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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/25/2025 has been entered.
Response to Amendment
Applicant’s amendments, see Page 11, Section I. Claim Objections, filed 08/21/2025, with respect to claims 1 and 13 have been fully considered and are persuasive. The objection to said claims in Office Action of 05/27/2025 has been withdrawn.
Applicant’s amendments, see Pages 11-15, Section II. Claim Rejections - 35 U.S.C. § 103, filed 08/21/2025, with respect to the rejection(s) of claim(s) 1, 3-13, and 15-24 under 35 U.S.C. § 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of newly found prior art reference US-2017/0245735-A1.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1, 3-13, and 15-24 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Objections
Claim 28 is objected to because of the following informalities:
lines 1-2 will be read as “The method of claim 13, wherein the at least one intensity regulator is disposed between the object and the at least one detector, and/or”
lines 3-4 will be read as “the at least one intensity regulator is controlled by the controller
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:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or non-obviousness.
Claim(s) 1, 4-7, 13, 16-19, 26 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fengler et al. (US 2019/0357757 A1) in view of Xia et al. (US 2010/0032582 A1) and Wang (US 2017/0245735 A1).
Regarding independent Claim 1, Fengler discloses a detection system for detecting an optical signal (Figure 1B: element 50 is a fluorescence endoscopy video system; [0025]) from a luminescent material applied to or incorporated within an object (Figure 1B: element 58 is a tissue sample; [0022]), the system comprising:
at least one light source (Figure 1B: element 52 is a multi-mode light source; [0022]) which generates light, as excitation light ([0022] “generates light for obtaining color and fluorescence images”), for illuminating at least a region of the object ([0022] “illuminates a tissue sample 58”);
at least one detector (Figure 1B: element 100 is a multi-mode camera; [0023]) which detects light (implicit for a camera to detect light), as collection light, from the object ([0025] “light that is collected from the tissue”) when illuminated by the excitation light ([0022] “illuminates a tissue sample 58”) and provides an output signal (Figure 1B; [0038] “processor/controller 64 as shown in FIGS. 1A and 1B receives the transduced image signals from the camera 100”, wherein “transduced image signals” are output signals provided to “processor/controller 64”) having a signal intensity in response to an intensity of the collection light ([0069] “the intensity of the reflected light and fluorescence light … results in transduced image signals”, wherein “transduced image signals”, i.e., output signals, with intensity being implicit, are in response to “the intensity of the reflected light and fluorescence light”, i.e., an intensity of the collection light); and
a controller (Figure 4A: element 64 is a processor/controller) which is adapted to control the output signal to have a signal intensity within a predetermined range or at substantially a constant value (Figure 4A; [0057] “processor/controller 64 may also send control signals to the cameras … to adjust the gains of the low light image sensor 104 and the monochrome image sensor 102, in order to maintain constant image brightness while keeping the relative gain constant”), but does not specifically teach:
an optical probe assembly which comprises a fiber and a probe which is optically connected to the fiber so as to allow for transmission of the excitation light to and collection of the collection light from the object, wherein the fiber comprises at least one excitation fiber element through which the excitation light is delivered to the probe, and a plurality of collection fiber elements disposed radially outwardly of the at least one excitation fiber element through which the collection light is delivered to the at least one detector; and
at least one intensity regulator for regulating an intensity of the collection light which is collected by the at least one detector, the at least one intensity regulator being a liquid crystal, which, by application of a bias voltage, regulates the intensity of the collection light.
However, Xia, in the same field of fluorescence detection systems, teaches an optical probe assembly (Figure 2: collectively, transmitting fiber element 120, fiber bundle probe element 12 and optical lens element 13 are interpreted as an optical probe assembly; [0021]) which comprises a fiber (Figure 2: element 120 is a transmitting fiber; [0021]) and a probe (Figure 2: element 12 is a fiber bundle probe; [0021]) which is optically connected (via flow of light) to the fiber (Figure 2: element 120 is a transmitting fiber; [0021]) so as to allow for transmission of the excitation light to (Figure 2; [0022] “for transmitting the excitation light to”) and collection of the collection light (Figure 2; [0022] “collect the fluorescence”, wherein “fluorescence” is collection light) from the object (Figure 2; [0022] “samples in an electrophoresis channel 17 of a microfluidic chip 16”), wherein the fiber comprises at least one excitation fiber element through which the excitation light is delivered (Figure 4: element 120 is a transmitting fiber; [0036] “transmitting fiber 120 with a radius of ro for transmitting the excitation light”) to the probe (Figure 2: element 12 is a fiber bundle probe; [0021]), and a plurality of collection fiber elements optionally disposed radially outwardly of the at least one excitation fiber element through which the collection light is delivered (Figure 4; [0036] “receiving fibers 26 are symmetrically surrounding the central fiber 120 for receiving fluorescence”, wherein “fluorescence” is collection light) to the at least one detector (Figure 2: elements 220, 221, 222 are detectors; [0031]).
