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 .
Response to Amendment
The Amendment filed 03/18/2026 has been entered. Claims 1-17 remain pending in the application. Claims 16-17 are withdrawn. Applicant’s amendments to the claims have overcome each and every objection and 112(a) and 112(b) rejections previously set forth in the Non-Final Office Action mailed 12/18/2025.
Claim Objections
Claim 1 is objected to because of the following informalities: In line 7, it is suggested to recite “a sample” as “the sample” if referring to the same sample as established in line 2. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Claim 1 recites the limitations “determine, based on information corresponding to each of the plurality of individual separated compartments after correction, whether a magnitude of a change in each individual separated compartment exceeds a predetermined threshold”.
In accordance with MPEP 2106, the claims are found to recite statutory subject matter (Step 1: YES) and are analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A: Prong 1).
In the instant application, the limitations of “determine, based on information corresponding to each of the plurality of individual separated compartments after correction, whether a magnitude of a change in each individual separated compartment exceeds a predetermined threshold” covers performance of a limitation in the mind, i.e. mental process or mathematical calculation. Regarding the limitations of “determine…”, the instant specification, paragraphs [0048]-[0054], discusses calculations, which could be performed mentally or by math. Other than “a processor and a memory”, if the claim limitations, under its broadest reasonable interpretation, covers performance of the limitations in the mind but for the recitation of generic computer components, then the claim limitations fall within the “Mental Processes” grouping of abstract ideas (MPEP 2106.05(f)). Accordingly, the claims recite abstract ideas (Step 2A: Prong 1: Yes).
This judicial exception is not integrated into a practical application because the claims do not recite any additional elements that reflects an improvement to technology or applies or uses the judicial exception in some other meaningful way (Step 2A, Prong 2: No). In claim 1, after the limitation of “determine, based on information corresponding to each of the plurality of individual separated compartments after correction, whether a magnitude of a change in each individual separated compartment exceeds a predetermined threshold”, no further action is performed. Therefore, the claimed limitations do not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea. The processor and memory limitations are recited at a high-level of generality (i.e., as generic computer) such that it amounts no more than mere instructions to apply the exception using a generic computer component; wherein a general purpose computer is not a particular machine (MPEP 2106.05(b)). Additionally, the preceding steps and limitations are used for data gathering in the abstract idea; wherein, data gathering to be used in the abstract idea is insignificant extra-solution activity, and not a particular practical application. See MPEP 2106.05(g). Therefore, the claimed limitations do not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea. Thus, the claims are directed to an abstract idea that is not integrated into a practical application (Step 2A, Prong 2: No).
The claims 1-15 do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Regarding the abstract idea, claim 1 merely recites the processor and memory, wherein the claimed limitations of the processor and memory amount to no more than mere instructions to apply the exception using a generic computer component; wherein a general purpose computer is not a particular machine (MPEP 2106.05(b)). Claim 1 and dependent claims 2-15 further recites limitations, however these limitations generally link the judicial exception to a particular field of use (MPEP 2106.05(h)) and are used for data gathering, wherein data gathering to be used in the abstract idea is an insignificant extra-solution activity, and not a practical application (see MPEP 2106.05(g)), which alone or in combination do not amount to significantly more. Additionally, the limitations of claims 1-15 are well-understood, routine and conventional activities as evidenced by the prior art of Chiu et al. (US 20170175174 A1) in view of Crandall et al. (US 20140226866 A1), Glezer et al. (US 20050142033 A1), and Hosseini et al. (US 20200368744 A1). See MPEP 2106.05(d). The additional elements of the claims 1-15 do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). The claims are not patent eligible.
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.
Claims 1-3 and 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over Chiu et al. (US 20170175174 A1) in view of Crandall et al. (US 20140226866 A1).
Regarding claim 1, Chiu teaches a nucleic acid analysis device (abstract teaches devices and systems for detection of nucleic acids) comprising:
a fluid distributor (Figs. 3-4 teaches pipetting structures for sample transferring; paragraph [0325] teaches a pipette loads reagents onto a multiwell plate) configured to distribute a sample including nucleic acid and a reagent to a plurality of individual separated compartments to form a set including the plurality of individual separated compartments and a portion other than the plurality of individual separated compartments (interpreted as a functional limitation, see MPEP 2114; Figs. 3-4 teaches pipetting structures for sample transferring; paragraph [0325] teaches a pipette loads reagents onto a multiwell plate; therefore, the pipette is structurally capable of distributing a sample and reagent into compartments and a portion other than the compartments as claimed);
a labeler (paragraphs [0016]-[0018] teaches a detectable agent which may label a sample to allow for presence or absence of the detectable agent to be determined from images) configured to cause a change in individual separated compartments to which a sample including target nucleic acid is distributed so that the individual separated compartments to which the sample including target nucleic acid is distributed and the individual separated compartments to which a sample excluding target nucleic acid is distributed are distinguishable from each other (interpreted as a functional limitation, see MPEP 2114; paragraphs [0016]-[0018] teaches a detectable agent which may label a sample to allow for presence or absence of the detectable agent to be determined from images; paragraph [0167] teaches a nucleotide labeled with the detectable agent; paragraph [0168] teaches a detectable agent binding a nucleic acid sample; thus, the detectable agent is an element capable of causing a change in each individual separated compartment to which the sample including target nucleic acid is distributed so that each individual separated compartment to which the sample including target nucleic acid is distributed and each individual separated compartment to which a sample excluding target nucleic acid is distributed are distinguishable from each other);
an optical imaging device (paragraph [0033], teaches imaging with a fluorescence microscope) configured to acquire an image information corresponding to the set (interpreted as a functional limitation, see MPEP 2114; paragraph [0033] teaches the fluorescence microscope imaging the multi-well plate, therefore is configured to acquire image information as claimed; paragraphs [0104]-[0107] teaches optical imaging to acquire images); and
