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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/9/2026 has been entered.
Response to Arguments
Claim Objection
The objection to claim 15 is overcome by amendment.
Rejections under 35 U.S.C. § 103
Applicant’s first argument is that Machida fails to teach the newly added limitations regarding two-dimensional imaging and detecting the signal from a two-dimensional region of the sample due to arranging the slit parallel to the motion of the sample rather than orthogonal to the motion of the sample, however, this argument is moot. The present action relies on Wu, rather than Machida, to teach the addition of an extra dimension of imaging by particular choice of which direction to move the sample.
Applicant’s second argument is that Machida only images a single point, however, this argument is not persuasive. As one of ordinary skill in the art would understand, if provided with a source of illumination that is spread out in the direction of the slit (which Machida is not relied on to provide), light of a particular wavelength from a small part of the sample would be imaged onto a small part in the slit and onto a small part of the detector array. Light of the same wavelength from a different part of the sample along the length of the slit would be imaged to a different position along the length of the slit and onto a different part of the imaging array, displaced along one of the dimensions of the detector array. Light of a different wavelength originating from the same position would be displaced on the imaging sensor along the other dimension. The result is that Machida produces an image that has one spatial dimension and one spectral dimension.
Applicant’s third argument is that Machida teaches away from a combination with Olarte, however, this argument is not persuasive. Machida does not appear to teach that such a combination would cause the device to become non-functional.
Claim Objections
Claims 4-5 and 12 are objected to because of the following informalities: these claims have a space following the number of the claim on which they directly depend. Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-4, 8, 10, 13-15, and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Machida (US Patent 6284119) in view of Wu (Non-Patent Literature “A light sheet based high throughput 3D-imaging flow cytometer for phytoplankton analysis”).
Regarding claim 1, Machida teaches a spectrometry apparatus comprising:
a detection object lens that signal light as Raman scattering (FIG. 2 shows Raman scattering data, as described in COL. 6, lines 23-25) light from a sample enters (FIG. 1, the combination of first lens 7 and second lens 11);
a slit having a slit opening through which the signal light passes (FIG. 1, slit 15);
a wavelength dispersive element that disperses the signal light having passed the slit opening in accordance with a wavelength (FIG. 1, grating 18);
a two-dimensional optical detector that detects the signal light that has been subjected to wavelength dispersion by the wavelength dispersive element for imaging the Raman scattering light (FIG. 1, CCD sensor 20, note that a 512 by 64-pixel CCD sensor (COL. 6, lines 7-9) images the light directed to it) from a predetermined range of the sample based on the signal light (FIG. 1, the linear portion of the sample, electrophoretic means 5, on which the detector setup is focused); and
an illumination optical system that makes illumination light enter the sample (FIG. 1, LD light source 1) from a side of the detection object lens (FIG. 1, the combination of first lens 7 and second lens 11) and condenses the illumination light on the sample along an illumination optical axis direction (FIG. 1, condenser lens 3, directing illumination light toward the bottom of the page), the illumination optical axis direction being a direction orthogonal to a detection optical axis of the detection object lens (FIG. 1, downward illumination light is shown as orthogonal to rightward signal light);
wherein the slit is disposed at a position conjugated with a focal surface of the detection object lens (FIG. 1, note that light from a single point in the sample is focused on a single point passing through the slit, which indicates that each of those points is conjugate to the other with respect to the multielement lens 7/11),
the illumination optical system condenses the illumination light on the sample (FIG. 1, condenser lens 3),
the illumination optical system condenses the illumination light in the direction along the detection optical axis of the detection object lens (FIG. 1, condenser lens 3 condenses the light to a particular point on the sample, which includes condensing light along the direction of the detection optical axis),
in the long-side direction of the slit opening, the two-dimensional optical detector detects the signal light from positions different from each other with pixels different from each other for measuring Raman spectrum, in the long-side direction of the slit opening, the two-dimensional optical detector detects the signal light from positions different from each other with pixels different from each other for measuring Raman spectrum (this will naturally occur with the setup shown in FIG. 1, with different positions in the direction perpendicular to the page mapping to different pixels in the CCD sensor 20, which are also separated in the direction perpendicular to the page).
