DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/10/2025 has been entered.
Following prior arts are considered pertinent to applicant's disclosure.
US20230258554 A1 (Shaked)
US 20220253016 A1 (Murakami)
US 20200116617 A1 (Sing)
Stain-free viability determination of cells with the fluidlab R-300, September 2020. retrieved from https://anvajo.com/inspiration/stain-free-viability-determination (FluidlabR300)
CATCH: Characterizing and Tracking Colloids Holographically Using Deep Neural Networks Published as part of The Journal of Physical Chemistry virtual special issue “Machine Learning in Physical Chemistry”, February 2020. Lauren E. Altman and David G. Grier (Altman)
US 20170205390 A1 (para 11, 165; Fig.1D, Fig.3A & 3E; viable sperm cell selection through digital holographic microscopy and RI)
Response to Remarks/Arguments
Applicant’s arguments with respect to claim prior art rejection have been fully considered but are moot in view of the new grounds of rejection
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1, 4-5 & 10 are rejected under 35 U.S.C. 103 as being unpatentable over FluidlabR300 in view of Sing.
Regarding Claim 1. FluidlabR300 teaches a method of characterizing cell viability of a plurality of cells dispersed in a fluid medium, comprising:
; [(First figure and description)]
determining optical properties of a first cell of the plurality of cells by:
generating a first holographic image based upon holographic video microscopy of the sample within the observation volume at a first time; [(section “What is digital holographic microscopy”)]
analyzing the first holographic image for one or more regions of interest corresponding to a first cell of the plurality of cells and applying a light scattering theory;[( section “What is digital holographic microscopy” and “How does the fluidlab R-300 analyze cell viability?”; 3rd figures shows detection region)] and
determining the refractive index of the first cell [(see section “How does the fluidlab R-300 analyze cell viability?”. “The determination of cell viability with DHM relies on a signal that is proportional to the intracellular refractive index”)] ;
determining a radius of the first cell based upon the analysis of the first holographic image and application of the light scattering theory [(see section “How does the fluidlab R-300 analyze cell viability?”; see cell size, using radius or diameter for cell size is well understood )]
characterizing the first cell as viable or not viable based upon comparing the refractive index to a known viable cell refractive index [(see section “How does the fluidlab R-300 analyze cell viability?”. “The determination of cell viability with DHM relies on a signal that is proportional to the intracellular refractive index”)] .
FluidlabR300 does not explicitly show that the cells are flowing through the observation volume
However, in the same/related field of endeavor, Sing teaches the cells are flowing through the observation volume to be analyzed by holographic microscope [(Sing Fig.1A; acquired 100 holograms per second {para 41})] also teaches determining radius [(para 36 diameter)]
Therefore, in light of above discussion it would have been obvious to one of the ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teaching of the prior arts because such combination would speed up the processing [(Sing para 41)]
The prior arts combination additionally teaches with regards to claim 4. The method of claim 1, further comprising: determining optical properties of a second cell of the plurality of cells by: analyzing the first holographic image for a second regions of interest corresponding to a second cell of the plurality of cells and applying the light scattering theory determining the refractive index of the second cell: and characterizing the second cell as viable or not viable based upon the refractive index. [(FluidlabR300 section “How does the fluidlab R-300 analyze cell viability?”; the different region of interest is different detection zone shown on the left frame)]
Regarding Claims 5 & 10: See the analysis of claim 1
Claims 1, 5 & 10 are rejected under 35 U.S.C. 103 as being unpatentable over Sing in view of Murakami.
Regarding Claim 1. Sing teaches a method of characterizing cell viability of a plurality of cells dispersed in a fluid medium, comprising:
flowing the plurality of cells dispersed in a medium through an observation volume that is in communication with a holographic microscope; [(Fig 1A; para 10, 42)]
determining optical properties of a first cell of the plurality of cells by:
generating a first holographic image based upon holographic video microscopy of the sample within the observation volume at a first time; [(Fig.1A hologram)]
analyzing the first holographic image for one or more regions of interest corresponding to a first cell of the plurality of cells and applying a light scattering theory;[(para 28, Fig.1B-1C)] and
determining the refractive index of the first cell [(para 30, 32)] ;
determining a radius of the first cell based upon the analysis of the first holographic image and application of the light scattering theory [(para 36 ; “Any change in the size and refractive index of cells is manifested in the intensity distribution of focused images obtained using DHM” para 21] ; and
characterizing the live cell based on refractive index[(para 32)]
Sing does not explicitly show viable or not viable based upon comparing the refractive index to a known viable cell refractive index
However, in the same/related field of endeavor, Murakami teaches viable or not viable based upon comparing the refractive index to a known viable cell refractive index
Therefore, in light of above discussion it would have been obvious to one of the ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teaching of the prior arts because such combination would provide predictable result with no change of their respective functionalities.
Regarding Claims 5 & 10: See the analysis of claim 1
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Sing in view of Murakami in view of FluidlabR300.
With regards to claim 4. Sing in view of Murakami does not explicitly show determining optical properties of a second cell of the plurality of cells by: analyzing the first holographic image for a second regions of interest corresponding to a second cell of the plurality of cells and applying the light scattering theory determining the refractive index of the second cell: and characterizing the second cell as viable or not viable based upon the refractive index.
However, in the same/related field of endeavor, FluidlabR300 teaches determining optical properties of a second cell of the plurality of cells by: analyzing the first holographic image for a second regions of interest corresponding to a second cell of the plurality of cells and applying the light scattering theory determining the refractive index of the second cell: and characterizing the second cell as viable or not viable based upon the refractive index. [(FluidlabR300 section “How does the fluidlab R-300 analyze cell viability?”; the different region of interest is different detection zone shown on the left frame)]
Therefore, in light of above discussion it would have been obvious to one of the ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teaching of the prior arts because such combination would provide predictable result with no change of their respective functionalities.
Claims 1, 5 & 10 are rejected under 35 U.S.C. 103 as being unpatentable over Shaked in view of Murakami.
Regarding Claim 1. Shaked teaches a method of characterizing cell viability of a plurality of cells dispersed in a fluid medium, comprising:
flowing the plurality of cells dispersed in a medium through an observation volume that is in communication with a holographic microscope; [(para 87, 66, 107, 64 {intact cancer cell})]
determining optical properties of a first cell of the plurality of cells by:
generating a first holographic image based upon holographic video microscopy of the sample within the observation volume at a first time; [(para 107, 111)]
analyzing the first holographic image for one or more regions of interest corresponding to a first cell of the plurality of cells and applying a light scattering theory;[(para 91, 103)] and
determining the refractive index of the first cell [(para 42)] ;
determining a radius of the first cell based upon the analysis of the first holographic image and application of the light scattering theory [(para 103 and Table 1)]; and
characterizing the first cell as intact/live based on refractive index[(para 64, 107, 42)]
Shaked does not explicitly show viable or not viable based upon comparing the refractive index to a known viable cell refractive index
However, in the same/related field of endeavor, Murakami teaches viable or not viable based upon comparing the refractive index to a known viable cell refractive index [(Murakami para 66)]
Therefore, in light of above discussion it would have been obvious to one of the ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teaching of the prior arts because such combination would provide predictable result with no change of their respective functionalities.
Regarding Claims 5 & 10: See the analysis of claim 1
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Shahan Rahaman whose telephone number is (571)270-1438. The examiner can normally be reached on 7am - 3:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Nasser Goodarzi can be reached at telephone number (571) 272-4195. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/SHAHAN UR RAHAMAN/Primary Examiner, Art Unit 2426