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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/08/2024 and 06/17/2025 were considered by the examiner.
Claim Objections
Claims 1, 14, 36, 42, 52, 60, 70, and 73 are objected to because of the following informalities:
Regarding claim 1, the claim recites “serially illuminating the sample” in line 2, which should read “serially illuminating said sample” as the rest of the claim uses the word “said” to refer to previously recited elements/steps. The same correction should be made for each instance of “the sample” in lines 4, 6, and 8.
Regarding claim 14, the claim recites “comprising directing a portion of said optical signal to an additional imager for generating also a non-spectral image”. The examiner suggests removing the word “also” from the claim to avoid possible ambiguity.
Regarding claim 36, the claim recites “a beam splitter, engaging…” in line 5. The examiner is unsure why the comma is used after beam splitter as it appears that the beam splitter is performing the function of engaging. The examiner suggests removing it to avoid possible ambiguity.
Regarding claim 42, the claim recites “said monolithic structure” which should read “said asymmetric monolithic structure” as recited in claim 36.
Regarding claim 52, the claim recites “serially illuminating the sample” in line 2, which should read “serially illuminating said sample” as the rest of the claim uses the word “said” to refer to previously recited elements/steps. The same correction should be made for each instance of “the sample” in lines 4, 5, 7, 11, and 13. Further, the claim recites “such said illumination system” in line 10 which should read “such that said illumination system”. Further, the word “responsively” does not make sense in the context of line 5 and should likely read “responsive.”
Regarding claim 60, the claim recites “the sample” in line 2 which should read “said sample”.
Regarding claim 70, the claim recites “a beam splitter, engaging…” in line 4. The examiner is unsure why the comma is used after beam splitter as it appears that the beam splitter is performing the function of engaging. The examiner suggests removing it to avoid possible ambiguity.
Regarding claim 73, the claim recites “said monolithic structure” which should read “said asymmetric monolithic structure” as recited in claim 70.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1, 2, 4, 8, 12, 14, 22, 34, 36, 38, 42, 46 and 60 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the claim recites “by an imager, serially acquiring from the sample image data representing optical signals received from the sample responsively to said plurality of light beams”, starting in line 4. Due to the arrangement of the comma in this phase, it is unclear that the imager is acquiring image data. Instead, it reads as if the imager is acquiring something from a newly recited “sample image data”. It is unclear what exactly the imager is acquiring based on this interpretation. Further, the word “responsively” does not make sense in the context of this phrase and should likely read “responsive.” For the purposes of examination, the claim is interpreted as “serially acquiring image data from said sample by an imager, wherein said image data represents optical signals received from said sample responsive to said plurality of light beams” similar to claim 2. This interpretation would help make the claimed “said image data acquisitions” in line 7 clear as well. Appropriate correction is required.
Regarding claim 8, the claim recites “wherein said illuminating is via beam splitter configured and positioned to reflect said light beams and transmit said optical signals or vice versa”. The term “vice vera” makes the claim indefinite because it is unclear what limitation the claim is intended to recite. It is unclear what part of the previous limitation is reversed. For example, the claim could be interpreted as switching the phrases “reflect said light beam” and “transmit said optical signals.” However, it appears that the claim intends for only “reflect” and “transmit” to be reversed. Further, the phrase “via beam splitter” would read better as “performed using a beam splitter” or at least adding “a beam splitter.” For the purposes of examination, the claim is interpreted as wherein said illuminating is performed using a beam splitter configured and positioned to reflect said light beams and transmit said optical signals, or transmit said light beams and reflect said optical signals. Appropriate correction is required.
Regarding claim 12, the claim recites “measuring a local spectrum of each optical signal, comparing said measured spectra to a local spectrum of said spectral image”. It is unclear that the “said measured spectra” is the same as the local spectrum of each optical signal which was measured. For the purposes of examination, the claim interpreted as “measuring a local spectrum of each optical signal, comparing said measured local spectrum of each optical signal to a local spectrum of said spectral image”. Appropriate correction is required.
