wherein the distal section is positioned at a non- zero angle with respect to the proximal section (the probe can be controlled with a AFM XYZ piezo 331 for probe movement, para. [0052], lines 30-31, that is, the latter allow for an angle to measure other angles, other than 0 and 360).
Regarding claim 8, Gaitas discloses a pipette holder (probe holder 307, para. [0052], lines 25-26) configured to carry the pipette (probe 304 functions as a nanoscale pipette, para. [0052], lines 9-10); and a robotic pipetting arm (the device that includes a tip with an opening 120 and a microarm 121, para. [0049], lines 2-3) configured to carry the pipette holder, wherein the piezo actuator is mechanically coupled with the pipette via the pipette holder (specialized micromanipulators—manual or motorized or piezoelectric or other or a combination of the aforementioned, are used to move the apparatus, para. [0075], lines 10-12).
Regarding claim 10, Gaitas discloses wherein the opening applies the negative pressure of the suction channel to the biological sample (a pumping unit is used as means to generate fluidic flow with bi - directional capabilities able to create a pressure, a vacuum, positive and negative pressures, para. [0108], lines 14-16; the tip is brought in contact with an item to be attached via suction (negative pressure; para. [0075], lines 2-5).
Regarding claim 11, Gaitas discloses further comprising: a vision system configured to determine when the removal of the surrounding cells satisfies a denudation condition, wherein the removal of the surrounding cells is stopped in response to the vision system determining that the denudation condition has been satisfied (a specialized AFM probe on a microfluidic chip; this device combines scanning probe microscopy (SPM) with CE to investigate single cell and nucleus biomolecules; a micromachined (MEMS) nanoscale fluidic scanning probe and scanning and analysis system with ability for imaging (morphology mapping with nanometer resolution) and low abundance biomolecule measurements of cells is claimed (para. [0052], lines 1-8. Further, Gaitas discloses AFM probe on a microfluidic chip—remove the cell from its environment and surrounding cells for analysis, para. [0052], lines 20-21).
Regarding claim 12, Gaitas discloses wherein: the biological sample is a cumulus-oocyte complex (COC, sample like a cell, para. [0049], line 18; the sample can be a cell and the analytes can be cellular biomolecules such as DNA or proteins, para. [0070], lines 6-9); the surrounding cells are cumulus cells of the COC; (cell embryos 103, para. [0047], line 3) the cumulus cells include corona cells and non-corona cumulus cells (cell embryos 103, para. [0047], line 3; the sample can be a cell and the analytes can be cellular biomolecules such as DNA or proteins, para. [0070], lines 6-9); and the system is configured to remove all of the non-corona cumulus cells and at least some of the corona cells (Gaitas discloses AFM probe on a microfluidic chip—remove the cell from its environment and surrounding cells for analysis, para. [0052], lines 20-21).
Regarding claim 13, Gaitas discloses wherein the denudation condition is satisfied by at least one of: the vision system determining that at least some of the non-corona cumulus cells and at least some of the corona cells have been removed from the COC (COC, cell embryos 103, para. [0047], line 3; the sample can be a cell and the analytes can be cellular biomolecules such as DNA or proteins, para. [0070], lines 6-9); the vision system determining that all of the surrounding cells have been removed (a specialized AFM probe on a microfluidic chip; this device combines scanning probe microscopy (SPM) with CE to investigate single cell and nucleus biomolecules; a micromachined (MEMS) nanoscale fluidic scanning probe and scanning and analysis system with ability for imaging (morphology mapping with nanometer resolution) and low abundance biomolecule measurements of cells is claimed (para. [0052], lines 1-8); and the removal of the surrounding cells having proceeded for a specified period of time (AFM probe on a microfluidic chip—remove the cell from its environment and surrounding cells for analysis, para. [0052], lines 20-21).
Regarding claim 14, Gaitas discloses wherein the system is configured to remove ones of the surrounding cells until a contiguous surface area of the biological sample larger than a specified size is exposed (AFM probe on a microfluidic chip—remove the cell from its environment and surrounding cells for analysis, para. [0052], lines 20-21; cell embryos 103, para. [0047], line 3).
Regarding claim 15, Gaitas discloses wherein the specified size is based on a diameter of an opening of a pipette (Fig. 1A shows a specified size of the sample—cell embryos 103).
Regarding claim 16, Gaitas discloses wherein substantially all of the surrounding cells that are removed from the biological sample are drawn into the suction channel (AFM probe on a microfluidic chip—remove the cell from its environment and surrounding cells for analysis, para. [0052], lines 20-21).
Regarding claim 17, Gaitas discloses wherein the system is configured to leave the pipette in a fixed position while the removing is being performed (the device includes a sensing and/or actuating element 122. For example, element 122 is a piezoelectric or piezoresistive element to sense movement or displacement of the device, para. [0049], lines 5-8; further, Gaitas discloses the pipette 102 is controlled by a micromanipulator 110, para. [0047], lines 9-10).
Regarding claim 18, Gaitas discloses wherein: the biological sample is a cumulus-oocyte complex (COC, sample like a cell, para. [0049], line 18; the sample can be a cell and the analytes can be cellular biomolecules such as DNA or proteins, para. [0070], lines 6-9) the surrounding cells include cumulus cells of the COC (cell embryos 103, para. [0047], line 3); and the system is configured to: control the piezo actuator to separate ones of the cumulus cells from an oocyte of the COC (specialized micromanipulators—manual or motorized or piezoelectric or other or a combination of the aforementioned, are used to move the apparatus, para. [0075], lines 10-12), and control the suction source to draw the separated ones of the cumulus cells into the suction channel (a precision suction pump 111 is also used, para. [0047], line 10, Fig. 1A; further, Gaitas discloses suction is applied via a pump connected via a tube to the apparatus's main body (also referred to as substrate or chip; the tip is brought in contact with an item to be attached via suction (negative pressure, para. [0075], lines 2-5; suction is applied to the device by the precision syringe pump, the suction pulls the encapsulated cell, para. [0051], lines 3-4).