an information processing system including a processor and a memory storing instructions (paragraphs [0019],[0021], teaches a computing device including a processor and memory; paragraph [0218] teaches the system includes processors and a memory device including instructions executable by the processors), wherein the processor is configured to:
extract, from acquired image information corresponding to the set, information corresponding to the plurality of individual separated compartments and information corresponding to the portion other than the plurality of individual separated compartments (paragraphs [0278]-[0283] teaches the computer device includes software programming to implement the methods; paragraph [0222] teaches signal intensity from a well or chamber can be determined, based on optical information using fluorescence microscopy, i.e. extract information of the components from acquired image information; paragraphs [0277],[0281],[0288] teaches imaging and analysis of a multi-well plate; paragraphs [0336]-[0341] teaches image analysis software to find pixels, i.e. extract information, in an image and the location and intensity were tracked; paragraph [0140] teaches binary digital output, i.e. extracted information, in which each chamber is identified as containing or not containing a target sequence; therefore, the programming is configured to extract, from the images acquired, including location and intensity information, from each compartment and portion other than the compartments of the multi-well plate); and
determine whether a magnitude of a change in each individual separated compartment exceeds a predetermined threshold (paragraphs [0278]-[0283] teaches the computer device includes software programming to implement the methods; paragraphs [0277],[0281],[0288] teaches imaging and analysis of a multi-well plate; paragraph [0150] teaches determining the presence of a product based on a threshold of fluorescence intensity from an image; paragraph [0140] teaches binary digital output in which each chamber is identified as containing or not containing a target sequence; paragraph [0451] teaches setting a threshold pixel intensity to exclude droplets lacking target sample and analyzing those containing the target sample; therefore, the programming is configured to identify each compartment or chamber in which an intensity threshold is exceeded).
Chiu fails to teach: the processor is configured to: to determine an artifact component based on the extracted information; use the artifact component to correct the extracted information corresponding to the plurality of individual separated compartments; determine, based on information corresponding to each of the plurality of individual separated compartments after correction, whether a magnitude of a change in each individual separated compartment exceeds a predetermined threshold.
Chiu teaches using a ratio or function to correct for possible instrumental artifacts when analyzing an image (paragraph [0275]). Chiu teaches a corrected set of background pixels can be determined (paragraph [0276]). Chiu teaches a user-defined criteria can be used to exclude droplets with more than a specified fraction circles of their boundary in the interior of the Group on the grounds that the circle is an artifact due to noise in the image distorting the exterior boundary of the Group (paragraph [0253]). Chiu teaches a computing system including programmed instructions to perform the methods (paragraph [0303]). Chiu teaches for cases involving chambers and wells the number of chambers or wells containing the target sample was first determined (paragraph [0445]). Chiu teaches amplification of a target sequence results in a binary digital output in which each chamber is identified as either containing or not containing the PCR product indicative of the presence of the corresponding target sequence (paragraph [0140]).
Crandall teaches systems and methods for standardizing fluorescence scanning instruments to a reference system by separating effects of drift and normalization (abstract). Crandall teaches correcting the sensitivity of a group of similar fluorescence microscopy imaging instruments, as well maintaining the sensitivity of individual instruments over time and/or environmental variations (paragraph [0002]). Crandall teaches imaging a region of a reference slide for normalization to increase correction inaccuracy (paragraphs [0050]-[0051]). Crandall teaches a shading correction module that operates to correct non-uniformity, i.e. artifact, in epifluorescence illumination optics and the scan camera (paragraph [0141]), wherein the shading correction module scans a small area of the sample of the slide at a particular location where no sample is present, i.e. a portion other than the samples (paragraph [0141]); the image captures background fluorescence from any residual dye present; and an illumination correction profile is calculated by comparing average intensity of each pixel column (paragraph [0141]). Crandall teaches information from image data allows for automatically determining regions of interest and regions of disinterests (paragraph [0147]). Crandall teaches tools for annotating images, where annotations can be a useful to guide to document artifacts in an image, regions of interest in an image, or to identify a region of an image for reporting or quantitative analysis (paragraph [0155]), wherein the visualization and analysis module may use predetermined or otherwise identified image features to locate similar image data or patterns using content based image retrieval techniques (paragraph [0156]).
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 processor of Chiu to incorporate Chiu’s teachings of correcting for possible instrumental artifacts when analyzing an image (paragraph [0275]), determining a corrected set of background pixels (paragraph [0276]), a criteria to exclude droplets due to artifact from noise (paragraph [0253]), and determining presence of absence of a target in each chamber (paragraph [0140]) and Crandall’s teachings of correcting fluorescence microscopy imaging instruments (abstract; paragraph [0002]), imaging a reference slide to increase correction inaccuracy (paragraphs [0050]-[0051]), a shading correction module to correct non-uniformity in epifluorescence illumination optics by scanning an area where no sample is present (paragraph [0141]), automatically determining regions of interest and disinterest (paragraph [0147]), and documenting artifacts in an image (paragraphs [0155]-[0156]) to provide: the processor is configured to: to determine an artifact component based on the extracted information; use the artifact component to correct the extracted information corresponding to the plurality of individual separated compartments; determine, based on information corresponding to each of the plurality of individual separated compartments after correction, whether a magnitude of a change in each individual separated compartment exceeds a predetermined threshold. Doing so would have a reasonable expectation of successfully improving sensitivity of the analysis device (e.g. whether compartments exceed a threshold to determine the presence of a target nucleic acid) by allowing for identification and correction of artifacts that can cause noise found in images from fluorescence imaging.
