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/Effective Filing Date
The present application was filed on July 24, 2023 and does not claim the benefit of any domestic applications or priority to any foreign applications.
Election/Restrictions
Claims 27-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim 13 is withdrawn from further consideration as being drawn to a nonelected species.
Election was made without traverse in the reply filed on March 17, 2026.
Claim Status
Claims 1-34 are currently pending in the application. Claims 13 and 27-34 were withdrawn without traverse in the reply filed on March 17, 2026. Claims 1-12 and 14-26 are under examination.
Specification
The abstract of the disclosure is objected to because it includes legal phraseology often used in patent claims. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Claim Objections
Claim 20 is objected to because of the following informalities: Apparent omission of an article “a” in line 3: “…wherein the resulting analyte is labeled with a fluorophore for fluorescence detection.”
Claim 22 is objected to because of the following informalities: singular noun used in place of a plural number of seconds: “…IT-N, range from 0.01 millisecond to 10 seconds.”
Appropriate corrections are required.
Claim Interpretation
Claims 1 and 6 (and dependent claims thereof) recite the phrase “duration(s) associated with a light signal associated with the presence of…analyte”. A light signal associated with the presence of an analyte has been interpreted as encompassing any light signal above a lower limit of detection, without limitation to a particular linear range or upper limit of quantitation of a particular assay or detector (as required, for example, by claim 17).
Claim 24 recites the phrase “wherein the bioassay comprises immunoassays or molecular assays”.
It is noted that “immunoassays” encompasses unelected species.
There is no specific limiting definition provided in the specification for the claim term “molecular assays”. The claim term “molecular assays” has been interpreted according to the definition known in the art: “Molecular assays currently in use are based on detection of the nucleic acid of the targeted pathogen by one of the following procedures: target amplification, signal amplification, and nonamplification methods.” Das et al., “The new frontier of diagnostics: Molecular assays and their role in infection prevention and control” American Journal of Infection Control 45 (2017) 158-69.
Therefore, the claim term “molecular assay” has been interpreted as “methods for detection of nucleic acids”.
Claim 19 depends from claim 18 and recites further limitations to “each barcoded solid substrate…”. It is noted that the alternative “solid substrates”: “digitally coded beads”, “color coded microbeads”, and “microarray settings on a planar surface” encompassed by claim 18 do not recite “barcode(s)”. Therefore, the further limitations recited by claim 19 are interpreted as applying only to the species of “solid substrates” that is “barcoded magnetic beads”.
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.
Claims 1-12 and 14-26 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1 and 6 recite the method steps: “…identifying, by the one or more processors, a first image…captured at a duration within the first range of integration duration associated with the light signal associated with the presence of the first analyte; and analyzing, by the one or more processors, the first image to determine the presence of the first analyte…”
It is unclear what is required by the “analyzing… the first image to determine the presence of the first analyte” step because the preceding step already requires “identifying a first image (having a) light signal associated with the presence of the first analyte” (i.e. selecting an image based on the presence of the light signal that is indicative of the presence of the first analyte). Therefore, the preceding “identifying” step requires “determining the presence of the first analyte” because images are “identified” (i.e. selected) based on the presence of the light signal (i.e. the first analyte).
Subsequently iterated steps for a “second analyte of the plurality of analytes” are similarly unclear.
Claim 2 recites the step “wherein the first range is calculated based on a signal-concentration response curve for the first analyte”. It is unclear whether the range of integration durations are calculated by the one or more processors based solely upon the observed variation in signal depending upon variation in the concentration of the first analyte (i.e. a signal-concentration response curve), or if something else is required, such as to observe the variation in signal at each point on the signal-concentration response curve dependent upon a second independent variable (i.e. integration time).
Claims 9-11, which depend upon “the method of claim 6”, recite the limitation "the beads" in line 1 of each claim. There is insufficient antecedent basis for this limitation in the claim because independent claim 6 does not recite “a bead”.
Claim 6 recites “binding pair members”. Claim 7 depends on claim 6 and recites “binding pair members are bound to a solid substrate”. Claim 8 depends on claim 7 and recites “the solid substrate comprises a plurality of beads”.
In the interest of compact prosecution, claims 9-11 have been interpreted as being dependent on claim 8, which provides antecedent basis for “a bead”, rather than directly upon claim 6 as presently claimed.
