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 statement (IDS) submitted on 06/19/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant's election with traverse of Group I, claims 16-32 in the reply filed on 07/10/2026 is acknowledged. The traversal is on the grounds that Ye does not explicitly teach correcting the first fluorescence signal by the second fluorescence signal. This is not found persuasive because Gao teaches correcting the first fluorescence signal by the second fluorescence signal.
The requirement is still deemed proper and is therefore made FINAL.
Claims 33-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 07/10/2026.
Claims Status
Claims 16-35 are pending with claims 16-32 being examined, claims 33-35 are withdrawn. Claims 1-15 are canceled.
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 16-18, and 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over Ye (Fight against background noise in stimulated emission depletion nanoscopy hereinafter “Ye”), in view of Gao (Precise background subtraction in stimulated emission double depletion nanoscopy; hereinafter “Gao”).
Regarding claim 16,Ye teaches a light microscopy method (Ye; fig. 1A), comprising
- illuminating a sample comprising fluorescent dye molecules (Ye; fig. 1 legend “fluorophores”) by an excitation light beam (Ye; fig. 1 “excitation light beam”) comprising excitation light capable of exciting the fluorescent dye molecules (Ye; fig. 1. “excitation beam”),
- illuminating the sample by a first impeding light beam comprising impeding light (Ye; fig. 1A “STED beam”) capable of impeding the fluorescence of the fluorescent dye molecules (Ye; fig. 1 “STED beam”),
- generating an intensity distribution (Ye; fig. 1b “doughnut spot” and page 4 Col. 1 lines 14-16) of the impeding light (Ye; fig. 1A. “STED beam”) with at least one local minimum (Ye; fig. 1B “doughnut spot”),
- providing additional impeding light in an area overlapping with the local minimum (Ye; fig. 1A. legend “second STED”),
- obtaining a first fluorescence signal from the area overlapping with the local minimum in the absence of the additional impeding light (Ye; fig. 1Band legend “the incoherent superposition”), and obtaining a second fluorescence signal from the area overlapping with the local minimum in the presence of the additional impeding light (Ye; page. 2 Col. 1 lines 6-8 “to further improve its resolving ability, a second beam is introduced” and legend “introducing a second STED hollow spot (overlap region with the local minimum)), and
wherein at each point of the intensity distribution at which the impeding light has a light intensity greater than a saturation intensity of the impeding light, (Ye; fig. 2a teaches STED power over the saturation power, Examiner notes that it is well known in the art that “impeding light is referred to the depletion laser beam”, it is also well known in the art that the power that control the depletion is the intensity of STED. Ye teaches in fig. 2a legend, the intensity the impeding light (STED) is greater than a saturation intensity of the impeding light “decrease in peak strength with increasing STED power) the light intensity of the impeding light differs by 20 % or less between the intensity distribution in the presence of the additional impeding light and the intensity distribution in the absence of the additional impeding light (Ye; fig. 2a illustrates a difference of 20% (right side plotting in 0.2 increments) or less between the intensity distribution (beams shape where the intensity is zero at the center) in the presence of the additional impeding light and the intensity distribution in the absence of the additional impeding light (Ye; fig. 2a legend STED power over saturation power).
Ye fails to teach correcting the first fluorescence signal by the second fluorescence signal.
However, Gao teaches in the analogous art of light microscopy (Gao; Title) that includes a first and second fluorescence signal (Gao; Abstract “STEDD stimulated emission double depletion” and page 832 Col. 1 lines 4-6 “STEDD has two redshifted pulses (STED1 and STED2)), wherein correcting the first fluorescence signal by the second fluorescence signal (Gao; Abstract “In STEDD the conventional doughnut shaped STED pulse depletes the excited fluorophore outside the center of the focal region is followed by a second Gaussian STED pulse which removes the background by calculating a weighted difference of the photon events collected before and after the second STED pulse”).
