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 .
Priority
Acknowledgement is made of Applicant’s claim of priority from the Italian patent application number IT102021000019490 filed on 07/22/2021.
Information Disclosure Statement
The information disclosure statement (“IDS”) filed on 01/19/2024 has been reviewed and the listed references have been considered.
Drawings
The 6-page drawings have been considered and placed on record in the file.
Status of Claims
Claims 1-27 and 30 are pending. Claims 28, 29 and 31-44 are cancelled.
Claim Objections
Claims 7-10, 20 and 21 are objected to for reciting multiple sentences. See also, MPEP 608.01 (m), each claim in a patent must be written as a single sentence.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 1 recites “said subcellular structure of interest”, “the center said voxel”, “said cloud of voxels (CI)”, “the statistical similarity”, “the other non-overlapped clouds of voxels”, “the hypothesis test”, “the mean value”, “the cloud of voxels”, “other clouds of voxels”, “the tomogram of occurrences”, “the tomogram”, and “the tomograms of occurrences”. There is insufficient antecedent basis for these limitations in the claims.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 2 recites “the two sets of values”. There is insufficient antecedent basis for the limitation in the claims.
Claim 4 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 4 recites “said cloud of reference”, and “the subcellular structure of interest”. There is insufficient antecedent basis for these limitations in the claims.
Claim 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 5 recites “said investigated voxel clouds”, and “the cell shell”. There is insufficient antecedent basis for these limitations in the claims.
Claim 6 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 6 recites “said investigated cubes (CI)”, and “said reference cube (CR)”. There is insufficient antecedent basis for these limitations in the claims.
Claim 7 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 7 recites “the RIs of the sole reference cube CR”, and “the investigated cubes CI”, “the preliminary subcellular structure set”. There is insufficient antecedent basis for these limitations in the claims.
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 8 recites “the preliminary subcellular structure set”, “the reduced subcellular structure set”, and “said vector”. There is insufficient antecedent basis for these limitations in the claims.
Claim 9 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 9 recites “the filtered subcellular structure set”, “the augmented cube”, “the resolution”, “the filtered nucleus set”, “the examined sub-cube”, “the refined nucleus set” and “the partial subcellular structure set”. There is insufficient antecedent basis for these limitations in the claims.
Claim 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 10 recites “the setting of an adaptive threshold”, “the final 3D subcellular structure”, “the K partial nucleus”, and “the percentage volume vector”. There is insufficient antecedent basis for these limitations in the claims.
Claim 11 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 11 recites “said resolution factor”. There is insufficient antecedent basis for the limitation in the claims.
Claim 19 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 19 recites “analysing a cell by a cyto-tomographic technique”. There is insufficient antecedent basis for the limitation in the claims as claim 1 previously recites a cell and a cyto-tomographic technique.
Claim 20 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 20 recites “analysing a cell by a cyto-tomographic technique”. There is insufficient antecedent basis for the limitation in the claims as claim 1 previously recites a cell and a cyto-tomographic technique.
Claim 21 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 21 recites “the rolling angles”, “the first frame”, “the generic frame”, “the images’ pair”, “the QPMs”, and “the frame of known rotation”. There is insufficient antecedent basis for these limitations in the claims.
Claim 22 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 22 recites “the local contrast image”. There is insufficient antecedent basis for the limitation in the claims.
Claim 23 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 23 recites “the global minimum of the TSI”. There is insufficient antecedent basis for the limitation in the claims.
Claim 25 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 25 recites “said TSI”, “the QPM”, “the first frame”, and “the other QPMs”. There is insufficient antecedent basis for these limitations in the claims.
Claim 30 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Specifically, Claim 30 recites “analysis on a cell”. There is insufficient antecedent basis for the limitation in the claims as claim 1 previously recites analysis on a cell.
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 1, 4, 5, 7-13, 15-19 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Cotte et al. (US 2019/0251330 A1) in view of Toriya et al. (US 2021/0003698 A1).