Therefore, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the system of Fengler, with an optical probe assembly which comprises a fiber and a probe which is optically connected to the fiber so as to allow for transmission of the excitation light to and collection of the collection light from the object, wherein the fiber comprises at least one excitation fiber element through which the excitation light is delivered to the probe, and a plurality of collection fiber elements optionally disposed radially outwardly of the at least one excitation fiber element through which the collection light is delivered to the at least one detector, as taught by Xia, because “in the illustrated embodiment in FIG. 2, the fluorescence detection system 20 comprises the fiber bundle probe 12 including more than one receiving fibers that can improve the signal-to-noise ratio of the system when all the receiving fibers are use [sic] for fluorescence intensity analysis, spectra, imaging or lifetime analyses.” (Xia, para 31)
Fengler is also silent with respect to at least one intensity regulator for regulating an intensity of the collection light which is collected by the at least one detector, the at least one intensity regulator being a liquid crystal, which, by application of a bias voltage, regulates the intensity of the collection light.
However, Wang, in the same field of imaging devices, teaches at least one intensity regulator (Figure 7: element 2 is a wavefront modulator; [0040]) for regulating an intensity ([0027] “a modification in the light intensity”) of the collection light ([0005] “a wavefront modulator located to receive collected light”) which is collected by the at least one detector (Figure 7: element 3 is a sensor array; [0005] “an imaging array located to receive phase-modulated light segments”), the at least one intensity regulator being a liquid crystal (Figure 7; [0023] “pixels of such a wavefront modulator 2 can be controlled through various mechanisms, …; the active component of a pixel can also be a liquid crystal device”), which, by application of a bias voltage (Figure 7; [0023] “pixels of such a wavefront modulator 2 can be controlled through various mechanisms, such as a piezoelectric force, an electrostatic force, or an electromagnetic force”, wherein “various mechanisms, such as a piezoelectric force, an electrostatic force, or an electromagnetic force” require application of a voltage, as known in the art), regulates the intensity ([0027] “a modification in the light intensity”) of the collection light ([0005] “a wavefront modulator located to receive collected light”).
Therefore, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the system of Fengler, with at least one intensity regulator for regulating an intensity of the collection light which is collected by the at least one detector, the at least one intensity regulator being a liquid crystal, which, by application of a bias voltage, regulates the intensity of the collection light, as taught by Wang, “for obtaining optical images of a targeted object or scene such as a person's organ or tissue based on a fiber bundle having imaging optical fibers and optical phase modulation for improved imaging quality without using an objective lens to receive light from a target.” (Wang, para 4)
Regarding Claim 4, modified Fengler discloses the system of claim 1, wherein the at least one light source (Figure 2A: element 52 is a light source; [0026]) (i) is a laser, optionally a pulse-modulated laser, optionally having a controllable modulation duty cycle, optionally a solid-state laser, optionally a diode-pumped, solid-state laser, (ii) comprises one or more laser diodes ([0026] “Alternatively, …, solid state devices (such as light emitting diodes or diode lasers), … may be used”), or (iii) comprises one or more light-emitting diodes (LEDs), optionally one or more high-power LEDs.
Regarding Claim 5, modified Fengler discloses the system of claim 1, wherein the excitation light has (i) a wavelength within a range of from about 250 nm to about 1100 nm (Figure 6A: blue filter 79A, [0046] “This filter transmits light in the wavelength range from 370-460 nm”; Figure 6B: red filter 79B, [0047] “This filter transmits light in the wavelength range from 590-750 nm”; Figure 6C: green filter 79C, [0048] “This filter transmits light in the wavelength range from 480-570 nm”), optionally a wavelength of about 532 nm or about 266 nm, and/or (ii) a power of from about 100 mW to about 2 kW, optionally operating in a continuous-wave mode.
Regarding Claim 6, modified Fengler discloses the system of claim 1, further comprising:
(I) at least one filter (Figure 4A: element 118 is a spectral filter; [0034]), optionally transmissive (Figure 4A: spectral filter element 118 transmits light to low light image sensor element 104; [0034]) or reflective, for regulating a wavelength of the collection light ([0049] “for defining the primary fluorescence image”) which is collected by the at least one detector (Figure 4A: element 104 is a low light image sensor; [0034]), wherein optionally the at least one filter is a bandpass filter, wherein optionally the at least one filter is configured to filter out light of wavelengths outside the range of from about 450 nm to about 1600 nm ([0049] “the filter characteristics are such that any light outside of the wavelength range of 480-570 nm, or any desired subset of wavelengths in this range, contributes no more than 0.1% to the light transmitted by the filter”).
