DETAILED ACTION
Response to Arguments
Rejections under 35 USC §102 and 35 USC §103
Applicant's arguments with respect to the rejections under 35 USC 102 and 35 USC 103 have been fully considered.
The remarks regarding the rejection under 35 USC 102 of amended independent claim 43 are found to be persuasive. Eliminating the word “can” and using “configured to” requires the apparatus be arranged to perform the claimed function, rather than merely capable of the claimed function. In view of the amendment, a new ground of rejection under 35 USC 103 is made in view of Roy, et. al. (US 20030224601 A1).
In the remarks filed 03/20/ 2026 the Applicant asserts that Gorelick does not teach all of the limitations of claim 27 because Gorelick is not capable of simultaneous interaction of the FIB and the optical microscope at least at the same location. The remarks regarding the rejection under 35 USC 102 of amended claim 27 are found to be unpersuasive because Gorelick does teach the features of the amended claim under the broadest reasonable interpretation. First, see interview conducted on 03/18/2026 regarding the language in the limitation “wherein the light optical microscope and the focused ion beam exposure system are arranged in the apparatus such that they can interact simultaneously with the sample on the sample holder.” Even though Gorelick is not intended to be operated in a simultaneous manner, as pointed out by Applicant, Gorelick, in Figs 1—2, demonstrates the capability of simultaneous interaction since the ion beam and light microscope appear capable of interacting with the sample at different locations on the sample at the same time.
With regard to the amended portions of the claim, the claim now teaches “…projecting a focused ion beam onto a first position where, in use, the focused ion beam impinges on the sample held by the sample holder…” and “…the light optical microscope having the optical axis…” and “…where the focused ion beam impinges on the sample at the first position, wherein the first position is arranged on the optical axis of the light optical microscope.”
The amended limitations do not overcome the cited art because Gorelick teaches projecting a focused ion beam onto a first position on the sample (cryo-FIB impinges on sample at a first position on the sample, pg. 2 first full paragraph and Fig. 1e). Gorelick further teaches that the first position (ROI) that is processed by the focused ion beam is arranged on the optical axis of the light optical microscope in step 1a and 1h of Fig. 1. Consequently, Gorelick teaches that the focused ion beam impinges on the sample at the first position and the first position is arranged on the optical axis of the light optical microscope. Though this occurs in different instances of time in Gorelick, the claim language does not require that the arrangement of first position on the optical axis of the light microscope occur simultaneously with the focused ion beam impingement on the sample at the first position under the broadest reasonable interpretation of the claim.
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 § 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 27-30, 33, 35, 37-39, and 42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gorelick, et. al. (Gorelick, et. al. PIE-scope, integrated cryo-correlative light and FIB/SEM microscopy. eLife 8:e45919. 2019.), hereinafter Gorelick.
Regarding claim 27, Gorelick teaches a method for micromachining a sample using an apparatus for micromachining of samples (pg. 1, Introduction, first paragraph teaches cryo-focused ion beam microscope (FIB) to thin the sample a produce flat electron-transparent lamellas, see also flowchart at the top of Fig. 1), wherein the apparatus comprises an integral combination of:
a sample holder for holding the sample (sample holder, last paragraph on pg. 3),
a light optical microscope having an optical axis (cryo-LM/light microscope, Fig. 1, pg. 3 second and 3rd full paragraphs), wherein the light optical microscope is configured for imaging or monitoring the sample on the sample holder (pg. 3, line 3-4 teaches sample is imaged using cryo-LM. Fig. 1 teaches monitoring of sample, see steps c-f in image and caption.), and
a focused ion beam exposure system comprising an assembly for projecting a focused ion beam onto a first position where, in use, the focused ion beam impinges on the sample held by the sample holder (cryo-FIB impinges on sample at a first position on the sample, pg. 2 first full paragraph and Fig. 1e),
wherein the light optical microscope and the focused ion beam exposure system are arranged in the apparatus such that they can interact simultaneously with the sample on the sample holder (Fig. 2 depicts a light microscope (LM) directly adjacent to a focused ion beam system (FIB) such that the integrated arrangement would be capable of interacting simultaneously with the sample on the cryo-stage. See MPEP 2114 (II).),