While the two-dimensional CCD sensor of Machida would produce images that have one spatial dimension and spectral dimension, Machida does not explicitly teach two-dimensional imaging by detecting the signal light from a two-dimensional region of the sample,
that the illumination is condensed as sheet-shaped illumination,
that, in an orthogonal plane orthogonal to the direction along the detection optical axis, the sheet shaped illumination light is spreading wider than a field of vision in an orthogonal direction orthogonal to a long-side direction of the slit opening, or
that a position of the sample relative to the object lens is moved in the orthogonal direction in the orthogonal plane or the detection optical axis direction.
In the same field of endeavor of flow cytometry, Wu does teach two-dimensional imaging by detecting the signal light from a two-dimensional region of the sample (FIG. 5(e) shows a pair of two-dimensional images where one of the dimensions is along the flow and the other is perpendicular to that first dimension),
that the illumination is condensed as sheet-shaped illumination (section 2.1 describes the light sheet generation unit),
that, in an orthogonal plane orthogonal to the direction along the detection optical axis, the sheet shaped illumination light is spreading wider than a field of vision (FIG. 1, horizontally on the page, as the propagation direction of the beam is wider than the field of view of the objective) in an orthogonal direction orthogonal to a long-side direction of the slit opening (while Wu alone does not teach a slit opening, the combination of Machida as modified by Wu could easily arrange the slit perpendicular to propagation direction of the light sheet, which would cause the light sheet to be wider in the orthogonal direction), and
that a position of the sample relative to the object lens is moved in the orthogonal direction in the orthogonal plane or the detection optical axis direction (FIG. 1, the position of the sample is moved along the detection optical axis direction). By using a light sheet, Wu is able to image a particular slice of the sample along an orthogonal plane, and by arranging the flow direction along the detection optical axis, Wu can stack those slices to gain an extra spatial dimension of imaging along the direction of motion of the sample (going from two dimensions to three dimensions in the case of Wu).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the spectrometry apparatus of Machida with the light sheet illumination and flow direction of Wu to gain the benefit of being able to image the sample in two spatial dimensions and one spectral dimension instead of merely one spatial and one spectral dimension of Machida alone or only spatial dimensions like Wu alone.
Regarding claim 2, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 1 (as described above).
Machida further teaches means for scanning the sample or the illumination light (FIG. 5, sample feed unit 61 can scan the sample through the detection region via capillary 5).
Regarding claim 3, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 1 (as described above).
Machida further teaches that a flow channel (FIG. 5, capillary 5) and a means for feeding the sample into the flow channel (FIG. 5, sample feed unit 61).
Regarding claim 4, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 1 (as described above).
Machida does not explicitly teach that an arrangement direction of pixels in the two-dimensional optical detector is inclined diagonally to a dispersing direction of the wavelength dispersive element.
Merely rearranging parts of a device, such as orienting the dispersing direction of the wavelength dispersive element diagonal relative to the pixels of the image sensor, does not generally create a nonobvious patentable distinction from prior art. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the spectrometry device of Machida, as modified by Olarte, to orient the dispersion direction diagonal to the detector, obtaining the predictable result of imaging the different wavelengths passing through the slit into a parallelogram-shaped region instead of a rectangular region so that the spectrum measured fits differently into the image.
Regarding claim 8, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 1 (as described above).
Machida further teaches an illumination object lens that condenses the illumination light on the sample (FIG. 1, condenser lens 3); and a filter that is disposed between the illumination object lens and the sample and transmits the illumination light (FIG. 7, short-pass filter 2).
Regarding claim 10, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 3 (as described above).
Machida further teaches that the sample flows in the flow channel (FIG. 1, electrophoretic means 5), and
the optical axis of the illumination light that enters the sample is in a direction orthogonal to a direction of the flow channel (FIG. 1, the direction of flow is shown as orthogonal to the page, which is orthogonal to the optical axis of the illumination light, which is oriented along the page).