Claim 18 recites the phrase “the solid substrates include one or more of …, or microarray settings on a planar surface”. It is unclear what structural limitations of “solid substrate” are required by “microarray settings”. It is unclear whether “microarray settings” is meant to mean: a) any application that is a microarray (i.e. the term “settings” is used to mean a general environment or locale), b) some unspecified microarray configuration (i.e. “settings” is used to mean some unspecified option(s) or control(s) for a particular device comprising a microarray), c) a mounting on a microarray to which the plurality of analytes are attached, or d) something else.
Claim 20 is indefinite because it does not end with a period. As provided in MPEP 608, each claim begins with a capital letter and ends with a period.
Claim 20 depends from claim 19, which requires that “each barcoded solid substrate is immobilized with a specific biomolecular probe which can react with a specific analyte…”. Claim 20 further limits “the resulting analyte is labeled with fluorophore…”.
It is unclear whether claim 20 requires that: a) the barcoded probe comprises a fluorophore that reacts with the specific analyte to produce the “resulting” fluorophore-labeled analyte, b) the analyte has been pre-labeled with fluorophore such that after the probe reacts with the specific analyte, the “resulting” probe-bound analyte is labeled with a fluorophore, c) whether there is an unclaimed additional step of labeling the “resulting” analyte with fluorophore after the probe reacts with the specific analyte (such as in so-called “sandwich” assays known in the art), or d) something else.
Claim 21 recites the limitation “…wherein said a plurality of signals, N=2 - 5 signals.” This claim term has been interpreted as expressing a range of numbers of signals in the plurality encompassing 2, 3, 4, or 5 signals (i.e. not the impossibility of negative three signals obtained by evaluating the recited mathematical expression). The claim is rendered indefinite because it is unclear whether “N=” is intended to mean that the range of numbers of signals in the plurality “comprises between 2 and 5 signals” (i.e. there are between at least 2 and at least 5 signals in the plurality), or “consists of between 2 and 5 signals” (i.e. the plurality is only 2, only 3, only 4, or only 5 signals). The ordinary artisan would not be apprised of the metes and bounds of the claim because of this ambiguity in the claim language.
Claims 23, 24, and 25 recite “detecting a signal associated with the quantitative measurement of an analyte in a multiplex bioassay comprising for multiplex bioassays of claim 17…” (claim 23) “detecting a signal associated with the quantitative measurement of an analyte in a multiplex bioassay comprising multiplex bioassays of claim 17…” (claim 24) and “detecting a signal associated with the quantitative measurement of an analyte in a multiplex bioassay comprising in multiplex bioassays of claim 17…” (claim 25). It is unclear whether the claim phrase “comprising for” is a typographical error for “a multiplex bioassay comprising multiplex bioassays…”, a typographical error for “comprising four multiplex bioassays…”, or whether the phrase “comprising for multiplex bioassays” is unintentionally inserted and the claim is meant to recite: “detecting a signal associated with the quantitative measurement of an analyte in a multiplex bioassay of claim 17…”
Claim 23 depends from claim 17 and further requires “wherein said multiple signals are obtained from optical sensors, comprising CCD, CMOS camera, photo diode, and photomultiplier tubes.” It is unclear whether the claim is intended to recite types of optical sensors in the alternative (i.e. “CCD, CMOS camera, photo diode, or photomultiplier tubes”), or whether the claim is meant to require the combination of all four listed types of optical sensors. If the claim requires the combination of optical sensors, it is unclear whether the claim requires that each of the multiple signals are obtained by said combination (i.e. signal 1 is obtained by CCD, CMOS camera, photo diode, and photomultiplier tubes, etc.) or whether the claim requires that the multiple signals are obtained by different optical sensors (e.g. signal 1 by CCD, signal 2 by CMOS camera, signal 3 by photo diode, signal 4 by photomultiplier tubes, etc.).
Claims 2-5, 7-16, and 18-26 are rendered indefinite because the include the indefinite limitations of the claim(s) from which they depend.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-8, 11, 12, and 14-26 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Liu et al., US 2012/0202714 A1 (published August 9, 2012).
Regarding claim 1, Liu et al. teach methods comprising conducting bioassays for detecting multiple analytes (Liu et al., paragraph 0007-0009 and 0015) comprising the steps: providing a light source wherein an emission signal indicates the presence/quantity of a particular analyte (Liu et al., paragraph 0016 and 0068-0069), capturing a plurality of images of the plurality of analytes at a plurality of durations, determining a range of integration durations associates with a light signal associated with the analyte, identifying an image captured at a duration within the range of integration durations, and analyzing the image to determine the presence of an analyte: “a biosensor system… integrates analyte signal to increase the signal-to-noise ratio of the detection of analytes. Integration may be performed by increasing the frame collection time of the detector for the light arising from the array… the image sensor is operated in a far slower regime… to integrate the array signal impinging on the sensor… collection time… may be controlled… to integrate analyte detection…increas[ing] signal to noise ratio and enhance[ing] detection of analytes, allowing a lower concentration of analyte to be detected (Liu et al., paragraph 0069 and 0079-0080).