Regarding claim 1, Cotte teaches, A computer-implemented (Cotte, ¶0012: “a computer system may be used to process the data”) method for identifying (Cotte, ¶0020: “method of digital characterization of a microscopic object”) a subcellular structure of a cell (Cotte, ¶0386: “segmentation of the different subcellular structures is possible by an object characterization”) analysed by a cyto-tomographic technique, (Cotte, ¶0007: “quantitative cell tomography, in vitro”) preferably, but not limited to, flow cytometry condition, (Cotte, ¶0487: “gating of cytometry analysis”) which method comprises the following steps: i) retrieving 3D Refractive Index (RI) tomogram of said cell; (Cotte, ¶0060: “a refractive index (RI) distribution of a cell obtained by quantitative cell tomography”) ii) identifying a single voxel supposed belonging to said subcellular structure of interest; (Cotte, ¶0362: “The nucleus can be identified as a distinct feature of the cell and the nuclear volume can be measured”) iii) defining a reference cloud of voxels (CR) having as the center said voxel in (Cotte, ¶0102: “the central cell where values of measured RI are reported”) ii), wherein said cloud of voxels (Ci) means a group of adjacent voxels (Cotte, ¶0355: “the parameter ranges of the organelles (e.g. cell membrane, cytoskeleton, nuclear membrane, nucleoli) are within the parameter range of the whole cell”) belonging to a cube having a side of E pixels; (Cotte, Fig. 3: cubes with x, y, and z sides) iv) calculating the statistical similarity between the reference cloud of voxels and all the other non-overlapped clouds of voxels of the same size (Cotte, ¶0125: “update the characterization of a feature, compare data of a feature with other data of a same or similar feature, constitute a reference dataset for a given feature and any other operation regarding the use or interactive modification of a dataset describing a feature of a microscopic object”) by using a statistical similarity test, wherein the said test can be one of the hypothesis test on the mean value; (Cotte, ¶0279: “statistical models to prove or disprove research hypotheses and may also be used in the present invention to improve object characterization”) v) grouping the clouds of voxels having simultaneously higher statistical similarity (Cotte, ¶0355: “Subgrouped parameters (FIG. 20) could be used to put in evidence simultaneously features inside of another feature characterized”) and spatial proximity among them and (Cotte, ¶0358: “(a) physical data means quantitative data (in 5 dimensions: three spatial, and two RI based) which are therefore inherently prone to be compared”) respect to the references cloud of voxels; (Cotte, ¶0358: “(b) a ground-truth correlation (obtained for instance through reference data”) vi) removing statistical outlier clouds of voxels erroneously grouped in v), (Cotte, ¶0276: “characterizing various features of microscopic object may be calibrated through… non-rigid error analysis”) wherein said outliers are clouds of voxels that differ significantly from other clouds of voxels grouped in v); (Cotte, ¶0366: “stains to be defined on regions with similar structural characteristics. Only the voxels with those specific physical characteristics are automatically segmented”) vii) repeating steps iii) to vi) by (Cotte, ¶0487: “quantify the measurements and produce parameters that allow for quantitative analysis”) times steps iii) to vii) to create K estimations of the said subcellular structure of interest; (Cotte, ¶0487: “objectively and repeatedly quantify the measurements and produce parameters that allow for quantitative analysis”) ix) adding up all the K estimations in viii) (Cotte, ¶0247: “add more than one object characterization (digital stain), by repeating the 1.sup.st, 2.sup.nd or 6.sup.th points”) to create the tomogram of occurrences, (Cotte, ¶0435: “calibrated objects (e.g. sem tomograms of organelles”) wherein said tomograms of occurrences is the tomogram wherein each voxel can take integer values within [0, K], (Cotte, ¶0172: “a mapping that counts the cumulative number of {tilde over (M)} in all of the voxels, i.e. the frequency of RI distribution within the measured microscopic object”) according to how many times that voxel has been included within an estimation of said subcellular structure of interest; (Cotte, ¶0172: “a mapping that counts the cumulative number of {tilde over (M)} in all of the voxels, i.e. the frequency of RI distribution within the measured microscopic object”) x) defining a threshold value for each voxel belonging to the tomograms of occurrence for which values greater than said threshold is assigned to the said subcellular structure of interest. (Cotte, ¶0385: “Using the object characterization program according to an embodiment of the invention, one may characterize a typical RI increase during meta- and anaphase and accordingly define a threshold T.sub.RI related to the RI so to predict the occurrence of Mitosi”). However, Cotte does not explicitly teach, setting as the reference cloud of voxels a sub-group of voxels randomly selected from the grouped clouds of voxels of vi) with a halved value of E.