If it is determined that Chiu fails to explicitly teach: extract, from acquired image information corresponding to the set, information corresponding to the portion other than the plurality of individual separated compartments, Crandall teaches imaging a region of a reference slide for normalization to increase correction inaccuracy (paragraphs [0050]-[0051]). Crandall teaches a shading correction module that operates to correct non-uniformity, i.e. artifact, in epifluorescence illumination optics and the scan camera (paragraph [0141]), wherein the shading correction module scans a small area of the sample of the slide at a particular location where no sample is present, i.e. a portion other than the samples (paragraph [0141]); the image captures background fluorescence from any residual dye present; and an illumination correction profile is calculated by comparing average intensity of each pixel column (paragraph [0141]). Crandall teaches information from image data allows for automatically determining regions of interest and regions of disinterests (paragraph [0147]).
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 processor of Chiu to incorporate Crandall’s teachings of correcting fluorescence microscopy imaging instruments (abstract; paragraph [0002]), imaging a reference slide to increase correction inaccuracy (paragraphs [0050]-[0051]), a shading correction module to correct non-uniformity in epifluorescence illumination optics by scanning an area of a slide where no sample is present (paragraph [0141]), automatically determining regions of interest and disinterest (paragraph [0147]), and documenting artifacts in an image (paragraphs [0155]-[0156]) to provide: the processor is configured to: extract, from acquired image information corresponding to the set, information corresponding to the portion other than the plurality of individual separated compartments. Doing so would have a reasonable expectation of successfully improving sensitivity of the analysis device by obtaining information of regions of interest and disinterest, e.g. an area where no sample is present, therefore allowing for identification and correction of artifacts that can cause noise found in images from fluorescence imaging.
Regarding claim 2, Chiu further teaches wherein the change comprises generation of fluorescence (paragraphs [0016]-[0018] teaches a detectable agent which may label a sample to allow for presence or absence of the detectable agent to be determined from images; paragraphs [0121],[0127] teaches the detectable agent is fluorescent), and wherein the information corresponding to the set includes a fluorescent image of the set (paragraph [0033] teaches the fluorescence microscope imaging the multi-well plate, i.e. fluorescent imaging; paragraphs [0104]-[0107] teaches optical imaging to acquire images).
Regarding claim 3, modified Chiu fails to teach wherein the information corresponding to the set includes a bright-field image of the set.
Chiu teaches the image stack may be obtained by optical imaging, which can be performed by epifluorescence microscopy, bright field imaging, or a combination thereof (paragraphs [0187],[0208],[0221],[0286]).
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 information processing system of modified Chiu to incorporate the teachings of optical imaging including bright field imaging of Chiu (paragraphs [0187],[0208],[0221],[0286]) to provide wherein the information corresponding to the set includes a bright-field image of the set. Doing so would have a reasonable expectation of successfully improving analysis and imaging of the set.
Regarding claim 5, Chiu further teaches wherein the plurality of individual separated compartments comprise wells (Figs. 3-4 shows a multiwell plate comprising wells; note that “the plurality of individual separated compartments” is not positively recited structurally and is interpreted as a functional limitation of the analysis device) including the sample including nucleic acid and the reagent that have been distributed (paragraphs [0032]-[0033] teaches a sample and PCR components are loaded onto the multiwell plate; note that “sample” is not positively recited structurally and is interpreted as a functional limitation of the analysis device), and wherein the set comprises a well plate including the wells (Figs. 3-4 shows a multiwell plate comprising wells; note that “set” is not positively recited structurally and is interpreted as a functional limitation of the analysis device).
Regarding claim 6, Chiu further teaches the set including the portion, the portion other than the plurality of individual separated compartments includes a part of a region other than the wells of the well plate (Figs. 3-4 shows a microwell plate, which includes regions other than wells of the well plate). Modified Chiu fails to teach: wherein the portion other than the plurality of individual separated compartments includes a part of a region other than the wells of the well plate.
Crandall teaches systems and methods for standardizing fluorescence scanning instruments to a reference system by separating effects of drift and normalization (abstract). Crandall teaches correcting the sensitivity of a group of similar fluorescence microscopy imaging instruments, as well maintaining the sensitivity of individual instruments over time and/or environmental variations (paragraph [0002]). Crandall teaches imaging a region of a reference slide for normalization to increase correction inaccuracy (paragraphs [0050]-[0051]). Crandall teaches a shading correction module that operates to correct non-uniformity, i.e. artifact, in epifluorescence illumination optics and the scan camera (paragraph [0141]), wherein the shading correction module scans a small area of the sample of the slide at a particular location where no sample is present (paragraph [0141]); the image captures background fluorescence from any residual dye present; and an illumination correction profile is calculated by comparing average intensity of each pixel column (paragraph [0141]). Crandall teaches information from image data allows for automatically determining regions of interest and regions of interests (paragraph [0147]). Crandall teaches tools for annotating images, where annotations can be a useful to guide to document artifacts in an image, regions of interest in an image, or to identify a region of an image for reporting or quantitative analysis (paragraph [0155]), wherein the visualization and analysis module may use predetermined or otherwise identified image features to locate similar image data or patterns using content based image retrieval techniques (paragraph [0156]).