wherein the method comprises the steps of:
capturing one or more light microscopy images of the sample held by the sample holder using the light optical microscope having the optical axis (pg. 3, line 3-4 teaches sample is imaged using cryo-LM);
determining a position and physical dimensions of a region of interest in the sample based on the one or more light microscopy images (Fig. 1, step c, see image and caption);
establishing from the one or more light microscopy images settings of the sample holder and/or the focused ion beam exposure system for micromachining the sample to reduce a distance between at least part of the region of interest and the surface of the sample or to produce a lamella which embodies at least part of the region of interest (Fig. 1 steps c-f, see image and caption. In particular, angle, translation, and tilt are discussed. See also pg. 6-7 full paragraph as well as Fig. 3 caption which details the stage translation calibration when translating the region of interest found using the cryo-LM to the FIB and the corresponding stage orientation); and
activating the focused ion beam exposure system in accordance with the settings for micromachining the sample, where the focused ion beam impinges on the sample at the first position (Fig. 1, step e, see image and caption), wherein the first position is arranged on the optical axis of the light optical microscope (the first position (ROI) that is processed by the focused ion beam is arranged on the optical axis of the light optical microscope in step 1a and 1h of Fig. 1 (optical verification of the ROI, where the ROI is the same position on the sample that is processed by the FIB). Note that the claim language does not require that the arrangement of first position on the optical axis of the light microscope to occur simultaneously with the focused ion beam impingement on the sample at the first position.).
Regarding claim 28, Gorelick teaches further comprising the step of: establishing from the one or more light microscopy images which part or parts of the sample need to be micro-machined by the focused ion beam exposure system to reduce the distance between at least part of the region of interest and the surface of the sample or to produce a lamella which embodies at least part of the region of interest (Fig. 1 and caption, steps c-e).
Regarding claim 29, Gorelick teaches wherein the settings comprise a position on the sample where to arrange the first position, wherein the method further comprises the step of: moving the sample or at least an intended trajectory of the focused ion beam to locate the first position on the position on the sample accordingly, before activating the focused ion beam exposure system for micromachining the sample (selected region of interest is brought under the FIB, step d of Fig. 1. This region inherently includes a first location within the region of interest at which the focused ion beam is activated to begin the milling process. See also Fig. 3 and pg. 6 which details how the locations selected under the optical microscope are translated to the FIB for milling by the FIB).
Regarding claim 30, Gorelick teaches further comprising the step of: monitoring the locating of the first position on the sample and/or monitoring the micromachining of the sample using the light optical microscope (Fig. 1 and caption, steps c-f, and Fig. 3 and caption and pg. 6).
Regarding claim 33, Gorelick teaches wherein the method further comprises the step of: providing structures around the region of interest with first fluorescent labels which can be observed by the light optical microscope (Fig. 1 and caption, step c, and Fig. 5 and caption with pink, blue and purple fluorescent labels placed around ROI and observed by fluorescence microscopy imaging), and
monitoring the micromachining by observing fluorescence light from said first fluorescent labels using the light optical microscope (Fig. 1 and caption, steps c-f, pg. 9 section “Cryo-CLEM on biological samples”).
Regarding claim 35, Gorelick teaches wherein the method further comprises the step of: providing the region of interest with second fluorescent labels which can be observed by the light optical microscope (Fig. 1 and caption, step c, and Fig. 5 and caption with pink, blue and purple fluorescent labels placed around ROI and observed by fluorescence microscopy imaging), and
monitoring the micromachining by observing fluorescence light from said second fluorescent labels using the light optical microscope (Fig. 1 and caption, steps c-f, pg. 9 section “Cryo-CLEM on biological samples”).