Note that Wu also teaches that the sample flows in the flow channel (FIG. 1 shows the sample flowing in the flow channel), and the optical axis of the illumination light that enters the sample is in a direction orthogonal to a direction of the flow channel (FIG. 1, the light enters along an axis pointing toward the right-hand side of the page, which is orthogonal to the downward flow of the sample. The orthogonal arrangement between the light sheet and the flow allows the particles in the sample to be lit by the sheet only when they are in focus of the microscope.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have built the spectrometry apparatus of Machida, as modified by Wu, with the orthogonal sample flow and illumination path of Wu to be able to measure and stack images of slices of the sample as the sample flows across the light sheet.
Regarding claim 13, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 1 (as described above).
While Machida is silent as to the level of magnification used and whether the signal light is detected at a magnification at which a cell as the sample corresponds to one pixel of the two dimensional optical detector in a direction orthogonal to a wavelength dispersing direction of the wavelength dispersive element, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the spectrometry of Machida, as modified by Wu, through routine optimization of the magnification of the detected signal to correspond the size of a cell to the detection area of a pixel, achieving the predictable result of increasing the features to be detected (by increasing magnification), while also increasing contrast (by decreasing magnification, so that a cell does not spill from one pixel to another too much), with a reasonable expectation of success.
Regarding claim 14, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 1 (as described above).
Machida does not explicitly teach that the sample or the illumination light is scanned in a direction along an optical axis of the detection object lens.
In the same field of endeavor of flow cytometry, Wu does teach that the sample or the illumination light is scanned in a direction along an optical axis of the detection object lens (FIG. 1 show the sample scanning through the focal region of the lens and through the illumination along the optical axis of the detection objective). The axial arrangement between the detection objective and the flow allows the particles in the sample to be lit by the sheet and in focus of the microscope only at a particular z position.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have built the spectrometry apparatus of Machida, as modified by Wu, with the axial sample flow and detection objective of Wu to be able to measure and stack images of slices of the sample as the sample flows across the light sheet.
Regarding claim 15, Machida a spectrometry method comprising:
a step of illuminating a sample with using an illumination optical system from a side of a detection object lens (FIG. 1, LD light source 1);
a step of causing signal light as Raman scattering (FIG. 2 shows Raman scattering data, as described in COL. 6, lines 23-25) light from the sample to enter the detection object lens (FIG. 1, the combination of first lens 7 and second lens 11);
a step of causing the signal light to pass a slit opening of a slit (FIG. 1, slit 15);
a step of causing the signal light having passed the slit opening to be subjected to wavelength dispersion by a wavelength dispersive element (FIG. 1, grating 18); and
a step of detecting the signal light subjected to the wavelength dispersion by the wavelength dispersive element, with a two-dimensional optical detector for imaging the Raman scattering light (FIG. 1, CCD sensor 20, note that a 512 by 64-pixel CCD sensor (COL. 6, lines 7-9) images the light directed to it) from a predetermined range of the sample based on the signal light (FIG. 1, the linear portion of the sample, electrophoretic means 5, on which the detector setup is focused);
wherein the illumination optical system condenses an illumination light on the sample (FIG. 1, LD light source 1) along an illumination optical axis direction, the illumination optical axis direction being a direction orthogonal to a detection optical axis of the detection object lens (FIG. 1, downward illumination light is shown as orthogonal to rightward signal light),
wherein the slit is disposed at a position conjugated with a focal surface of the detection object lens (FIG. 1, note that light from a single point in the sample is focused on a single point passing through the slit, which indicates that each of those points is conjugate to the other with respect to the multielement lens 7/11),
the illumination optical system condenses the illumination light on the sample (FIG. 1, condenser lens 3),
the illumination optical system condenses the illumination light in the direction along the detection optical axis of the detection object lens (FIG. 1, condenser lens 3 condenses the light to a particular point on the sample, which includes condensing light along the direction of the detection optical axis),
in the long-side direction of the slit opening, the two-dimensional optical detector detects the signal light from positions different from each other with pixels different from each other for measuring Raman spectrum (this will naturally occur with the setup shown in FIG. 1, with different positions in the direction perpendicular to the page mapping to different pixels in the CCD sensor 20, which are also separated in the direction perpendicular to the page).