Regarding Claim 7, modified Fengler discloses the system of claim 1, wherein the at least one detector is (i) a photomultiplier module, optionally a silicon photomultiplier module (SiPM), (ii) a photodiode, optionally an avalanche photodiode, (iii) a photomultiplier tube (PMT), (iv) a multipixel photon counting device (MPPC), (v) a charge-coupled device (CCD), or (vi) a complementary metal-oxide-semiconductor (CMOS) device (Figure 4A; [0036] “low light image sensor 104 preferably comprises a charge coupled device with charge carrier multiplication (of the same type as the Texas Instruments TC253 or the Marconi Technologies CCD65), electron beam charge coupled device (EBCCD), intensified charge coupled device (ICCD), charge injection device (CID), charge modulation device (CMD), complementary metal oxide semiconductor image sensor (CMOS) or charge coupled device (CCD) type sensor”).
Regarding independent Claim 13, Fengler discloses a method of detecting an optical signal from a luminescent material applied to or incorporated within an object, comprising:
providing a detection system (Figure 1B: element 50 is a fluorescence endoscopy video system; [0025]) comprising at least one light source (Figure 1B: element 52 is a multi-mode light source; [0022]) which generates light, as excitation light ([0022] “generates light for obtaining color and fluorescence images”), which illuminates at least a region of the object ([0022] “illuminates a tissue sample 58”), at least one detector (Figure 1B: element 100 is a multi-mode camera; [0023]) which detects light (implicit for a camera to detect light), as collection light, from the object ([0025] “light that is collected from the tissue”) when illuminated by the excitation light ([0022] “illuminates a tissue sample 58”) and provides an output signal (Figure 1B; [0038] “processor/controller 64 as shown in FIGS. 1A and 1B receives the transduced image signals from the camera 100”, wherein “transduced image signals” are output signals provided to “processor/controller 64”) having a signal intensity in response to an intensity of the collection light ([0069] “the intensity of the reflected light and fluorescence light … results in transduced image signals”, wherein “transduced image signals”, i.e., output signals, with intensity being implicit, are in response to “the intensity of the reflected light and fluorescence light”, i.e., an intensity of the collection light); and
controlling the output signal (Figure 4A: element 64 is a processor/controller) to have a signal intensity within a predetermined range or at substantially a constant value (Figure 4A; [0057] “processor/controller 64 may also send control signals to the cameras … to adjust the gains of the low light image sensor 104 and the monochrome image sensor 102, in order to maintain constant image brightness while keeping the relative gain constant”), but does not specifically teach that the system further comprises:
an optical probe assembly which comprises a fiber and a probe which is optically connected to the fiber so as to transmit the excitation light to and collect the collection light from the object, wherein the fiber comprises at least one excitation fiber element through which the excitation light is delivered to the probe,
a plurality of collection fiber elements, optionally disposed radially outwardly of the at least one excitation fiber element through which the collection light is delivered to the at least one detector, and
at least one intensity regulator for regulating an intensity of the collection light which is collected by the at least one detector, the at least one intensity regulator being a liquid crystal, which, by application of a bias voltage, regulates the intensity of the collection light.
However, Xia, in the same field of fluorescence detection systems, teaches an optical probe assembly (Figure 2: collectively, transmitting fiber element 120, fiber bundle probe element 12 and optical lens element 13 are interpreted as an optical probe assembly; [0021]) which comprises a fiber (Figure 2: element 120 is a transmitting fiber; [0021]) and a probe (Figure 2: element 12 is a fiber bundle probe; [0021]) which is optically connected (via flow of light) to the fiber (Figure 2: element 120 is a transmitting fiber; [0021]) so as to transmit the excitation light to (Figure 2; [0022] “for transmitting the excitation light to”) and collect the collection light (Figure 2; [0022] “collect the fluorescence”, wherein “fluorescence” is collection light) from the object (Figure 2; [0022] “samples in an electrophoresis channel 17 of a microfluidic chip 16”), wherein the fiber comprises at least one excitation fiber element through which the excitation light is delivered (Figure 4: element 120 is a transmitting fiber; [0036] “transmitting fiber 120 with a radius of ro for transmitting the excitation light”) to the probe (Figure 2: element 12 is a fiber bundle probe; [0021]), and
a plurality of collection fiber elements, optionally disposed radially outwardly of the at least one excitation fiber element through which the collection light is delivered (Figure 4; [0036] “receiving fibers 26 are symmetrically surrounding the central fiber 120 for receiving fluorescence”, wherein “fluorescence” is collection light) to the at least one detector (Figure 2: elements 220, 221, 222 are detectors; [0031]).
