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 Arguments
The Amendment filed 08/14/2025 has been entered. Claims 1-15 remain pending in the application. Applicant’s amendments to the claims have overcome each and every 112(b) rejections previously set forth in the Non-Final Office Action mailed 04/14/2025.
Claim Objections
Claim 1 is objected to because of the following informalities: In line 19, it is suggested to recite “a second image surface” as “a second imaging surface” for consistency of terminology to “the second imaging surface” in the last paragraph and in claim 2. Appropriate correction is required.
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.
Claims 1-11 and 13-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kain (US 20080117425 A1; cited in the IDS filed 02/18/2022).
Regarding claim 1, Kain teaches a system (Fig. 14) for monitoring a PCR-reaction in a microfluidic reactor (interpreted as an intended use of the claimed system, see MPEP 2114; Fig. 14 teaches the system 118 comprising CCD sensors 164,164 that monitors a microarray 14, and paragraph [0043] teaches the microarray includes a support for DNA probes; therefore, the system is structurally capable of monitoring a PCR-reaction as claimed at a later time; note that “a microfluidic reactor” is not positively recited structurally), the system comprising:
a first light source (Fig. 14, laser 120) illuminating the microfluidic reactor (interpreted as a functional limitation of the first light source; Fig. 14 shows laser 120 illuminating a microarray 14, therefore the laser is capable of performing the functional limitation) through a first excitation light filter (Fig. 14, filter 128) providing light of a first excitation wavelength range (paragraphs [0078]-[0080] teach laser 120 and filter wheel 128 provides for a wavelength) adapted to excite a first fluorophore in the microfluidic reactor (interpreted as a functional limitation of the first light source; paragraphs [0078]-[0080] teach laser 120 and filter wheel 128 provides for a wavelength depending on the dye; paragraph [0082] teaches dyes are excited by the excitation beam; therefore, the laser 120 and filter wheel 128 provides for a wavelength that is capable of exciting a first fluorophore in a microfluidic reactor), whereby fluorescent light of a first emission wavelength range is emitted by the first fluorophore (interpreted as an intended use of the first light source; note that the “first fluorophore” is not positively recited structurally; paragraphs [0065],[0082] teaches multiple fluorophores or fluorescent dyes that produce different emission signals when excited at different wavelengths),
a second light source (Fig. 14, laser 122) illuminating the microfluidic reactor (interpreted as a functional limitation of the second light source; Fig. 14 shows laser 122 illuminating a microarray 14, therefore the laser is capable of performing the functional limitation) through a second excitation light filter (Fig. 14, filter 130) providing light of a second excitation wavelength range (paragraphs [0078]-[0080] teach laser 122 and filter wheel 130 provides for a wavelength) adapted to excite a second fluorophore in the microfluidic reactor (interpreted as a functional limitation of the second light source; paragraphs [0078]-[0080] teach laser 122 and filter wheel 130 provides for a wavelength depending on the dye; paragraph [0082] teaches dyes are excited by the excitation beam; therefore, the laser 122 and filter wheel 130 provides for a wavelength that is capable of exciting a second fluorophore in a microfluidic reactor), whereby fluorescent light of a second emission wavelength range is emitted by the second fluorophore (interpreted as an intended use of the first light source; note that the “second fluorophore” is not positively recited structurally; paragraphs [0065],[0082] teaches multiple fluorophores or fluorescent dyes that produce different emission signals when excited at different wavelengths),
a first emission filter (Fig. 14, one of the filter wheel 158) adapted to transmit fluorescent light of the first emission wavelength range and block fluorescent light of the second emission wavelength range (interpreted as a functional limitation of the first emission filter; paragraph [0082] teaches the bandpass filter wheel filters the beam to obtain a desired output wavelength, wherein light from the microarray is split and directed through different bandpass filter wheels; paragraph [0065] teaches different emissions signals can be collected from fluorophores that produce different emission signals; therefore, one of the bandpass filter wheels is capable of transmitting a first emission wavelength range while blocking a second emission wavelength range in order to collect the desired different emission signals),
a second emission filter (Fig. 14, one of the filter wheel 158) adapted to transmit fluorescent light of the second emission wavelength range and block fluorescent light of the first emission wavelength range (interpreted as a functional limitation of the second emission filter; paragraph [0082] teaches the bandpass filter wheel filters the beam to obtain a desired output wavelength, wherein light from the microarray is split and directed through different bandpass filter wheels; paragraph [0065] teaches different emissions signals can be collected from fluorophores that produce different emission signals; therefore, one of the bandpass filter wheels is capable of transmitting a second emission wavelength range while blocking a first emission wavelength range in order to collect the desired different emission signals),