Regarding claim 22, the claim recites the limitation "the entry angle" in line 3. There is insufficient antecedent basis for this limitation in the claim. Appropriate correction is required. For the purposes of examination, the claim interpreted as “an entry angle”. Appropriate correction is required.
Regarding claim 60, the claim recites “comprising an optical system positioned on an optical path between the sample and said imager and being characterized by varying optical transmission properties”. The phrasing of the claim makes it unclear what is being characterized by varying optical transmission properties. Is it the optical system or possibly the system of claim 52? Based on claim 22, it appears that the optical system is characterized by varying optical transmission properties. For the purposes of examination, the claim interpreted as “comprising an optical system characterized by varying optical transmission properties positioned on an optical path between the sample and said imager”. Appropriate correction is required.
Claims 2, 4, 14, 36, 38, 42, and 46 are rejected due to their dependencies.
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.
(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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 70 and 72 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US5784152A by Heffelfinger et al. (hereinafter "Heffelfinger"; cited in the IDS).
Regarding claim 70, Heffelfinger teaches a Sagnac interferometer (Fig. 7), comprising:
two attached prisms (prism 701, 703) forming an asymmetric monolithic structure (col 6 line 61; Fig. 7 shows asymmetric shape since second prism 703 has interference mirror 713 that creates asymmetry) having an entry facet (path 707) at one prism and an exit facet (path 715) at another prism (col 6 lines 65-67; col 7 lines 1-5); and
a beam splitter, engaging a portion of an attachment area (area where two prisms meet) between said prisms and being configured for splitting an optical signal entering through said entry facet into two secondary optical signals (rays 711, 709) exiting through said exit facet (beam splitter coating 705; col 7 lines 1-5);
wherein a size of said beam splitter is selected to ensure that optical paths of said secondary optical signals impinge on said attachment area both at locations engaged by said beam splitter and at locations not engaged by said beam splitter (Fig. 7 shows that light beams reflected between mirrors 713 are not engaged by the beam splitter, thus the size was selected appropriately; Fig. 7 shows the same optical paths as applicants Fig. 12).
Regarding claim 72, Heffelfinger teaches the Sagnac interferometer according to claim 70 and further teaches, wherein said two prisms have different shapes thus ensuring said asymmetry (col 6 line 61; Fig. 7 shows asymmetric shape since second prism 703 has interference mirror 713 that creates asymmetry by making it a different shape than prism 701).
Claim Rejections - 35 USC § 103
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 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 71 and 75 are rejected under 35 U.S.C. 103 as being unpatentable over Heffelfinger in view of CN1949087A by Xu et al. (hereinafter "Xu"; cited in the IDS; translation with paragraph numbers provided).
Regarding claim 71, Heffelfinger teaches the Sagnac interferometer according to claim 70, but Heffelfinger is silent as to wherein said two prisms are identical but are attached offset to one another thus ensuring said asymmetry.
However, Xu does address this limitation. Heffelfinger and Xu are considered to be analogous to the present invention as they are in the same field of lateral shear interferometry (note that a Sagnac interferometer is a type of shearing interferometer).
Xu teaches wherein said two prisms are identical but are attached offset to one another thus ensuring said asymmetry (Fig. 10d shows identical prisms; [0118] relative movement of the contact surfaces of the half pentaprisms 414 and 415 introduces a certain amount of shear).
It would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to attach identical prisms at an offset. Therefore, it would have been obvious to modify Heffelfinger to include wherein said two prisms are identical but are attached offset to one another thus ensuring said asymmetry as suggested by Xu in order to improve optical transmission characteristics of the interferometer by adjusting the shear amount.
Regarding claim 75, Heffelfinger teaches the Sagnac interferometer according to claim 70, but Heffelfinger is silent as to wherein said two prisms are attached to form a penta-prism.
