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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/18/2026 has been entered.
Response to Amendment
The Amendment filed 05/18/2026 has been entered. Claims 1, 3, and 5-12 remain pending in the application.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 6, and 8-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fan et al. (WO 2018125925 A1; cited in the IDS filed 04/26/2024).
Regarding claim 1, Fan teaches an imaging system (abstract; Fig. 19) comprising:
a laser cavity (Fig. 19, scanning cavity 254) configured to receive a biological sample (interpreted as a functional limitation of the cavity, MPEP 2114; Fig. 19 and paragraph [0119], shows cavity 254 receiving tissue sample 264; note that “biological sample” is not positively recited structurally), the biological sample is treated with a fluorophore (note that the biological sample and fluorophore are not positively recited structurally; paragraph [0103] teaches tissue samples are stained or labeled with fluorophores), wherein the laser cavity (Fig. 19, scanning cavity 254) is defined by a first mirror (Fig. 19 and paragraph [0119], second reflection surface 262, i.e. top mirror) and a second mirror (Fig. 19 and paragraph [0119], first reflection surface 260, i.e. bottom mirror) and the biological sample is disposed between the first mirror and the second mirror (Fig. 19 and paragraph [0119], tissue sample 264 is between mirrors 260,262);
an excitation light source (Fig. 19, laser 252) configured to direct energy at the laser cavity causing an emission from the biological sample (interpreted as a functional limitation of the light source, see MPEP 2114; Fig. 19 and paragraph [0119]), the emission simultaneously including a laser emission at a first spectral band and a fluorescence emission at a second spectral band (interpreted as a functional limitation of the light source, see MPEP 2114; Fig. 19 and paragraph [0120] teach detection of multiplexed emissions from the sample, therefore the light source is capable of causing simultaneously emission as claimed; [0075] teaches concurrent acquisition of fluorescent, bright field images, and laser emission images from the same tissue sample; [0139],[0141] teaches simultaneous acquisition of laser emission and bright field imaging; note that the biological sample is not positively recited structurally);
a first detector (Fig. 19, CCD 274) configured to measure the laser emission generated by the biological sample (Fig. 19 and paragraph [0120] teach the CCD 274 measures laser emission from the sample, i.e. LEM image);
a second detector (Fig. 19, spectrometer 278) configured to measure the fluorescence emission generated by the biological sample (paragraph [0200] teaches emission light is analyzed by the spectrometer, thus is capable of measuring fluorescence emission from the sample);
a splitter (Fig. 19, beam splitters 280) configured to direct the laser emission to the first detector and the fluorescence emission to the second detector (Fig. 19 and paragraph [0120] teaches multiplexed emissions from at least two distinct fluorophores from tissue sample 264 are detected since the emission are directed to CCD 274 and spectrometer 278 via beam splitters 280; Fig. 19 shows emissions from tissue sample 264 are directed to CCD imager unit 274 and spectrometer 278 by the beam splitters 280 and the CCD detecting a LEM image, i.e. laser emission microscopy image); and
a controller (Fig. 19, computer processing unit 258) interfaced with the excitation light source, the first detector, and the second detector (paragraph [0120] teaches detectors are outputted to a computer processing unit; paragraph [0172] teaches control of laser signals; therefore, it is inherent that the controller interfaces the light source and detectors in order for the system to properly control and receive information from the light source and detectors),
wherein a reflectivity of the first mirror (Fig. 19 and paragraph [0119], second reflection surface 262, i.e. top mirror) is greater than a first threshold within the first spectral band (Fig. 19 and paragraph [0120] teach the reflectivity of the second reflection surface around the lasing emission wavelength 535-555nm is 99.80%, which is interpreted as greater than a threshold within the first spectral band; paragraph [0094] teaches reflectivity of the second reflection surface for a select wavelength or range of wavelengths) so as to allow the first detector to detect the laser emission (interpreted as an intended use, MPEP 2114; Fig. 19 shows the reflectivity of the second reflection surface 262 allows laser emission to be detected by CCD 271; Fig. 19 and paragraph [0120] teach the CCD 274 measures laser emission from the sample, i.e. LEM image), and a transmission of the first mirror is above a second threshold within the second spectral band (paragraph [0198] teaches the top mirror has a high transmission for light to pass through; paragraph [0139] teaches other bands of wavelengths, such