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 .
Response to Amendment
The amendment filed February 2nd, 2026 is acknowledged. Regarding the Office Action mailed November 6th, 2025:
Maintained, modified, or new rejections are set forth below, as necessitated by the amendments. Responses to arguments, if necessary, follow their respective rejection sections.
Claim Summary
Claims 1, 12, and 16 have been amended. Claims 1-20 are pending. Claims 17-20 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 1-16 are under examination and discussed in this Office action.
Specification - Maintained
The Examiner would like to note for the Applicant that the paragraph numbering provided in the filed specification currently denotes 2 different sets of paragraphs numbered [0001] through [0031]. To reduce confusion in responding to the Remarks, the Examiner has referred to the publicly available published version of the specification and the paragraph numbering provided therein when discussing particular paragraphs.
Claim Interpretation - Maintained
Prior to analysis of the prior art, the claims must be construed. The instant claims are drawn to a system for nucleic acid amplification. Sections 2114 and 2115 of the MPEP provide guidance for examination of claims drawn to an apparatus. Section 2114 of the MPEP states, “While features of an apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function. In re Schreiber, 128 F.3d 1473, 1477-78, 44 USPQ2d 1429, 1431-32 (Fed. Cir. 1997); see also In re Swinehart, 439 F.2d 210, 212-13, 169 USPQ 226, 228-29 (CCPA 1971); In re Danly, 263 F.2d 844, 847, 120 USPQ 528, 531 (CCPA 1959); and Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990).”
Section 2114 of the MPEP further states, "A claim containing a ‘recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus’ if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987).”
Section 2115 of the MPEP indicates that the contents present in an apparatus during its normal operation and the material worked on by the apparatus are not accorded patentable weight during the examination process, stating, “Expressions relating the apparatus to contents thereof during an intended operation are of no significance in determining patentability of the apparatus claim. Ex parte Thibault, 164 USPQ 666, 667 (Bd. App. 1969). Furthermore, inclusion of material or article worked upon by a structure being claimed does not impart patentability to the claims. In re Young, 75 F.2d 996, 25 USPQ 69 (CCPA 1935) (as restated in In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963)).”
In short, sections 2114 and 2115 of the MPEP indicate that the structural features of an apparatus define its patentability rather than the contents of the apparatus, the material worked on or produced by the apparatus, or the manner of operating the apparatus. This is specifically applicable to the aspects of the solution in the instant claims, which will be addressed where needed in the rest of this Office Action.
Claim Rejections - 35 USC § 112(b) – Modified – Necessitated by Amendment
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
There are a number of issues identified for claim 1, which are as follows:
First, claim 1 recites the limitation “a light source configured to emit a first excitation light based on a control signal towards a solution comprising a plurality of first nucleic acids (NAs) and a plurality of first fluorophores, to heat and excite the solution for amplifying the plurality of first NAs”. It is unclear from this recitation what is meant by “to…excite the solution for amplifying the plurality of first NAs”. There is no clear description of what this entails in the instant disclosure. Turning to the instant specification, there is description related to exciting the plurality of first NAs, and that this could mean heating them for amplification (see paragraph [0041]). However, it also appears that excitation could be a separate process from the amplification of the NAs, where fluorophores can then bind to the NAs (see paragraph [0041]). This does not serve to clear up the confusion regarding the limitation because it is unclear how this relates to exciting the solution. Furthermore, it is unclear how excitation of the solution or the NAs would be any different from heating them. It is also unclear from this recitation how the fluorophores in solution and not bound to the NAs will not always fluoresce if exposed to an excitation light. It is generally understood that fluorophores will fluoresce when exposed to the right wavelength of light, regardless of their otherwise intended purpose. In the instant case, the solution would fluoresce whether fluorophores are bound to the NAs or not since the same light appears to both heat and excite, and therefore it is unclear how the fluorophores would be able to indicate anything substantial about the status of the NAs. These issues are not further or fully clarified in any following dependent claim and therefore, claims 2-15 are rejected due to their lack of clarification and dependence on claim 1. Claim 16 suffers from the same issues as claim 1, and is also rejected for the same reason.
