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 .
Drawings
The drawings with 7 Sheets of Figs. 1-7B received on 12/11/2024 are acknowledged and accepted.
Claim Objections
Claims 15,16,18-20, objected to because of the following informalities:
Claims 15,16,18-20 recites “wherein the non-transitory memory storing computer code further cause the processor to”. This is grammatically incorrect. It is suggested to be replaced with -- wherein the non-transitory memory storing computer code further causes the processor to--.
Claims 16 is dependent on claim 15 and claims 19-20 are dependent on claim 18 and hence inherit its deficiencies.
Appropriate correction is required.
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.
Claim(s) 1-6,12-17, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dave et al (US 10,746,985 B2, of record).
Regarding Claim 1, Dave teaches (fig 1-4) a method (“a method for using an imager having an auto-focuser to acquire target information from subject targets on a planar substrate”, col 4, lines 59-61) for autofocusing a microscopy unit (imager 150, col 9, lines 10-15, imager 150 is a light microscope, col 10), the method comprising:
imaging a first field of view of a biological sample (target 110, col 9, lines 9-10) with the microscopy unit (imager 150, col 9), the biological sample (target 110,120, col 9, lines 9-10) housed within a cartridge chamber (“targets are suspended in a medium”, col 9, lines 29-32, substrate 100, “substrate can have a curved surface such as a section of a cylinder or sphere”, col 9, lines 35-48) inserted into the microscopy unit;
detecting a plurality of artificial particles (facilitative targets 120, col 9, lines 18-20, “the added facilitative targets 120 are microparticles”, col 13, fig 1, 220,222,224, fig 2) within the first field of view (“in a first focusing step, using the auto-focuser, focusing the imager with respect to facilitative targets within a first region”, col 4, lines 60-67),
the plurality of artificial particles (facilitative targets 120, col 9, lines 18-20) dispersed within the biological sample within the cartridge chamber (“forming a mixture of subject targets and facilitative targets on a planar substrate”, col 4, lines 60-67, “targets are suspended in a medium”, col 9, lines 29-32); and
determining a focus curve (“an auto-focuser can focus on the facilitative targets (microparticles), and then achieve focused, or nearly focused, images of subject particles, without having to refocus. In other embodiments, optimized focal parameters for the facilitative targets (e.g., microparticles) can serve as a starting point for further refinements/focus adjustments”, col 14, lines 9-15, also col 13, lines 45-col 14, line 15) for each of the plurality of artificial particles (facilitative targets 120, col 9, lines 18-20).
Regarding Claim 2, Dave teaches the method of claim 1,
further comprising determining a focus for the first field of view (field of view 325, col 16, lines 7-27, fig 3) based at least in part on the focus curve for each of the plurality of artificial particles (facilitative targets 120, col 9, lines 18-20, microparticle additives 360, col 16, lines 7-27) (“the optimal focal planes are 291, 293, and 295, respectively, wherein the facilitative targets/microparticles have been chosen to reside in”, col 13, lines 63-67)
Regarding Claim 3, Dave teaches the method of claim 2, further comprising repeating the aforementioned steps for at least one subsequent field of view (field of view 335, col 16, lines 7-27) (“particles within the boundary defined by the intersection of field of view 325 and field of view 335 will be common to the regional images taken of regions 321 and 331”, col 16, lines 7-27) .
Regarding Claim 4, Dave teaches the method of claim 3, wherein:
the biological sample comprises cells (“subject target particles (e.g. cells) 210,212,214”, col 13, lines 46-52) that are offset from a bottom surface of the cartridge chamber (see fig 2b, c).
Regarding Claim 5, Dave teaches the method of claim 1,
wherein the focus curve for each of the plurality of artificial particles (facilitative targets 120, col 9, lines 18-20, “the added facilitative targets 120 are microparticles”, col 13, fig 1, 220,222,224, fig 2) in each field of view are determined in a single depth of field (“the optimal focal planes are 291, 293, and 295, respectively, wherein the facilitative targets/microparticles have been chosen to reside in”, col 13, lines 63-67, this indicates a single depth of field).