as greater than 550 nm can transmit through the top mirror; paragraph [0094] teaches the second reflection surface has a transmissivity and concurrently permits a distinct wavelength or range of wavelengths to transmit and pass therethrough; therefore, the first mirror, i.e. top mirror, has a transmission above a threshold within a second spectral band) so as to allow the second detector to detect the fluorescence emission (Fig. 19 and paragraph [0198] teaches the top mirror has a high transmission for light to pass through, and emission light is directed towards the spectrometer 278, therefore is capable of detecting fluorescence emission) such that the first detector and the second detector are able to simultaneously measure the generated laser emission and fluorescent emission from the biological sample (Fig. 19 and [0075],[0139],[0141] teach concurrent or simultaneous acquisition of fluorescent, bright field images, and laser emission images from the same tissue sample using CCD 271 and spectrometer 278; paragraph [0198] teaches the first mirror has a high reflectivity in the spectral range of 500-555 nm and high transmission; paragraph [0139] teaches the top mirror has a high reflectivity for certain wavelengths, such as 510-550 nm, while other bands less than 510 nm or greater than 550 nm can transmit through the top mirror; therefore the CCD 274 and spectrometer 278 are simultaneously capable of measuring laser emission within the first spectral band and fluorescent emission from a biological sample within the second spectral band).
Note that “biological sample” and “fluorophore” are not positively recited structurally and is interpreted as a functional limitation of the claimed system. A claim is only limited by positively recited elements; thus, inclusion of the material or article (“biological sample” and “fluorophore”) worked upon by a structure (laser cavity; first mirror; second mirror; excitation light source; first detector; second detector; splitter; controller) being claimed does not impart patentability to the claims (see MPEP 2115).
Note that a functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the functional limitations, then it meets the claim. See MPEP 2114. The system of Fan is identical to the presently claimed structure. Fan discloses the claimed laser cavity defined by a first and second mirror, an excitation light source, a first detector, a second detector, a splitter, and a controller as claimed and therefore, would have the ability to perform the use recited in the claim. See MPEP 2112.01 (I). Moreover, Fan teaches concurrent, i.e. simultaneous, acquisition of fluorescent, bright field images, and laser emission images from the same tissue sample using CCD 271 and spectrometer 278 (Fig. 19 and paragraphs [0075],[0139],[0141]); teaches the first mirror has a high reflectivity in the spectral range of 500-555 nm and high transmission (paragraph [0198]); and teaches the top mirror has a high reflectivity for certain wavelengths, such as 510-550 nm, while other bands less than 510 nm or greater than 550 nm can transmit through the top mirror (paragraph [0139]). Thus, the structures of first mirror, first detector, and second detector are structurally capable of performing the claimed functional limitations to simultaneously measure the laser emission and fluorescence emission.
Regarding claim 3, Fan further teaches wherein the first mirror is arranged parallel to the second mirror (Fig. 19 teaches the second reflection surface 262 is parallel to the first reflection surface 260).
Regarding claim 6, note that the “biological sample” and therefore “first spectral band” and “second spectral band” are not positively recited structurally and is interpreted as a functional limitation of the claimed system. A claim is only limited by positively recited elements; thus, inclusion of the material or article (“biological sample”) worked upon by a structure (system) being claimed does not impart patentability to the claims (see MPEP 2115).
Fan teaches an excitation light source (Fig. 19, laser 252) configured to direct energy at the laser cavity causing an emission from the biological sample (interpreted as a functional limitation of the light source, see MPEP 2114; Fig. 19 and paragraph [0119]), the emission including a laser emission at a first spectral band and a fluorescence emission at a second spectral band (interpreted as a functional limitation of the light source, see MPEP 2114; Fig. 19 and paragraph [0120] teach detection of multiplexed emissions from the sample, therefore the light source is capable of causing an emission as claimed; note that the biological sample is not positively recited structurally). Therefore, the laser is capable of causing an emission of a biological sample wherein the first spectral band is between 524 nm and 570 nm, and the second spectral band is greater than 590 nm at a later time. Note that Fan teaches obtaining laser emission images, fluorescent images, and bright field images (paragraph [0141]).