Therefore, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method of Fengler, such that the system further comprises: an optical probe assembly which comprises a fiber and a probe which is optically connected to the fiber so as to transmit the excitation light to and collect the collection light from the object, wherein the fiber comprises at least one excitation fiber element through which the excitation light is delivered to the probe, and a plurality of collection fiber elements, optionally disposed radially outwardly of the at least one excitation fiber element through which the collection light is delivered to the at least one detector, as taught by Xia, because “in the illustrated embodiment in FIG. 2, the fluorescence detection system 20 comprises the fiber bundle probe 12 including more than one receiving fibers that can improve the signal-to-noise ratio of the system when all the receiving fibers are use [sic] for fluorescence intensity analysis, spectra, imaging or lifetime analyses.” (Xia, para 31)
Fengler is also silent with respect to at least one intensity regulator for regulating an intensity of the collection light which is collected by the at least one detector, the at least one intensity regulator being a liquid crystal, which, by application of a bias voltage, regulates the intensity of the collection light.
However, Wang, in the same field of imaging devices, teaches at least one intensity regulator (Figure 7: element 2 is a wavefront modulator; [0040]) for regulating an intensity ([0027] “a modification in the light intensity”) of the collection light ([0005] “a wavefront modulator located to receive collected light”) which is collected by the at least one detector (Figure 7: element 3 is a sensor array; [0005] “an imaging array located to receive phase-modulated light segments”), the at least one intensity regulator being a liquid crystal (Figure 7; [0023] “pixels of such a wavefront modulator 2 can be controlled through various mechanisms, …; the active component of a pixel can also be a liquid crystal device”), which, by application of a bias voltage (Figure 7; [0023] “pixels of such a wavefront modulator 2 can be controlled through various mechanisms, such as a piezoelectric force, an electrostatic force, or an electromagnetic force”, wherein “various mechanisms, such as a piezoelectric force, an electrostatic force, or an electromagnetic force” require application of a voltage, as known in the art), regulates the intensity ([0027] “a modification in the light intensity”) of the collection light ([0005] “a wavefront modulator located to receive collected light”).
Therefore, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method of Fengler, with at least one intensity regulator for regulating an intensity of the collection light which is collected by the at least one detector, the at least one intensity regulator being a liquid crystal, which, by application of a bias voltage, regulates the intensity of the collection light, as taught by Wang, “for obtaining optical images of a targeted object or scene such as a person's organ or tissue based on a fiber bundle having imaging optical fibers and optical phase modulation for improved imaging quality without using an objective lens to receive light from a target.” (Wang, para 4)
Regarding Claim 16, modified Fengler discloses the method of claim 13, wherein the at least one light source (Figure 2A: element 52 is a light source; [0026]) (i) is a laser, optionally a pulse-modulated laser, optionally having a controllable modulation duty cycle, optionally a solid-state laser, optionally a diode-pumped, solid-state laser, (ii) comprises one or more laser diodes ([0026] “Alternatively, …, solid state devices (such as light emitting diodes or diode lasers), … may be used”), or (iii) comprises one or more light-emitting diodes (LEDs), optionally one or more high-power LEDs.
Regarding Claim 17, modified Fengler discloses the method of claim 13, wherein the excitation light has (i) a wavelength within a range of from about 250 nm to about 1100 nm (Figure 6A: blue filter 79A, [0046] “This filter transmits light in the wavelength range from 370-460 nm”; Figure 6B: red filter 79B, [0047] “This filter transmits light in the wavelength range from 590-750 nm”; Figure 6C: green filter 79C, [0048] “This filter transmits light in the wavelength range from 480-570 nm”), optionally a wavelength of about 532 nm or about 266 nm, and/or (ii) a power of from about 100 mW to about 2 kW, optionally operating in a continuous-wave mode.
Regarding Claim 18, modified Fengler discloses the method of claim 13, wherein the system further comprises (I) at least one filter (Figure 4A: element 118 is a spectral filter; [0034]), optionally transmissive (Figure 4A: spectral filter element 118 transmits light to low light image sensor element 104; [0034]) or reflective, to regulate a wavelength of the collection light ([0049] “for defining the primary fluorescence image”) which is collected by the at least one detector (Figure 4A: element 104 is a low light image sensor; [0034]), wherein optionally the at least one filter is a bandpass filter, optionally the at least one filter is configured to filter out light of wavelengths outside the range of from about 450 nm to about 1600 nm ([0049] “the filter characteristics are such that any light outside of the wavelength range of 480-570 nm, or any desired subset of wavelengths in this range, contributes no more than 0.1% to the light transmitted by the filter”).
Regarding Claim 19, modified Fengler discloses the method of claim 13, wherein the at least one detector is (i) a photomultiplier module, optionally a silicon photomultiplier module (SiPM), (ii) a photodiode, optionally an avalanche photodiode, (iii) a photomultiplier tube (PMT), (iv) a multipixel photon counting device (MPPC), (v) a charge-coupled device (CCD), or (vi) a complementary metal-oxide-semiconductor (CMOS) device (Figure 4A; [0036] “low light image sensor 104 preferably comprises a charge coupled device with charge carrier multiplication (of the same type as the Texas Instruments TC253 or the Marconi Technologies CCD65), electron beam charge coupled device (EBCCD), intensified charge coupled device (ICCD), charge injection device (CID), charge modulation device (CMD), complementary metal oxide semiconductor image sensor (CMOS) or charge coupled device (CCD) type sensor”).