To one of ordinary skill in the art before the effective filing date of the invention it would have been obvious to modify Ye’s first fluorescence signal to be corrected by the second fluorescence signal as taught by Gao because Gao teaches light microscopy (Gao; Title) that includes a first and second fluorescence signal (Gao; Abstract “STEDD stimulated emission double depletion” and page 832 Col. 1 lines 4-6 “STEDD has two redshifted pulses (STED1 and STED2)), wherein correcting the first fluorescence signal by the second fluorescence signal (Gao; Abstract “In STEDD the conventional doughnut shaped STED pulse depletes the excited fluorophore outside the center of the focal region is followed by a second Gaussian STED pulse which removes the background by calculating a weighted difference of the photon events collected before and after the second STED pulse”).
The modification allows to remove the background by calculating a weighted difference of the photon events collected before and after the second STED pulse (Gao; Abstract).
Regarding claim 17, Ye teaches the method according to claim 16 (see above), wherein the light intensity of the impeding light differs by 10 % or less between the intensity distribution in the presence of the additional impeding light or less between the intensity distribution (Ye; fig. 2a illustrates a difference of 20% (right side plotting in 0.2 increments) (beams shape where the intensity is zero at the center)) and the intensity distribution in the absence of the additional impeding light (Ye; fig. 2a legend STED power over saturation power).
Regarding claim 18, Ye teaches the method according to claim 16 (see above), wherein the method comprises adjusting a light intensity of the additional impeding light by a variable amount independently of adjusting a power of the first impeding light beam (Ye; page 7 Col. 1 lines 2-3 “STED power is increased”).
Regarding claim 31, Ye teaches the method according to claim 16 (see above), wherein the method further comprises illuminating the sample in the area overlapping with the local minimum by a second impeding light beam capable of impeding the fluorescence of the fluorescent dye molecules to provide the additional impeding light in the area overlapping the local minimum (Ye; fig. 1b illustrates illuminating the sample in the area overlapping with the local minimum by a second impeding light beam capable of impeding the fluorescence of the fluorescent dye molecules to provide the additional impeding light in the area overlapping the local minimum).
Examiner notes that the STED beam is a doughnut shaped beam that is co-aligned with the excitation spot as illustrated also in fig. 1a blue dot is the fluorescence and the red doughnut is the second impeding light beam capable of impeding the fluorescence.
Regarding claim, 32, Ye teaches the method according to claim 16 (see above), wherein the method comprises generating a series of first pulses, and a series of second pulses of the impeding light (Ye; page 7 Col 1 line 24-27 ”STED1 and STED2”), wherein the first pulses are interleaved with the second pulses (Ye; page 7 Col. 1 lines 24-27 “STED2 with a delay of around half of the fluorescence lifetime after STED1”), and wherein the additional impeding light is provided during the second pulses (Ye; page 7 Col. 2 line 1 “STED2 has a Gaussian intensity”).
Claims 19, 22-23 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Ye (Fight against background noise in stimulated emission depletion nanoscopy hereinafter “Ye”), in view of Gao (Precise background subtraction in stimulated emission double depletion nanoscopy; hereinafter “Gao”), further in view of Booth et al. (US 20150226950 A1; hereinafter “Booth”).
Regarding claim 19, Ye teaches the method according to claim 18 (see above) to include light intensity adjusting (see above).
Ye fails to teach wherein an amplitude distribution, a polarization or a phase distribution of the impeding light is modified by a variable amount to adjust the light intensity of the additional impeding light by the variable amount.
However, Booth teaches in the analogous art of light microscopy (Booth; Title) that includes light intensity adjusting (Booth; [0039] “laser power adjustment”), wherein an amplitude distribution, a polarization or a phase distribution of the impeding light is modified by a variable amount (Booth; [0014] “adjusting the pattern of the first light modulator”) to adjust the light intensity of the additional impeding light by the variable amount (Booth; [0014] “to align the depleting light path”).
Applicant discloses [0063] amplitude distribution modification can be achieved by adjusting the wavefront modulator. Booth [0046] teaches a wavefront modulator (SLM “Spatial light modulator”) where aberration correction was realized using the SLM placed in the depletion path.
To one of ordinary skill in the art before the effective filing date of the invention it would have been obvious to modify Ye’s light intensity adjusting wherein an amplitude distribution, a polarization or a phase distribution of the impeding light is modified by a variable amount to adjust the light intensity of the additional impeding light by the variable amount as taught by Booth because Booth teaches light microscopy (Booth; Title) that includes light intensity adjusting (Booth; [0039] “laser power adjustment”), wherein an amplitude distribution, a polarization or a phase distribution of the impeding light is modified by a variable amount (Booth; [0014] “adjusting the pattern of the first light modulator”) to adjust the light intensity of the additional impeding light by the variable amount (Booth; [0014] “to align the depleting light path”).