Regarding claim 37, Gorelick teaches wherein the method further comprises the step of: manufacturing of one or more lamella from the sample which includes at least part of the region of interest, wherein said lamella is a thin cut out from a thicker sample (Fig. 1 step e, caption), with a thickness suitable for studying the lamella in a TEM (Fig. 1 and caption, step i, teaches that the thinned sample produced by FIB in step e is analyzed by TEM, so it inherently must be suitable for TEM).
Regarding claim 38, Gorelick teaches wherein the to be produced lamella is configured to comprise an observation surface, wherein method comprises the step of: orienting the sample and the FIB with respect to each other such that the FIB impinges on the sample at an oblique or grazing angle with respect to said observation surface (See Fig. 1e).
Regarding claim 39, Gorelick teaches wherein the method further comprises the step of: monitoring the creation of the lamella using the light optical microscope (Fig. 1 and caption, steps c-f, where f includes verification of the prepared lamella by the FIB process in the preceding step and where g and h include an optional repeat of e and f where the lamella can be further thinned if needed).
Regarding claim 42, Gorelick teaches wherein the sample holder comprises a cooling system for cooling the sample, wherein the method further comprises the step of: cooling the sample prior to the micromachining of the sample by the FIB (Fig. 1 and caption, step b), cooling the sample down to a cryogenic temperature (pg. 3, lines 1-11).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 31 is rejected under 35 U.S.C. 103 as being unpatentable over Gorelick (Gorelick, et. al. PIE-scope, integrated cryo-correlative light and FIB/SEM microscopy. eLife 8:e45919. 2019.) in view of Asahata, et. al. (US 20150270102 A1), hereinafter Asahata.
Regarding claim 31, Gorelick does not explicitly teach wherein the settings comprise a spot size of the focused ion beam at the first position and/or a beam current of the focused ion beam.
Asahata teaches wherein the settings comprise a spot size of the focused ion beam at the first position and/or a beam current of the focused ion beam ([0033]).
Asahata modifies Gorelick by suggesting the beam current of the focused ion beam as a setting.
Since both inventions are directed towards FIB, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Asahata because the beam current is a value representing a processing condition and allow controlling this value allows for manufacturing a thin sample as desired (Asahata, [0032]-[0033]).
Claims 32 is rejected under 35 U.S.C. 103 as being unpatentable over Gorelick (Gorelick, et. al. PIE-scope, integrated cryo-correlative light and FIB/SEM microscopy. eLife 8:e45919. 2019.) in view of Wolff, et. al. (Wolff, G., Hagen, C., Grünewald, K. and Kaufmann, R. (2016), Towards correlative super-resolution fluorescence and electron cryo-microscopy. Biol. Cell, 108: 245-258.), hereinafter Wolff.
Regarding claim 32, Gorelick teaches wherein the light optical microscope comprises a super resolution microscopy system (pg. 7 3rd paragraph of “Characterising the system”, particularly lines 7 from the bottom to end of page.), including types that use structured illumination (pg. 5 2nd full paragraph teaches that structured-light illumination (SIM) can be implemented).
Gorelick does not explicitly teach wherein the super resolution microscopy system provides position information of at least part of the region of interest with a resolution of approximately 300 nm or smaller.
Wolff teaches wherein the super resolution microscopy system provides position information of at least part of the region of interest with a resolution of approximately 300 nm or smaller (pg. 250, right column, section “Cryo-SIM” teaches lateral resolution of ~180 nm and teaches correlation accuracies of 200-300 nm).
Wolff modifies Gorelick by suggesting the capability of locating a region of interest with a resolution smaller than 300 nm.
Wolff renders the claimed invention obvious because “In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.” See MPEP 2144.05 I.
Claims 43-44, 47-49, and 53-57 are rejected under 35 U.S.C. 103 as being unpatentable over Gorelick (Gorelick, et. al. PIE-scope, integrated cryo-correlative light and FIB/SEM microscopy. eLife 8:e45919. 2019.) in view of Roy, et. al. (US 20030224601 A1), hereinafter Roy.