However, Xu does address this limitation. Heffelfinger and Xu are considered to be analogous to the present invention as they are in the same field of lateral shear interferometry (note that a Sagnac interferometer is a type of shearing interferometer).
Xu teaches wherein said two prisms are attached to form a penta-prism (Fig. 10b; [0118] lateral shearing interferometer 405, is made up of two and half pentaprisms, thus forming a penta-prism).
It would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to use two prisms attached to form a penta-prism. Therefore, it would have been obvious to modify Heffelfinger to include wherein said two prisms are attached to form a penta-prism as suggested by Xu in order to provide a stable configuration for lateral shear interferometry ([0118]).
Claims 73 and 74 are rejected under 35 U.S.C. 103 as being unpatentable over Heffelfinger in view of US20200409162A1 by Lavi et al. (hereinafter "Lavi"; cited in the IDS as WO 2020261235 A1).
Regarding claim 73, Heffelfinger teaches the Sagnac interferometer according to claim 70, and although Heffelfinger does not explicitly teach wherein said monolithic structure comprises a spacer at said attachment area, spaced apart from said beam splitter away from any of said optical paths, the applicant describes the purpose of the spacer is to allow for easy alignment of the two prisms so that they remain parallel to each other. The applicant further describes that the spacer may be made of the same material as the beam splitter ([0162]). Heffelfinger teaches the beam splitter is made of a coating 705 (col 7 lines 1-5) and from Fig. 7 it does not appear that the beamsplitter coating creates a gap between the two prisms which remain parallel.
Further, Lavi does address this limitation. Lavi and Heffelfinger are considered to be analogous to the present invention as they are in the same field of Sagnac interferometers.
Lavi teaches in other embodiments, the hypotenuse sides are simply juxtaposed, or placed in good mechanical contact with each other, optionally by means of an additional transparent liquid or gel to improve optical contact between the prisms 12, 22 and to eliminate small detrimental air pockets in the interface region between the prisms 12, 22 ([0081]).
Thus, it would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to provide a spacer, in a location that would not interference with the measurement, to align the prisms. Therefore, it would have been obvious to modify Heffelfinger to include wherein said monolithic structure comprises a spacer at said attachment area, spaced apart from said beam splitter away from any of said optical paths as suggested by Lavi in order to eliminate small detrimental air pockets in the interface region between the prisms ([0081]).
Regarding claim 74, Heffelfinger modified by Lavi teaches the Sagnac interferometer according to claim 73, but Heffelfinger is silent as to wherein said spacer is made of the same material and thickness as said beam splitter.
However, Lavi does address this limitation.
Lavi teaches wherein said monolithic structure comprises a thin piece of material, such as, for example, a sheet, foil, or thin glass plate, that has a beamsplitter coating deposited thereon and extends along a portion (preferably a majority portion) or the entirety of the hypotenuse sides of the two constituent prisms 12, 22, can be cemented between the hypotenuse sides of the two constituent prisms 12 to form the unitary prism assembly 30 ([0082]).
Thus as the beam splitter can act as a spacer, it would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention that a spacer to be made out of the same material as the beam splitter. Further, it has been held to be within the general skill of a worker in the art to select a known material on the basis of its suitability for the intended use as a matter of obvious design choice. In re Leshin, 125 USPQ 416.Therefore, it would have been obvious to modify Heffelfinger to include wherein said spacer is made of the same material and thickness as said beam splitter in order to eliminate small detrimental air pockets in the interface region between the prisms ([0081]).
Claims 1, 2, 4, 8, 22, 34, 36, 46, 52, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Heffelfinger in view of US20190339203A1 by Miller et al. (hereinafter "Miller"; cited in the IDS).