Second, claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: binding of the first fluorophores to the first NAs (see paragraph [0041] of the instant specification). This is considered an essential step because binding of the first fluorophores results in the emission of the third light, which in claim 1 is claimed as coming from amplification of the first NAs. It is unclear from the claimed recitation how a plurality of NAs will emit a light in response to amplification without integration of a light emitting molecule, like a fluorophore. While earlier in the claim a plurality of first fluorophores are introduced, there is no step where these fluorophores bind or interact in any way with the NAs. Therefore, the binding of the fluorophores to the NAs is an essential step to production of the third light as claimed. This issue is not further or fully clarified in any following dependent claims and therefore, claims 2-15 are rejected due to their lack of clarification and dependence on claim 1. Claim 16 suffers from the same issue as claim 1, and is also rejected for the same reason.
Third, claim 1 as a whole recites configurations of components that seem to rely on specific aspects of other components. However, it is unclear from the recitations presented how each of these components imparts a structural limitation on other components. For instance, a detector configured to detect a light related to heat and a light related to fluorescence is not reliant on the structure of the claimed first excitation light for the structural components of detecting heat and fluorescence. In addition, a controller configured to generate a control signal to pulse a light source is not reliant on the structure of the claimed first excitation light for the structural components of simply pulsing a light source. Overall, it is unclear what to extrapolate from these limitations beyond the aspects of what each specific component is configured to do. This is not further clarified in any following dependent claim and therefore, claims 2-15 are rejected due to their lack of clarification and dependence on claim 1. Claim 16 suffers these same issues as claim 1, and is also rejected for the same reason.
Finally, claim 1 recites several limitations related to the contents and aspects of the solution. It is unclear from the claim as a whole how the configurations of the solution will impart a structural limitation on the system of claim 1. A solution in which amplification and excitation of NAs occurs provides no structural limitations to the rest of the system beyond that which is needed to provide, detect, and control light and temperature, and hold the solution. Therefore, it is unclear what to extrapolate from the limitations related to the solution beyond providing, detecting, and controlling light and temperature, and holding the solution. This is not further clarified in any following dependent claim, it is only added to, such as in claim 11 where the plurality of NAs are defined and in claim 12 where more NAs are added to the solution. Therefore, claims 2-15 are rejected due to their lack of clarification and dependence on claim 1. Claim 16 suffers from the same issue as claim 1 in regards to the solution, and is also rejected for the same reason.
Claim 12 recites the limitation “wherein the solution further comprises a plurality of second NAs and a plurality of second fluorophores, wherein the light source comprises a green LED and is further configured to emit a second excitation light towards the solution to heat and excite the solution for amplifying the plurality of second NAs, and wherein the detector is further configured to detect a fourth light emitted by the solution in response to the amplification of the plurality of second NAs by the second excitation light.” It is unclear from this recitation how the light source comprising a green LED and configured to emit a second excitation light functions as instantly claimed. It cannot be determined from the specification or claims how the first excitation light as recited in claim 1 and the second excitation light as recited in claim 12 differentiates between two different populations of nucleic acids as instantly claimed with regard to specific amplification of the first plurality of NAs and the second plurality of NAs. The instant disclosure states “[r]eferring to FIG. 2A, in some embodiments, the solution 131 in the reaction chamber 130 includes more than one type of NA, for example, the first NAs 132 a and second NAs 132 b, which respond to different excitation lights. Here, the light source 110-1 emits an additional second excitation light toward the reaction chamber…[o]nce the second NAs 132 b are excited and amplified by the second excitation light, the solution 131 emits a fourth light” at paragraphs [0055]-[0056], but otherwise does not provide detail on how a second excitation light specifically amplifies the second NAs. Ultimately, amplification occurs due to the heat of the light source, as claimed in both claim 1 and claim 12. Therefore, the first excitation light will amplify the plurality of second NAs along with the plurality of first NAs due to generally providing heat for the amplification reaction. As such, it is unclear what structural feature of the system is actually required for the intended amplification purposes recited therein. Claim 12 also suffers from similar issues as analyzed for claim 1 regarding how the solution is excited, how the second fluorophores will fluoresce when excited regardless of intended purpose, and the missing essential step of fluorophores binding to the second NAs. The analysis applied for claim 1 also applies here in relation to the solution, the second NAs, and the second fluorophores. Claims 13-15, which all ultimately depend from claim 12, do not further clarify the issues of claim 12 and are also rejected.
Response to Arguments
Applicant's arguments filed February 2nd, 2026 have been fully considered but they are not fully persuasive.