first imaging optics (Fig. 14, one of lens 160) adapted to image the microfluidic reactor onto a first imaging surface (interpreted as a functional limitation of the first imaging optics; Fig. 14 teach one of lens 160 imaging the microarray 14 onto a surface of one CCD sensor 164 or 166), by fluorescent light of the first emission wavelength range transmitted through the first emission filter (Fig. 14 and paragraph [0082] teach output of fluorescence from the dyes is transmitted through one of the filters 158 onto a surface of one CCD sensor 164 or 166), whereby the image on the first imaging surface is indicative of a first reaction parameter of the PCR-reaction associated with the first fluorophore (interpreted as an intended use of first imaging optics; note that the “PCR-reaction” and “first fluorophore” are not positively recited structurally; paragraphs [0065],[0082] teaches multiple fluorophores or fluorescent dyes that produce different emission signals when excited at different wavelengths and Fig. 14 shows the emitted light is directed onto CCD sensors 164 and 166; paragraph [0046] teaches fluorescence due to the presence of dyes are indicative of an interaction of a target with a site, i.e. a parameter of a reaction; therefore, the first imaging optics is capable of the imaging as claimed), and
second imaging optics (Fig. 14, another one of lens 160) adapted to image the microfluidic reactor onto a second image surface (interpreted as a functional limitation of the second imaging optics; Fig. 14 teach one of lens 160 imaging the microarray 14 onto a surface of one CCD sensor 164 or 166), by fluorescent light of the second emission wavelength range transmitted through the second emission filter (Fig. 14 and paragraph [0082] teach output of fluorescence from the dyes is transmitted through one of the filters 158 onto a surface of one CCD sensor 164 or 166), thereby monitoring a second reaction parameter of the PCR-reaction associated with the second fluorophore (interpreted as an intended use of second imaging optics; note that the “PCR-reaction” and “second fluorophore” are not positively recited structurally; paragraphs [0065],[0082] teaches multiple fluorophores or fluorescent dyes that produce different emission signals when excited at different wavelengths and Fig. 14 shows the emitted light is directed onto CCD sensors 164 and 166; paragraph [0046] teaches fluorescence due to the presence of dyes are indicative of an interaction of a target with a site, i.e. a parameter of a reaction; therefore, the second imaging optics is capable of the imaging as claimed),
wherein the first imaging optics (Fig. 14, one of lens 160) is a single imaging optic of the system (Fig. 14 shows one of lens 160 being a single imaging optic of the system) adapted to image the microfluidic reactor onto the first imaging surface (interpreted as a functional limitation of the first imaging optics; Fig. 14 teach one of lens 160 imaging the microarray 14 onto a surface of one CCD sensor 164 or 166) by the fluorescent light of the first emission wavelength range (Fig. 14 and paragraph [0082] teach output of fluorescence from the dyes is transmitted through one of the filters 158 onto a surface of one CCD sensor 164 or 166), and
wherein the second imaging optics (Fig. 14, another one of lens 160) is a single imaging optic of the system (Fig. 14 shows another one of lens 160 being a single imaging optic of the system) adapted to image the microfluidic reactor onto the second imaging surface (interpreted as a functional limitation of the second imaging optics; Fig. 14 teach one of lens 160 imaging the microarray 14 onto a surface of one CCD sensor 164 or 166) by the fluorescent light of the second emission wavelength range (Fig. 14 and paragraph [0082] teach output of fluorescence from the dyes is transmitted through one of the filters 158 onto a surface of one CCD sensor 164 or 166).
Note that the “PCR-reaction”, “microfluidic reactor”, “first excitation light filter”, “second excitation light filter”, “first fluorophore”, “second fluorophore”, “first imaging surface”, and “second image surface” are not positively recited structurally and thus are interpreted as intended uses and functional limitations of the claimed system. The functional limitations are given patentable weight to the extent which effects the structure of the claimed system. The prior art structure is capable of performing the functional limitations as discussed above. Further, inclusion of the material or article (e.g. “PCR-reaction”, “microfluidic reactor”, “first fluorophore”, “second fluorophore”, “first imaging surface”, “second image surface”) worked upon by a structure (e.g. system) being claimed does not impart patentability to the claims (see MPEP 2115). It is suggested to positively recite that the system comprises the “microfluidic reactor”, “first excitation light filter”, “second excitation light filter”, “first fluorophore”, “second fluorophore”, “first imaging surface”, and “second image surface” if applicant desires to structurally recite the elements.
Note that the functional recitations that describe the first light source, second light source, first emission filter, second emission filter, first imaging optics, and second imaging optics are interpreted as intended uses and functional limitations of the claimed system and are given patentable weight to the extent which effects the structure of the claimed system. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the functional limitation, then it meets the claim. See MPEP 2114. The apparatus of Kain is identical to the presently claimed structure. Kain discloses the first light source, second light source, first emission filter, second emission filter, first imaging optics, and second imaging optics as claimed and therefore, would have the ability to perform the functions recited in the claim. See MPEP 2112.01(I).