Regarding Claim 26, modified Fengler discloses the system of claim 1, but does not specifically teach that the at least one intensity regulator is disposed between the object and the at least one detector, and/or
wherein the at least one intensity regulator is controlled by the controller to regulate the intensity of the collection light which is received by the at least one detector, the intensity of the collection light is regulated by (i) applying a continuously- increasing bias voltage across a full dynamic range of the at least one intensity regulator, or (ii) closed-loop control between the at least one intensity regulator and the at least one detector, and/or
wherein the system comprises:
a plurality of intensity regulators, optionally a first intensity regulator between the at least one light source and the object and a second intensity regulator between the object and the at least one detector.
However, Wang, in the same field of imaging devices, teaches that the at least one intensity regulator (Figure 7: element 2 is a wavefront modulator; [0040]) is disposed between the object (Figure 7: element 6 is an object; [0022]) and the at least one detector (Figure 7: element 3 is a sensor array; [0040]), and/or
wherein the at least one intensity regulator (Figure 7: element 2 is a wavefront modulator; [0040]) is controlled by the controller ([0041] “the wavefront modulator can be a deformable mirror or a spatial light modulator having a plurality of independently controllable pixels that respond to the commands of a control unit”) to regulate the intensity ([0027] “a modification in the light intensity”) of the collection light ([0005] “a wavefront modulator located to receive collected light”) which is received by the at least one detector (Figure 7: element 3 is a sensor array; [0005] “an imaging array located to receive phase-modulated light segments”), the intensity of the collection light is regulated by (i) applying a continuously- increasing bias voltage across a full dynamic range of the at least one intensity regulator (moot), or (ii) closed-loop control (Figure 7; [0040] “The control unit also implements a feedback control”) between the at least one intensity regulator (Figure 7: element 2 is a wavefront modulator; [0040]) and the at least one detector (Figure 7: element 3 is a sensor array; [0040]), and/or
wherein the system comprises:
a plurality of intensity regulators, optionally a first intensity regulator between the at least one light source and the object and a second intensity regulator between the object and the at least one detector (moot).
Therefore, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the system of Fengler, such that the at least one intensity regulator is disposed between the object and the at least one detector, and/or wherein the at least one intensity regulator is controlled by the controller to regulate the intensity of the collection light which is received by the at least one detector, the intensity of the collection light is regulated by (i) applying a continuously- increasing bias voltage across a full dynamic range of the at least one intensity regulator, or (ii) closed-loop control between the at least one intensity regulator and the at least one detector, as taught by Wang, “for obtaining optical images of a targeted object or scene such as a person's organ or tissue based on a fiber bundle having imaging optical fibers and optical phase modulation for improved imaging quality without using an objective lens to receive light from a target.” (Wang, para 4)
Regarding Claim 28, modified Fengler discloses the method of claim 13, but does not specifically teach that the at least one intensity regulator is disposed between the object and the at least one detector, and/or
the at least one intensity regulator is controlled by the controller to regulate the intensity of the collection light which is received by the at least one detector, and/or
the intensity of the collection light is regulated by (i) applying a continuously- increasing bias voltage across a full dynamic range of the at least one intensity regulator, or (ii) closed-loop control between the at least one intensity regulator and the at least one detector; and/or
wherein the system comprises a plurality of intensity regulators, optionally a first intensity regulator between the at least one light source and the object and a second intensity regulator between the object and the at least one detector.
However, Wang, in the same field of imaging devices, teaches that the at least one intensity regulator (Figure 7: element 2 is a wavefront modulator; [0040]) is disposed between the object (Figure 7: element 6 is an object; [0022]) and the at least one detector (Figure 7: element 3 is a sensor array; [0040]), and/or
the at least one intensity regulator (Figure 7: element 2 is a wavefront modulator; [0040]) is controlled by the controller ([0041] “the wavefront modulator can be a deformable mirror or a spatial light modulator having a plurality of independently controllable pixels that respond to the commands of a control unit”) to regulate the intensity ([0027] “a modification in the light intensity”) of the collection light ([0005] “a wavefront modulator located to receive collected light”) which is received by the at least one detector (Figure 7: element 3 is a sensor array; [0005] “an imaging array located to receive phase-modulated light segments”), and/or
the intensity of the collection light is regulated by (i) applying a continuously- increasing bias voltage across a full dynamic range of the at least one intensity regulator (moot), or (ii) closed-loop control (Figure 7; [0040] “The control unit also implements a feedback control”) between the at least one intensity regulator (Figure 7: element 2 is a wavefront modulator; [0040]) and the at least one detector (Figure 7: element 3 is a sensor array; [0040]); and/or
wherein the system comprises a plurality of intensity regulators, optionally a first intensity regulator between the at least one light source and the object and a second intensity regulator between the object and the at least one detector (moot).