Regarding claim 2, Liu et al. further teach a standard curve can be used to generate a dose-response curve (i.e. a signal-concentration response curve) to determine an unknown concentration of an analyte (i.e. the range of integration durations are calculated based on a signal-concentration response curve) (Liu et al., paragraph 0100).
Regarding claim 3, Liu et al. teach the light source is a light emitting diode (Liu et al., paragraph 0087) and the light-emitting label encompasses fluorescent dyes such as Cy3, Cy5, Alexa Fluor 488, fluorescein, rhodamine, Texas red… ethidium bromide…, etc. (Liu et al., paragraph 0083). It is noted that several of these labels including Cy3, Cy5, Alexa Fluor 488, fluorescein, rhodamine, Texas red are excited by visible light (i.e. the light source is visible light).
Regarding claim 4, Liu et al. teach the light source is a light emitting diode (Liu et al., paragraph 0087) and the light-emitting label encompasses fluorescent dyes such as Cy3, Cy5, Alexa Fluor 488, fluorescein, rhodamine, Texas red… ethidium bromide…, etc. (Liu et al., paragraph 0083). It is noted that ethidium bromide is excited by ultraviolet light (i.e. the light source is ultraviolet light).
Regarding claim 5, Liu et al. teach optical detection of the analyte is accomplished by binding to a (detectable label)-conjugated probe (i.e. the assay is a specific binding assay) (Liu et al., paragraph 0083).
Regarding claim 6, Liu et al. teach methods of conducting specific binding assays for multiple analytes wherein the presence/quantity of each analyte is associated with a light signal (Liu et al., paragraph 0007-0009 and 0015) comprising the steps: contacting a sample comprising the analytes with specific binding pair members that bind to specific analytes of the multiple analytes, wherein stably bound probes are detectable by providing a light source wherein an emission signal indicates the presence/quantity of a particular analyte (Liu et al., paragraph 0016 and 0068-0069). Liu et al. further teach determining the presence/quantity of analytes based upon the emission of light signals from the stably bound probe:analyte complexes comprising: capturing a plurality of images of the plurality of analytes at a plurality of durations, determining a range of integration durations associates with a light signal associated with the analyte, identifying an image captured at a duration within the range of integration durations, and analyzing the image to determine the presence of an analyte: “a biosensor system… integrates analyte signal to increase the signal-to-noise ratio of the detection of analytes. Integration may be performed by increasing the frame collection time of the detector for the light arising from the array… the image sensor is operated in a far slower regime… to integrate the array signal impinging on the sensor… collection time… may be controlled… to integrate analyte detection…increas[ing] signal to noise ratio and enhance[ing] detection of analytes, allowing a lower concentration of analyte to be detected (Liu et al., paragraph 0069 and 0079-0080).
Regarding claim 7, Liu et al. teach an array of probes are coupled to a polymer (i.e. binding pair members are bound to a solid substrate) (Liu et al., paragraph 0007-0009).
Regarding claim 8, Liu et al. teach the solid substrate comprises a plurality of beads. Liu et al. teach biomolecular probes are conjugated to a polymer (Liu et al., paragraphs 0027-0029) and the polymer can be a solid in the form of beads (Liu et al., paragraph 0031).
Regarding claim 11, Liu et al. teach the label or label species to which capable of producing a detectable signal indicative of the presence of a target polynucleotide (i.e. a binding pair member) can be magnetic particles (Liu et al., paragraph 0016)
Regarding claim 12, Liu et al. teach two or more specific binding pair members are bound to different locations on an array (i.e. a solid substrate) (Liu et al., paragraph 0069-0070).
Regarding claim 14, Liu et al. teach the specific binding assay is a nucleic acid hybridization assay (Liu et al., paragraph 0053 and 0055).
Regarding claim 15, Liu et al. teach the hybridization assay is a DNA hybridization assay (Liu et al., paragraph 0053 and 0096).
Regarding claim 16, Liu et al. teach the hybridization assay is an RNA hybridization assay (Liu et al., paragraph 0053 and 0096).