Regarding claim 1, Heffelfinger teaches a method of imaging a sample (sample 101; col 3 line 21) comprising (at least Fig. 1, 2 and 7):
serially illuminating the sample by a plurality of light beams (Light source 105 can operate at one or more wavelengths; col 9 lines 46-50), each having a different central wavelength (col 3 lines 46-50 one or more wavelengths; col 7 lines 18-20 specific wavelength band is selected using tuning section 107);
by an imager (detector 111; col 3 line 60-62), serially acquiring from the sample image data representing optical signals received from the sample responsively to said plurality of light beams (col 3 lines 60-62 Fluorescence);
shifting a field-of-view of the sample relative to said imager (col 4 lines 10-13 Positioners 123 allow sample 101 to be moved in two orthogonal directions (i.e., X and Y) with respect to source 105, detector 111, and detector 117) and repeating said serial illumination and said image data acquisitions for said shifted field-of-view (col 7 lines 50-55 multiple locations within each sample well); and
generating a spectral image of the sample using image data acquired by said imager (col 10 lines 8-10 spectral data to generate image) at a plurality of field-of-views for each of said plurality of light beams (col 7 lines 54-61 processor 125 would then test each sample well at four locations; col 9 lines 53-54 an image of the sample is formed and presented to the user on a monitor.)
Even if Heffelfinger does not explicitly teach serially illuminating the sample and serially acquiring from the sample image data and repeating said serial illumination and said image data acquisitions for said shifted field-of-view, Heffelfinger teaches an embodiment where sample 101 is raster scanned, thus allowing an entire image to be serially captured and recorded. This embodiment is especially beneficial when weak probes are used, since both the excitation radiation and the emitted fluorescence are focused. (col 10 lines 38-45). Further, Heffelfinger teaches an embodiment where the user selects the step size of the successive locations as well as the sampling time (col 8 lines 28-32), thus it would appear that Heffelfinger does teach repeating said serial illumination and said image data acquisitions for said shifted field-of-view since the other embodiments would inherently include these parameters even when not selected by the user.
Further, Miller does address this limitation. Heffelfinger and Miller are considered to be analogous to the present invention as they are in the same field of fluorescence microscopy.
Miller teaches serially illuminating the sample by a plurality of light beams ([0078] captures N different sample images, each of which corresponds to a different combination of an excitation wavelength band of filter 206 (which controls the spectral distribution of illumination light that is incident on sample 250)), each having a different central wavelength ([0072] Light source 202 is an adjustable source that can produce light having a variable distribution of illumination wavelengths)
by an imager (detector 212; [0076]), serially acquiring from the sample image data representing optical signals received from the sample responsively to said plurality of light beams ([0078] captures N different sample images);
shifting a field-of-view of the sample relative to said imager and repeating said serial illumination and said image data acquisitions for said shifted field-of-view ([0075] Motion of stage 210 in the x- and y-directions allows the filtered illumination light to be directed to different regions of the sample).
Thus, it would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to serially illuminate and serially acquire images and repeat this process for different fields of view. Therefore, it would have been obvious to modify Heffelfinger to include, if not inherent, serially illuminating the sample and serially acquiring from the sample image data and repeating said serial illumination and said image data acquisitions for said shifted field-of-view in order to provide the most robust measurement of the entire sample.
Regarding claim 2, Heffelfinger modified by Miller teaches the method according to claim 1, and although, Heffelfinger does not explicitly teach wherein said serially acquiring image data is while said field-of-view is static, the examiner believes this would like be an inherent part of performing the series of measurements. Heffelfinger teaches in one embodiment that the user can specify the actual locations within a sample well at which testing is to be performed and the system can then be programmed to either analyze only the selected sample well or to use the same locations for measuring every sample well within the microplate (col 7 lines 62-67; col 8 lines 1-17). It would not make sense to acquire image data while the field-of-view is moving between locations since it would negatively impact image quality.
Further, Miller does address this limitation.
Miller teaches wherein said serially acquiring image data is while said field-of-view is static ([0078] system 200 typically captures N different sample images, each of which corresponds to a different combination of an excitation wavelength band; as the images correspond to different combinations of wavelengths, it would be implied that each image has the same field of view in order to accurately compare them).