Regarding claim 43, Gorelick teaches an apparatus for micromachining of samples (pg. 1, Introduction, first paragraph teaches cryo-focused ion beam microscope (FIB) to thin the sample a produce flat electron-transparent lamellas, see also flowchart at the top of Fig. 1), wherein the apparatus comprises an integral combination of:
a sample holder for holding a sample (sample holder, last paragraph on pg. 3),
a focused ion beam exposure system comprising an assembly for projecting a focused ion beam onto a first position where, in use, the focused ion beam impinges on the sample held by the sample holder (cryo-FIB, pg. 2 first full paragraph and Fig. 1),
a light optical microscope (cryo-LM/light microscope, Fig. 1, pg. 3 second and 3rd full paragraphs), wherein the light optical microscope is configured for imaging or monitoring said first position (pg. 3, line 3-4 teaches sample is imaged using cryo-LM. Fig. 1 teaches monitoring of sample, see steps c-f in image and caption.).
Gorelick does not teach wherein the light optical microscope and the focused ion beam exposure system are configured to interact simultaneously with a sample on the sample holder.
Roy teaches the light optical microscope and the focused ion beam exposure system are configured to interact simultaneously with a sample on the sample holder ([0003] teaches “This IDS OptiFIB system includes the focused ion beam column coaxial with a light optical microscope for simultaneous optical observation of the milling process.” See also [0033], [0040]-[0041] and device under test (DUT) 66 on stage 64 in Fig. 6a).
Roy modifies Gorelick by suggesting that the light optical microscope and the focused ion beam exposure system are configured to interact simultaneously on a sample on a sample holder.
Since Roy and Gorelick are both directed to FIB and light optical microscope systems, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Roy because simultaneous interaction allows for real-time optical observation of the milling process throughout the steps of etching a substrate to ensure precise etching , ([0003]-[0004], [0009]).
Regarding claim 44, Gorelick teaches wherein the apparatus further comprises a controller (pg. 5 3rd paragraph, computer/PIE-scope-commander with interface/software for controlling the CLEM) which is configured for controlling the apparatus to perform, in use, the steps of: capturing one or more light microscopy images of the sample held by the sample holder (pg. 5 3rd-5th paragraph); determining a position and physical dimensions of a region of interest in the sample based on the one or more light microscopy images (pg. 5 3rd-5th paragraph, and Fig. 1 and caption); establishing from the one or more light microscopy images settings of the sample holder and/or the focused ion beam exposure system for micromachining the sample to reduce a distance between at least part of the region of interest and the surface of the sample or to produce a lamella which embodies at least part of the region of interest (pg. 5 3rd-5th paragraph, and Fig. 1 and caption); and activating the focused ion beam exposure system in accordance with the settings for micromachining the sample (pg. 5 3rd-5th paragraph, and Fig. 1 and caption).
Regarding claim 47, Gorelick teaches wherein light optical microscope comprises a focus tracker, wherein the focus tracker is configured to focus the light optical microscope on the sample and/or on a lamella that is being created by micromachining the sample using the focused ion beam exposure system (LM focus drive, Fig. 2b and caption, pg. 3 last paragraph- pg. 4 first paragraph).
Regarding claim 48, Gorelick teaches wherein the light optical microscope is a fluorescence microscope and/or a super resolution light optical microscope (pg. 7, 10 lines from bottom-bottom of page).
Regarding claim 49, Gorelick teaches wherein the sample holder comprises a cooling system for cooling the sample, wherein the cooling system is configured for cooling the sample down to a cryogenic temperature (top of pg. 3 teaches that the sample must be transferred and maintained at cryogenic temperature. Pg. 3 last paragraph teaches cryo-stage).
Regarding claim 53, Roy does not teach wherein the light optical microscope and the focused ion beam exposure system are configured to interact simultaneously with the sample on the sample holder at the first position.
Gorelick teaches wherein the light optical microscope and the focused ion beam exposure system are configured to interact simultaneously with the sample on the sample holder at the first position ([0003] teaches “This IDS OptiFIB system includes the focused ion beam column coaxial with a light optical microscope for simultaneous optical observation of the milling process.” See also [0033], [0040]-[0041] and device under test (DUT) 66 on stage 64 in Fig. 6a).