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 device of modified Chiu to incorporate Crandall’s teachings imaging a reference slide to increase correction inaccuracy (paragraphs [0050]-[0051]), a shading correction module to correct non-uniformity in epifluorescence illumination optics by scanning an area where no sample is present (paragraph [0141]), automatically determining regions of interest and disinterest (paragraph [0147]), and documenting artifacts in an image (paragraphs [0155]-[0156]) to provide: wherein the portion other than the plurality of individual separated compartments includes a part of a region other than the wells of the well plate. Doing so would have a reasonable expectation of successfully improving sensitivity of the analysis device by allowing for identification and correction of artifacts found in images from fluorescence imaging via scanning of areas where no sample is present, e.g. a region other than wells of the well plate.
Regarding claim 7, Chiu further teaches wherein the plurality of individual separated compartments (Figs. 3-4 shows a multiwell plate comprising wells; note that “the plurality of individual separated compartments” is not positively recited structurally and is interpreted as a functional limitation of the analysis device) comprise liquid droplets including the sample including nucleic acid and the reagent that have been distributed (paragraphs [0032]-[0033] teaches a droplet of a sample and PCR components are loaded onto the multiwell plate; note that “liquid droplets including the sample” is not positively recited structurally and is interpreted as a functional limitation of the analysis device), and wherein the set includes the liquid droplets and a dispersion medium (paragraphs [0032]-[0033] teaches a droplet of a sample, oil, and PCR components are loaded onto the multiwell plate; paragraphs [0059],[0061] teaches a variety of fluids or liquids, i.e. dispersion medium, are used to prepare an emulsion; note that “set” is not positively recited structurally and is interpreted as a functional limitation of the analysis device).
Regarding claim 8, Chiu further teaches the set including the portion, the portion other than the plurality of individual separated compartments includes a part of the dispersion medium (Figs. 3-4 shows a microwell plate and paragraphs [0032]-[0033] teaches a droplet of a sample, oil, and PCR components are loaded onto the multiwell plate; therefore, the microwell plate includes regions that include a part of the dispersion medium). Modified Chiu fails to teach: wherein the portion other than the plurality of individual separated compartments includes a part of the dispersion medium.
Crandall teaches systems and methods for standardizing fluorescence scanning instruments to a reference system by separating effects of drift and normalization (abstract). Crandall teaches correcting the sensitivity of a group of similar fluorescence microscopy imaging instruments, as well maintaining the sensitivity of individual instruments over time and/or environmental variations (paragraph [0002]). Crandall teaches imaging a region of a reference slide for normalization to increase correction inaccuracy (paragraphs [0050]-[0051]). Crandall teaches a shading correction module that operates to correct non-uniformity, i.e. artifact, in epifluorescence illumination optics and the scan camera (paragraph [0141]), wherein the shading correction module scans a small area of the sample of the slide at a particular location where no sample is present (paragraph [0141]); the image captures background fluorescence from any residual dye present; and an illumination correction profile is calculated by comparing average intensity of each pixel column (paragraph [0141]). Crandall teaches information from image data allows for automatically determining regions of interest and regions of interests (paragraph [0147]). Crandall teaches tools for annotating images, where annotations can be a useful to guide to document artifacts in an image, regions of interest in an image, or to identify a region of an image for reporting or quantitative analysis (paragraph [0155]), wherein the visualization and analysis module may use predetermined or otherwise identified image features to locate similar image data or patterns using content based image retrieval techniques (paragraph [0156]).
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 device of modified Chiu to incorporate Crandall’s teachings imaging a reference slide to increase correction inaccuracy (paragraphs [0050]-[0051]), a shading correction module to correct non-uniformity in epifluorescence illumination optics by scanning an area where no sample is present (paragraph [0141]), automatically determining regions of interest and disinterest (paragraph [0147]), and documenting artifacts in an image (paragraphs [0155]-[0156]) to provide: wherein the portion other than the plurality of individual separated compartments includes a part of the dispersion medium. Doing so would have a reasonable expectation of successfully improving sensitivity of the analysis device by allowing for identification and correction of artifacts found in images from fluorescence imaging via scanning of areas where no sample is present, e.g. a part of the dispersion medium.
Claims 4 and 9-14 are rejected under 35 U.S.C. 103 as being unpatentable over Chiu in view of Crandall as applied to claims 1 and 2 above, and further in view of Glezer et al. (US 20050142033 A1).
Regarding claim 4, modified Chiu fails to teach: wherein the instructions, when executed by the processor, further cause the information processing system to use a default mask based on a shape of each of the plurality of individual separated compartments in the set.
Glezer teaches luminescence test measurements using an assay module (abstract), wherein the measurements include the use of multi-well assay plates (paragraph [0088]). Glezer teaches creating and applying an image mask that correspond to a microplate layout being imaged (paragraph [0841]). Glezer teaches the user could be required to specify certain parameters in order to create the appropriate image mask for a particular microplate configuration; for example, a user could specify the following parameters to define the plate configuration: the plate type that defines the number of wells in the mask; well radius and well spacing that could be in absolute units or in units as a function of the predefined image size; well shape, such as circle, square, or the like; and the coordinates of the center mask in, for example, column (X) and row (Y) coordinates (paragraph [0842]). Glezer teaches an embodiment where the parameters could be automatically specified by a label or indicator on the plate (paragraph [0842]).
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 instructions of modified Chiu to incorporate the teachings of creating and applying an image mask for a microplate that defines wells of Glezer (paragraphs [0841]-[0842]) to provide: wherein the instructions, when executed by the processor, further cause the information processing system to use a default mask based on a shape of each of the plurality of individual separated compartments in the set. Doing so would have a reasonable expectation of successfully improving automated image analysis of desired locations of a well plate as taught by Glezer (paragraphs [00841]-[0842]).