In an analogous field of endeavor, Toriya teaches, setting as the reference cloud of voxels a sub-group of voxels randomly selected from the grouped clouds of voxels (Toriya, ¶0079: “processing of randomly extracting an area extractable as a block within the search range, and determining whether the extracted area (block) is similar to the reference block”) of vi) with a halved value of E; (Toriya, ¶0054: “reference block setting unit 111 can set any small area in the SAR image as the reference block”).
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 Cotte using the teachings of Toriya to introduce a random selection. A person skilled in the art would be motivated to combine the known elements as described above and achieve the predictable result of matching for similar characteristics to characterize a random voxel belonging to an organelle. Therefore, it would have been obvious to combine the analogous arts Cotte and Toriya to obtain the invention in claim 1.
Regarding claim 4, Cotte in view of Toriya teaches, The method according to claim 1, wherein said cloud of reference (CR) is a cube containing E3 voxels supposed belonging to the subcellular structure of interest, (Cotte, ¶0386: “segmentation of the different subcellular structures is possible by an object characterization”) chosen among the cubes obtained by centering the 3D Refractive Index Tomogram (Cotte, ¶0060: “a refractive index (RI) distribution of a cell obtained by quantitative cell tomography”) of the analyzed cell in its Lx x Ly x Lz array and dividing it into distinct cubes, each of which has an edge measuring E pixel. (Cotte, Fig. 3: Cubes with x, y, and z edges).
Regarding claim 5, Cotte in view of Toriya teaches, The method according to claim 1, wherein said investigated voxel clouds (Ci) are cubes completely contained within the cell shell of the 3D Refractive Index Tomogram of the analyzed cell (Cotte, ¶0060: “a refractive index (RI) distribution of a cell obtained by quantitative cell tomography”) centered in its Lx x Ly x Lz array, and divided into distinct cubes, each of which has an edge measuring E pixel. (Cotte, Fig. 3: Cubes with x, y, and z edges).
Regarding claim 7, Cotte in view of Toriya teaches repeated loops (Cotte, ¶0453: “a feedback loop improves the accuracy of identifying and characterizing features (for instance organelles) of a microscopic biological specimen”).
Regarding claim 8, Cotte in view of Toriya teaches removing subcellular structures that are different from the target structures (Cotte, ¶0366: “Only the voxels with those specific physical characteristics are automatically segmented”).
Regarding claim 9, Cotte in view of Toriya refines the detected subcellular structures (Cotte, ¶0458: “adjust and refine the segmentation process by shrinking or stretching the digital stain edges to include or exclude voxels based on their RI and RI gradient values in real-time from the observation of the segmentation applied onto the RI data”).
Regarding claim 10, Cotte in view of Toriya sets an adaptive threshold (Cotte, ¶0385: “one may characterize a typical RI increase during meta- and anaphase and accordingly define a threshold T.sub.RI related to the RI so to predict the occurrence of Mitosi”).
Regarding claim 11, Cotte in view of Toriya teaches, The method according to claim 1, wherein said resolution factor E parameter is an even number higher than 5 px, preferably 10 px with a suitable spatial resolution, otherwise less than 10 px. (Cotte, ¶0088: “The scales bar are illustrates a (A) 20 μm for the 2D view. (B) 10 μm (C) 10 μm”).
Regarding claim 12, Cotte in view of Toriya teaches, The method according to claim 1, wherein said K parameter is a number greater than 10, preferably 20. (Cotte, ¶0487: “repeatedly quantify the measurements and produce parameters that allow for quantitative analysis”).
Regarding claim 13, Cotte in view of Toriya teaches, The method according to claim 7, wherein said M parameter is a number from 5 to 15, preferably 10. (Cotte, ¶0487: “repeatedly quantify the measurements and produce parameters that allow for quantitative analysis”).
Regarding claim 15, Cotte in view of Toriya teaches, The method according to claim 9, wherein said α parameter is a number from 0 to 1, preferably 0.9. (Cotte, ¶0228: “values between 0 to 1; alpha—the opacity maximum”).