The modification allows to correct aberration in the STED phase mask (Booth; [0046]).
Regarding claim 22, Ye teaches the method according to claim 16 (see above) to include a wavefront modulator (see above).
Ye fails to teach the method further comprises modulating a wavefront of the impeding light, such that a phase pattern and/or amplitude pattern of the impeding light is generated in a back aperture of an objective through which the sample is illuminated by the impeding light.
However, Booth teaches in the analogous art of light microscopy (Booth; Title) that includes an impeding light (Booth; fig. 5. 10 and [0048] “depletion path 10”) and a wavefront modulator (Booth; [0046] “SLM 22”), wherein the method further comprises modulating a wavefront of the impeding light (Booth; [0046] “SLM 22 placed in the depletion path”), such that a phase pattern and/or amplitude pattern of the impeding light (Booth; [0046] “STED phase mask”) is generated in a back aperture of an objective through which the sample is illuminated by the impeding light (Brown; fig. 5. 2) and [0044] “laser 2 was tuned for depletion (impeding light) and excitation”, laser powers measured at the objective back aperture”).
To one of ordinary skill in the art before the effective filing date of the invention it would have been obvious to modify Ye’s wavefront modulator to modulate a wavefront of the impeding light, such that a phase pattern and/or amplitude pattern of the impeding light is generated in a back aperture of an objective through which the sample is illuminated by the impeding light as taught by Booth because Booth teaches light microscopy (Booth; Title) that includes an impeding light (Booth; fig. 5. 10 and [0048] “depletion path 10”) and a wavefront modulator (Booth; [0046] “SLM 22”), wherein the method further comprises modulating a wavefront of the impeding light (Booth; [0046] “SLM 22 placed in the depletion path”), such that a phase pattern and/or amplitude pattern of the impeding light (Booth; [0046] “STED phase mask”) is generated in a back aperture of an objective through which the sample is illuminated by the impeding light (Brown; fig. 5. 2) and [0044] “laser 2 was tuned for depletion (impeding light) and excitation”, laser powers measured at the objective back aperture”).
The modification allows to correction of the STED phase mask and aberration correction (Booth; [0046]).
Regarding claim 23, Ye teaches the method according to claim 22 (see above) to include a wavefront modulator (see above).
Ye fails to teach the wavefront is modulated by a wave front modulator comprising an active area arranged in a pupil plane or intersecting a pupil plane of the objective, wherein the method further comprises modifying the phase distribution or amplitude distribution by a variable amount by adjusting the wave front modulator to adjust the light intensity of the additional impeding light by the variable amount.
However, Booth teaches in the analogous art of light microscopy (Booth; Title) that includes a wavefront modulator (Booth; [0046] “SLM 22”), wherein the wavefront is modulated by a wave front modulator comprising an active area arranged in a pupil plane or intersecting a pupil plane of the objective (Booth [0052] “an active pupil was defined on the SLM 22”), wherein the method further comprises modifying the phase distribution or amplitude distribution by a variable amount (Booth; [0014] “adjusting the pattern of the first light modulator”) by adjusting the wave front modulator to adjust the light intensity of the additional impeding light by the variable amount (Booth; fig. 5. 2, 10, 22 and [0048]).
To one of ordinary skill in the art before the effective filing date of the invention it would have been obvious to modify Ye’s wavefront modulator to include an active area arranged in a pupil plane or intersecting a pupil plane of the objective, wherein the method further comprises modifying the phase distribution or amplitude distribution by a variable amount by adjusting the wave front modulator to adjust the light intensity of the additional impeding light by the variable amount as taught by Booth because Booth teaches light microscopy (Booth; Title) that includes a wavefront modulator (Booth; [0046] “SLM 22”), wherein the wavefront is modulated by a wave front modulator comprising an active area arranged in a pupil plane or intersecting a pupil plane of the objective (Booth [0052] “an active pupil was defined on the SLM 22”), wherein the method further comprises modifying the phase distribution or amplitude distribution by a variable amount (Booth; [0014] “adjusting the pattern of the first light modulator”) by adjusting the wave front modulator to adjust the light intensity of the additional impeding light by the variable amount (Booth; fig. 5. 2, 10, 22 and [0048]).