Regarding Claim 6, Dave teaches the method of claim 5,
wherein the single depth of field is greater than 2 microns (Example 1, col 19, “glass beads, approximately 10-30 microns”, this indicates that the facilitative target particles are 10-30 micron approximately and hence the single depth of field is greater than 2 micron).
Regarding Claim 12, Dave teaches the method of claim 1,
further comprising determining cellular characteristics (cells 335, col 16, lines 7-27, fig 3, “cells 441,443,447”, col 17, lines 1-10, fig 4) of the biological sample (biological material, cellular particles, col 8, lines 20-37) within the first field of view (field of view 335, col 16, lines 7-27) (“Cells 441 and 447 are labeled with a fluorophore that emits green light (“green fluorophore”);. “Green channel image 415.sub.G was taken by selectively collecting light from the green fluorophores. The targets visible in green channel image 415.sub.G are those that were labeled with green fluorophore, namely, subject targets/cells 441, 443, and 447, and facilitative target/microparticle 431. (In FIGS. 4B, 4D, and 4E green color is represented by vertical hatching). These targets produce green target images 441.sub.G, 443.sub.G, 447.sub.G”, col 17, lines 10-17),
Regarding Claim 13, Dave teaches the method of claim 12,
further comprising estimating cellular characteristics of cells (cells 335, col 16, lines 7-27) of the biological sample (biological material, cellular particles, col 8, lines 20-37) based on the determined cellular characteristics of the biological sample within the first field of view (field of view 335, col 16, lines 7-27) “Green channel image 415.sub.G was taken by selectively collecting light from the green fluorophores. The targets visible in green channel image 415.sub.G are those that were labeled with green fluorophore, namely, subject targets/cells 441, 443, and 447, and facilitative target/microparticle 431. (In FIGS. 4B, 4D, and 4E green color is represented by vertical hatching). These targets produce green target images 441.sub.G, 443.sub.G, 447.sub.G”, col 17, lines 10-17).
Regarding Claim 14, Dave teaches (fig 1-4) the microscopy unit (imager 150, col 9, lines 10-15, imager 150 is a light microscope, col 10) comprising:
an imaging sensor (target information receiver 160, col 9, lines “60-65); and
an imaging system communicatively coupled to the imaging sensor (target information receiver 160, col 9, lines “60-65), the imaging system comprising a processor (target information processor 165, col 11, lines 64-67) and a non-transitory memory (target information memory 167, col 11, lines 64-67) storing computer code (“controller 175 could execute a series of incremental adjustments until image quality (as determined by processing the received target information 192) is optimized “, col 12, lines 9-15, this indicates code) which, when executed by the processor, cause the processor (target information processor 165, col 11, lines 64-67) to:
image a first field of view (field of view 325, col 16, lines 7-27, fig 3) of a biological sample (target 110, col 9, lines 9-10) with the microscopy unit (imager 150, col 9),
the biological sample (target 110,120, col 9, lines 9-10) housed within a cartridge chamber (“targets are suspended in a medium”, col 9, lines 29-32, substrate 100, “substrate can have a curved surface such as a section of a cylinder or sphere”, col 9, lines 35-48);
detect a plurality of artificial particles (facilitative targets 120, col 9, lines 18-20, “the added facilitative targets 120 are microparticles”, col 13, fig 1, 220,222,224, fig 2) within the first field of view (field of view 325, col 16, lines 7-27, fig 3) (“in a first focusing step, using the auto-focuser, focusing the imager with respect to facilitative targets within a first region”, col 4, lines 60-67),
the plurality of artificial particles (facilitative targets 120, col 9, lines 18-20) dispersed within the biological sample within the cartridge chamber (“forming a mixture of subject targets and facilitative targets on a planar substrate”, col 4, lines 60-67, “targets are suspended in a medium”, col 9, lines 29-32); and
determine a focus curve (“an auto-focuser can focus on the facilitative targets (microparticles), and then achieve focused, or nearly focused, images of subject particles, without having to refocus. In other embodiments, optimized focal parameters for the facilitative targets (e.g., microparticles) can serve as a starting point for further refinements/focus adjustments”, col 14, lines 9-15, also col 13, lines 45-col 14, line 15) for each of the plurality of artificial particles (facilitative targets 120, col 9, lines 18-20).