Additionally, Fan teaches the reflectivity of the second reflection surface around the lasing emission wavelength 535-555nm (paragraph [0120]) and other bands of wavelengths, such as greater than 550 nm can transmit through the top mirror (paragraph [0139]). Therefore, Fan’s first mirror (Fig. 19 and paragraph [0119], second reflection surface 262, i.e. top mirror) has a reflectivity greater than a first threshold within the first spectral band of between 524 nm and 570 nm (paragraph [0120], 535-555 nm), and a transmission above a second threshold within the second spectral band of greater than 590 nm (paragraph [0139], greater than 550 nm, which includes greater than 590 nm).
Regarding claim 8, Fan further teaches the imaging system of claim 1, further comprising: a motorized stage (Fig. 19 and paragraph [0119], scanning stage 256), wherein the laser cavity is disposed on the motorized stage (Fig. 19).
Regarding claim 9, Fan further teaches wherein the controller (Fig. 19, computer processing unit 254) further interfaces with the motorized stage (Fig. 19 and paragraph [0119]) and the controller is configured to adjust a position of the laser cavity relative to the excitation light source using the motorized stage (Fig. 19, paragraph [0119]).
Regarding claim 10, Fan further teaches wherein the controller is configured to align a first location of the laser cavity with the excitation light source, and subsequently, to align a second location of the laser cavity with the excitation light source (paragraphs [0119]-[0120] teaches the scanning stage can be translated or moved, thus translating the scanning cavity with respect to the laser source; paragraph [0145] teaches generating a two-dimension scan of the tissue sample; therefore, the controller is configured to align the cavity with the light source at at least two locations subsequently for scanning of the tissue sample).
Regarding claim 11, Fan further teaches wherein the splitter is a first splitter (Fig. 19, first beam splitter 280 below CCD 274) and the imaging system further comprises: at least one of a beam expansion lens set (not required due to “at least one”), a mirror (not required due to “at least one”), a mirror scanning system (not required due to “at least one”), a scanning lens set (not required due to “at least one”), a second splitter (Fig. 19, second beam splitter 280 below element 282), and an objective lens (Fig. 19, objective lens 284) configured to direct the energy at the laser cavity (Fig. 19).
Regarding claim 12, Fan further teaches wherein the splitter is a first splitter (Fig. 19, second beam splitter 280 below element 282) and the imaging system further comprises: at least one of a second splitter (Fig. 19, first beam splitter 280 below CCD 274), a tube lens (not required due to “at least one”), and an objective lens (Fig. 19, objective lens 284) configured to direct the emission to the first splitter (Fig. 19).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Fan as applied to claim 1 above, and further in view of Engelhardt et al. (US 20020027202 A1; cited in the IDS filed 04/26/2024).
Regarding claim 5, Fan further teaches wherein the splitter (Fig. 19, beam splitters 280) is configured to separate the fluorescence emission and the laser emission included in the emission from the biological sample (Fig. 19 and paragraph [0120] teaches the beam splitters 280 separate and direct laser emission and fluorescence emission to the CCD and spectrometer respectively).
Fan fails to explicitly teach the splitter is a dichroic mirror.
Engelhardt teaches an apparatus for detection of fluorescent light in scanning microscopy (abstract). Engelhardt teaches a canning mirror 9, mounted tiltably and configured as a dichroic beam splitter, reflects the three partial illuminating beams 8 and deflects them as a result of the tilting, so that specimen 1 can be scanned by the deflection of scanning mirror 9 (Fig. 1; paragraph [0041]).
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 splitter of Fan to incorporate the teachings of a dichroic mirror of Engelhardt (Fig. 1; paragraph [0041]) to provide: the splitter is a dichroic mirror. Doing so would have a reasonable expectation of successfully utilizing known beam splitters for improving reflecting and deflecting desired wavelengths towards optical components.
Regarding claim 7, Fan fails to explicitly teach wherein the excitation light source is configured to perform at least one of single-photon excitation and multi-photon excitation.