While the two-dimensional CCD sensor of Machida would produce images that have one spatial dimension and spectral dimension, Machida does not explicitly teach detecting the signal light from a two-dimensional region of the sample,
that the illumination is condensed as sheet-shaped illumination,
that, in an orthogonal plane orthogonal to the direction along the detection optical axis, the sheet shaped illumination light is spreading wider than a field of vision in an orthogonal direction orthogonal to a long-side direction of the slit opening, or
that a position of the sample relative to the object lens is moved in the orthogonal direction in the orthogonal plane or the detection optical axis direction to capture a two-dimensional Raman spectral image of the sample.
In the same field of endeavor of flow cytometry, Wu does teach detecting the signal light from a two-dimensional region of the sample (FIG. 5(e) shows a pair of two-dimensional images where one of the dimensions is along the flow and the other is perpendicular to that first dimension),
that the illumination is condensed as sheet-shaped illumination (section 2.1 describes the light sheet generation unit),
that, in an orthogonal plane orthogonal to the direction along the detection optical axis, the sheet shaped illumination light is spreading wider than a field of vision (FIG. 1, horizontally on the page, as the propagation direction of the beam is wider than the field of view of the objective) in an orthogonal direction orthogonal to a long-side direction of the slit opening (while Wu alone does not teach a slit opening, the combination of Machida as modified by Wu could easily arrange the slit perpendicular to propagation direction of the light sheet, which would cause the light sheet to be wider in the orthogonal direction), and
that a position of the sample relative to the object lens is moved in the orthogonal direction in the orthogonal plane or the detection optical axis direction (FIG. 1, the position of the sample is moved along the detection optical axis direction) to capture a two-dimensional Raman spectral image of the sample (FIG. 5(e) shows a pair of two-dimensional images where one of the dimensions is along the flow and the other is perpendicular to that first dimension). By using a light sheet, Wu is able to image a particular slice of the sample along an orthogonal plane, and by arranging the flow direction along the detection optical axis, Wu can stack those slices to gain an extra spatial dimension of imaging along the direction of motion of the sample (going from two dimensions to three dimensions in the case of Wu).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the spectrometry apparatus of Machida with the light sheet illumination and flow direction of Wu to gain the benefit of being able to image the sample in two spatial dimensions and one spectral dimension instead of merely one spatial and one spectral dimension of Machida alone or only spatial dimensions like Wu alone.
Regarding claim 17, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 1 (as described above).
Machida further teaches a processing unit that generates a spectral image, based on a detection signal of the two-dimensional optical detector (FIG. 2, signal processing circuit outputs the data from the CCD sensor 20, which generates a spectral image).
Claim(s) 5-6 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Machida (US Patent 6284119) in view of Wu (Non-Patent Literature “A light sheet based high throughput 3D-imaging flow cytometer for phytoplankton analysis”) and further in view of Fujita (US Patent Publication 20200003618).
Regarding claim 5, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 1 (as described above).
Machida does not explicitly teach that the slit is a multi-slit having a plurality of slit openings.
In the same field of endeavor of spectrometry, Fujita does teach that the slit is a multi-slit having a plurality of slit openings (FIG. 1, multi-slit part 3). By including a multi-slit, Fujita can measure the spectrum of incoming light for several parts of the sample in different parts of the photodetector, spread out along the photodetector’s X axis.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the spectrometry device of Machida, as modified by Wu, with the multi-slit of Fujita, motivated to gain the benefit of measuring the spectrum of light for several lines at once on different parts of the photodetector.
Regarding claim 6, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 5 (as described above).
Machida further teaches the slit opening is formed along a direction that is orthogonal or parallel to an optical axis direction of the illumination light that enters the sample (FIG. 1, slit 15 is shown oriented orthogonal to the page, while the optical axis of the illumination light is shown as being along the page (from the top of the page toward the bottom)).