Regarding claim 17, Liu et al. teach methods of conducting specific binding assays for multiple analytes wherein the quantity of each analyte (Liu et al., paragraph 0100) is associated with a light signal (Liu et al., paragraph 0007-0009 and 0015) comprising the steps: contacting a sample comprising the analytes with specific binding pair members that bind to specific analytes of the multiple analytes, wherein stably bound probes are detectable by providing a light source wherein an emission signal indicates the presence/quantity of a particular analyte (Liu et al., paragraph 0016 and 0068-0069). Liu et al. further teach determining the presence/quantity of analytes based upon the emission of light signals from the stably bound probe:analyte complexes comprising: capturing a plurality of images of the plurality of analytes at a plurality of durations, determining a range of integration durations associates with a light signal associated with the analyte, identifying an image captured at a duration within the range of integration durations, and analyzing the image to determine the presence of an analyte: “a biosensor system… integrates analyte signal to increase the signal-to-noise ratio of the detection of analytes. Integration may be performed by increasing the frame collection time of the detector for the light arising from the array… the image sensor is operated in a far slower regime… to integrate the array signal impinging on the sensor… collection time… may be controlled… to integrate analyte detection…increas[ing] signal to noise ratio and enhance[ing] detection of analytes, allowing a lower concentration of analyte to be detected (Liu et al., paragraph 0069 and 0079-0080). Liu et al. further teach identifying each analyte by capturing a plurality of signals at a series of integration durations for each analyte, selecting an integration duration within a linear range, normalizing and combining the plurality of light signals by their different integration times to expand the linear range of the analyte(s) (Liu et al., paragraph 0108 and 0118); see also example 7, Liu et al., paragraph 0132-0138).
Regarding claims 18 and 19, Liu et al. teach the solid substrates are microarrays on a planar surface (Liu et al., paragraphs 0015 and 0028) and each of the immobilized probes react with a particular analyte of the plurality of analytes and not other analytes (Liu et al., paragraph 0003 and 0057). It is noted that limitations upon “each barcoded solid substrate” recited by claim 19 limits the alternative embodiment of claim 18 wherein the solid substrates include “barcoded magnetic beads”.
Regarding claim 20, Liu et al. teach the analyte is labeled with a fluorophore after binding to the specific biomolecular probe (Liu et al., paragraph 0083).
Regarding claim 21, Liu et al. teach up to about 100,000 groups of probes can be immobilized to the substrate, wherein each group of probes is specific to a particular nucleic acid sequence (i.e. the plurality of signals comprises 2-5 signals) (Liu et al., paragraphs 0056-0057).
Regarding claim 22, Liu et al. teach the series of optical integration durations ranges from about 50 to about 600 milliseconds (i.e. within the claimed range of 0.01 millisecond to 10 seconds) (Liu et al., paragraph 0118).
Regarding claim 23, Liu et al. teach the optical sensors comprise CCD, photomultiplier tube, photo diode (Liu et al., paragraph 0090), and CMOS camera (Liu et al., paragraph 0087).
Regarding claim 24, Liu et al. teach the multiplex bioassay comprises molecular assays (i.e. nucleic acid assays) (Liu et al., paragraph 0023 and 0027).
Regarding claim 25, Liu et al. teach the light signals are fluorescence or chemiluminescence signals (Liu et al., paragraph 0083).
Regarding claim 26 teach up to about 100,000 groups of probes can be immobilized to the substrate, wherein each group of probes is specific to a particular nucleic acid sequence (i.e. the number of analytes comprises 2-4096 signals) (Liu et al., paragraphs 0056-0057).
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.
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 1-12, and 14-26 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al., US 2012/0202714 A1 (published August 9, 2012) in view of Gunderson et al. US 2022/0214350 A1 (published July 7, 2022).
Regarding claim 1, Liu et al. teach methods comprising conducting bioassays for detecting multiple analytes (Liu et al., paragraph 0007-0009 and 0015) comprising the steps: providing a light source wherein an emission signal indicates the presence/quantity of a particular analyte (Liu et al., paragraph 0016 and 0068-0069), capturing a plurality of images of the plurality of analytes at a plurality of durations, determining a range of integration durations associates with a light signal associated with the analyte, identifying an image captured at a duration within the range of integration durations, and analyzing the image to determine the presence of an analyte: “a biosensor system… integrates analyte signal to increase the signal-to-noise ratio of the detection of analytes. Integration may be performed by increasing the frame collection time of the detector for the light arising from the array… the image sensor is operated in a far slower regime… to integrate the array signal impinging on the sensor… collection time… may be controlled… to integrate analyte detection…increas[ing] signal to noise ratio and enhance[ing] detection of analytes, allowing a lower concentration of analyte to be detected (Liu et al., paragraph 0069 and 0079-0080).