Regarding claim 2, note that the “first imaging surface” and “second image surface” are not positively recited structurally and thus are interpreted as intended uses and functional limitations of the claimed system. The functional limitations are given patentable weight to the extent which effects the structure of the claimed system. The prior art structure is capable of performing the functional limitations as discussed above. Further, inclusion of the material or article (e.g. “first imaging surface” and “second image surface”) worked upon by a structure (e.g. system) being claimed does not impart patentability to the claims (see MPEP 2115). It is suggested to positively recite that the system comprises the “first imaging surface” and “second image surface”.
However, for compact prosecution purposes, the “first imaging surface” and “second image surface” are interpreted as positively recited structurally:
Kain further teaches wherein the first imaging surface and the second imaging surface (Fig. 14, surfaces of CCD sensors 164 and 166) each corresponds to
a first portion and a second portion, respectively (Fig. 14, surfaces of CCD sensors 164 and 166 are interpreted as a first and second portion), of a single image sensor (in one interpretation, Fig. 14, CCD sensors 164 and 166 that are coupled to element 168 are interpreted as “a single image sensor”); or
a first image sensor, and a second image sensor, respectively (in another interpretation, Fig. 14, surfaces of CCD sensors 164 and 166 are interpreted as corresponding to a first image sensor and a second image sensor, i.e. CCD sensors 164 and 166),
wherein each of the first and the second portions of the image sensor; or each of the first image sensor and the second image sensor; are adapted to provide a digital representation of the image of the corresponding imaging surface (interpreted as a functional limitation of the first and the second portions or the first image sensor and the second image sensor; Fig. 14 and paragraphs [0082],[0086] teach CCD sensors 164 and 166 provide data for imaging, therefore, each of the CCD sensors 164 and 166 provides digital representation of the image of the respective or corresponding surfaces of CCD sensors 164 and 166).
Regarding claim 3, note that the “first imaging surface” and “second image surface” are not positively recited structurally and thus are interpreted as intended uses and functional limitations of the claimed system. The functional limitations are given patentable weight to the extent which effects the structure of the claimed system. The prior art structure is capable of performing the functional limitations as discussed above. Further, inclusion of the material or article (e.g. “first imaging surface” and “second image surface”) worked upon by a structure (e.g. system) being claimed does not impart patentability to the claims (see MPEP 2115). It is suggested to positively recite that the system comprises the “first imaging surface” and “second image surface”.
However, for compact prosecution purposes, the “first imaging surface” and “second image surface” are interpreted as positively recited structurally:
Kain further teaches wherein the single image sensor (in one interpretation, Fig. 14, CCD sensors 164 and 166 that are coupled to element 168 are interpreted as “a single image sensor”) is associated with two, or more, imaging pixels (paragraph [0084] teaches the CCD comprises pixels, therefore the single image sensor is associated with at least two imaging pixels); and the first and second image sensors (in another interpretation, Fig. 14, surfaces of CCD sensors 164 and 166 are interpreted as corresponding to a first image sensor and a second image sensor, i.e. CCD sensors 164 and 166) each are associated with one or more imaging pixels (paragraph [0084] teaches the CCD comprises pixels, therefore the first and second image sensors are each associated with at least one imaging pixel).
Regarding claim 4, Kain further teaches wherein the first and the second light sources (Fig. 14, lasers 120, 122) are arranged to provide light continuously, thereby allowing continuous monitoring of the first reaction parameter and the second reaction parameter (interpreted as a functional limitation of the claimed light sources; Fig. 14 and paragraph [0078] teach lasers 120, 122 are arranged to provide light; therefore, the lasers are structurally capable of providing continuous light for continuous monitoring as claimed; the light sources of Kain are identical to the presently claimed structure, and therefore, would have the ability to perform the function recited in the claim; See MPEP 2112.01(I)).
Regarding claim 5, Kain further teaches wherein the first and second light sources (Fig. 14, lasers 120, 122), the first and second emission filters (Fig. 14, filters 158), and the first and second imaging optics (Fig. 14, lenses 160) are arranged opposing the same side of the microfluidic reactor (Fig. 14 shows elements 120, 122, 158, 160 arranged to optically oppose one side of the microarray 14; therefore, the elements 120, 122, 158, 160 are structurally arranged and capable of optically opposing one side of a microfluidic reactor; note that the “microfluidic reactor” is not positively recited structurally).