Therefore, it would have been obvious to a person or ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method of Fengler, such that the at least one intensity regulator is disposed between the object and the at least one detector, and/or the at least one intensity regulator is controlled by the controller to regulate the intensity of the collection light which is received by the at least one detector, and/or the intensity of the collection light is regulated by (i) applying a continuously- increasing bias voltage across a full dynamic range of the at least one intensity regulator, or (ii) closed-loop control between the at least one intensity regulator and the at least one detector, as taught by Wang, “for obtaining optical images of a targeted object or scene such as a person's organ or tissue based on a fiber bundle having imaging optical fibers and optical phase modulation for improved imaging quality without using an objective lens to receive light from a target.” (Wang, para 4)
Claim(s) 3 & 25 and 15 & 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fengler et al. (US 2019/0357757 A1) and Xia et al. (US 2010/0032582 A1) and Wang (US 2017/0245735 A1) as applied to claims 1 and 13 respectively, and further in view of Messerschmidt et al. (US 2020/0000341 A1).
Regarding Claim 3, modified Fengler discloses the system of claim 1, but does not specifically teach that the probe comprises an optical arrangement which includes a lens for delivering the excitation light from the at least one excitation fiber element to an illumination spot and for delivering the collection light from the illumination spot to the at least one collection fiber element, wherein optionally the illumination spot has a diameter of from about 50 μm to about 1500 μm, wherein optionally the optical arrangement is configured to transmit and collect light (i) along an optical axis of the probe, optionally up to about 45 degrees in relation to the optical axis of the probe, or (ii) laterally of an optical axis of the probe, optionally from about 45 degrees to about 90 degrees in relation to the optical axis of the probe.
However, Messerschmidt, in the same field of optical probes, teaches that the probe (Figure 2: element 2 is an optical probe; [0033]) comprises an optical arrangement which includes a lens (Figure 2: element 3 is a lens; [0039]) for delivering the excitation light from the at least one excitation fiber element (Figure 2: element 11 is a second optical fiber; [0049]) to an illumination spot ([0046] “the excitation spot”) and for delivering the collection light from the illumination spot ([0046] “the excitation spot”) to the at least one collection fiber element (Figure 2: element 9 is a first optical fiber; [0049]), wherein optionally the illumination spot ([0046] “the excitation spot”) has a diameter of from about 50 μm to about 1500 μm (Figure 2; [0041] “outer fiber core 7 … has, for example, a core diameter between 20 and 300 μm”; [0049] “second optical fiber 11 preferably has a core diameter of about 3-300 μm”, whereby it is being interpreted that an illumination spot will have a diameter no larger than 300 μm), wherein optionally the optical arrangement is configured to transmit and collect light (i) along an optical axis of the probe, optionally up to about 45 degrees in relation to the optical axis of the probe (Figure 2: lens element 3 transmits and collects light along the optical axis of probe element 2), or (ii) laterally of an optical axis of the probe, optionally from about 45 degrees to about 90 degrees in relation to the optical axis of the probe.
Therefore, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the system of Fengler, such that the probe comprises an optical arrangement which includes a lens for delivering the excitation light from the at least one excitation fiber element to an illumination spot and for delivering the collection light from the illumination spot to the at least one collection fiber element, wherein optionally the illumination spot has a diameter of from about 50 μm to about 1500 μm, wherein optionally the optical arrangement is configured to transmit and collect light (i) along an optical axis of the probe, optionally up to about 45 degrees in relation to the optical axis of the probe, or (ii) laterally of an optical axis of the probe, optionally from about 45 degrees to about 90 degrees in relation to the optical axis of the probe, as taught by Messerschmidt, because “Due to the miniaturization, the probe advantageously enables the examination of the object with at least one imaging method and at least one spectroscopic method in a minimally invasive way, in particular by means of endoscopy.” (Messerschmidt, para 17)
Regarding Claim 25, modified Fengler discloses the system of claim 1, but does not specifically teach a beam splitter which is one of transmissive or reflective to light at a wavelength of the excitation light and the other of transmissive or reflective to light at a wavelength of the collection light, such that the excitation light is one of transmitted through or reflected by the beam splitter to the object and the collection light is the other of transmitted through or reflected by the beam splitter to the at least one detector.