Regarding claim 16, Cotte in view of Toriya teaches, The method according to claim 9, wherein said β parameter is a number from 0 to 1, preferably 0.5. (Cotte, ¶0250: “For the picked pixels, the object characterization program computes the mean and the standard deviation for the refractive index”).
Regarding claim 17, Cotte in view of Toriya teaches, The method according to claim 1, wherein said cyto- tomographic technique is a flow cyto-tomography. (Cotte, ¶0487: “gating of cytometry analysis”).
Regarding claim 18, Cotte in view of Toriya teaches, The method according to claim 1, wherein said subcellular structure is selected from the following ones: nucleus, mitochondria, rough endoplasmic reticulum, smooth endoplasmic reticulum, Golgi apparatus, peroxisome, lysosome, centrosome, centriole, cell membrane, cytoplasm, lipid droplets, nucleolus. (Cotte, ¶0115: “the RI holographic tomographic and the fluorescence data are captured on a same sample and overlayed for subsequent digital stain calibration. Examples are given here for mitochondria, nucleus and nucleoli, membrane, lipid droplets, nuclear membrane and lysosomes”).
Regarding claim 19, Cotte in view of Toriya teaches, The method according to claim 1, further comprising a step of analysing a cell by a cyto-tomographic technique before step i). (Cotte, ¶0119: “global sequence for analysis of a biological sample with digital stains generated by an object characterization system”).
Regarding claim 30, Cotte in view of Toriya teaches, a data processing device configured to execute the method of claim 1 (Cotte, ¶0059: “a computing apparatus comprising a processor and a memory having stored thereon instructions that, when executed by the processor, perform the method”).
Claims 2, 3, 6 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Cotte et al. (US 2019/0251330 A1) in view of Toriya et al. (US 2021/0003698 A1) and in further view of Albertson et al. (US 2022/0088070 A1).
Regarding claim 2, Cotte in view of Toriya teaches, The method according to claim 1. However, the combination of Cotte and Toriya does not explicitly teach, wherein said statistical similarity test is preferably the Wilcoxon-Mann-Whitney (WMW) test or any other statistical hypothesis test, used for determining in effective way a null hypothesis Ho which is that the two sets of values have been drawn from the same distribution.
In an analogous field of endeavor, Albertson teaches, wherein said statistical similarity test is preferably the Wilcoxon-Mann-Whitney (WMW) test or any other statistical hypothesis test, used for determining in effective way a null hypothesis Ho which is that the two sets of values have been drawn from the same distribution. (Albertson, ¶1641: “All comparisons were based on differences in median densities, and statistical significance were evaluated using uncorrected P values assessed via the (unpaired) Wilcoxon-Mann-Whitney nonparametric test”)
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 Cotte in view of Toriya using the teachings of Albertson to introduce Wilcoxon-Mann-Whitney test. A person skilled in the art would be motivated to combine the known elements as described above and achieve the predictable result of evaluating the statistical significance. Therefore, it would have been obvious to combine the analogous arts Cotte, Toriya and Albertson to obtain the invention in claim 2.
Regarding claim 3, Cotte in view of Toriya and in further view of Albertson teaches, The method according to claim 2, wherein said null hypothesis Ho of said WMW test can or cannot be rejected depending on the following cases, respectively: a) Ho is not rejected with the significance level y if the p-value is greater than or equal to y b) Ho is rejected with the significance level y if the p-value is lower than y wherein the said significance level y is the probability to reject the null hypothesis Ho when Ho is true, and said p-value is the probability of obtaining test results at least as extreme as the result actually observed, under the assumption that the null hypothesis Ho is correct. (Cotte, ¶0280: “statistical models to prove or disprove research hypotheses and may also be used in the present invention to improve object characterization”).
Regarding claim 6, Cotte in view of Toriya and in further view of Albertson teaches, The method according to claim 2, wherein said WMW test is carried out computing the p-value of each of said investigated cubes (Ci) with respect to said reference cube (CR), (Cotte, ¶0358: “(b) a ground-truth correlation (obtained for instance through reference data”) thus obtaining a variable threshold Tr value according to the p-values chosen as the maximum value less than or equal to r such that for at least one CI it happens that p- value is higher or equal to TP. (Cotte, ¶0385: “one may characterize a typical RI increase during meta- and anaphase and accordingly define a threshold T.sub.RI related to the RI so to predict the occurrence of Mitosi”).