Regarding claim 6, note that “the first and the second fluorophores” are not positively recited structurally and thus are interpreted as intended uses and functional limitations of the claimed system. The functional limitations are given patentable weight to the extent which effects the structure of the claimed system. The prior art structure is capable of performing the functional limitations as discussed above. Further, inclusion of the material or article (e.g. the first and the second fluorophores) worked upon by a structure (e.g. system) being claimed does not impart patentability to the claims (see MPEP 2115). It is suggested to positively recite that the system comprises the first and the second fluorophores. In this case, Kain teaches fluorophores produce different emission signals (paragraph [0065]), therefore the system is structurally capable of being used with first and the second fluorophores where the first emission wavelength range and the second emission wavelength range are not overlapping.
Additionally, the apparatus of Kain is identical to the presently claimed structure. Kain discloses the first light source, second light source, first emission filter, second emission filter, first imaging optics, and second imaging optics as claimed and therefore, would have the ability to perform the function recited in the claim. See MPEP 2112.01(I).
Regarding claim 7, note that “microfluidic reactor” is not positively recited structurally and thus are interpreted as intended uses and functional limitations of the claimed system. The functional limitations are given patentable weight to the extent which effects the structure of the claimed system. The prior art structure is capable of performing the functional limitations as discussed above. Further, inclusion of the material or article (e.g. the microfluidic reactor comprises a translucent wall portion arranged to allow imaging of at least a portion of the microfluidic reactor) worked upon by a structure (e.g. system) being claimed does not impart patentability to the claims (see MPEP 2115). In this case, the system of Kain (Fig. 14) is structurally capable of imaging a microfluidic reactor that comprises a translucent wall portion arranged to allow imaging of at least a portion of the microfluidic reactor at a later time.
Additionally, the apparatus of Kain is identical to the presently claimed structure. Kain discloses the first light source, second light source, first emission filter, second emission filter, first imaging optics, and second imaging optics as claimed and therefore, would have the ability to perform the function recited in the claim. See MPEP 2112.01(I).
Regarding claim 8, Kain further teaches wherein the first emission filter (Fig. 14, one of filter 158) further is adapted to block light outside of the first emission wavelength range (paragraph [0065] teaches different fluorophores produce different emission signals; paragraph [0082] teaches bandpass filter wheel 158 that filters the beam to obtain the desired output wavelength corresponding to one of the fluorescent dyes, therefore the filter 158 blocks light outside the first emission range in order to correspond to the emission wavelength outputted by one of the dyes), and the second emission filter (Fig. 14, one of filter 158) further is adapted to block light outside the second emission wavelength range (paragraph [0065] teaches different fluorophores produce different emission signals; paragraph [0082] teaches bandpass filter wheel 158 that filters the beam to obtain the desired output wavelength corresponding to one of the fluorescent dyes, therefore the filter 158 blocks light outside the second emission range in order to correspond to the emission wavelength outputted by one of the dyes).
Regarding claim 9, note that “the first fluorophore” is not positively recited structurally and thus are interpreted as intended uses and functional limitations of the claimed system. The functional limitations are given patentable weight to the extent which effects the structure of the claimed system. The prior art structure is capable of performing the functional limitations as discussed above. Further, inclusion of the material or article (e.g. the first fluorophore) worked upon by a structure (e.g. system) being claimed does not impart patentability to the claims (see MPEP 2115). It is suggested to positively recite that the system comprises the first fluorophore. In this case, Kain teaches fluorophores produce different emission signals (paragraph [0065]), therefore the system is structurally capable of being used with a first fluorophore associated with DNA produced in the PCR- reaction, whereby the image on the first imaging surface is indicative of an amount of produced DNA.
Additionally, the apparatus of Kain is identical to the presently claimed structure. Kain discloses the first light source, second light source, first emission filter, second emission filter, first imaging optics, and second imaging optics as claimed and therefore, would have the ability to perform the function recited in the claim. See MPEP 2112.01(I).
Regarding claim 10, note that “the first and the second reaction parameters” are not positively recited structurally and thus are interpreted as intended uses and functional limitations of the claimed system. Note that the first and second fluorophores are also not positively recited structurally. The functional limitations are given patentable weight to the extent which effects the structure of the claimed system. The prior art structure is capable of performing the functional limitations as discussed above, e.g. exciting and imaging a first and second fluorophore Further, inclusion of the material or article (e.g. the first and second fluorophore, and thus the first and the second reaction parameters) worked upon by a structure (e.g. system) being claimed does not impart patentability to the claims (see MPEP 2115). It is suggested to positively recite that the system comprises the first and second fluorophore and the first and the second reaction parameters. In this case, Kain teaches fluorophores produce different emission signals (paragraph [0065]), therefore the system is structurally capable of being used with first and second fluorophores where the first and the second reaction parameters are different and each is selected from the group consisting of: a temperature in the microfluidic reactor, an amount of produced DNA, an amount of a reactant, and pH.