The modification allows to direct a non-zero order diffracted beam that separates the phase-modulated light from any directly reflected (Booth; [0051]).
Regarding claim 30, Ye teaches the method according to claim 22 (see above) to include a first impeding light beam (see above).
Ye fails to teach the method further comprises generating a phase pattern of the first impeding light beam by a first active area of a wave front modulator, subsequently rotating the polarization direction of the impeding light by an angle by means of a second polarization modifying element, subsequently further modulating the first impeding light beam by a second active area of a polarization-sensitive wave front modulator, wherein the angle is adjusted to provide additional impeding light in the area overlapping the local minimum.
However, Booth teaches in the analogous art of light microscopy (Booth; Title) that includes an impeding light (Booth; fig. 5. 10 and [0048] “depletion path 10”) and a wavefront modulator (Booth; [0046] “SLM 22”), wherein the method further comprises generating a phase pattern of the first impeding light beam by a first active area of a wave front modulator (Booth; fig. 1. 10, and [0047]), subsequently further modulating the first impeding light beam by a second active area of a polarization-sensitive wave front modulator (Booth; fig. 1. 22), wherein the angle is adjusted to provide additional impeding light in the area overlapping the local minimum (Booth; [0080]).
To one of ordinary skill in the art before the effective filing date of the inventio it would have been obvious to modify Ye’s first impeding light beam to generate a phase pattern of the first impeding light beam by a first active area of a wave front modulator, subsequently rotating the polarization direction of the impeding light by an angle by means of a second polarization modifying element, subsequently further modulating the first impeding light beam by a second active area of a polarization-sensitive wave front modulator, wherein the angle is adjusted to provide additional impeding light in the area overlapping the local minimum as taught by Booth because Booth teaches of light microscopy (Booth; Title) that includes an impeding light (Booth; fig. 5. 10 and [0048] “depletion path 10”) and a wavefront modulator (Booth; [0046] “SLM 22”), wherein the method further comprises generating a phase pattern of the first impeding light beam by a first active area of a wave front modulator (Booth; fig. 1. 10, and [0047]), subsequently further modulating the first impeding light beam by a second active area of a polarization-sensitive wave front modulator (Booth; fig. 1. 22), wherein the angle is adjusted to provide additional impeding light in the area overlapping the local minimum (Booth; [0080]).
The modification allows to acquire the image with an optimized excitation and depletion path (Booth; [0080]).
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Ye (Fight against background noise in stimulated emission depletion nanoscopy hereinafter “Ye”), in view of Gao (Precise background subtraction in stimulated emission double depletion nanoscopy; hereinafter “Gao”), further in view of Booth et al. (US 20150226950 A1; hereinafter “Booth”) and Knebel et al. (US 20130107358 A1; hereinafter “Knebel).
Regarding claim 24, Ye teaches the method according to claim 22 (see above) to include a wavefront modulator (see above).
Ye fails to teach the method comprises modulating the wavefront of the impeding light by an array of tiltable micromirrors, such that an amplitude distribution of the impeding light is generated in the back aperture of the objective and modifying the amplitude pattern to provide the additional impeding light in the area overlapping with the local minimum by tilting a subset of the micromirrors.
However, Knebel teaches in the analogous art of light microscopy (Knebel; Abstract “SPIM microscopy”) that includes an array of tiltable mirrors (Knebel; fig. 5. 6.1) for modulating the wavefront of the impeding light by an array of tiltable micromirrors (Knebel; fig. 5. 2 and [0072] “tilting mirrors perform oscillating tilting to direct light strip or light beam”) such that an amplitude distribution of the impeding light is generated in the back aperture of the objective (Knebel; [0041] “the light path of the light strip from the pupil of the objective passes through the objective”, implying the light is generated in the back aperture of the objective) and modifying the amplitude pattern to provide the additional impeding light (Knebel; fig. 5. 1, 2, 6 and [0072] “beam deflector 6 forms light strip 2 from light beam 1”) in the area overlapping with the local minimum (Knebel; fig. 5. 4.1) by tilting a subset of the micromirrors (Knebel; fig. 5. 6.1 and [0072] “tilting mirrors 6.1 perform oscillating motion to direct light strip”).