Regarding claim 19, Gaitas discloses further comprising a pipette positioning system configured to position an end of the distal section of the pipette at a point relative to the biological sample (pipette 102 is shown in Fig. 1A, having a proximal section and a distal section, which is typical of pipettes; the probe functions as a nanoscale pipette allowing the extraction of biomolecular contents of individual nucleus or other organelles of a cell, para. [0052], lines 9-11).
Response to Arguments
Applicant's arguments filed 07/02/2026 have been fully considered but they are not persuasive. Page 1 of applicant’s remarks addresses the status of the claims, the interview summary (interview was held on 06/26/26), and objection to claims 2-17, which were cited in the Office Action mailed on 04/02/2026. Applicant’s arguments begin on page 7. Independent claim 1 of the instant application is recited on the top of page 7 of applicant’s remarks. Applicant asserts the following, regarding the primary reference, “Gaitas, does not disclose expressly or inherently, at least the features of claim 1 emphasized above. Gaitas discloses micro-arm or lab-on-a-pipette devices that use suction to collect, aspirate, or manipulate a cell or intracellular biomolecular material. Gaitas also discloses piezoelectric components for movement, positioning, displacement sensing, or force feedback of a probe or apparatus.”
Additionally, applicant asserts However, Gaitas has no disclosure, express or inherent, of using a piezo actuator to vibrate a pipette, as claim 1 requires. More particularly, Gaitas does not disclose using a piezo actuator to vibrate a pipette in a way that removes cells surrounding a biological sample. The Office Action appears to conflate controlling the position of a pipette, which is well-known in the art, with vibrating the pipette to remove cells, as recited by claim 1. The distinction between vibrating a pipette and positioning the pipette is made even more clear with reference to claim 2. Claim 2, which depends from claim 1, separately recites a pipette positioning system configured to position an end of the distal section of the pipette. In other words, positioning the pipette at a particular location is distinct from vibrating the pipette to remove cells at that location.
Also, applicant asserts: “specifically, the Office Action points to specialized micromanipulators used to move the apparatus of Gaitas ([0075]). However, Gaitas only broadly defines that these micromanipulators can be piezoelectric and that they may be used for general movement of the device. Gaitas does not describe using these micromanipulators-or any other device-to create vibrations that remove surrounding cells from a sample. The Office Action also points to [0052] of Gaitas, but that passage of Gaitas discusses extracting intracellular/nuclear material from a cell so that the cell does not have to be extracted from its environment.”
In response, the Office Action mailed on 04/02/2026 was not conflated but merely actual facts and features as disclosed on the Gaitas reference. During the interview on June 26, 2026, the Examiner not only directed the attorney of record to paragraph [0075] of Gaitas, but also, to paragraph [0049] of the same reference. More specifically, paragraph [0075] discloses specialized micromanipulators (manual or motorized or piezoelectric or other or a combination of the aforementioned) are used to move the apparatus. As discussed during the interview, piezo actuators are not novel in the art and the piezo actuator disclosed in Gaitas is capable of performing the same function as that claimed in independent claim 1 of the instant application.
Moreover, paragraph [0049] of Gaitas discloses the device includes a sensing and/or actuating element 122, for element 122 is a piezoelectric or piezoresistive element to sense movement or displacement of the device). That is, the actuating element 122, disclosed in Gaits, is a an actuator or actuating element (as disclosed in Gaitas) and thus, causes movement or displacement of the device. Gaitas also discloses these elements are used to move (actuate) the device (para. [0049]). Also, as discussed during the interview on June 26, 2026, the Examiner discussed the device of disclosed in Gaitas is capable of performing the same function as that recited in independent claim 1, in particular, “the piezo actuator mechanically coupled with the pipette and configured to drive piezo vibration of the pipette…”. The Examiner discussed the Gaitas reference disclosure of the piezo element, where Gaitas clearly describes it can be a piezo actuator, that it also, can provide piezo vibration. The attorney of record also, was not able to articulate how the piezo actuator was able to produce or “drive piezo vibration” other than just reiterating the claimed piezo actuator.
Also, as stated above in this section, and cited by the applicant, the Gaitas reference discloses specialized micromanipulators (manual or motorized or piezoelectric or other or a combination of the aforementioned) are used to move the apparatus, para. [0075]) and also, para. [0049], discussed above in this section. The latter citations of Gaitas continue to address the claim limitation of “the piezo actuator mechanically coupled with the pipette and configured to drive piezo vibration of the pipette…”. That is, the latter can provide for piezo actuators to cause piezo vibration, also discussed above. Lastly, applicant asserts on the bottom of page 7 and the top of page 8, “Gaitas does not describe using these micromanipulators or any other device to create vibrations that remove surrounding cells from a sample.” In response, the piezo actuator, element 122, and the specialized manipulators of Gaitas are capable of performing the device function as that of the claimed piezo actuator as claimed in independent claim 1 of the instant application. That is, the actuating element of Gaitas is capable of driving piezo vibration as well for the reasons discussed above in this section. Piezo actuators are well known in the art and are therefore known to convert electrical signals into mechanical (or manual) movement displacement into a rapid response; where vibrations are known to be rapid responses as well. Therefore, claims 1-17 and new claims, 18-19, stand rejected.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LENORA A. ABEL whose telephone number is (571)272-8270. The examiner can normally be reached Monday-Friday 7:00am-4:00pm.
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/L.A.A./ Examiner, Art Unit 1799 /MICHAEL L HOBBS/Primary Examiner, Art Unit 1799