Additionally, the apparatus of Kain is identical to the presently claimed structure. Kain discloses the first light source, second light source, first emission filter, second emission filter, first imaging optics, and second imaging optics as claimed and therefore, would have the ability to perform the function recited in the claim. See MPEP 2112.01(I).
Regarding claim 11, Kain further teaches wherein the system further comprising first excitation optics and second excitation optics (Fig. 9-11 and 14, line generator modules 94) , wherein the first excitation optics are arranged to transfer light from the first light source to the first excitation light filter (Fig. 14 shows line generator modules 94 transfers light from laser 120 to excitation light filter 128), and the second excitation optics are arranged to transfer light from the second light source to the second excitation light filter (Fig. 14 shows line generator modules 94 transfers light from laser 122 to excitation light filter 130).
Regarding claim 13, note that “microfluidic reactor” is not positively recited structurally and thus are interpreted as intended uses and functional limitations of the claimed system. The functional limitations are given patentable weight to the extent which effects the structure of the claimed system. The prior art structure is capable of performing the functional limitations as discussed above. Further, inclusion of the material or article (e.g. the microfluidic reactor comprises a translucent wall portion arranged to allow imaging of at least a portion of the microfluidic reactor) worked upon by a structure (e.g. system) being claimed does not impart patentability to the claims (see MPEP 2115). In this case, Kain teaches imaging of dyes at various sites (paragraph [0078]), therefore the system of Kain (Fig. 14) is structurally capable of imaging a microfluidic reactor that comprises a first and a second reaction compartment, wherein the first imaging optics further is adapted to image the first reaction compartment on the first imaging surface, and the second imaging optics further is adapted to image the second reaction compartment on the second imaging surface.
Additionally, the apparatus of Kain is identical to the presently claimed structure. Kain discloses the first light source, second light source, first emission filter, second emission filter, first imaging optics, and second imaging optics as claimed and therefore, would have the ability to perform the function recited in the claim. See MPEP 2112.01(I).
Regarding claim 14, Kain further teaches the system further comprising a processor (Fig. 14, system controller; paragraph [0086]) for controlling the monitoring (paragraph [0086]).
Regarding claim 15, Kain further teaches a device comprising the system according to claim 1 (see above claim 1, Kain teaches the system according to claim 1; Fig. 14).
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.
In an alternative interpretation, claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Kain as applied to claim 1 above, and further in view of Scott et al. (US 20030058440 A1; cited in the IDS filed 01/13/2025).
Regarding claim 4, if it is determined that Kain fails to explicitly teach wherein the first and the second light sources are arranged to provide light continuously, thereby allowing continuous monitoring of the first reaction parameter and the second reaction parameter:
Scott teaches a system for fluorescence detection for high-throughput DNA sequence identification (abstract; paragraph [0002]). Scott teaches continuous fluorescence monitoring, which has significant advantages over scanning systems, such as capturing minute fluorescent signals, having a simplified mechanical operation, and efficient laser light power (paragraph [0095]). Scott teaches lasers to employ continuous illumination for detection assays (paragraph [0114]).
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 first and second light sources of Kain to incorporate the teachings of continuous illumination of detection assays and continuous fluorescence monitoring of Scott (paragraphs [0095],[0114]) to provide wherein the first and the second light sources are arranged to provide light continuously, thereby allowing continuous monitoring of the first reaction parameter and the second reaction parameter. Doing so would have a reasonable expectation of successfully improving analysis and monitoring of a detection assay for high throughput analysis as taught by Scott (abstract; paragraphs [0095],[0114]).
In an alternative interpretation, claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Kain as applied to claim 1 above, and further in view of Straus (US 20030082516 A1).
Regarding claim 5, if it is determined that Kain (as taught in Fig. 14) fails to explicitly teach wherein the first and second light sources, the first and second emission filters, and the first and second imaging optics are arranged opposing the same side of the microfluidic reactor:
Straus teaches a system for imaging (Figs. 3-4). Straus teaches a light source, emission filters, and lenses are arranged opposing the same side of a sample (Figs. 3-4). Straus teaches a detection zone can include microfluidic chambers or channels (claim 51). Straus teaches the instrument can be adapted to multicolor analysis by incorporating multiple lasers and filter sets (paragraph [0230]).
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 first and second light sources, the first and second emission filters, and the first and second imaging optics of Kain to incorporate the teachings of optical elements arranged opposing a same side of a sample of Straus (Figs. 3-4) to provide: wherein the first and second light sources, the first and second emission filters, and the first and second imaging optics are arranged opposing the same side of the microfluidic reactor. Doing so would have a reasonable expectation of successfully allowing for proper analysis of a sample as taught by Straus (Figs. 3-4). Additionally, doing so would be an obvious rearrangement of parts, where shifting the position of the first and second light sources, the first and second emission filters, and the first and second imaging optics would not have modified the operation of the device (i.e. excitation and imaging of a microfluidic reactor) and the particular placement of the first and second light sources, the first and second emission filters, and the first and second imaging optics is an obvious matter of design choice (see MPEP 2144.04(VI)(C); In reJapikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950); In re Kuhle, 526 F.2d 553, 188 USPQ 7 (CCPA 1975)).