However, Messerschmidt, in the same field of optical probes, teaches a beam splitter (Figure 2: element 15 is a beam splitter filter; [0039]) which is one of transmissive or reflective to light at a wavelength of the excitation light and the other of transmissive or reflective to light at a wavelength of the collection light ([0014] “the excitation light of the spectroscopic method can be reflected by the beam splitter filter and the detected light can be transmitted. Alternatively, the excitation light of the spectroscopic method can be transmitted by the beam splitter filter and the detected light reflected”), such that the excitation light is one of transmitted through or reflected by the beam splitter (Figure 2: element 15 is a beam splitter filter; [0039]) to the object (Figure 2: element 1 is an object; [0033]) and the collection light is the other of transmitted through or reflected by the beam splitter (Figure 2: element 15 is a beam splitter filter; [0039]) to the at least one detector ([0050] “a spectrometer”, wherein “a spectrometer” is being interpreted as at least one detector).
Therefore, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the system of Fengler, with a beam splitter which is one of transmissive or reflective to light at a wavelength of the excitation light and the other of transmissive or reflective to light at a wavelength of the collection light, such that the excitation light is one of transmitted through or reflected by the beam splitter to the object and the collection light is the other of transmitted through or reflected by the beam splitter to the at least one detector, as taught by Messerschmidt, because “the sensitivity and specificity of an examination procedure that can be performed with the probe is advantageously increased.” (Messerschmidt, para 7)
Regarding Claim 15, modified Fengler discloses the method of claim 13, but does not specifically teach that the probe comprises an optical arrangement which includes a lens for delivering the excitation light from the at least one excitation fiber element to an illumination spot and for delivering the collection light from the illumination spot to the at least one collection fiber element, wherein optionally the illumination spot has a diameter of from about 50 μm to about 1500 μm, wherein optionally the optical arrangement is configured to transmit and collect light (i) along an optical axis of the probe, optionally up to about 45 degrees in relation to the optical axis of the probe, or (ii) laterally of an optical axis of the probe, optionally from about 45 degrees to about 90 degrees in relation to the optical axis of the probe.
However, Messerschmidt, in the same field of optical probes, teaches that the probe (Figure 2: element 2 is an optical probe; [0033]) comprises an optical arrangement which includes a lens (Figure 2: element 3 is a lens; [0039]) for delivering the excitation light from the at least one excitation fiber element (Figure 2: element 11 is a second optical fiber; [0049]) to an illumination spot ([0046] “the excitation spot”) and for delivering the collection light from the illumination spot ([0046] “the excitation spot”) to the at least one collection fiber element (Figure 2: element 9 is a first optical fiber; [0049]), wherein optionally the illumination spot ([0046] “the excitation spot”) has a diameter of from about 50 μm to about 1500 μm (Figure 2; [0041] “outer fiber core 7 … has, for example, a core diameter between 20 and 300 μm”; [0049] “second optical fiber 11 preferably has a core diameter of about 3-300 μm”, whereby it is being interpreted that an illumination spot will have a diameter no larger than 300 μm), wherein optionally the optical arrangement is configured to transmit and collect light (i) along an optical axis of the probe, optionally up to about 45 degrees in relation to the optical axis of the probe (Figure 2: lens element 3 transmits and collects light along the optical axis of probe element 2), or (ii) laterally of an optical axis of the probe, optionally from about 45 degrees to about 90 degrees in relation to the optical axis of the probe.
Therefore, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method of Fengler, such that the probe comprises an optical arrangement which includes a lens for delivering the excitation light from the at least one excitation fiber element to an illumination spot and for delivering the collection light from the illumination spot to the at least one collection fiber element, wherein optionally the illumination spot has a diameter of from about 50 μm to about 1500 μm, wherein optionally the optical arrangement is configured to transmit and collect light (i) along an optical axis of the probe, optionally up to about 45 degrees in relation to the optical axis of the probe, or (ii) laterally of an optical axis of the probe, optionally from about 45 degrees to about 90 degrees in relation to the optical axis of the probe, as taught by Messerschmidt, because “Due to the miniaturization, the probe advantageously enables the examination of the object with at least one imaging method and at least one spectroscopic method in a minimally invasive way, in particular by means of endoscopy.” (Messerschmidt, para 17)
Regarding Claim 27, modified Fengler discloses the method of claim 13, but does not specifically teach that the system further comprises a beam splitter which is one of transmissive or reflective to light at a wavelength of the excitation light and the other of transmissive or reflective to light at a wavelength of the collection light, such that the excitation light is one of transmitted through or reflected by the beam splitter to the object and the collection light is the other of transmitted through or reflected by the beam splitter to the at least one detector.