Regarding Claim 15, Dave teaches the microscopy unit of claim 14,
wherein the non-transitory memory (target information memory 167, col 11, lines 64-67) storing computer code (“controller 175 could execute a series of incremental adjustments until image quality (as determined by processing the received target information 192) is optimized “, col 12, lines 9-15, this indicates code) further cause the processor to:
determine a focus for the first field of view (field of view 325, col 16, lines 7-27, fig 3) based at least in part on the focus curve for each of the plurality of artificial particles (facilitative targets 120, col 9, lines 18-20, microparticle additives 360, col 16, lines 7-27) (“the optimal focal planes are 291, 293, and 295, respectively, wherein the facilitative targets/microparticles have been chosen to reside in”, col 13, lines 63-67).
Regarding Claim 16, Dave teaches the microscopy unit of claim 15,
wherein the non-transitory memory storing computer code further cause the processor to:
repeat the aforementioned steps for at least one subsequent field of view(field of view 335, col 16, lines 7-27) (“particles within the boundary defined by the intersection of field of view 325 and field of view 335 will be common to the regional images taken of regions 321 and 331”, col 16, lines 7-27) .
Regarding Claim 17, Dave teaches the microscopy unit of claim 14,
wherein the focus curve for each of the plurality of artificial particles(facilitative targets 120, col 9, lines 18-20, “the added facilitative targets 120 are microparticles”, col 13, fig 1, 220,222,224, fig 2) in each field of view are determined in a single depth of field (“the optimal focal planes are 291, 293, and 295, respectively, wherein the facilitative targets/microparticles have been chosen to reside in”, col 13, lines 63-67, this indicates a single depth of field).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 7-11,18-20, is/are rejected under 35 U.S.C. 103 as being unpatentable over Dave et al (US 10,746,985 B2, of record) in view of Chan et al (US 2017/0108686 A1, of record).
Regarding Claim 7, Dave teaches the method of claim 1.
However, Dave does not teach
further comprising determining a tilt level of the cartridge chamber based on the focus curve for each of the plurality of artificial particles.
Dave and Chan are related as cartridge chambers and focus.
Chan teaches (fig 1),
further comprising determining a tilt level (“A travel tilt of the stage may be measured, to identify a suitable offset to be applied to a transillumination range, a candidate focal position, a photoluminescence range, and/or a best photoluminescence focal position for subsequent locations of the sample holder”, para 60) of the cartridge chamber (sample holder 78, para 29) based on the focus curve (“The positional relationship of the sample 52 and objective 66 relative to one another defines the focal position (also called the focus) of the system”, para 29) for each of the plurality of artificial particles (sample 52, particles, “Sample 52 may be any suitable material, substance, isolate, extract, particles, or the like”, para 35).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Dave to include the determining a tilt level of the cartridge chamber of Chan for the purpose of identifying a suitable offset to be applied to a candidate focal position (para 60).
Regarding Claim 8, Dave teaches the method of claim 7.
However, Dave does not teach
further comprising determining the tilt level of the cartridge chamber for the first field of view and at least one subsequent field of view.
Dave and Chan are related as cartridge chambers and focus.
Chan teaches (fig 1),
further comprising determining the tilt level (“A travel tilt of the stage may be measured, to identify a suitable offset to be applied to a transillumination range, a candidate focal position, a photoluminescence range, and/or a best photoluminescence focal position for subsequent locations of the sample holder”, para 60) of the cartridge chamber for the first field of view and at least one subsequent field of view (“the candidate focal position may be adjusted mathematically by a predetermined offset to produce the (nominally) best photoluminescence focal position for subsequent photoluminescence imaging of the sample for the same field of view (or other fields of view)”, para 52)(“ The method steps described above are suitable for finding a candidate focal position and a best (or nominally best) photoluminescence focal position for the initial field of view of a sample holder and/or sample. These method steps can be modified significantly for subsequent fields of view with the same sample holder or sample, after at least one candidate focal position and/or best photoluminescence focal position has been obtained for the initial field of view. The subsequent fields of view represent different locations (e.g., wells) across the sample holder”, para 59).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Dave to include the determining a tilt level of the cartridge chamber for a first and a subsequent views of Chan for the purpose of identifying a suitable offset to be applied to a candidate focal position (para 60).