Roy modifies Gorelick by suggesting that the light optical microscope and the focused ion beam exposure system are configured to interact simultaneously on a sample on a sample holder at the same position.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Roy because simultaneous interaction allows for real-time optical observation of the milling process throughout the steps of etching a substrate to ensure precise etching , ([0003]-[0004], [0009]).
Regarding claim 54, Gorelick teaches wherein the apparatus is configured to monitor with the light optical microscope, the micromachining of the sample by the focused ion beam (Fig. 1 and caption, steps c-f, and Fig. 3 and caption and pg. 6).
Gorelick does not teach during the micromachining of the sample by the focused ion beam.
Roy teaches the monitoring of the micromachining with the light optical microscope occurs during the micromachining of the sample by the focused ion beam. ([0003] teaches “This IDS OptiFIB system includes the focused ion beam column coaxial with a light optical microscope for simultaneous optical observation of the milling process.” See also [0033], [0040]-[0041]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Roy because simultaneous interaction allows for real-time optical observation of the milling process throughout the steps of etching a substrate to ensure precise etching , ([0003]-[0004], [0009]).
Regarding claim 55, Gorelick teaches wherein the light optical microscope has an optical axis, and wherein the first position is arranged on the optical axis of the light optical microscope (the first position (ROI) that is processed by the focused ion beam is arranged on the optical axis of the light optical microscope in step 1a and 1h of Fig. 1 (optical verification of the ROI, where the ROI is the same position on the sample that is processed by the FIB).).
Regarding claim 56, Gorelick teaches a method for micromachining a sample using an apparatus for micromachining of samples, wherein the apparatus comprises an integral combination of:
a sample holder forholding the sample (sample holder, last paragraph on pg. 3),
a focused ion beam exposure system comprising an assembly for projecting a focused ion beam onto a first position where, in use, the focused ion beam impinges on the sample held by the sample holder (cryo-FIB impinges on sample at a first position on the sample, pg. 2 first full paragraph and Fig. 1e), and
a light optical microscope (cryo-LM/light microscope, Fig. 1, pg. 3 second and 3rd full paragraphs), wherein the light optical microscope is configured for imaging or monitoring the sample on the sample holder (pg. 3, line 3-4 teaches sample is imaged using cryo-LM. Fig. 1 teaches monitoring of sample, see steps c-f in image and caption.),
wherein the method comprises the steps of:
capturing one or more light microscopy images of the sample held by the sample holder (pg. 3, line 3-4 teaches sample is imaged using cryo-LM);
determining a position and physical dimensions of a region of interest in the sample based on the one or more light microscopy images (Fig. 1, step c, see image and caption);
establishing from the one or more light microscopy images settings of the sample holder and/or the focused ion beam exposure system for micromachining the sample to reduce a distance between at least part of the region of interest and the surface of the sample or to produce a lamella which embodies at least part of the region of interest (Fig. 1 steps c-f, see image and caption. In particular, angle, translation, and tilt are discussed. See also pg. 6-7 full paragraph as well as Fig. 3 caption which details the stage translation calibration when translating the region of interest found using the cryo-LM to the FIB and the corresponding stage orientation);
activating the focused ion beam exposure system in accordance with the settings for micromachining the sample (Fig. 1, step e, see image and caption)
Gorelick does not teach wherein during said method the light optical microscope and the focused ion beam exposure system interact simultaneously with the sample at the first position.
Roy teaches during said method the light optical microscope and the focused ion beam exposure system interact simultaneously with the sample at the first position ([0003] teaches “This IDS OptiFIB system includes the focused ion beam column coaxial with a light optical microscope for simultaneous optical observation of the milling process.” See also [0033], [0040]-[0041]).
Roy modifies Gorelick by suggesting that the light optical microscope and the focused ion beam exposure system interact simultaneously at the same position on the sample.