In an alternative interpretation, claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Kain as applied to claim 1 above, and further in view of Ying et al. (US 20160230213 A1).
Regarding claim 6, for compact prosecution purposes where the first and the second fluorophores are interpreted as positively recited structurally: Kain fails to explicitly teach wherein the first and the second fluorophores are selected such that the first emission wavelength range and the second emission wavelength range are not overlapping.
Ying teaches a multiplexed CPR detection system for DNA detection including a CCD camera, probes, and an imaging chamber (abstract). Ying teaches significant spectral overlap between two (or more) fluorophores such that mixtures of these fluorophores may be difficult to resolve (paragraph [0038]). Ying teaches the excitation spectra of the selected fluorophores should not overlap one another and the emission spectra of the fluorophores should only minimally overlap with one another (paragraph [0042]).
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 first and second fluorophores of Kain to incorporate the teachings of excitation and emission spectra of fluorophores should not overlap or minimally overlap with one another (paragraph [0042]) to provide wherein the first and the second fluorophores are selected such that the first emission wavelength range and the second emission wavelength range are not overlapping. Doing so would have a reasonable expectation of successfully improving resolving and differentiation between at least two different fluorophores as taught by Ying (paragraphs [0038],[0042]).
In an alternative interpretation, claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Kain as applied to claim 1 above, and further in view of Vann et al. (US 20050208539 A1).
Regarding claim 7, for compact prosecution purposes where the microfluidic reactor is interpreted as positively recited structurally: Kain fails to teach the system comprises a microfluidic reactor, wherein the microfluidic reactor comprises a translucent wall portion arranged to allow imaging of at least a portion of the microfluidic reactor.
Vann teaches a system for detection of target nucleic acid copies, the system comprising optical assemblies and reaction assemblies having reaction chambers for amplification of target nucleic acid molecules (abstract). Vann teaches the system comprises a channel device with multiple channels connecting wells and target wells (paragraph [0124]), wherein fluid flow within a microfluidic device is directed by walls of a channel to contain fluid (paragraph [0183]). Vann teaches a substrate and assay chamber may be translucent to allow passage of optical radiation for fluorescent detection of target nucleic acid molecules (paragraphs [0126], [0146],[0181], [0220],[0222]). Vann teaches detecting multiple target nucleic acid molecules within different wells with differently colored dyes simultaneously (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 system of Kain to incorporate the teachings of translucent substrates and chambers of Vann (paragraphs [0126], [0146],[0181], [0220],[0222]) and fluid flow within channels, such as a microfluidic device, of Vann (paragraphs [0124],[0183]) to provide the system comprises a microfluidic reactor, wherein the microfluidic reactor comprises a translucent wall portion arranged to allow imaging of at least a portion of the microfluidic reactor. Doing so would have a reasonable expectation of successfully improving control of fluids for analysis and improving optical detection of multiple target nucleic acid molecules within different wells with differently colored dyes simultaneously as taught by Vann (paragraph [0124],[0147]).
In an alternative interpretation, claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Kain as applied to claim 1 above, and further in view of Cerrone et al. (US 20070238161 A1).
Regarding claim 9, for compact prosecution purposes where the first fluorophore is interpreted as positively recited structurally and it is determined that Kain fails to teach wherein the first fluorophore is associated with DNA produced in the PCR-reaction, whereby the image on the first imaging surface is indicative of an amount of produced DNA:
Cerrone teaches an optical instrument that monitors PCR replication of DNA in a reaction apparatus, wherein the instrument comprises dyes, a CCD, and processor (abstract). Cerrone teaches quantitative monitoring of DNA replication in a PCR apparatus using different dyes (paragraph [0006]). Cerrone teaches a means for directing light beams, a light detector, and means for processing data signals, wherein the detector generates data signals of the emission beam from a dye, which corresponds to a concentration of DNA (paragraph [0008]).
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 first fluorophore of Kain to incorporate the teachings of dyes that correspond to a concentration of DNA and the use of additional reference dyes of Cerrone (paragraphs [0008],[0024]) to provide: wherein the first fluorophore is associated with DNA produced in the PCR-reaction, whereby the image on the first imaging surface is indicative of an amount of produced DNA. Doing so would have a reasonable expectation of successfully improving and allowing for quantitative analysis of DNA as discussed by Cerrone (paragraphs [0006],[0008]).