It would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to keep the field-of-view static while performing a series of measurements in order to obtain a clear image. Therefore, it would have been obvious to modify Heffelfinger to include wherein said serially acquiring image data is while said field-of-view is static as suggested by Miller in order to efficiently compare images and reduce error.
Regarding claim 4, Heffelfinger modified by Miller teaches the method according to claim 1, and Heffelfinger further teaches wherein said sample contains a plurality of fluorophores each having a different emission spectrum (col 10 lines 16-17 many of the probes will contain multiple dyes; fluorophores are dyes, and since the invention is measuring fluorescence, one would understand they are fluorophores which would inherently have a different emission spectrum; col 5 lines 13-15 fluorochromes is fluorophore) , and wherein a spectral bandwidth of at least one of said light beams is selected to excite at least two different fluorophores (col 5 lines 13-15 "reflect those wavelengths necessary for exciting the selected fluorochromes").
Regarding claim 8, Heffelfinger modified by Miller teaches the method according to claim 1, and Heffelfinger further teaches wherein said illuminating is via beam splitter configured and positioned to reflect said light beams and transmit said optical signals or vice versa (Fig. 2 beam splitter 205; col 5 lines 1-20).
Regarding claim 22, Heffelfinger modified by Miller teaches the method according to claim 1, and Heffelfinger further teaches comprising passing said optical signal through an optical system (interferometer 700) characterized by varying optical transmission properties that vary according to the entry angle (Fig. 7 shows varying optical transmission properties that vary according to the entry angle; col 6 lines 60-67; col 7 lines 1-5; interferometer 700 is a type of Sagnac interferometer also shown in Fig. 6 and would provide a similar function described in col 6 lines 38-60 which describes that light from the sample is directed to interferometer then directed to the detector).
Regarding claim 34, Heffelfinger modified by Miller teaches the method according to claim 22, and Heffelfinger further teaches wherein said optical system comprises a Sagnac interferometer (interferometer 700 is a type of Sagnac interferometer; col 6 lines 38-60).
Regarding claim 36, Heffelfinger modified by Miller teaches the method according to claim 34, and Heffelfinger further teaches
wherein said Sagnac interferometer (interferometer 700) comprises:
two attached prisms (prism 701, 703) forming an asymmetric monolithic structure (col 6 line 61; Fig. 7 shows asymmetric shape since second prism 703 has interference mirror 713 that creates asymmetry) having an entry facet (path 707) at one prism and an exit facet (path 715) at another prism (col 6 lines 65-67; col 7 lines 1-5) and
a beam splitter, engaging a portion of an attachment area (area where two prims meet) between said prisms and being configured for splitting an optical signal entering through said entry facet into two secondary optical signals (rays 711, 709) exiting through said exit facet (beam splitter coating 705; col 7 lines 1-5);
wherein a size of said beam splitter is selected to ensure that optical paths of said secondary optical signals impinge on said attachment area both at locations engaged by said beam splitter and at locations not engaged by said beam splitter (Fig. 7 shows that light beams reflected between mirrors 713 are not engaged by the beam splitter, thus the size was selected appropriately; Fig. 7 shows the same optical paths as applicants Fig. 12).
Regarding claim 46, Heffelfinger modified by Miller teaches the method according to claim 1, but Heffelfinger does not explicitly teach in this embodiment a method of imaging a pathological slide stained with multiple stains having different spectral properties, comprising: executing the method according to claim 1; analyzing said spectral image for a relative contribution of each stain; and generating a displayable density map of said stains based on said relative contribution.
However, Heffelfinger teaches in alternate embodiments generating displayable images using five different dyes (col 10 lines 9-15) and generating a displayable density map (col 8 lines 22-24 processor 125 would present on monitor 903 the optical density readings at each analyzed location for each well.) Heffelfinger further teaches that the samples are contained in a variety of sample containers can be analyzed with the present invention (col 7 lines 32-35).
Further, Miller does address this limitation.