Regarding claim 9, modified Chiu fails to teach: wherein the instructions, when executed by the processor, further cause the information processing system to determine the artifact component through estimation involving approximation using a basis function.
Chiu teaches using a ratio or function to correct for possible instrumental artifacts when analyzing an image (paragraph [0275]). Chiu teaches a corrected set of background pixels can be determined (paragraph [0276]).
Crandall teaches a shading correction module that operates to correct non-uniformity, i.e. artifact, in epifluorescence illumination optics and the scan camera (paragraph [0141]), wherein the shading correction module scans a small area of the sample of the slide at a particular location where no sample is present (paragraph [0141]); the image captures background fluorescence from any residual dye present; and an illumination correction profile is calculated by comparing average intensity of each pixel column (paragraph [0141]).
Glezer teaches luminescence test measurements using an assay module (abstract), wherein the measurements include the use of multi-well assay plates (paragraph [0088]). Glezer teaches luminescence data is acquired both before and after activation of the assay to obtain background readings that represent a dark condition, and dark values are acquired to remove effect of electronic drift, i.e. artifact, wherein an estimate of the dark signal can be generated using both measurements and a linear, quadratic or other model could be used to correct for any background light that may originate from, for example, the plate when a white microplate is used to increase collection efficiency (for example, due to phosphorescence) (paragraph [0856]).
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 instructions of modified Chiu to incorporate Chiu’s teachings of correcting for instrument artifacts and a corrected set of background pixels (paragraphs [0275]-[0276]), Crandall’s teachings of capturing background fluorescence for shading correction (paragraph [0141]) and Glezer’s teachings of estimation of a dark signal using linear models to correct for background light (paragraph [0856]) to provide: wherein the instructions, when executed by the processor, further cause the information processing system to determine the artifact component through estimation involving approximation using a basis function (e.g. a linear model). Doing so would have a reasonable expectation of successfully improving sensitivity of image analysis by removing effects of electronic drift or noise as taught by Glezer (paragraph [0856]).
Regarding claim 10, modified Chiu further teaches: wherein the basis function comprises a linear function (see above claim 9; the combination of Chiu in view of Glezer teaches using basis function, such as a linear model; Glezer, paragraph [0856], teaches estimation of a dark signal using linear models to correct for background light).
Regarding claim 11, modified Chiu fails to teach: wherein the instructions, when executed by the processor, further cause the information processing system to determine the artifact component through estimation using a regularization term.
Chiu teaches using a ratio or function to correct for possible instrumental artifacts when analyzing an image (paragraph [0275]). Chiu teaches a corrected set of background pixels can be determined (paragraph [0276]).
Crandall teaches a shading correction module that operates to correct non-uniformity, i.e. artifact, in epifluorescence illumination optics and the scan camera (paragraph [0141]), wherein the shading correction module scans a small area of the sample of the slide at a particular location where no sample is present (paragraph [0141]); the image captures background fluorescence from any residual dye present; and an illumination correction profile is calculated by comparing average intensity of each pixel column (paragraph [0141]).
Glezer teaches luminescence test measurements using an assay module (abstract), wherein the measurements include the use of multi-well assay plates (paragraph [0088]). Glezer teaches luminescence data is acquired both before and after activation of the assay to obtain background readings that represent a dark condition, and dark values are acquired to remove effect of electronic drift, i.e. artifact, wherein an estimate of the dark signal, i.e. regularization term, can be generated using both measurements and a linear, quadratic or other model could be used to correct for any background light that may originate from, for example, the plate when a white microplate is used to increase collection efficiency (for example, due to phosphorescence) (paragraph [0856]). Glezer teaches background luminescence used in correction can be adjusted as an exponential decay with a time constant, i.e. regularization term, or by using a linear approximation of an exponential decay (paragraph [0204]).
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 instructions of modified Chiu to incorporate Chiu’s teachings of correcting for instrument artifacts and a corrected set of background pixels (paragraphs [0275]-[0276]), Crandall’s teachings of capturing background fluorescence for shading correction (paragraph [0141]) and Glezer’s teachings of estimation of a dark signal using linear models to correct for background light (paragraph [0856]) and correction of background luminescence (paragraph [0204]) to provide: wherein the instructions, when executed by the processor, further cause the information processing system to determine the artifact component through estimation using a regularization term. Doing so would have a reasonable expectation of successfully improving sensitivity of image analysis by removing effects of electronic drift or noise as taught by Glezer (paragraph [0856]).
Regarding claim 12, modified Chiu fails to teach: wherein the instructions, when executed by the processor, further cause the information processing system to determine the artifact component through estimation involving approximation using a polynomial.
Chiu teaches using a ratio or function to correct for possible instrumental artifacts when analyzing an image (paragraph [0275]). Chiu teaches a corrected set of background pixels can be determined (paragraph [0276]).
Crandall teaches a shading correction module that operates to correct non-uniformity, i.e. artifact, in epifluorescence illumination optics and the scan camera (paragraph [0141]), wherein the shading correction module scans a small area of the sample of the slide at a particular location where no sample is present (paragraph [0141]); the image captures background fluorescence from any residual dye present; and an illumination correction profile is calculated by comparing average intensity of each pixel column (paragraph [0141]).
