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
The Office Action is in response to the remarks and amendments filed on 10/15/2025. The objections to the Drawings have been withdrawn in light of the amendments filed. The objections to the Specification have been withdrawn in light of the amendments filed. The rejections pursuant to 35 U.S.C. 112(b) have been withdrawn in light of the amendments filed. Claim 5 is cancelled. Accordingly, claims 1-4 and 6-19 are pending for consideration in this Office Action.
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, 2, 4,6, 8, 10 and 12-17 are rejected under 35 U.S.C. 103 as being unpatentable over Remigy (US20170169991A1) in view of Han (US20210144990A1).
Regarding Claim 1, Remigy teaches a method of preparing a cryogenic sample [0001], herein the method comprises the following steps:
providing a sample [sample S, Figure 3A], said sample comprising a specimen provided on a planar specimen carrier [where sample S comprises a planar grid; 0090];
providing at least one flow device [conduits 31a and 31b; Figure 3A] for transporting cryogenic fluid to said sample [0082], wherein said flow device comprises a first nozzle [mouthpiece 33a, Figure 3A; 0082] for directing a flow of cryogenic fluid onto said sample [where mouthpieces 33a and 33b are exit orifices through which cryogenic fluid can emerge; 0082; where nozzle is defined to include mouthpieces as well as orifices in Applicant Specification; p. 1, lines 28 - 33]; and
positioning said sample next to said first nozzle [where sample S is positioned in the gap 35 between mouthpieces 33a and 33b, Figure 3B; 0082] and providing a flow of cryogenic fluid out of said first nozzle in such a way that the sample is cryogenically cooled [where cryogenic fluid flushes a sample S in gap 35, Figure 3A; 0088], wherein the first nozzle comprises a single nozzle opening [where the mouthpieces 33a and 33b are exit orifices; 0082].
Remigy does not teach the single nozzle opening that is rectangular that has a width, measured in a second direction, of at least 2.5 mm and a height, measured in a first direction, between 0.3 mm and 1mm.
However, Han teaches ultra-fast cooling of biomaterials [0003] where a single nozzle opening [liquid cryogen jets 314 and vapor cryogen jets 313, Figure 3] is rectangular [blade shaped jets, Figure 3; 0111] and has a width, measured in a second direction, of at least 2.5 mm [where the cross sectional shape of a liquid cryogen perpendicular to the direction of flow is in the shape of a blade with a length longer than its width, such as 10/1, where when the width is 1mm the length would be 10mm;0111] and a height, measured in a first direction, between 0.3 mm and 1mm [where the width of the exit port in a direction perpendicular to the plane of the blades would be 1 mm, Figure 6 and 7;0111 ] where one of ordinary skill in the art would have been capable of applying the substitution of a known element, a circular opening, for another, a rectangular opening, and yield predictable results, i.e., improving area of coverage compared to procedure of maintaining a conical shape of liquid jet [0006]
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of Remigy to where the nozzle opening is rectangular in view of the teachings of Han where the substitution of an element for another would have yielded predictable results, i.e., improving area of coverage compared to procedure of maintaining a conical shape of liquid jet [0006]
Regarding Claims 2 , Remigy, as modified, teaches the invention of claim 1 and further teaches where the width exceeds a dimension of the specimen carrier, as measured in the first direction [where the planar grid diameter is 3 mm and the diameter of the mouth pieces 33a and 33b may be 3 to 4 mm;0090].
Regarding Claim 4, Remigy, as modified, teaches the invention of claim 1 and further teaches wherein said specimen carrier [where sample S comprises a planar grid; 0090] comprises a central part [straight wire portions 21b, Figure 1D; 0075] and a peripheral part [ring 21a, Figure 1D; 0075], wherein said nozzle [where mouthpieces 33a and 33b include exit orifices through which cryogenic fluid can emerge; 0082; where nozzle is defined to include mouthpieces as well as orifices in Applicant Specification; p. 1, lines 28 - 33] opening is directed to said specimen carrier in such a way that said central part and said peripheral part experience equal cooling rates [where the area cooled by the mouthpieces 33a and 33b would be equal to or larger than the planar grid; 0090].