Regarding claim 2, Liu et al. further teach a standard curve can be used to generate a dose-response curve (i.e. a signal-concentration response curve) to determine an unknown concentration of an analyte (i.e. the range of integration durations are calculated based on a signal-concentration response curve) (Liu et al., paragraph 0100).
Regarding claim 3, Liu et al. teach the light source is a light emitting diode (Liu et al., paragraph 0087) and the light-emitting label encompasses fluorescent dyes such as Cy3, Cy5, Alexa Fluor 488, fluorescein, rhodamine, Texas red… ethidium bromide…, etc. (Liu et al., paragraph 0083). It is noted that several of these labels including Cy3, Cy5, Alexa Fluor 488, fluorescein, rhodamine, Texas red are excited by visible light (i.e. the light source is visible light).
Regarding claim 4, Liu et al. teach the light source is a light emitting diode (Liu et al., paragraph 0087) and the light-emitting label encompasses fluorescent dyes such as Cy3, Cy5, Alexa Fluor 488, fluorescein, rhodamine, Texas red… ethidium bromide…, etc. (Liu et al., paragraph 0083). It is noted that ethidium bromide is excited by ultraviolet light (i.e. the light source is ultraviolet light).
Regarding claim 5, Liu et al. teach optical detection of the analyte is accomplished by binding to a (detectable label)-conjugated probe (i.e. the assay is a specific binding assay) (Liu et al., paragraph 0083).
Regarding claim 6, Liu et al. teach methods of conducting specific binding assays for multiple analytes wherein the presence/quantity of each analyte is associated with a light signal (Liu et al., paragraph 0007-0009 and 0015) comprising the steps: contacting a sample comprising the analytes with specific binding pair members that bind to specific analytes of the multiple analytes, wherein stably bound probes are detectable by providing a light source wherein an emission signal indicates the presence/quantity of a particular analyte (Liu et al., paragraph 0016 and 0068-0069). Liu et al. further teach determining the presence/quantity of analytes based upon the emission of light signals from the stably bound probe:analyte complexes comprising: capturing a plurality of images of the plurality of analytes at a plurality of durations, determining a range of integration durations associates with a light signal associated with the analyte, identifying an image captured at a duration within the range of integration durations, and analyzing the image to determine the presence of an analyte: “a biosensor system… integrates analyte signal to increase the signal-to-noise ratio of the detection of analytes. Integration may be performed by increasing the frame collection time of the detector for the light arising from the array… the image sensor is operated in a far slower regime… to integrate the array signal impinging on the sensor… collection time… may be controlled… to integrate analyte detection…increas[ing] signal to noise ratio and enhance[ing] detection of analytes, allowing a lower concentration of analyte to be detected (Liu et al., paragraph 0069 and 0079-0080).
Regarding claim 7, Liu et al. teach an array of probes are coupled to a polymer (i.e. binding pair members are bound to a solid substrate) (Liu et al., paragraph 0007-0009).
Regarding claim 8, Liu et al. teach the solid substrate comprises a plurality of beads. Liu et al. teach biomolecular probes are conjugated to a polymer (Liu et al., paragraphs 0027-0029) and the polymer can be a solid in the form of beads (Liu et al., paragraph 0031).
Regarding claims 9 and 10, Liu et al. do not explicitly teach the beads are labeled, or that said labels are a bar code.
However, Gunderson et al. teach methods for conducting specific binding assays for multiple analytes comprising hybridizing target nucleic acids (i.e. individual analytes of the plurality of analytes) to probes that are immobilized to solid supports (Gunderson et al., paragraph 0028, 0099) wherein the solid supports can comprise beads, microbeads, an array, or magnetic beads (Gunderson et al., paragraph 0081) and the beads can further comprise barcode labels that are useful for the purpose of highly multiplexed analysis of analytes of different abundance classes (Gunderson et al., paragraphs 0164, 0169).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention for one of ordinary skill in the art to have modified the methods taught by Liu et al. comprising detection of multiple analytes using a specific binding assay wherein the specific binding pair members for the analytes are coupled to polymer beads with the teachings of Gunderson et al. that inclusion of binding-pair member specific barcode labels on the particular beads to which a specific binding pair member is coupled is useful when assaying analytes of different abundance classes (i.e. analytes having very different concentrations/dynamic ranges) (Gunderson et al., paragraph 0164).