Glezer teaches luminescence test measurements using an assay module (abstract), wherein the measurements include the use of multi-well assay plates (paragraph [0088]). Glezer teaches luminescence data is acquired both before and after activation of the assay to obtain background readings that represent a dark condition, and dark values are acquired to remove effect of electronic drift, i.e. artifact, wherein an estimate of the dark signal can be generated using both measurements and a linear or quadratic model, i.e. polynomial, could be used to correct for any background light that may originate from, for example, the plate when a white microplate is used to increase collection efficiency (for example, due to phosphorescence) (paragraph [0856]).
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 instructions of modified Chiu to incorporate Chiu’s teachings of correcting for instrument artifacts and a corrected set of background pixels (paragraphs [0275]-[0276]), Crandall’s teachings of capturing background fluorescence for shading correction (paragraph [0141]) and Glezer’s teachings of estimation of a dark signal using linear or quadratic models to correct for background light (paragraph [0856]) to provide: wherein the instructions, when executed by the processor, further cause the information processing system to determine the artifact component through estimation involving approximation using a polynomial. Doing so would have a reasonable expectation of successfully improving sensitivity of image analysis by removing effects of electronic drift or noise as taught by Glezer (paragraph [0856]).
Regarding claim 13, modified Chiu fails to teach: wherein the instructions, when executed by the processor, further cause the information processing system to determine the artifact component through calculation using binning.
Chiu teaches using a ratio or function to correct for possible instrumental artifacts when analyzing an image (paragraph [0275]). Chiu teaches a corrected set of background pixels can be determined (paragraph [0276]).
Glezer teaches luminescence test measurements using an assay module (abstract), wherein the measurements include the use of multi-well assay plates (paragraph [0088]). Glezer teaches use of a CCD camera for image acquisition and/or analysis of a microplate typically requires that certain factors be taken into account and that certain measures be taken to insure precision, accuracy and or integrity of the data; wherein typical factors include defect correction, background image subtraction/correction, cosmic ray removal/correction, hardware binning, and software binning (paragraph [0823]). Glezer teaches another factor that typically is considered when using a CCD camera for image acquisition/analysis is the use of hardware binning to improve detection limits of the CCD camera (paragraph [0836]), wherein binning of CCD pixels in hardware can be used to reduce read noise per unit area and binning advantageously has the added benefit of faster readout time and reduced image data (paragraph [0836]).
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 instructions of modified Chiu to incorporate Chiu’s teachings of correcting for instrument artifacts and a corrected set of background pixels (paragraphs [0275]-[0276]) and Glezer’s teachings of estimation of the use of binning for hardware and software correction of imaging (paragraphs [0823],[0836]) to provide: wherein the instructions, when executed by the processor, further cause the information processing system to determine the artifact component through calculation using binning. Doing so would have a reasonable expectation of successfully improving precision, accuracy, and integrity of image analysis by reducing noise as taught by Glezer (paragraphs [0823],[0836]).
Regarding claim 14, modified Chiu fails to teach: wherein the information and the artifact component each include information on coordinates and a brightness at the coordinates, and wherein the instructions, when executed by the processor, further cause the information processing system to perform one of:
subtracting the brightness of the artifact component from the brightness of the information corresponding to the plurality of individual separated compartments; or
dividing the brightness of the information corresponding to the plurality of individual separated compartments by the brightness of the artifact component.
Chiu teaches identifying and locating droplets (paragraph [0035]-[0036]). Chiu teaches using a ratio or function to correct for possible instrumental artifacts when analyzing an image; and intensities can be background subtracted (paragraph [0275]). Chiu teaches a user-defined criteria can be used to exclude droplets with more than a specified fraction circles of their boundary in the interior of the Group on the grounds that the circle is an artifact due to noise in the image distorting the exterior boundary of the Group (paragraph [0253]). Chiu teaches image analysis software to find pixels in an image and the location and intensity were tracked (paragraphs [0235],[0336]-[0341]). Chiu teaches the average value of the background pixels or a multiple thereof can be subtracted from the pixel intensifies within the droplets before the fluorescence intensities of the indicator and reference intensities are compared; therefore determining whether a droplet contains a target molecule or not (paragraph [0219]).
Glezer teaches luminescence test measurements using an assay module (abstract), wherein the measurements include the use of multi-well assay plates (paragraph [0088]). Glezer teaches unintentional luminescence may be reduced and a data processing algorithm is used to subtract background luminescence (paragraph [0204]). Glezer teaches the computer has software for subtracting background light and/or eliminating cosmic ray induced artifacts and/or any defects in the photodetector (paragraph [0493]). Glezer teaches an advantageous way for background luminescence to be subtracted, wherein the apparatus is adapted to characterize the background of a given instrument and subtract those values from the processed chemiluminescence data (paragraph [0688]). Glezer teaches use of a CCD camera for image acquisition and/or analysis of a microplate typically requires that certain factors be taken into account and that certain measures be taken to insure precision, accuracy and or integrity of the data; wherein typical factors include defect correction and background image subtraction/correction (paragraph [0823]). Glezer teaches luminescence data is acquired both before and after activation of the assay to obtain background readings that represent a dark condition, and dark values are acquired to remove effect of electronic drift, i.e. artifact, wherein an estimate of the dark signal can be generated using both measurements and a linear, quadratic or other model could be used to correct for any background light and a dark signal estimate is subtracted from the measured signal and the resulting waveform is integrated in time to obtain the final reading (paragraph [0856]).