Engelhardt teaches an apparatus for detection of fluorescent light in scanning microscopy using multi-photon excitation (abstract). Engelhardt teaches the invention provides a method so that the fluorescent photon yield of the fluorescing materials that are excited to fluoresce by multi-photon excitation is optimized or increased in order to enable optimum specimen detection (paragraph [0006]). Engelhardt teaches a lasers as the light source for multi-photon excitation of fluorescing materials (paragraphs [0027]-[0031]). Engelhardt teaches in very particularly advantageous fashion, to prevent saturation of the excitation of fluorescing materials at a single specimen point, provision is made for simultaneous illumination or excitation of multiple specimen regions; wherein in this fashion, the excitation light output made available by the light source to the multi-photon light source can be distributed simultaneously to multiple specimen points, so that the fluorescing materials located there are simultaneously excited to fluoresce (paragraph [0033]).
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 excitation light source of Fan to incorporate the teachings of fluorescent scanning microscopy using multi-photon excitation of Engelhardt (abstract; paragraphs [0006],[0027]-[0031],[0033]) to provide: wherein the excitation light source is configured to perform at least one of single-photon excitation and multi-photon excitation. Doing so would have a reasonable expectation of successfully optimizing or increasing specimen detection as discussed by Engelhardt (paragraphs [0006],[0033]).
Response to Arguments
Applicant's arguments, see pages 5-7, with respect to the claim rejections under 35 U.S.C. 102(a)(1), specifically regarding amended claim 1, have been fully considered but they are not persuasive.
In response to applicant’s arguments that Fan fails to teach simultaneous emissions and measurements of laser emission and fluorescence emission (Remarks, pages 6-7), the examiner disagrees.
With respect to the limitations related to “simultaneously”, claim 1 recites: “the emission simultaneously including a laser emission at a first spectral band and a fluorescence emission at a second spectral band” and “such that the first detector and the second detector are able to simultaneously measure the generated laser emission and fluorescent emission from the biological sample”.
Fan teaches:
the emission simultaneously including a laser emission at a first spectral band and a fluorescence emission at a second spectral band (interpreted as a functional limitation of the light source, see MPEP 2114; Fig. 19 and paragraph [0120] teach detection of multiplexed emissions from the sample, therefore the light source is capable of causing simultaneously emission as claimed; [0075] teaches concurrent acquisition of fluorescent, bright field images, and laser emission images from the same tissue sample; [0139],[0141] teaches simultaneous acquisition of laser emission and bright field imaging; note that the biological sample is not positively recited structurally); and
such that the first detector and the second detector are able to simultaneously measure the generated laser emission and fluorescent emission from the biological sample (Fig. 19 and [0075],[0139],[0141] teach concurrent or simultaneous acquisition of fluorescent, bright field images, and laser emission images from the same tissue sample using CCD 271 and spectrometer 278; paragraph [0198] teaches the first mirror has a high reflectivity in the spectral range of 500-555 nm and high transmission; paragraph [0139] teaches the top mirror has a high reflectivity for certain wavelengths, such as 510-550 nm, while other bands less than 510 nm or greater than 550 nm can transmit through the top mirror; therefore the CCD 274 and spectrometer 278 are simultaneously capable of measuring laser emission within the first spectral band and fluorescent emission from a biological sample within the second spectral band)
Therefore, Fan teaches an imaging system structurally capable of simultaneous measurements of laser emission and fluorescence emission as claimed.
Additionally, note that “biological sample” and “fluorophore” are not positively recited structurally and is interpreted as a functional limitation of the claimed system. A claim is only limited by positively recited elements; thus, inclusion of the material or article (“biological sample” and “fluorophore”) worked upon by a structure (laser cavity; first mirror; second mirror; excitation light source; first detector; second detector; splitter; controller) being claimed does not impart patentability to the claims (see MPEP 2115).
A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the functional limitations, then it meets the claim. See MPEP 2114. The system of Fan is identical to the presently claimed structure. Fan discloses the claimed laser cavity defined by a first and second mirror, an excitation light source, a first detector, a second detector, a splitter, and a controller as claimed and therefore, would have the ability to perform the use recited in the claim. See MPEP 2112.01 (I). Moreover, Fan teaches concurrent or simultaneous acquisition of fluorescent, bright field images, and laser emission images from the same tissue sample using CCD 271 and spectrometer 278 (Fig. 19 and paragraphs [0075],[0139],[0141]); teaches the first mirror has a high reflectivity in the spectral range of 500-555 nm and high transmission around 465 nm (paragraph [0198]); and teaches the top mirror has a high reflectivity for certain wavelengths, such as 510-550 nm, while other bands less than 510 nm or greater than 550 nm can transmit through the top mirror (paragraph [0139]). Thus, the structure of first mirror, first detector, and second detector are structurally capable of performing the claimed functional limitations to simultaneously measure the laser emission and fluorescence emission.