To one of ordinary skill in the art before the effective filing date of the invention it would have been obvious to modify Ye’s wavefront modulator to modulate the wavefront of the impeding light by an array of tiltable micromirrors, such that an amplitude distribution of the impeding light is generated in the back aperture of the objective and modifying the amplitude pattern to provide the additional impeding light in the area overlapping with the local minimum by tilting a subset of the micromirrors as taught by Knebel because Knebel teaches light microscopy (Knebel; Abstract “SPIM microscopy”) that includes an array of tiltable mirrors (Knebel; fig. 5. 6.1) for modulating the wavefront of the impeding light by an array of tiltable micromirrors (Knebel; fig. 5. 2 and [0072] “tilting mirrors perform oscillating tilting to direct light strip or light beam”) such that an amplitude distribution of the impeding light is generated in the back aperture of the objective (Knebel; [0041] “the light path of the light strip from the pupil of the objective passes through the objective”, implying the light is generated in the back aperture of the objective) and modifying the amplitude pattern to provide the additional impeding light (Knebel; fig. 5. 1, 2, 6 and [0072] “beam deflector 6 forms light strip 2 from light beam 1”) in the area overlapping with the local minimum (Knebel; fig. 5. 4.1) by tilting a subset of the micromirrors (Knebel; fig. 5. 6.1 and [0072] “tilting mirrors 6.1 perform oscillating motion to direct light strip”).
The modification allows to direct light strip (Knebel; [0072]).
Claims 25-29 are rejected under 35 U.S.C. 103 as being unpatentable over Ye (Fight against background noise in stimulated emission depletion nanoscopy hereinafter “Ye”), in view of Gao (Precise background subtraction in stimulated emission double depletion nanoscopy; hereinafter “Gao”), further in view of Booth et al. (US 20150226950 A1; hereinafter “Booth”) and Timlin et al. (US 8686363 B1; hereinafter “Timlin”).
Regarding claim 25, Ye teaches he method according to claim 22 (see above) to include a wavefront modulator (see above).
Ye fails to teach wherein the wavefront of the impeding light is modulated such that a vortex-shaped phase pattern of the impeding light is obtained at the back aperture of the objective, wherein the vortex-shaped phase pattern comprises a phase increasing from zero to a maximum value in a circumferential direction in respect of an optical axis of the first impeding light beam, wherein the method further comprises circularly polarizing the first impeding light beam after obtaining the vortex- shaped phase pattern, and wherein the method further comprises modifying the phase pattern to provide the additional impeding light in the area overlapping with the local minimum.
However, Timlin teaches in the analogous art of light microscopy (Timlin; Title) that includes an impeding light (Timlin; fig. 1. 122) and a wavefront (Timlin; fig. 2. 242), wherein the wavefront of the impeding light is modulated such that a vortex-shaped phase pattern of the impeding light (Timlin; fig. 2. 226, 242 and (Col. 6 lines 39-41) is obtained at the back aperture of the objective (Timlin; fig. 1. 122, 132 illustrates the vortex shaped phase pattern 122 is obtained at the back of the microscope 132 which would have the objective), wherein the vortex-shaped phase pattern comprises a phase increasing from zero to a maximum value in a circumferential direction in respect of an optical axis of the first impeding light beam (Timlin; Col. 6 lines 14-19), wherein the method further comprises circularly polarizing the first impeding light beam after obtaining the vortex- shaped phase pattern (Timlin; Col. 6 lines 14-19 “light source is polarized from 0 to 90 degrees”), and wherein the method further comprises modifying the phase pattern to provide the additional impeding light in the area overlapping with the local minimum (Timlin; Col. 56 lines 41-48 “the spiral phase plate includes an optical device that that twists light like a corkscrew..”).