Regarding claim 11, Liu et al. teach the label or label species to which capable of producing a detectable signal indicative of the presence of a target polynucleotide (i.e. a binding pair member) can be magnetic particles (Liu et al., paragraph 0016)
Regarding claim 12, Liu et al. teach two or more specific binding pair members are bound to different locations on an array (i.e. a solid substrate) (Liu et al., paragraph 0069-0070).
Regarding claim 14, Liu et al. teach the specific binding assay is a nucleic acid hybridization assay (Liu et al., paragraph 0053 and 0055).
Regarding claim 15, Liu et al. teach the hybridization assay is a DNA hybridization assay (Liu et al., paragraph 0053 and 0096).
Regarding claim 16, Liu et al. teach the hybridization assay is an RNA hybridization assay (Liu et al., paragraph 0053 and 0096).
Regarding claim 17, Liu et al. teach methods of conducting specific binding assays for multiple analytes wherein the quantity of each analyte (Liu et al., paragraph 0100) is associated with a light signal (Liu et al., paragraph 0007-0009 and 0015) comprising the steps: contacting a sample comprising the analytes with specific binding pair members that bind to specific analytes of the multiple analytes, wherein stably bound probes are detectable by providing a light source wherein an emission signal indicates the presence/quantity of a particular analyte (Liu et al., paragraph 0016 and 0068-0069). Liu et al. further teach determining the presence/quantity of analytes based upon the emission of light signals from the stably bound probe:analyte complexes comprising: capturing a plurality of images of the plurality of analytes at a plurality of durations, determining a range of integration durations associates with a light signal associated with the analyte, identifying an image captured at a duration within the range of integration durations, and analyzing the image to determine the presence of an analyte: “a biosensor system… integrates analyte signal to increase the signal-to-noise ratio of the detection of analytes. Integration may be performed by increasing the frame collection time of the detector for the light arising from the array… the image sensor is operated in a far slower regime… to integrate the array signal impinging on the sensor… collection time… may be controlled… to integrate analyte detection…increas[ing] signal to noise ratio and enhance[ing] detection of analytes, allowing a lower concentration of analyte to be detected (Liu et al., paragraph 0069 and 0079-0080). Liu et al. further teach identifying each analyte by capturing a plurality of signals at a series of integration durations for each analyte, selecting an integration duration within a linear range, normalizing and combining the plurality of light signals by their different integration times to expand the linear range of the analyte(s) (Liu et al., paragraph 0108 and 0118); see also example 7, Liu et al., paragraph 0132-0138).
Regarding claims 18 and 19, Liu et al. teach the solid substrates are microarrays on a planar surface (Liu et al., paragraphs 0015 and 0028) and each of the immobilized probes react with a particular analyte of the plurality of analytes and not other analytes (Liu et al., paragraph 0003 and 0057). It is noted that limitations upon “each barcoded solid substrate” recited by claim 19 limits the alternative embodiment of claim 18 wherein the solid substrates include “barcoded magnetic beads”.
Regarding claim 20, Liu et al. teach the analyte is labeled with a fluorophore after binding to the specific biomolecular probe (Liu et al., paragraph 0083).
Regarding claim 21, Liu et al. teach up to about 100,000 groups of probes can be immobilized to the substrate, wherein each group of probes is specific to a particular nucleic acid sequence (i.e. the plurality of signals comprises 2-5 signals) (Liu et al., paragraphs 0056-0057).
Regarding claim 22, Liu et al. teach the series of optical integration durations ranges from about 50 to about 600 milliseconds (i.e. within the claimed range of 0.01 millisecond to 10 seconds) (Liu et al., paragraph 0118).
Regarding claim 23, Liu et al. teach the optical sensors comprise CCD, photomultiplier tube, photo diode (Liu et al., paragraph 0090), and CMOS camera (Liu et al., paragraph 0087).
Regarding claim 24, Liu et al. teach the multiplex bioassay comprises molecular assays (i.e. nucleic acid assays) (Liu et al., paragraph 0023 and 0027).
Regarding claim 25, Liu et al. teach the light signals are fluorescence or chemiluminescence signals (Liu et al., paragraph 0083).
Regarding claim 26 teach up to about 100,000 groups of probes can be immobilized to the substrate, wherein each group of probes is specific to a particular nucleic acid sequence (i.e. the number of analytes comprises 2-4096 signals) (Liu et al., paragraphs 0056-0057).
Conclusion
No claim is allowed.
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/Z.M.T./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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