However, Messerschmidt, in the same field of optical probes, teaches a beam splitter (Figure 2: element 15 is a beam splitter filter; [0039]) which is one of transmissive or reflective to light at a wavelength of the excitation light and the other of transmissive or reflective to light at a wavelength of the collection light ([0014] “the excitation light of the spectroscopic method can be reflected by the beam splitter filter and the detected light can be transmitted. Alternatively, the excitation light of the spectroscopic method can be transmitted by the beam splitter filter and the detected light reflected”), such that the excitation light is one of transmitted through or reflected by the beam splitter (Figure 2: element 15 is a beam splitter filter; [0039]) to the object (Figure 2: element 1 is an object; [0033]) and the collection light is the other of transmitted through or reflected by the beam splitter (Figure 2: element 15 is a beam splitter filter; [0039]) to the at least one detector ([0050] “a spectrometer”, wherein “a spectrometer” is being interpreted as at least one detector).
Therefore, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the method of Fengler, with a beam splitter which is one of transmissive or reflective to light at a wavelength of the excitation light and the other of transmissive or reflective to light at a wavelength of the collection light, such that the excitation light is one of transmitted through or reflected by the beam splitter to the object and the collection light is the other of transmitted through or reflected by the beam splitter to the at least one detector, as taught by Messerschmidt, because “the sensitivity and specificity of an examination procedure that can be performed with the probe is advantageously increased.” (Messerschmidt, para 7)
Claim(s) 8-11 and 20-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fengler et al. (US 2019/0357757 A1) and Xia et al. (US 2010/0032582 A1) and Wang (US 2017/0245735 A1) as applied to claims 1 and 13 respectively, and further in view of Krattiger (US 2009/0266999 A1).
Regarding Claim 8, modified Fengler discloses the system of claim 1, but does not specifically teach that the at least one detector is (I) a one-dimensional array, optionally a spectrometer, wherein optionally the controller is configured to determine an intensity ratio of two emission peaks, with an amplitude of one peak being controlled to a desired level, as a control peak, and an intensity of the other peak being measured, as a measured peak, with a ratio of the intensities of the control and measured peaks being determined as the intensity ratio, or (II) a two-dimensional array, optionally a camera, wherein optionally the at least one light source is a pulsed light source configured to illuminate a two-dimensional illumination area on the object with the excitation light, and the at least one detector images a two-dimensional image area, as a field of view, on the object repeatedly at different delay times so as to acquire a lifetime decay.
However, Krattiger, in the same field of fluorescent imaging, teaches that the at least one detector (Figure 5: element 50 is an image sensor; [0072]) is (I) a one-dimensional array, optionally a spectrometer, wherein optionally the controller is configured to determine an intensity ratio of two emission peaks, with an amplitude of one peak being controlled to a desired level, as a control peak, and an intensity of the other peak being measured, as a measured peak, with a ratio of the intensities of the control and measured peaks being determined as the intensity ratio, or (II) a two-dimensional array (Figure 5; [0074] “image sensor 50 may be configured as phase-sensitive solid state image sensor, which pixel by pixel registers the intensity of the incident fluorescent beam and the phase-displacement”, wherein “pixel by pixel” is understood as a two-dimensional array), optionally a camera (Figure 5: element 330 is a video camera unit; [0088]), wherein optionally the at least one light source is a pulsed light source ([0017] “If for this purpose a light source with intrinsically pulse-type output, for instance a supercontinuum laser, is used, the generated light pulses must be transformed into a continuous or continuously modulated beam, for instance by means of an optical pulse stretcher”, whereby it is understood that a pulsed light source is used) configured to illuminate a two-dimensional illumination area on the object with the excitation light (Figure 5; [0069] “The fluorescence excitation beam and the white light are conducted to object end 23 (the distal end, at a distance from the observer) of endoscope 20 by means of endoscope light conductors 21, 21′. Enlarging lenses 22, 22′ are positioned to serve to uniformly distribute the illumination ray onto the area to be examined, for instance an object 2”), and the at least one detector (Figure 5: element 50 is an image sensor; [0072]) images a two-dimensional image area (implicit for an image sensor to image a two-dimensional image area), as a field of view ([0042] “visual fields of the first and at least one additional image sensor”), on the object (Figure 5: element 2 is an object; [0069]) repeatedly at different delay times ([0074] “the phase-displacement, that is, the time lapse between fluorescence excitation beam and incident fluorescent beam”, wherein “the time lapse” is delay time) so as to acquire a lifetime decay ([0074] “From data supplied by this image sensor, it is possible to reconstruct a fluorescence lifetime image, a fluorescence intensity image, and/or 3D data”, wherein “to reconstruct a fluorescence lifetime image” is to acquire a lifetime decay).
Therefore, it would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the system of Fengler, such that the at least one detector is (I) a one-dimensional array, optionally a spectrometer, wherein optionally the controller is configured to determine an intensity ratio of two emission peaks, with an amplitude of one peak being controlled to a desired level, as a control peak, and an intensity of the other peak being measured, as a measured peak, with a ratio of the intensities of the control and measured peaks being determined as the intensity ratio, or (II) a two-dimensional array, optionally a camera, wherein optionally the at least one light source is a pulsed light source configured to illuminate a two-dimensional