Miller teaches a method of imaging a pathological slide stained with multiple stains having different spectral properties ([0004] multiple dyes or stains are applied to a sample, and then the sample is imaged over a broad range of wavelengths), comprising:
executing the method according to claim 1 ([0004]; see claim 1);
analyzing said spectral image for a relative contribution of each stain ([0004] Contributions of each of the sample components are separated by analyzing); and
generating a displayable density map of said stains based on said relative contribution ([0052] one or more displays on which sample images that represent spectral contributions corresponding to individual applied dyes are displayed to pathologists).
It would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to image a pathological slide stained with multiple stains having different spectral properties and analyze the image based on the stains. Therefore, it would have been obvious to modify Heffelfinger to include, if not inherent, a method of imaging a pathological slide stained with multiple stains having different spectral properties, comprising: executing the method according to claim 1; analyzing said spectral image for a relative contribution of each stain; and generating a displayable density map of said stains based on said relative contribution as a suggested by Miller in order to accurately measure a multi-spectral sample using well known methods.
Regarding claim 52, Heffelfinger teaches a system for imaging a sample (sample 101; col 3 line 21), comprising (at least Fig. 1, 2 and 7):
an illumination system configured for serially illuminating the sample by a plurality of light beams (Light source 105 can operate at one or more wavelengths; col 9 lines 46-50), each having a different central wavelength (col 3 lines 46-50 one or more wavelengths; col 7 lines 18-20 specific wavelength band is selected using tuning section 107);
an imager (detector 111; col 3 line 60-62), configured for acquiring image data from the sample, said image data representing optical signals received from the sample responsively to said plurality of light beams (col 3 lines 60-62 Fluorescence)
a stage configured for shifting a field-of-view of the sample relative to said imager (col 4 lines 10-13 Positioners 123 allow sample 101 to be moved in two orthogonal directions (i.e., X and Y) with respect to source 105, detector 111, and detector 117; col 11, claim 1 details sample holding stage);
a controller (col 4 lines 19-28 data processor 25 controls positioners 123 which control the stage), configured to control said stage to shift said field-of-view in steps (col 8 lines 28-32 see explanation below), and to control said illumination system and said imager such said illumination system serially illuminates the sample by said light beams and said imager serially acquires said image data (col 7 lines 50-55 multiple locations within each sample well); and
an image processor configured to generate a spectral image of the sample using image data acquired by said imager at a plurality of field-of-views for each of said plurality of light beams (col 10 lines 8-10 spectral data to generate image).
Even if Heffelfinger does not explicitly teach serially illuminating the sample and to control said stage to shift said field-of-view in steps and said imager serially acquires said image data in this embodiment, Heffelfinger teaches an embodiment where sample 101 is raster scanned, thus allowing an entire image to be serially captured and recorded. This embodiment is especially beneficial when weak probes are used, since both the excitation radiation and the emitted fluorescence are focused. (col 10 lines 38-45). Further, Heffelfinger teaches an embodiment where the user selects the step size of the successive locations as well as the sampling time (col 8 lines 28-32), thus it would appear that Heffelfinger does teach to shift said field-of-view in steps since the other embodiments would inherently include these parameters even when not selected by the user.
Further, Miller does address this limitation. Miller and Heffelfinger are considered to be analogous to the present invention as they are in the same field of fluorescence microscopy.
Miller teaches an illumination system configured for serially illuminating the sample by a plurality of light beams ([0078] captures N different sample images, each of which corresponds to a different combination of an excitation wavelength band of filter 206 (which controls the spectral distribution of illumination light that is incident on sample 250)) each having a different central wavelength ([0072] Light source 202 is an adjustable source that can produce light having a variable distribution of illumination wavelengths);
an imager (detector 212; [0076]), configured for acquiring image data from the sample, said image data representing optical signals received from the sample responsively to said plurality of light beams ([0078] captures N different sample images);
a stage configured for shifting a field-of-view of the sample relative to said imager (stage 210; [0075])
a controller (controller [0075]), configured to control said stage to shift said field-of-view in steps ([0075] By moving the sample relative to the focal region of the illumination light, illumination light can be directed to multiple different regions of the sample, permitting whole-slide imaging of sample 250) and to control said illumination system and said imager such said illumination system serially illuminates the sample by said light beams and said imager serially acquires said image data ([0075]).