Regarding Claim 6, Remigy, as modified, teaches the invention of claim 1, and further teaches where said width is equal to a dimension of said specimen carrier as measured in the first direction [where width and diameter are equal for circular geometry for all directions; 0090]
Regarding Claim 8, Remigy, as modified, teaches the invention of claim 1 and does not teach where a width-height ratio is one selected from a group consisting of between 2:1 and 10:1 and 6:1.
However, Han teaches ultra-fast cooling of biomaterials [0003] where the width- height ratio is of 10:1 [where the cross sectional shape of a liquid cryogen perpendicular to the direction of flow is in the shape of a blade with a length longer than its width, such as 10/1] where one of ordinary skill in the art would have been capable of applying the substitution of a known element, a circular opening, for another, an elliptical or rectangular opening, and yield predictable results, i.e., improving area of coverage compared to procedure of maintaining a conical shape of liquid jet [0006]
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of Remigy to have where a width-height ratio is one selected from a group consisting of between 2:1 and 10:1 and 6:1 in view of the teachings of Han where the substitution of an element for another would have yielded predictable results, i.e., improving area of coverage compared to procedure of maintaining a conical shape of liquid jet [0006]
Regarding Claim 10, Remigy, as modified, teaches the invention of claim 1 and further teaches where a width of the nozzle opening of the first nozzle [mouthpiece 33a, where mouthpiece 33a is an exit orifice, Figure 3A; 0082] is at least 3.5 mm [where the diameter of the mouthpieces may be 3 to 4 mm, Figure 3A; 0090, where width and diameter are equal for circular geometry for all directions; 0090].
Regarding Claim 12, Remigy, as modified, teaches the invention of claim 1 and further teaches where a velocity of the flow out of said nozzle opening of the first nozzle [mouthpiece 33a, where mouthpiece 33a is an exit orifice, Figure 3A; 0082] is one selected from a group consisting of between 1.0 m/s and 20 m/s [where the flow rate from mouth pieces 31 a and 31 b may be 5 to 15 m/s; 0090].
Regarding Claim 13, Remigy, as modified, teaches the invention of claim 1 and further teaches where a flow rate of the cryogenic fluid out of said nozzle opening of the first nozzle [mouthpiece 33a, where mouthpiece 33a is an exit orifice, Figure 3A; 0082] is one selected from a group consisting of between 2 ml/s and 80 ml/s, between 25 ml/s and 55 ml/s, and 10 ml/s [where the flow rate from mouth piece 33a, an exit orifice, may be 5 m/s and the diameter of the exit orifice may be 3 mm such that the flow rate would be 35.4 ml/s (note volumetric flow rate = velocity from opening x area of opening and 1 cubic mm is 0.001 ml)]
Regarding Claim 14, Remigy, as modified, teaches the invention of claim 1 and further teaches where said flow device [conduits 31a and 31b; Figure 3A] comprises a second nozzle [mouthpiece 33b, Figure 3A], positioned at a distance from said first nozzle [gap 35, Figure 3A] and wherein the method comprises the further steps of:
positioning the sample in between said first nozzle and said second nozzle [where sample S is positioned in the gap 35 between mouthpieces 33a and 33b, Figure 3B; 0082]; and
providing a flow of cryogenic fluid through the first nozzle and through the second nozzle to cryogenically cool the sample from two opposing sides [where cryogenic fluid flushes a sample S in gap 35, Figure 3A; 0088].
Regarding Claim 15, Remigy, as modified, teaches the invention of claim 14, where said nozzle opening of said second nozzle [mouthpiece 33b, Figure 3A] is identical to said nozzle opening of the first nozzle [where mouthpieces 33a and 33b may both be between 3 to 4 mm in diameter; Figure 3A; 0090].