To one of ordinary skill in the art before the effective filing date of the invention it would have been obvious to modify Ye’s wavefront modulator wherein the wavefront of the impeding light is modulated such that a vortex-shaped phase pattern of the impeding light is obtained at the back aperture of the objective, wherein the vortex-shaped phase pattern comprises a phase increasing from zero to a maximum value in a circumferential direction in respect of an optical axis of the first impeding light beam, wherein the method further comprises circularly polarizing the first impeding light beam after obtaining the vortex- shaped phase pattern, and wherein the method further comprises modifying the phase pattern to provide the additional impeding light in the area overlapping with the local minimum as taught by Timlin because Timlin teaches light microscopy (Timlin; Title) that includes an impeding light (Timlin; fig. 1. 122) and a wavefront (Timlin; fig. 2. 242), wherein the wavefront of the impeding light is modulated such that a vortex-shaped phase pattern of the impeding light (Timlin; fig. 2. 226, 242 and (Col. 6 lines 39-41) is obtained at the back aperture of the objective (Timlin; fig. 1. 122, 132 illustrates the vortex shaped phase pattern 122 is obtained at the back of the microscope 132 which would have the objective), wherein the vortex-shaped phase pattern comprises a phase increasing from zero to a maximum value in a circumferential direction in respect of an optical axis of the first impeding light beam (Timlin; Col. 6 lines 14-19), wherein the method further comprises circularly polarizing the first impeding light beam after obtaining the vortex- shaped phase pattern (Timlin; Col. 6 lines 14-19 “light source is polarized from 0 to 90 degrees”), and wherein the method further comprises modifying the phase pattern to provide the additional impeding light in the area overlapping with the local minimum (Timlin; Col. 6 lines 41-48 “the spiral phase plate includes an optical device that that twists light like a corkscrew…”).
The modification allows to deplete fluorescence from the fluorophores excited by the excitation beam in essentially all but a center portion of the torus-shaped depletion zone (Timlin; Col 5 lines 41-44).
Regarding claim 26, Ye teaches the method according to claim 25 (see above), wherein to include a phase pattern (see above).
Ye fails to teach the phase pattern is modified by overlaying a ring or circular shaped phase pattern having a constant phase with the vortex-shaped phase pattern to generate the additional impeding light in the area overlapping with the local minimum.
However, Timlin teaches in the analogous art of light microscopy (Timlin; Title) that includes a phase pattern (Timlin; fig. 2. 226, 242 and (Col. 6 lines 39-41), wherein the phase pattern is modified by overlaying a ring or circular shaped phase pattern having a constant phase with the vortex-shaped phase pattern (Timlin; Col. 6 lines 41-48 “the spiral phase plate includes an optical device that that twists light like a corkscrew..”) to generate the additional impeding light in the area overlapping with the local minimum (Timlin; Col. 5 lines 31-44).
To one of ordinary skill in the art before the effective filing dare of the invention it would have been obvious to modify Ye’s phase pattern wherein the phase pattern is modified by overlaying a ring or circular shaped phase pattern having a constant phase with the vortex-shaped phase pattern to generate the additional impeding light in the area overlapping with the local minimum as taught by Timlin because Timlin teaches light microscopy (Timlin; Title) that includes a phase pattern (Timlin; fig. 2. 226, 242 and (Col. 6 lines 39-41), wherein the phase pattern is modified by overlaying a ring or circular shaped phase pattern having a constant phase with the vortex-shaped phase pattern (Timlin; Col. 6 lines 41-48 “the spiral phase plate includes an optical device that that twists light like a corkscrew..”) to generate the additional impeding light in the area overlapping with the local minimum (Timlin; Col. 5 lines 31-44).
The modification allows to an additional light from the excitation light to deplete fluorescence from essentially all but a selected subset of two or more different fluorophores (Timlin; Col. 5 lines 31-44).
Regarding claim 27, Ye teaches the method according to claim 25 (see above) to include a phase pattern (see above).
Ye fails to teach wherein the phase pattern is modified by modifying the maximum value of the phase pattern.
However, Timlin teaches in the analogous art of light microscopy (Timlin; Title) that includes a phase pattern (Timlin; fig. 2. 226, 242 and (Col. 6 lines 39-41), wherein the phase pattern is modified by modifying the maximum value of the phase pattern (Timlin; Col. 6 lines 30-48 teaches the depletion light source includes a zoom lens, and a spiral phase plate to generate the torus shaped depletion light beam, Timlin further teaches the zoom lens is used to correct for beam asymmetry).