Thus, it would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to serially illuminate and serially acquire images and to control the stage in steps. Therefore, it would have been obvious to modify Heffelfinger to include, if not inherent, serially illuminating the sample and serially acquiring from the sample image data and controlling said stage to shift said field-of-view in steps in order to provide the most robust measurement of the entire sample.
Regarding claim 60, Heffelfinger modified by Miller teaches the system according to claim 52, and Heffelfinger further teaches comprising an optical system (interferometer 700) positioned on an optical path between the sample and said imager and being characterized by varying optical transmission properties (Fig. 7 shows varying optical transmission properties that vary according to the entry angle; col 6 lines 60-67; col 7 lines 1-5; interferometer 700 is a type of Sagnac interferometer also shown in Fig. 6 and would provide a similar function described in col 6 lines 38-60 which describes that light from the sample is directed to interferometer then directed to the detector).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Heffelfinger in view Miller as applied to claim 1 above, and in further view of US5784162 by Cabib et al. (hereinafter "Cabib"; cited in the IDS).
Regarding claim 12, Heffelfinger modified by Miller teaches the method according to claim 1, and although Heffelfinger does not explicitly teach a separate spectrometer, Heffelfinger does teach directing a portion of said optical signal to the imager for measuring a local spectrum of each optical signal, comparing said measured spectra to a local spectrum of said spectral image, and generating a report pertaining to said comparison (col 10 lines 4-8 a first portion of sample 1 is imaged onto a first pixel; a second portion of sample 1 is imaged onto a second pixel; col 10 lines 9-11 Once the spectral data for each pixel of array 111 has been determined, processor 125 can be used to generate a variety of useful images on monitor 903; where the useful images constitute a report pertaining to a comparison between optical signals ).
This appears to be consistent with the applicant's specification describing the local spectrum, the spectral image provided at 304 thus comprises data arranged over a plurality of pixels each storing a plurality of a set of intensity values which respectively correspond to a set of wavelength components of the optical signal and therefore represent the local spectrum of the optical signal at that pixel (applicant’s specification [0108]).
Further, Cabib does address this limitation. Cabib and Heffelfinger are considered to be analogous to the present invention as they are in the same field of fluorescence microscopy.
Cabib teaches a calibration procedure in which a spectrum measured prior to sample analysis is used to divide the spectrum of each of the pixels in the spectral image (col 21 lines 65-67; col 22 lines 1-5). Cabib further teaches a spectrometer is an apparatus designed to accept light, to separate (disperse) it into its component wavelengths, and measure the lights spectrum, that is the intensity of the light as a function of its wavelength (col 1 lines 25-29).
It would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to use a spectrometer to measure a portion of an optical signal and compare to a spectral image. Therefore, it would have been obvious to modify Heffelfinger to include directing a portion of said optical signal to a spectrometer for measuring a local spectrum of each optical signal, comparing said measured spectra to a local spectrum of said spectral image, and generating a report pertaining to said comparison in order to perform calibration as suggested by Cabib, thus reducing error.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Heffelfinger in view Miller as applied to claim 1 above, and in further view of US6403947B1 Hoyt et al. (hereinafter "Hoyt").
Regarding claim 14, Heffelfinger modified by Miller teaches the method according to claim 1, and Heffelfinger teaches an additional imager (detector 117 col 4 lines 2-3).
Heffelfinger does not explicitly teach comprising directing a portion of said optical signal to an additional imager for generating also a non-spectral image. The examiner notes that the applicant describes examples of a non-spectral image as an RGB image having 3 intensity values per pixel, or a grey-level image having a single intensity value per pixel ([0152]).