Regarding claim 14, Cotte in view of Toriya and in further view of Albertson teaches, The method according to claim 6, wherein said Ƭ is a number less than or equal to 0.99, preferably 0.99. (Cotte, ¶0174: “k parameters or thresholds, where k∈[1 . . . K] of L”).
Claims 20-27 are rejected under 35 U.S.C. 103 as being unpatentable over Cotte et al. (US 2019/0251330 A1) in view of Toriya et al. (US 2021/0003698 A1) and in further view of Masaeli et al. (US 2017/0333903 A1).
Regarding claim 20, Cotte in view of Toriya teaches, The method according to claim 17 wherein said step of analysing a cell by a cyto- tomographic technique comprising the following steps: a) (Cotte, ¶0008: “three-dimensional (3D), four dimensional (4D), or higher dimensional data, acquired for instance using the abovementioned holographic tomography”) c) processing of holographic data to retrieve the 3D RI tomogram of said cell (Cotte, ¶0009: “reconstructing the 3D, 4D or higher dimensional refractive index distribution of a microscopic biological specimen”) d) using any quantitative phase imaging technique capable of estimating phase contrast distributions. (Cotte, ¶0009: “quantitative phase imaging can be derived from the intensity transport equation”). However, the combination of Cotte and Toriya does not explicitly teach, injecting of said cell into a microfluidic channel being part of any device for tomographic flow cytometry.
In an analogous field of endeavor, Masaeli teaches, injecting of said cell (Masaeli, ¶0005: “a perfusion system configured to inject a sample into the flow cell via the inlet”) into a microfluidic channel being part of any device for tomographic flow cytometry. (Masaeli, ¶0005: “a cytological classification system including an imaging system, a flow cell including an inlet, an outlet, and a microfluidic channel including an imaging region”).
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 Cotte in view of Toriya using the teachings of Masaeli to introduce a microfluidic channel. A person skilled in the art would be motivated to combine the known elements as described above and achieve the predictable result of flowing cell imaging and classification system. Therefore, it would have been obvious to combine the analogous arts Cotte, Toriya and Masaeli to obtain the invention in claim 20.
Regarding claim 21, Cotte in view of Toriya and in further view of Masaeli teaches rolling angles to record holographic data (Cotte, ¶0007: “The sample beam is then rotated by a small angle and the process is repeated, with one hologram recorded for each beam position”).
Regarding claim 22, Cotte in view of Toriya and in further view of Masaeli teaches contrast imaging (Cotte, ¶0386: “determine the refractive index of an isolated mitochondria using retardation-modulated differential interference contrast microscopy”).
Regarding claim 23, Cotte in view of Toriya and in further view of Masaeli teaches recovering the global minimum (Cotte, ¶0458: “optimization can be automated by optimization algorithms to find the global minimum”).
Regarding claim 24, Cotte in view of Toriya and in further view of Masaeli teaches a rolling angle (Cotte, ¶0007: “The sample beam is then rotated by a small angle and the process is repeated, with one hologram recorded for each beam position”).
Regarding claim 25, Cotte in view of Toriya and in further view of Masaeli teaches obtaining frame data (Cotte, ¶0367: “A frame every minute was extracted”).
Regarding claim 26, Cotte in view of Toriya and in further view of Masaeli teaches tomographic reconstruction (Cotte, ¶0491: “3D RI Tomographic reconstruction in Real space of RI”).
Regarding claim 27, Cotte in view of Toriya and in further view of Masaeli teaches quantification of subcellular structure (Cotte, ¶0007: “quantitative cell tomography”).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MEHRAZUL ISLAM whose telephone number is (571)270-0489. The examiner can normally be reached Monday-Friday: 8am-5pm.
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/MEHRAZUL ISLAM/Examiner, Art Unit 2662
/AMANDEEP SAINI/ Supervisory Patent Examiner, Art Unit 2662