To one of ordinary skill in the art before the effective filing date of the invention it would have been obvious to modify Ye’s phase pattern to be modified by modifying the maximum value of the phase pattern as taught by Timlin because Timlin teaches light microscopy (Timlin; Title) that includes a phase pattern (Timlin; fig. 2. 226, 242 and (Col. 6 lines 39-41), wherein the phase pattern is modified by modifying the maximum value of the phase pattern (Timlin; Col. 6 lines 30-48 teaches the depletion light source includes a zoom lens, and a spiral phase plate to generate the torus shaped depletion light beam, Timlin further teaches the zoom lens is used to correct for beam asymmetry).
The modification allows to adjust for beam asymmetry (Timlin; Colo. 6 lines 31-32).
Regarding claim 28, The method according to claim 22 to include wavefront of the impeding light (see above).
Ye fails to teach wherein the wavefront of the impeding light is modulated such that a phase pattern comprising a first area comprising a constant first phase and a second area comprising a constant second phase, which differs from the first phase, is generated, wherein the first area and the second area each extend perpendicular to an optical axis of the first impeding light beam, and wherein the method further comprises adjusting the first phase and/or the second phase or adjusting the size of the first area and/or the second area to provide the additional impeding light in the area overlapping with the local minimum.
However, Timlin teaches in the analogous art of light microscopy (Timlin; Title) that includes an impeding light (Timlin; fig. 1. 122) and a wavefront (Timlin; fig. 2. 242), wherein the wavefront of the impeding light is modulated such that a phase pattern comprising a first area comprising a constant first phase (Timlin; Col. 6 lines 46-48 “the optical vortex looks like a ring of light (first area)”), and a second area comprising a constant second phase which differs from the first phase is generated (Timlin; Col. 6 lines 46-48 “the optical vortex with a dark hole in the center (second area)”), wherein the first area and the second area each extend perpendicular to an optical axis of the first impeding light beam (Timlin; Col. 6 lines 46-48 ring of light).
Examiner notes that the ring of light would extend perpendicularly on a flat surface from the first impeding light beam, and wherein the method further comprises adjusting the first phase and/or the second phase or adjusting the size of the first area and/or the second area to provide the additional impeding light in the area overlapping with the local minimum (Timlin; Col. 6 lines 30-48 teaches the depletion light source includes a zoom lens, and a spiral phase plate to generate the torus shaped depletion light beam, Timlin further teaches the zoom lens is used to correct for beam asymmetry).
To one of ordinary skill in the art before the effective filing date of the invention it would have been obvious to modify Ye’s wavefront of impeding light wherein the wavefront of the impeding light is modulated such that a phase pattern comprising a first area comprising a constant first phase and a second area comprising a constant second phase, which differs from the first phase, is generated, wherein the first area and the second area each extend perpendicular to an optical axis of the first impeding light beam, and wherein the method further comprises adjusting the first phase and/or the second phase or adjusting the size of the first area and/or the second area to provide the additional impeding light in the area overlapping with the local minimum as taught by Timlin because Timlin teaches light microscopy (Timlin; Title) that includes an impeding light (Timlin; fig. 1. 122) and a wavefront (Timlin; fig. 2. 242), wherein the wavefront of the impeding light is modulated such that a phase pattern comprising a first area comprising a constant first phase (Timlin; Col. 6 lines 46-48 “the optical vortex looks like a ring of light (first area)”), and a second area comprising a constant second phase which differs from the first phase is generated (Timlin; Col. 6 lines 46-48 “the optical vortex with a dark hole in the center (second area)”), wherein the first area and the second area each extend perpendicular to an optical axis of the first impeding light beam (Timlin; Col. 6 lines 46-48 ring of light), and wherein the method further comprises adjusting the first phase and/or the second phase or adjusting the size of the first area and/or the second area to provide the additional impeding light in the area overlapping with the local minimum (Timlin; Col. 6 lines 30-48 teaches the depletion light source includes a zoom lens, and a spiral phase plate to generate the torus shaped depletion light beam, Timlin further teaches the zoom lens is used to correct for beam asymmetry).
The modification allows to adjust for beam asymmetry (Timlin; Colo. 6 lines 31-32).