Regarding Claim 16, Remigy, as modified, teaches the invention of claim 1, and further teaches where said flow device [conduits 31a and 31b; Figure 3A] comprises a plunger [plunger P, Figure 3A; 0088], wherein:
said plunger comprises at least one flow channel [conduits 31a and 31b; Figure 3A] having an inlet provided on an underside of the plunger [entrance orifices 37 a, 37 b, Figure 3A at underside Pu; 0088], wherein downstream of said inlet the flow channel is provided with the first nozzle [mouthpiece 33a, Figure 3A], and wherein the plunger comprises a gap for positioning said sample in a topside of the plunger [gap 35, Figure 3A];
A bath of cryogenic fluid is provided beneath said plunger [container 5 of cryogen 7, Figure 3A; 0088]; and
Said sample [sample S, Figure 3A] is inserted into said gap using a tool [tool T, Figure 3A] that applies downward pressure on said plunger [where tool T applies downward force on plunger P; 0088], thereby at least partially submerging the plunger and causing cryogenic fluid to flow out of said first nozzle [where when underside of plunger Pu moves beneath surface 9, cryogen 7 is forced through entrance orifices 37a and 37b, Figure 3A-3C; 0088].
Regarding Claim 17, Remigy teaches an apparatus for preparing a cryogenic sample [0001], said apparatus comprising:
at least one flow device [conduits 31a and 31b; Figure 3A] for transporting cryogenic fluid to a sample [sample S, Figure 3A], wherein said flow device comprises a first nozzle [mouthpieces 33a, Figure 3A] for directing a flow of cryogenic fluid onto said sample [where mouthpieces 33a and 33b are exit orifices through which cryogenic fluid can emerge; 0082; where nozzle is defined to include mouthpieces as well as orifices in Applicant Specification; p. 1, lines 28 – 33]; and
does not teach where the first nozzle comprises a single nozzle opening that is rectangular with a width, measured in a second direction, of at least 2.5 mm and a height, measured in a first direction, between 0.3 mm and 1mm
However, Han teaches ultra-fast cooling of biomaterials [0003] where a single nozzle opening [liquid cryogen jets 314 and vapor cryogen jets 313, Figure 3] is rectangular [blade shaped jets, Figure 3; 0111] and has a width, measured in a second direction, of at least 2.5 mm [where the cross sectional shape of a liquid cryogen perpendicular to the direction of flow is in the shape of a blade with a length longer than its width, such as 10/1, where when the width is 1mm the length would be 10mm;0111] and a height, measured in a first direction, between 0.3 mm and 1mm [where the width of the exit port in a direction perpendicular to the plane of the blades would be 1 mm, Figure 6 and 7;0111 ] where one of ordinary skill in the art would have been capable of applying the substitution of a known element, a circular opening, for another, a rectangular opening, and yield predictable results, i.e., improving area of coverage compared to procedure of maintaining a conical shape of liquid jet [0006]
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the assembly of Remigy to where the nozzle opening is rectangular in view of the teachings of Caliskan where the substitution of an element for another would have yielded predictable results, i.e., improving area of coverage compared to procedure of maintaining a conical shape of liquid jet [0006]
Claims 3, 7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Remigy in view of Han (US20210144990A1) as applied to claim 1 above and further in view Trávníček et al. (CZ306506B6).
Regarding Claim 3, Remigy, as modified, teaches the invention of claim 1 and does not teach where said height subceeds a dimension of the specimen carrier, as measured in the second direction.
However, Trávníček teaches a method and device for cooling cylindrical bodies with streams of cooling fluid [0001] where the height [where the width of the slot nozzle 6 is 0.36 mm; 0030; where the width is understood to be the small dimension of the slot nozzle 6 in the vertical direction of Figure 4; refer to pertinent art] subceeds a dimension [where the diameter of the cylinder being cooled is 1.21 mm; 0029] of the object being cooled [cylinder body 2, Figure 4], as measured in the second direction [in the vertical direction along the upper 19 and lower streams 20, Figure 4] where one of ordinary skill in the art would have been capable of applying this known technique to a known device, a sample carrier, that was ready for improvement and the results would have been predictable to one of ordinary skill in the art i.e., improving fluid utilization during heat transfer by leveraging the jet impingement effect of a slot nozzle where fluid diverges to cool a large area beyond the width of the nozzle [Trávníček, 0005, 00031].