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 information processing system of modified Chiu to incorporate Chiu’s teachings of image analysis to track location and intensity of pixels and background subtraction of intensities (paragraphs [0035]-[0036],[0219] [0235], [0253],[0275],[0336]-[0341]) and Glezer’s teachings of correction of images and reduction of unintentional luminescence by background subtraction (paragraphs [0204],[0493], [0688], [0823], [0856]) to provide: wherein the information and the artifact component each include information on coordinates and a brightness at the coordinates, and wherein the instructions, when executed by the processor, further cause the information processing system to perform subtracting the brightness of the artifact component from the brightness of the information corresponding to the plurality of individual separated compartments. Doing so would have a reasonable expectation of successfully improving precision, accuracy, and integrity of image analysis by reducing defects in images and reducing noise as taught by Glezer (paragraphs [0204],[0493], [0688], [0823], [0856]).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Chiu in view of Crandall as applied to claim 2 above, and further in view of Hosseini et al. (US 20200368744 A1).
Regarding claim 15, modified Chiu fails to teach: wherein the reagent contains an effector protein, crRNA to be bound to the target nucleic acid, and a reporter molecule, wherein the crRNA is bound to the target nucleic acid to activate the effector protein, and wherein the labeler is configured to modify the reporter molecule by the activated effector protein to generate fluorescence.
Chiu teaches manipulation and analysis of species including genetic materials and proteins (paragraph [0051]). Chiu teaches an embodiment where the detectable agent is a Taqman probe, which hybridizes to the target DNA, and undergoes cleavage of a fluorescent reporter from the probe DNA during the next amplification step (paragraph [0149]).
Hosseini teaches an apparatus for rapid identification of a microorganism within a sampling device, wherein the device has a plurality of reaction chambers having reactive agent for reacting with the microorganism to indicate the presence of a microorganism, and a detector for detecting the presence of the microorganism (abstract). Hosseini teaches the invention automates CRISPR CAS 12 and/or CAS 13 methods (abstract). Hosseini teaches each chambers comprise crRNA for top infectious diseases and protein CAS 12 or CAS 13, i.e. effector protein (paragraph [0026]), wherein two fluorescent indicator molecules are attached to generic designed RNA (paragraph [0026]). Hosseini teaches a pathogen cause hybridization to take place and crRNA and the CAS protein gets activated, the protein cleaves a reporter RNA, and the fluorescently labeled reporter emits measurable fluorescence when cleaved by the RNase activity of CRISPR-Cas system; and this results in major changes in the radiated fluorescent when the reaction chamber excited with the pump laser (paragraph [0026]). Hosseini teaches a fluorescence labeled reporter RNA molecule, and if the hybridization takes place between the target genetic material and gRNA then CAS 13 gets activated, wherein fluorescent emission can be detected which indicates a pathogen in a chamber exists (paragraph [0112]). Hosseini teaches CRISPR based diagnostics is ample and very accurate; and read out is fast and it helps to get the accurate results very fast (paragraphs [0032]-[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 labeler of modified Chiu to incorporate Chiu’s teachings of manipulation and analysis of species including genetic materials and proteins, such as a detectable agent which hybridizes to a target DNA which cleaves a fluorescent reporter (paragraphs [0051],[0149]) and Hosseini’s teachings of rapid identification of a microorganism using CAS protein, crRNA, and a fluorescent reporter, wherein the fluorescently labeled reporter emits measurable fluorescence when cleaved by the RNase activity of CRISPR-Cas system (paragraphs [0026],[0112]) to provide: wherein the reagent contains an effector protein, crRNA to be bound to the target nucleic acid, and a reporter molecule, wherein the crRNA is bound to the target nucleic acid to activate the effector protein, and wherein the labeler is configured to modify the reporter molecule by the activated effector protein to generate fluorescence. Doing so would have a reasonable expectation of successfully improving accuracy and efficiency of diagnosis of a target nucleic acid as discussed by Hosseini (paragraphs [0032]-[0033],[0051],[0149]).
Response to Arguments
Applicant’s arguments, see page 8, filed 03/18/2026, with respect to the interpretations under 35 U.S.C. 112(f) and the rejections under 35 U.S.C. 112(a) and 112(b) have been fully considered and are persuasive. The interpretations under 35 U.S.C. 112(f) and the rejections under 35 U.S.C. 112(a) and 112(b) of 12/18/2025 have been withdrawn.
Applicant's arguments, see page 9, filed 03/18/2026, with respect to the rejections under 35 U.S.C. 101, have been fully considered but they are not persuasive. As discussed above in the rejections under 35 U.S.C. 101 in view of the amended claims, the claimed invention is directed to an abstract idea without significantly more.
Applicant's arguments, see pages 9-13, filed 03/18/2026, with respect to the rejections under 35 U.S.C. 103, specifically regarding claim 1, have been fully considered but they are not persuasive.
In response to applicant’s argument that Chiu fails to teach use of acquired image information as claimed (Remarks, pages 10-11), the examiner agrees. Specifically, as stated in the rejection of claim 1 under 35 U.S.C. 103, Chiu fails to teach: the processor is configured to: to determine an artifact component based on the extracted information; use the artifact component to correct the extracted information corresponding to the plurality of individual separated compartments; determine, based on information corresponding to each of the plurality of individual separated compartments after correction, whether a magnitude of a change in each individual separated compartment exceeds a predetermined threshold. However, note that Chiu in combination of Crandall is used to arrive at the missing limitations of Chiu.
In response to applicant's arguments against the references individually (Remarks, pages 9-13, regarding Chiu and Crandall), one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, Chiu provides teachings of correcting for possible instrumental artifacts when analyzing an image (paragraph [0275]), determining a corrected set of background pixels (paragraph [0276]), a criteria to exclude droplets due to artifact from noise (paragraph [0253]), and determining presence of absence of a target in each chamber based on a binary digital output (paragraph [0140]).