Regarding Claim 9, Dave teaches the method of claim 7.
However, Dave does not teach
further comprising: determining the tilt level of the cartridge chamber at corners of the cartridge chamber; and interpolating the tilt level of the cartridge chamber from each of the tilt levels at the corners of the cartridge chamber.
Dave and Chan are related as cartridge chambers and focus.
Chan teaches (fig 1-5, 10-12),
further comprising:
determining the tilt level (“Fiducials may be imaged to determine the travel tilt of the stage and/or to provide an estimate of the position of a sample along the z-axis”, para 61, Example 5, figs. 10-12, of the cartridge chamber at corners of the cartridge chamber (“four fiducials 190 are disposed outside but near the periphery of the sample holder (e.g., near the four corners of the sample holder)”, para 74); and
interpolating (“Accordingly, the best transillumination focus determined for the fiducials can be compared to the known elevations of the fiducials in the absence of tilt, to determine the extent, if any, of stage travel tilt”, para 75) the tilt level of the cartridge chamber from each of the tilt levels at the corners of the cartridge chamber (“Accordingly, the pattern of each fiducial may be imaged over a range of focal positions with transillumination to identify a best focus for transmitted light”, para 75).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Dave to include the determining a tilt level of the cartridge chamber and interpolating the tilt level of Chan for the purpose of identifying a suitable offset to be applied to a candidate focal position (para 60).
Regarding Claim 10, Dave teaches the method of claim 7.
However, Dave does not teach
further comprising
generating a three-dimensional model of a bottom surface of the cartridge chamber.
Dave and Chan are related as cartridge chambers and focus.
Chan teaches (fig 1-5, 10-12),
further comprising:
generating a three-dimensional model of a bottom surface of the cartridge chamber (“The fiducial may have a body 192, and a pattern 194 formed on a top side (or a bottom side) of the body”, “The pattern may cover only a portion of the top side (or bottom side) of body 192, such that elements of the pattern produce regions of high contrast at their peripheries”, para 75, “the pattern of each fiducial may be imaged over a range of focal positions with transillumination to identify a best focus for transmitted light. The fiducials may have known elevations relative to one another on the z-axis when the stage exhibits no tilt”, para 75, this indicates 3d model of the fiducials on the bottom surface of the sample holder)
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Dave to include the 3d model of Chan for the purpose of identifying a suitable offset to be applied to a candidate focal position (para 60).
Regarding Claim 11, Dave teaches the method of claim 7.
However, Dave does not teach
further comprising selecting a focus position of the microscopy unit based on the tilt level of the cartridge chamber.
Dave and Chan are related as cartridge chambers and focus.
Chan teaches (fig 1-5, 10-12),
further comprising:
selecting a focus position (“The best transillumination focus for fiducial 190 may be used to estimate a best transillumination focal position for a sample, based on known vertical offsets of the system. The elevation of pattern 194 on the fiducial corresponds to the best transillumination focus for fiducial 190”, para 76) of the microscopy unit based on the tilt level of the cartridge chamber (sample holder).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Dave to include the selecting a focus position of the microscopy unit based on the tilt level of the cartridge chamber of Chan for the purpose of identifying a suitable offset to be applied to a candidate focal position (para 60).
Regarding Claim 18, Dave teaches the microscopy unit of claim 14.
However, Dave does not teach
wherein the non-transitory memory storing computer code further cause the processor to:
determine a tilt level of the cartridge chamber based on the focus curve for each of the plurality of artificial particles. ;
Dave and Chan are related as cartridge chambers and focus.