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of Remigy to have where said height subceeds a dimension of the specimen carrier, as measured in the second direction in view of the teachings of Trávníček where this known technique could have been applied to a known device that was ready for improvement and the results would have been predictable, i.e., improving fluid utilization during heat transfer by leveraging the jet impingement effect of a slot nozzle where fluid diverges to cool a large area beyond the width of the nozzle [Trávníček, 0005, 00031].
Regarding Claim 7 , Remigy, as modified, teaches the invention of claim 1 and does not teach where said height is one selected from a group consisting of less than 50% of a dimension of the specimen carrier as measured in the second direction, less than 35% of the dimension of the specimen carrier as measured in the second direction, and less than 20% of the dimension of the specimen carrier as measured in the second direction.
However, Trávníček teaches a method and device for cooling cylindrical bodies with streams of cooling fluid [0001] where the height of the first nozzle [where the width of the slot nozzle 6 is 0.36 mm; 0030; where the width is understood to be the small dimension of the slot opening in the vertical direction of Figure 4; refer to pertinent art] is less than 35% of the dimension of the object being cooled [where the diameter of the cylinder being cooled is 1.21 mm; 0029] as measured in the second direction [in the vertical direction along the upper 19 and lower streams 20, Figure 4] where one of ordinary skill in the art would have been capable of applying this known technique to a known device, a sample carrier, that was ready for improvement and the results would have been predictable to one of ordinary skill in the art i.e., improving fluid utilization during heat transfer by leveraging the jet impingement effect of a slot nozzle where fluid diverges to cool a large area beyond the width of the nozzle [Trávníček, 0005, 00031].
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of Remigy to have where said height is less than 20% of the dimension of the specimen carrier in view of the teachings of Trávníček where this known technique could have been applied to a known device that was ready for improvement and the results would have been predictable, i.e., improving fluid utilization during heat transfer by leveraging the jet impingement effect of a slot nozzle where fluid diverges to cool a large area beyond the width of the nozzle [Trávníček, 0005, 00031].
Regarding Claim 9, Remigy, as modified, teaches the invention of claim 1 and further does not explicitly teach where the nozzle opening of the first nozzle [mouthpiece 33a, Figure 3A] is positioned in such a way that the width dimension is positioned level (i.e. horizontal, Applicant Specification, p. 7, lines 16-21).
However, Trávníček teaches a method and device for cooling cylindrical bodies with streams of cooling fluid [0001] where the nozzle opening of the first nozzle [nozzle 6, Figure 4] is positioned in such a way that the width dimension [going into the page of Figure 4, where Figure 4 is a perpendicular cross section of the body to be cooled; 0026] is positioned level [where the generator is preferably located through the opening of its nozzle directed perpendicular to the longitudinal axis of the body to be cooled; 0014] where one of ordinary skill in the art would have been capable of applying this known technique to a known device, a sample carrier, that was ready for improvement and the results would have been predictable to one of ordinary skill in the art i.e., maximizing heat transfer by orienting the fluid jet of the nozzle to be perpendicular to the surface of the object to be cooled [Trávníček, 0005].
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the method of Remigy to have where the nozzle opening of the first nozzle is positioned in such a way that the width dimension is positioned level in view of the teachings of Trávníček where this known technique could have been applied to a known device that was ready for improvement and the results would have been predictable, i.e., maximizing heat transfer by orienting the fluid jet of the nozzle to be perpendicular to the surface of the object to be cooled [Trávníček, 0005].