In an alternative interpretation, claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Kain as applied to claim 1 above, and further in view of Cerrone et al. (US 20070238161 A1) and Bass (US 6022141 A).
Regarding claim 10, for compact prosecution purposes where the first and second fluorophores are interpreted as positively recited structurally and it is determined that Kain fails to teach wherein the first and the second reaction parameters are different and each is selected from the group consisting of: a temperature in the microfluidic reactor, an amount of produced DNA, an amount of a reactant, and pH:
Cerrone teaches an optical instrument that monitors PCR replication of DNA in a reaction apparatus, wherein the instrument comprises dyes, a CCD, and processor (abstract). Cerrone teaches quantitative monitoring of DNA replication in a PCR apparatus using different dyes (paragraph [0006]). Cerrone teaches a means for directing light beams, a light detector, and means for processing data signals, wherein the detector generates data signals of the emission beam from a dye, which corresponds to a concentration of DNA (paragraph [0008]). Cerrone teaches a dye that attaches to DNA so as to fluoresce in proportion to the quantity of DNA and samples may also contain an additional, passive dye (independent of the DNA) to serve as a reference (paragraph [0024]). Cerrone teaches reference emitters are used to compensate for drift (abstract) and are used for computing of concentration of DNA (paragraph [0042]).
Bass teaches an apparatus for measuring a temperature of a reaction in a microwell by introducing a dye target and a dye into a solution, wherein the detectable signal exhibits a temperature dependent signal (abstract). Bass teaches measuring the signal (e.g., fluorescence) and comparing it to a set of calibration standards to determine the temperature; wherein the process is particularly useful for microwell reactions that involve temperatures below 100 degrees Celsius (column 3, lines 8-14). Bass teaches experiments of measuring fluorescence as a function of DNA concentration at various temperatures (column 4, lines 19-32).
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 first and second fluorophores of Kain to incorporate the teachings of dyes that correspond to a concentration of DNA and the use of additional reference dyes of Cerrone (paragraphs [0008],[0024]) and the teachings of dye that exhibits temperature dependent signals of Bass (abstract; column 3, lines 8-14) to provide: wherein the first and the second reaction parameters are different and each is selected from the group consisting of: a temperature in the microfluidic reactor, an amount of produced DNA, an amount of a reactant, and pH. Doing so would have a reasonable expectation of successfully improving calibration and correction of fluorescent signals to improve analysis of fluorophores in a sample as taught by Cerrone (paragraph [0042]) and Bass (column 3, lines 8-14; column 4, lines 19-32).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Kain as applied to claim 1 above.
Regarding claim 12, Kain fails to teach wherein the system (Fig. 14) further comprising a
third light source illuminating the microfluidic reactor through a third excitation light filter providing light of a third excitation wavelength range adapted to excite a third fluorophore in the microfluidic reactor, whereby fluorescent light of a third emission wavelength range is emitted by the third fluorophore,
a third emission filter adapted to transmit fluorescent light of the third emission wavelength range and block fluorescent light of the first and the second emission wavelength ranges, and
third imaging optics adapted to image the microfluidic reactor onto a third imaging surface, by fluorescent light of the third emission wavelength range transmitted through the third emission filter, whereby the image on the third imaging surface is indicative of a third reaction parameter of the PCR-reaction associated with the third fluorophore,
wherein the first and the second emission filters further are adapted to block fluorescent light of the third emission wavelength range,
wherein the third imaging optics is a single imaging optic of the system adapted to image the microfluidic reactor onto the third imaging surface by the fluorescent light of the third emission wavelength range.
Kain teaches the invention can be carried out with a larger sets of sensor elements, such as three sensor elements that are separated from each other (paragraph [0107]). Kain teaches an embodiment (Fig. 5) wherein at least three beams of light are directed towards three different spots on a microarray, and the respective spots are imaged (paragraph [0052]). Kain teaches an embodiment of a parallel multi-spectral fluorescence imaging using at least three imaging sensors (Fig. 26; paragraph [0110]), wherein a multi-band filter set is used to excite and detect multiple fluorescent molecules and each sensor is mapped to a narrow band spectral range (paragraph [0110]). Kain teaches each line excites a sample region of a different wavelength to excite different fluorescent molecules, and each sensor generates a corresponding fluorescent image, wherein a filter is used to block residual and scattered radiation (paragraph [0111]). Kain teaches exciting fluorescence of multiple dyes in different spectral ranges simultaneously and the use of multiple lasers and filters to provide for efficient fluorescence detection (paragraph [0113]). Kain teaches the use of multiple radiation sources that generate radiation at different wavelengths can be useful, for example, in applications wherein a sample includes one or more fluorophores that produce different emission signals when excited at different wavelengths; and different emission signals can be collected simultaneously, for example, using multiple detection arms (paragraph [0065]). Kain teaches an embodiment of four lasers (paragraph Fig. 16).