Regarding claim 11, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 10 (as described above).
Machida does not explicitly teach that at least one surface of the flow channel is a reflection surface that reflects the signal light.
In the same field of endeavor of spectrometry, Fujita teaches teach that at least one surface of the flow channel is a reflection surface that reflects the signal light (FIG. 12, dichroic mirror 307), thereby increasing the amount of signal light detected.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the spectrometry device of Machida, as modified by Wu, with the dichroic mirror of Fujita to increase the amount of signal detected.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Machida (US Patent 6284119) in view of Wu (Non-Patent Literature “A light sheet based high throughput 3D-imaging flow cytometer for phytoplankton analysis”) and further in view of Olarte (Non-Patent Literature “Light-sheet microscopy: a tutorial”).
Regarding claim 7, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 1 (as described above).
Machida does not explicitly teach that the illumination optical system condenses the illumination light on the sample as a Bessel beam or lattice illumination.
In the same field of endeavor of light sheet microscopy, Olarte does teach that the illumination optical system condenses the illumination light on the sample as a Bessel beam (sections 5.4c-e) or lattice illumination (section 5.4f). Olarte uses Bessel beams to allow larger fields of view while avoiding the problems caused by scattering (section 5.4c, sentence 1), while optical lattices are used to improve high-resolution subcellular imaging (section 5.4f, sentence 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the spectrometry apparatus of Machida, as modified by Wu, with the specialized beam types of Olarte in order to allow larger fields of view while avoiding the problems caused by scattering or improve high-resolution subcellular imaging.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Machida (US Patent 6284119) in view of Wu (Non-Patent Literature “A light sheet based high throughput 3D-imaging flow cytometer for phytoplankton analysis”) and further Saito (Non-Patent Literature “Polarization-Controlled Raman Microscopy and Nanoscopy”).
Regarding claim 9, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 1 (as described above).
Machida further teaches an illumination object lens that condenses the illumination light on the sample (FIG. 1, condenser lens 3).
Machida does not explicitly teach a polarization control element that makes a polarized state in a direction parallel to an optical axis of the illumination light on the sample, wherein the slit opening is formed along the optical axis direction.
Merely rearranging parts of a device, such as orienting the slit along the optical axis of the illumination light, does not generally create a nonobvious patentable distinction from prior art. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the spectrometry device of Machida, as modified by Wu, to orient the slit along the optical axis of the illumination light, obtaining the predictable result of imaging along that direction instead of along an axis orthogonal to the optical axis of the illumination light.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the spectrometry device of Machida, as modified by Wu, with the z-polarization equipment of Saito to emphasize and deemphasize particular Raman modes as desired.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Machida (US Patent 6284119) in view of Wu (Non-Patent Literature “A light sheet based high throughput 3D-imaging flow cytometer for phytoplankton analysis”) and further in view of Hu (Non-Patent Literature “Time-Delayed Integration−Spectral Flow Cytometer (TDI-SFC) for Low-Abundance-Cell Immunophenotyping”).
Regarding claim 12, Machida, as modified by Wu, teaches or renders obvious the spectrometry apparatus according to claim 3 (as described above).
Machida further teaches that the signal light from the sample flowing in the flow channel is detected in a plurality of pixels in the two-dimensional optical detector (FIG. 1, CCD sensor 20).
Machida does not explicitly teach that detection signals from the plurality of pixels are integrated.
Hu does teach that detection signals from the plurality of pixels are integrated (FIG. 1 B, the different rows of pixels are integrated so that the readings of the cell across multiple frames are integrated). This improves the strength of the signal by adding it across frames.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the spectrometry device of Machida, as modified by Wu, with the time-delay integration of Hu to increase the detected strength of the signal by integrating across a plurality of pixels.
Conclusion
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/PAUL SCHNASE/Examiner, Art Unit 2877
/TARIFUR R CHOWDHURY/Supervisory Patent Examiner, Art Unit 2877