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Remigy in view of Han (US20210144990A1) as applied to claim 1 above and further in view Caliskan et al. (Caliskan, S. et al., “Experimental and numerical investigation of geometry effects on multiple impinging air jets,” International Journal of Heat and Mass Transfer, Vol. 75, August 2014, pp 685-703, [retrieved on 15 July 2025]. Retrieved from Internet <DOI: https://doi.org/10.1016/j.ijheatmasstransfer.2014.04.005>).
Regarding Claim 11, Remigy, as modified, teaches the invention of claim 1 above and does not teach where a height of the nozzle opening of the first nozzle is 0.7 mm.
However, Caliskan teaches nozzle geometries [impinging jet exit geometries, Table 1] including a height of the nozzle opening of the first nozzle [minor axis b, Table 1;p.688] where one of ordinary skill in the art would have been capable of applying routine optimization of a known result effective variable, aspect ratio of the opening, to achieve a recognized result, i.e., improving efficiency of convective heat transfer [where higher jet aspect ratios can be used as a passive enhancement technique, Caliskan, Conclusion, p.702]
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the assembly of Remigy to have where a height of the nozzle opening of the first nozzle is 0.7 mm in view of the teachings of Caliskan where the modification constitutes routine optimization of a known result-effective variable to achieve a recognized result, i.e., improving efficiency of convective heat transfer [where higher jet aspect ratios can be used as a passive enhancement technique, Caliskan, Conclusion, p.702]
Claims 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Remigy in view of Han (US20210144990A1) as applied to claim 17 above and in further view of Weissenberger et al. (Weissenberger et al., “Understanding the invisible hands of sample preparation for cryo-EM,” Nat Methods, May 2021, pp. 463–471, [retrieved on 15 July 2025]. Retrieved from Internet <DOI: https://doi.org/10.1038/s41592-021-01130-6>).
Regarding Claim 18, Remigy, as modified, teaches the invention of claim 17 and does not teach an applicator device for applying a specimen to a specimen carrier.
However, Weissenberger teaches techniques in the preparation of vitrified samples for the electron microscope [Abstract] where an applicator device [where droplets are pipetted onto a grid, Table 1; Blotting, p. 465, col. 2, para. 1] is used for applying a specimen to a specimen carrier [where blotting is a standard and most used technique to create a thin film of liquid of macromolecules; Deposition, p.465, col. 1, para. 1 and Blotting, p. 465, col. 2, para. 1] where one of ordinary skill in the art would have been capable of applying this known technique to a known device that was ready for improvement and the results would have been predictable to one of ordinary skill in the art, i.e., providing a low-cost deposition technique [Blotting, p. 465, col. 2, para. 3]
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the assembly of Remigy to have an applicator device for applying a specimen to a specimen carrier in view of the teachings of Weissenberger where this known technique could have been applied to a known device that was ready for improvement and the results would have been predictable, i.e., providing a low-cost deposition technique [Blotting, p. 465, col. 2, para. 3]
Regarding Claim 19, Remigy, as modified, teaches the invention of claim 18 and a blotting device [blotting paper; 0076] for removing excess liquid from said specimen carrier [0076].
Response to Arguments
Applicant’s arguments with respect to claims 1 and 17 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
On pages 9-12 of the Remarks filed 10/15/2025, Applicant argues in regards to amended claim 1 that Remigy fails to teach or suggest any specific dimensions of a rectangular nozzle and further Caliskan and Trávníček do not teach or suggest the dimensions as claimed. Applicant’s arguments have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Independent claim 17, as amended recites similar subject matter as amended claim 1. Applicant does not separately argue the rejection of claims 3,7,9 and 11 except for their dependence upon claim 1. Applicant does not separately argue the rejection of claims 18-19 except for their dependence upon claim 17. Accordingly, the rejections of record are considered proper and remain.
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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/KEONA LAUREN BANKS/Examiner, Art Unit 3763
/ELIZABETH J MARTIN/Primary Examiner, Art Unit 3763
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