Crandall provides teachings and motivation of correcting the sensitivity of a group of similar fluorescence microscopy imaging instruments, as well maintaining the sensitivity of individual instruments over time and/or environmental variations (abstract; paragraph [0002]), imaging a reference slide to increase correction inaccuracy (paragraphs [0050]-[0051]), a shading correction module to correct non-uniformity in epifluorescence illumination optics (paragraph [0141]), scanning a small area of the sample of the slide at a particular location where no sample is present, i.e. a portion other than a sample location (paragraph [0141]), automatically determining regions of interest and disinterest from information from image data, i.e. acquired image information (paragraph [0147]), and documenting artifacts in an image for quantitative analysis based on images (paragraphs [0155]-[0156]).
It would have been obvious to one of ordinary skill in the art to have modified the processor of Chiu to incorporate Chiu’s teachings of correcting for possible instrumental artifacts when analyzing an image (paragraph [0275]), determining a corrected set of background pixels (paragraph [0276]), a criteria to exclude droplets due to artifact from noise (paragraph [0253]), and determining presence of absence of a target in each chamber (paragraph [0140]) and Crandall’s teachings of correcting fluorescence microscopy imaging instruments (abstract; paragraph [0002]), imaging a reference slide to increase correction inaccuracy (paragraphs [0050]-[0051]), a shading correction module to correct non-uniformity in epifluorescence illumination optics (paragraph [0141]), scanning a small area of the sample of the slide at a particular location where no sample is present, i.e. a portion other than a sample location (paragraph [0141]), automatically determining regions of interest and disinterest (paragraph [0147]), and documenting artifacts in an image (paragraphs [0155]-[0156]) to provide: the processor is configured to: to determine an artifact component based on the extracted information; use the artifact component to correct the extracted information corresponding to the plurality of individual separated compartments; determine, based on information corresponding to each of the plurality of individual separated compartments after correction, whether a magnitude of a change in each individual separated compartment exceeds a predetermined threshold. Doing so would have a reasonable expectation of successfully improving sensitivity of the analysis device (e.g. whether compartments exceed a threshold to determine the presence of a target nucleic acid) by allowing for identification and correction of artifacts that can cause noise found in images from fluorescence imaging.
Therefore, there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art for one of ordinary skill in the art to have modified the processor to provide using acquired image information (e.g. fluorescent images obtained by the fluorescent microscope of Chiu that include information to portions of the compartments and portions other than the compartment) to determine artifacts in the images in order to correct the images of the set of samples in wells of the microplate and therefore allow for improving the “determine” step as claimed, i.e. improving sensitivity of the analysis device (e.g. whether compartments exceed a threshold to determine the presence of a target nucleic acid) by allowing for identification and correction of artifacts that can cause noise found in images from fluorescence imaging.
It is suggested to further incorporate additional structural details of the device and/or further defining the specific “information” and “portion other than the plurality of individual separated components” to differentiate the claims from the prior art.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Modavis et al. (US 20090097013 A1) teaches a system for scan interrogation, including a biosensor for use in microplate image analysis (abstract). Modavis teaches as an imaging reader, it can use plates with chemically blocked (reference) sub-regions, or with patterns of protein within the wells (signal) sub-regions (paragraph [0083]). Modavis teaches a method for analyzing a biosensor to determine, for example, the presence and extent of biosensor binding, the method comprising: scanning an area of the biosensor; selecting a first-limit signal-region and a second-limit reference-region within the scanned area; scanning at least one sub-region within the first-limit signal-region and at least one sub-region within the second-limit reference-region; calculating a standard deviation for all .DELTA..lamda. points scanned in each sub-region; selecting all sampled points within each of the scanned sub-regions having a minimum standard deviation as a signal sub-region and as a reference sub-region (paragraphs [0048]-[0053]). Modavis teaches often a portion of each sensor can be chemically or physically blocked to prevent binding, to act as a reference signal for removing false wavelength shifts that arise from environmental changes such as bulk refractive index changes, material drift, non-specific compound binding, thermal events, or like events (paragraph [0072]). Modavis teaches the disclosed 2D method uses 2D regions for both the signal and reference regions in which the optimum signal and reference regions are found by searching (paragraph [0102]).
Fontaine et al. (US 20060106557 A1) teaches a system for self-referencing a sensor used to detect a biomolecular binding event (abstract). Fontaine teaches the image of the response of the sensor 102 was divided by the computer 118 into two regions including a reference region 116a and a detection region 116b (paragraph [0032], FIG. 6A).
Cunningham et al. (US 20090079976 A1) teaches sensors for microwell plates (abstract). Cunningham teaches images are obtained and grids of sensor regions are selected, wherein each grid can be designated as "active" or "reference", and PWV shifts from reference regions can be associated with any desired active region for subtraction of common-mode artifacts (paragraph [0104]). Cunningham teaches the sensors of this disclosure allows reference channels to be incorporated in close physical proximity to active channels for highly accurate correction of temperature or buffer variability; and because active and reference regions are small, many reference regions may be easily incorporated onto a single chip (paragraph [0115]).
Ewart et al. (US 20130161190 A1) teaches a test device for performing optical assays (abstract). Ewart teaches locating a color reference area or areas on the assay substrate adjacent to the capture zone eliminates or greatly reduces the need for homogeneous excitation (paragraph [0073]). Ewart teaches the image capture software can identify each spot and determine from the spot intensity, for example, one or more of the presence or absence of the analyte, analyte concentration, or a calibration signal; and adjacent areas of the test device that are accessible to the imager can also provide a flat field correction grid which acts as an integrated internal assay set of reference spots (paragraph [0095]).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
Prosecution Insights