Chan teaches (fig 1),
wherein the non-transitory memory storing computer code further cause the processor to:
determine a tilt level (“A travel tilt of the stage may be measured, to identify a suitable offset to be applied to a transillumination range, a candidate focal position, a photoluminescence range, and/or a best photoluminescence focal position for subsequent locations of the sample holder”, para 60) of the cartridge chamber (sample holder 78, para 29) based on the focus curve (“The positional relationship of the sample 52 and objective 66 relative to one another defines the focal position (also called the focus) of the system”, para 29) for each of the plurality of artificial particles (sample 52, particles, “Sample 52 may be any suitable material, substance, isolate, extract, particles, or the like”, para 35).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microscopy unit of Dave to include the processor for determining a tilt level of the cartridge chamber of Chan for the purpose of identifying a suitable offset to be applied to a candidate focal position (para 60).
Regarding Claim 19, Dave teaches the microscopy unit of claim 18.
However, Dave does not teach
wherein the non-transitory memory storing computer code further cause the processor to:
determine the tilt level of the cartridge chamber for the first field of view and at least one subsequent field of view.
Dave and Chan are related as cartridge chambers and focus.
Chan teaches (fig 1),
wherein the non-transitory memory storing computer code further cause the processor to:
determine the tilt level (“A travel tilt of the stage may be measured, to identify a suitable offset to be applied to a transillumination range, a candidate focal position, a photoluminescence range, and/or a best photoluminescence focal position for subsequent locations of the sample holder”, para 60) of the cartridge chamber for the first field of view and at least one subsequent field of view (“the candidate focal position may be adjusted mathematically by a predetermined offset to produce the (nominally) best photoluminescence focal position for subsequent photoluminescence imaging of the sample for the same field of view (or other fields of view)”, para 52)(“ The method steps described above are suitable for finding a candidate focal position and a best (or nominally best) photoluminescence focal position for the initial field of view of a sample holder and/or sample. These method steps can be modified significantly for subsequent fields of view with the same sample holder or sample, after at least one candidate focal position and/or best photoluminescence focal position has been obtained for the initial field of view. The subsequent fields of view represent different locations (e.g., wells) across the sample holder”, para 59).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microscopy unit of Dave to include the processor for determining a tilt level of the cartridge chamber for a first and a subsequent views of Chan for the purpose of identifying a suitable offset to be applied to a candidate focal position (para 60).
Regarding Claim 20, Dave teaches the microscopy unit of claim 18.
However, Dave does not teach
wherein the non-transitory memory storing computer code further cause the processor to:
determine the tilt level of the cartridge chamber at corners of the cartridge chamber; and interpolate the tilt level of the cartridge chamber from each of the tilt levels at the corners of the cartridge chamber.
Dave and Chan are related as cartridge chambers and focus.
Chan teaches (fig 1-5, 10-12),
wherein the non-transitory memory storing computer code further cause the processor to:
determine the tilt level (“Fiducials may be imaged to determine the travel tilt of the stage and/or to provide an estimate of the position of a sample along the z-axis”, para 61, Example 5, figs. 10-12, of the cartridge chamber at corners of the cartridge chamber (“four fiducials 190 are disposed outside but near the periphery of the sample holder (e.g., near the four corners of the sample holder)”, para 74); and
interpolating (“Accordingly, the best transillumination focus determined for the fiducials can be compared to the known elevations of the fiducials in the absence of tilt, to determine the extent, if any, of stage travel tilt”, para 75) the tilt level of the cartridge chamber from each of the tilt levels at the corners of the cartridge chamber (“Accordingly, the pattern of each fiducial may be imaged over a range of focal positions with transillumination to identify a best focus for transmitted light”, para 75).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microscopy unit of Dave to include the processor for determining a tilt level of the cartridge chamber and interpolating the tilt level of Chan for the purpose of identifying a suitable offset to be applied to a candidate focal position (para 60).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Harfouche et al (US 2022/0179187 A1) teaches a digital microscopy method obtaining data of one image of a portion of a cell sample which comprises focus analysis regions.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JYOTSNA V DABBI whose telephone number is (571)270-3270. The examiner can normally be reached M-Fri: 9:00am-5:00pm.
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, STEPHONE ALLEN can be reached at 571-272-2434. 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.
/JYOTSNA V DABBI/Primary Examiner, Art Unit 2872 9/28/2026