Since Roy and Gorelick are both directed to FIB and light optical microscope systems, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Roy because simultaneous interaction allows for real-time optical observation of the milling process throughout the steps of etching a substrate to ensure precise etching , ([0003]-[0004], [0009]).
Regarding claim 57, Gorelick teaches wherein the method further comprises the step of: monitoring with the light optical microscope, the micromachining of the sample by the focused ion beam during the micromachining of the sample by the focused ion beam (Fig. 1 and caption, steps c-f, and Fig. 3 and caption and pg. 6).
Claims 45 is rejected under 35 U.S.C. 103 as being unpatentable over Gorelick (Gorelick, et. al. PIE-scope, integrated cryo-correlative light and FIB/SEM microscopy. eLife 8:e45919. 2019.) in view of Roy (US 20030224601 A1), further in view of Masuya, et. al. (US 20230100225 A1), hereinafter Masuya.
Regarding claim 45, Gorelick does not explicitly teach wherein the light optical microscope comprises a cylindrical lens.
Masuya teaches wherein the light optical microscope (Fig. 1, observation device [0068]) comprises a cylindrical lens ([0089]).
Masuya modifies Gorelick by suggesting a cylindrical lens in the light optical microscope.
Since both inventions are directed towards light optical microscopes, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Masuya because the cylinder lens allows for the forming of an image on a detector (Masuya, [0089]).
Claims 46 is rejected under 35 U.S.C. 103 as being unpatentable over Gorelick (Gorelick, et. al. PIE-scope, integrated cryo-correlative light and FIB/SEM microscopy. eLife 8:e45919. 2019.) in view of Roy (US 20030224601 A1), further in view of Wang, et. al. (US 20020132316 A1), hereinafter Wang.
Regarding claim 46, Gorelick teaches the light optical microscope (LM, Fig. 2 and caption) comprises an optical objective lens having an optical axis (LM has an objective, see FIG. 2 and caption, see also first paragraph of pg. 5. An objective inherently has an optical axis.).
Gorelick does not teach wherein the apparatus comprises a mirror which is arranged on the optical axis at a position spaced apart from the optical objective lens, and wherein the sample holder is configured for holding a sample in between the optical objective lens and the mirror.
Wang teaches an optical objective lens having an optical axis (objective 104, [0099]), wherein the apparatus comprises a mirror (mirror 108, [0099]) which is arranged on the optical axis at a position spaced apart from the optical objective lens (mirror 108 is spaced apart from objective 104 on optical axis, see Fig. 4), and wherein the sample holder is configured for holding a sample in between the optical objective lens and the mirror (mirror 108 is disposed beneath sample plate 106 such that the sample is between objective 104 and mirror 108, [0099], Fig. 4).
Wang modifies Gorelick by suggesting a mirror on the optical axis of an objective lens, where the sample holder is between the objective lens and the sample holder with the sample.
Since both inventions are directed towards light optical microscopy, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Wang because “The scattering force caused by the beam 102 as initially illuminates the sample plate 106 may be counteracted, in whole or in part, by directing the reflected radiation from mirror 108 back toward the sample. …the reflected light and the upward scattering force reduce the overall effects of the scattering forces, such that the gradient forces may be more effectively utilized” (Wang, [0099]).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Arnold, et. al. Site-specific cryo-focused ion beam sample preparation guided by 3D correlative microscopy. Biophysical Journal. Vol. 110. Febraury 2016. 860-869.
Agronskaia, et. al. Integrated fluorescence and transmission electron microscopy. Journal of Structural Biology. Volume 164, Issue 2. 2008. Pages 183-189.
Thermo-Fisher Scientific. iFLM Correlative System Enables Light Microscopy Inside the Aquilos 2 Cryo-FIB. PR Newswire. May 19, 2021. https://www.prnewswire.com/news-releases/thermo-scientific-iflm-correlative-system-enables-light-microscopy-inside-the-aquilos-2-cryo-fib-301294322.html
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LAURA E TANDY
Examiner
Art Unit 2881
/DAVID E SMITH/Examiner, Art Unit 2881