In response to applicant’s arguments that Fan fails to teach “any capability for measurement of laser emission and fluorescence emissions simultaneously” since Fan is limited to “the overlaying of laser and fluorescence measurements after measurement” and measurement can be done separately through “removing the first reflection surface or through a total reduction in the reflectivity of the first reflection surface” (Remarks, page 6, third paragraph), the examiner disagrees. Applicant’s discussion regarding “removing the first reflection surface” is directed to a different embodiment of Fan (paragraphs [0076],[0140],[0142]). As seen in Fig. 19, which was not argued by the applicant, CCD 274 measures laser emission from the sample, i.e. LEM image, simultaneously as spectrometer 278 measures fluorescence emission. Additionally, Fan teaches concurrent or simultaneous acquisition of fluorescent, bright field images, and laser emission images from the same tissue sample using CCD 271 and spectrometer 278 (paragraphs [0075],[0139],[0141]). Note that claim 1 does not exclude “overlaying”. Since Fan’s CCD 274 and spectrometer 278 are structurally capable of simultaneous measuring of laser emission and fluorescence emission respectively, Fan’s teaches the claimed imaging system. As discussed above, Fan’s first mirror, first detector, and second detector are structurally capable of performing the claimed functional limitations to simultaneously measure the laser emission and fluorescence emission.
In response to applicant’s argument that paragraph [0139] of Fan provides no pointers towards the claimed invention since paragraph [0139] provides an alternative teaching of an overall reduction in reflectivity of the first mirror to allow for fluorescence measurement (Remarks, page 6, last paragraph - page 7, first paragraph), the examiner disagrees.
Paragraph [0139] states: “In certain aspects, the present disclosure contemplates the concurrent acquisition of bright-field imaging and lasing emission images from cells within tissue samples. Bright field image can be obtained directly through the first reflection surface (or top mirror). Because the first reflection surface has a high reflectivity for a certain select band of wavelengths (for example, 510 nm - 550 nm), this band of wavelengths will not appear or show up in the bright field. However, other bands of wavelengths (for example, less than about 510 nm or greater than about 550 nm) can still transmit through the first reflection surface top mirror and form bright field images. In this manner, the bright field images can also be collected concurrently with the lasing emission images and be overlaid with one another.”
Paragraph [0139] of Fan does not state “overall reduction in reflectivity of the first mirror to allow for fluorescence measurement” as argued by the applicant (Remarks, page 7, first paragraph). Additionally, the paragraph does not discuss “no dye is required…the wavelength…can be chosen to be outside that of the wavelength emitted from the dye…” as argued by the applicant (Remarks, page 6, last paragraph - page 7, first paragraph).
Rather, paragraph [0139] of Fan points to the ability of the top mirror (i.e. the claimed first mirror) to allow for bright field images and lasing emission images to simultaneously collected or measured. Additionally, Fan teaches concurrent or simultaneous acquisition of fluorescent, bright field images, and laser emission images from the same tissue sample using CCD 271 and spectrometer 278 (Fig. 19 and paragraphs [0075],[0139],[0141]).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., Remarks, page 6, first paragraph, “tuning the reflectivity and transmissivity…”; Remarks, page 6, third paragraph, “the specific tuning of reflectivity and transmission within specific spectral bands”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Gourley (US 5793485 A; cited in the OA filed 09/29/2025) teaches an imaging system (Fig. 1) comprising a laser cavity (12), laser (26), two detectors (36,38), splitter (40), display with a computer (42), and sample (100) between two mirrors of the cavity (14,16); wherein emission spectra is recorded with spectrometer 38 and laser mode images is recorded with CCD camera 36 (column 18, lines 22-26). Gourley a beamsplitter or otherwise a dichroic mirror that reflects a beam while transmitting a portion of the beam (column 6, lines 23-28). Gourley teaches a channel with two reflective layers that form a Fabry-Perot cavity (paragraph [0134]).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HENRY H NGUYEN whose telephone number is (571)272-2338. The examiner can normally be reached M-F 7:30A-5:00P.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached at (571) 270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
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