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 system of Kain to incorporate the teachings of embodiments of parallel multi-spectral fluorescence imaging using at least three sensors, multiple radiation sources, exciting and detection different dyes with different excitation and emission signals, and filters to block desired wavelengths of Kain (Figs. 5, 16, 26; paragraphs [0107],[0110]-[0113],[0065]) to provide: the system further comprising a third light source illuminating the microfluidic reactor through a third excitation light filter providing light of a third excitation wavelength range adapted to excite a third fluorophore in the microfluidic reactor, whereby fluorescent light of a third emission wavelength range is emitted by the third fluorophore, a third emission filter adapted to transmit fluorescent light of the third emission wavelength range and block fluorescent light of the first and the second emission wavelength ranges, and third imaging optics adapted to image the microfluidic reactor onto a third imaging surface, by fluorescent light of the third emission wavelength range transmitted through the third emission filter, whereby the image on the third imaging surface is indicative of a third reaction parameter of the PCR-reaction associated with the third fluorophore, wherein the first and the second emission filters further are adapted to block fluorescent light of the third emission wavelength range, wherein the third imaging optics is a single imaging optic of the system adapted to image the microfluidic reactor onto the third imaging surface by the fluorescent light of the third emission wavelength range. Doing so would have a reasonable expectation of successfully improving efficiency of excitation and detection of at least three different fluorophores for improved parallel multi-spectral fluorescence imaging.
In an alternative interpretation, claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Kain as applied to claim 1 above, and further in view of Belkin et al. (US 20070281288 A1).
Regarding claim 13, for compact prosecution purposes where the microfluidic reactor is interpreted as positively recited structurally: while Kain teaches an embodiment of a series of directed beams of radiation to irradiate and image multiple sites of a microarray simultaneously (paragraphs [0015],[0052]; Fig. 5), and a microarray with a plurality of sites arranged in portions or regions of a substrate (paragraph [0046]), Kain fails to teach the system comprises a microfluidic reactor, wherein the microfluidic reactor comprises a first and a second reaction compartment, wherein the first imaging optics further is adapted to image the first reaction compartment on the first imaging surface, and the second imaging optics further is adapted to image the second reaction compartment on the second imaging surface.
Belkin teaches detecting a presence of an analyte in a sample using a device comprising reaction chambers and microfluidic channels (abstract). Belkin teaches the device and invention provides solutions to the problems associated with prior art techniques aimed at multiplexed detection of a plurality of analytes (paragraph [0035]). Belkin teaches the device is preferably a microfluidic device so as to facilitate forming therein or integrating therewith a large number of reaction chambers and fluid channels; the reaction chambers comprise different sensors to allow for the device to provide a multiplexed detection of an enormous amount of different analytes (paragraph [0242]). Belkin teaches optical signals generated in different reaction chambers are spatially separated so as to prevent cross talks between the different optical signals, which is done by collimating signals to propagate in parallel directions (paragraph [0305]). Belkin teaches imaging optics (Fig. 13, optical focusing device 112 with microlenses) for respective reaction chambers (12) to focus signal onto a detector (108). Belkin teaches when sensors of a particular reaction chamber emit optical signal detector detects this signal at the respective addressable region (paragraph [0329]). Belkin teaches tags can be detected by amplification methods such as PCR (paragraph [0353]).
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 system of Kain to incorporate the teachings of a microfluidic device comprising multiple reaction chambers for multiplexed detection of analytes and imaging optics for respective chambers of Belkin (Fig. 13; paragraphs [0242],[0305],[0329],[0353]) to provide the system comprises a microfluidic reactor, wherein the microfluidic reactor comprises a first and a second reaction compartment, wherein the first imaging optics further is adapted to image the first reaction compartment on the first imaging surface, and the second imaging optics further is adapted to image the second reaction compartment on the second imaging surface. Doing so would have a reasonable expectation of successfully improving control of fluids for analysis and improving multiplexed analysis of a sample while preventing cross talk as discussed by Belkin (Fig. 13; paragraphs [0242],[0305],[0329],[0353]).
Response to Arguments
Applicant’s arguments, see page 6, filed 08/14/2025, with respect to the rejections under 35 U.S.C. 112(b) have been fully considered and are persuasive. The rejections under 35 U.S.C. 112(b) of 04/14/2025 have been withdrawn.
Applicant's arguments, see pages 6-7, filed 08/14/2025, with respect to the rejections under 35 U.S.C. 102, specifically in view of amended claim 1, have been fully considered but they are not persuasive.
In response to applicant’s argument that Kain fails to disclose that the first and second imaging optics each