Regarding claim 29, Ye teaches the method according to claim 22 (see above) to include a phase pattern (see above)
Ye fails to teach the method further comprises modifying a phase pattern of the impeding light by a first polarization modifying element and rotating the first polarization modifying element around an optical axis of the first impeding light beam by a variable angle smaller than 45° to provide the additional impeding light in the area overlapping the local minimum.
However, Timlin teaches in the analogous art of light microscopy (Timlin; Title) that includes a phase pattern (Timlin; fig. 2. 226, 242 and (Col. 6 lines 39-41), wherein the method further comprises modifying a phase pattern of the impeding light by a first polarization modifying element and rotating the first polarization modifying element (Timlin; fig. 2. 220) around an optical axis of the first impeding light beam by a variable angle smaller than 45° (Timlin; Col. 6 lines 14-16 “incident light is polarized at about 45 degrees”) to provide the additional impeding light in the area overlapping the local minimum (Timlin; Col. 6 lines 20-23 to equal power of the first light beam and the second beam”).
To one of ordinary skill in the art before the effective filing date of the invention it would have been obvious to modify Ye’s phase pattern to modify a phase pattern of the impeding light by a first polarization modifying element and rotating the first polarization modifying element around an optical axis of the first impeding light beam by a variable angle smaller than 45° to provide the additional impeding light in the area overlapping the local minimum as taught by Tamlin because Tamlin teaches light microscopy (Timlin; Title) that includes a phase pattern (Timlin; fig. 2. 226, 242 and (Col. 6 lines 39-41), wherein the method further comprises modifying a phase pattern of the impeding light by a first polarization modifying element and rotating the first polarization modifying element (Timlin; fig. 2. 220) around an optical axis of the first impeding light beam by a variable angle smaller than 45° (Timlin; Col. 6 lines 14-16 “incident light is polarized at about 45 degrees”) to provide the additional impeding light in the area overlapping the local minimum (Timlin; Col. 6 lines 20-23 to equal power of the first light beam and the second beam”).
The modification allows the beams to be efficiently recombined later (Timlin; Col. 6 lines 21-22).
Allowable Subject Matter
Claims 20 and 21 (as being dependent on claim 20) would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The cited prior art of record, whether alone or in combination, fails to teach or fairly suggest, in the context of claims 16 and 20, wherein the light intensity of the additional impeding light at the local minimum is 20 % or less of a maximum light intensity of the impeding light, wherein the maximum light intensity refers to the impeding light in the absence of the additional impeding light according to claim 20, and there is no motivation to modify Ye to provide this method.
Response to Arguments
Applicant's arguments filed 07/10/226 have been fully considered but they are not persuasive.
Applicant argues Ye does not explicitly teach correcting the first fluorescence signal by the second fluorescence signal.
This is not found persuasive because Gao teaches correcting the first fluorescence signal by the second fluorescence signal. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues Ye does not teach that at each point of the intensity distribution at which the impeding light has a light intensity greater than a saturation intensity of the impeding light, the light intensity of the impeding light differs by 20% or less between the intensity distribution in the presence of the additional impeding light and the intensity distribution in the absence of the additional impeding light.
As to the impeding light, Applicant has not defined what the impending light is, furthermore, Ye teaches plotting the STED power in increments of 20%, see Ye fig. 2B “normalized fluorescence intensity” plotted in increments of 0.2 (20%).
Applicant notes that the examiner has not demonstrated that a serious search and examination burden would be imposed if restriction were not required.
Examiner recognizes that the same corresponding technical feature is common to the groups. MPEP 1850 (II) states, in part:
Lack of unity of invention may be directly evident "a priori," i.e., before considering the claims in relation to any prior art, or may only become apparent "a posteriori," i.e., after taking the prior art into consideration. For example, independent claims to A + X, A + Y, X + Y can be said to lack unity a priori as there is no subject matter common to all claims. In the case of independent claims to A + X and A + Y, unity of invention is present a priori as A is common to both claims. However, if it can be established that A is known, there is lack of unity a posteriori, since A (be it a single feature or a group of features) is not a technical feature that defines a contribution over the prior art.
Examiner’s citation of art establishes that the common technical feature does not make a contribution over the prior art. As the technical feature does not define over the art, unity of invention is lacking.
Conclusion
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/A.R./Examiner, Art Unit 1798
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