However, Hoyt does address this limitation. Hoyt and Heffelfinger are considered to be analogous to the present invention as they are in the same field of fluorescence.
Hoyt teaches using a color CCD camera to obtain raw intensity images (col 3 lines 26-27).
It would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to use an additional imager to provide a non-spectral image. Therefore, it would have been obvious to modify Heffelfinger to include comprising directing a portion of said optical signal to an additional imager for generating also a non-spectral image as suggested by Hoyt in order to provide a more robust measurement.
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over Heffelfinger in view Miller as applied to claim 36 above, and in further view of Xu.
Regarding claim 38, Heffelfinger modified by Miller teaches the method according to claim 36, but Heffelfinger is silent as to wherein said two prisms are identical but are attached offset to one another thus ensuring said asymmetry.
However, Xu does address this limitation. Heffelfinger and Xu are considered to be analogous to the present invention as they are in the same field of lateral shear interferometry (note that a Sagnac interferometer is a type of shearing interferometer).
Xu teaches wherein said two prisms are identical but are attached offset to one another thus ensuring said asymmetry (Fig. 10d; [0118] relative movement of the contact surfaces of the half pentaprisms 414 and 415 introduces a certain amount of shear).
It would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to attach identical prisms at an offset. Therefore, it would have been obvious to modify Heffelfinger to include wherein said two prisms are identical but are attached offset to one another thus ensuring said asymmetry as suggested by Xu in order to improve optical transmission characteristics of the interferometer by adjusting the shear amount.
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over Heffelfinger in view Miller as applied to claim 36 above, and in further view of Lavi.
Regarding claim 42, Heffelfinger modified by Miller teaches the method according to claim 36, and although Heffelfinger does not explicitly teach wherein said monolithic structure comprises a spacer at said attachment area, spaced apart from said beam splitter away from any of said optical paths, the applicant describes the purpose of the spacer is to allow for easy alignment of the two prisms so that they remain parallel to each other. The applicant further describes that the spacer may be made of the same material as the beam splitter ([0162]). Heffelfinger teaches the beam splitter is made of a coating 705 (col 7 lines 1-5) and from Fig. 7 it does not appear that the beamsplitter coating creates a gap between the two prisms which remain parallel.
Further, Lavi does address this limitation. Lavi and Heffelfinger are considered to be analogous to the present invention as they are in the same field of Sagnac interferometers.
Lavi teaches in other embodiments, the hypotenuse sides are simply juxtaposed, or placed in good mechanical contact with each other, optionally by means of an additional transparent liquid or gel to improve optical contact between the prisms 12, 22 and to eliminate small detrimental air pockets in the interface region between the prisms 12, 22 ([0081]).
Thus, it would have been well known to someone of ordinary skill in the art before the effective filing date of the claimed invention to provide a spacer, in a location that would not interference with the measurement, to align the prisms. Therefore, it would have been obvious to modify Heffelfinger to include wherein said monolithic structure comprises a spacer at said attachment area, spaced apart from said beam splitter away from any of said optical paths as suggested by Lavi in order to eliminate small detrimental air pockets in the interface region between the prisms ([0081]).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US5995645A by Soenksen teaches a method, similar to claim 46, for cancer cell detection including the steps of (a) staining an analyzed sample with at least first and second dyes, the dyes being selected such that the first dye better adheres to normal cells whereas the second dye better adheres to cancer cells; (b) spectrally imaging the sample through an optical device being optically connected to an imaging spectrometer thereby obtaining a spectrum of each pixel of the sample; (c) based on the spectra, evaluating concentrations of the first and second dyes for each of the pixels; and (d) based on the concentrations detecting the presence of cancer cells in the sample (Abstract).
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/KAITLYN E KIDWELL/Examiner, Art Unit 2877
/TARIFUR R CHOWDHURY/Supervisory Patent Examiner, Art Unit 2877