The Applicant first provides a copy of claim 1 as amended, stating that claim 16 has been similarly amended (Page 7 of the Remarks filed February 2nd, 2026). The Applicant argues that based on the test for indefiniteness, and as conceded by the Examiner, one skilled in the art would understand that to amplify nucleic acids, different components may be used (Page 7 of the Remarks filed February 2nd, 2026). The Applicant argues that one skilled in the art would understand that such components may be included or eliminated from a solution containing nucleic acids to be amplified (Page 8 of the Remarks filed February 2nd, 2026). The Applicant notes, for example that one skilled in the art would understand that different types of amplification would require different polymerases (Page 8 of the Remarks filed February 2nd, 2026). The Applicant argues that given this knowledge of one skilled in the art, the claims are not required to recite any particular components of the solution beyond the recited nucleic acids and the recited fluorophores for one skilled in the art to understand what is claimed by the recited “light source configured to emit a first excitation light…to heat and excite the solution for amplifying the plurality of first NAs” (Page 8 of the Remarks filed February 2nd, 2026).
It is noted that these arguments are found persuasive, and this aspect of the rejection has been withdrawn.
The Applicant next summarizes the Examiner’s analysis from the previous Office Action regarding fluorophores fluorescing whether bound to the NAs or not (Page 8 of the Remarks filed February 2nd, 2026). The Applicant argues that the fluorescence of a fluorophore prior to binding with a nucleic acid is understood in the art to be less than the fluorescence of the fluorophore once bound to the nucleic acid (Page 8 of the Remarks filed February 2nd, 2026). The Applicant states that as a plurality of nucleic acids amplify, more fluorophores may bind to the amplified nucleic acids and the collective fluorescence of the solution emitted as the recited “third light” indicates amplification of the nucleic acids (Page 8 of the Remarks filed February 2nd, 2026).
In response to these arguments, it is noted that the arguments rely upon a step of fluorophores binding to nucleic acids. However, as has already been noted in the rejection of claims 1 and 16, there is no step claimed of fluorophores binding to nucleic acids. These features upon which applicant relies are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Therefore, these arguments are not found persuasive.
It is further noted that there is no argument directed towards the indefiniteness identified for exciting the solution, the missing step of binding of fluorophores to the first NAs, or the configurations of the components and the solution. These rejections regarding both claim 1 and 16 are still applicable and thus maintained. There is also no argument directed towards the indefiniteness identified for claim 12, and this rejection is thus maintained.
Claim Rejections - 35 USC § 103 – Modified – Necessitated by Amendments and Further Considerations
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2, 4-6, and 11-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Biro et al. (US20180361379A1; previously cited), in view of Khorasaninejad (Metalenses: Versatile multifunctional photonic components, Science, October 2017, 358, 1-8).
Regarding instant claim 1, Biro teaches a system for nucleic acid (NA) amplification (Page 1, paragraph [0006]), the system comprising: a light source configured to emit a light based on a control signal towards a solution comprising a plurality of first nucleic acids (NAs) and a plurality of first fluorophores, to heat the solution for amplifying the plurality of first NAs (Pages 7-8, paragraph [0056]; Page 9, paragraph [0061]; Pages 9-10, paragraph [0063]), and a light source configured to emit a light based on a control signal towards a solution comprising a plurality of first nucleic acids (NAs) and a plurality of first fluorophores, to excite the solution for amplifying the plurality of first NAs (Pages 7-8, paragraph [0056]; Page 9, paragraph [0061]; Pages 9-10, paragraph [0063]; Page 14, paragraphs [0080]-[0081]); a reaction chamber configured to house the solution (Page 3, paragraph [0038]); a detector configured to detect a second light emitted by the solution in response to heating by the first excitation light and a third light emitted by the solution in response to amplification of the plurality of first NAs by the first excitation light, and to generate a temperature signal corresponding to the second light and a first fluorescence signal corresponding to the third light (Page 3, paragraph [0039]; Pages 11-12, paragraph [0070]); a lens module configured to focus the second and third lights onto the detector (Page 13, paragraph [0074]); and a controller configured to generate the control signal to pulse the first excitation light based on the temperature signal (Page 1, paragraph [0007]; Pages 3-4, paragraph [0039]; Page 11, paragraph [0070]; Page 17, paragraph [0101]; Pages 17-18, paragraph [0103]; Figure 11), the control signal having a variable pulse width and being based on the temperature signal and a target temperature of the solution (Page 11, paragraph [0070]; Page 17, paragraph [0101]; Pages 17-18, paragraph [0103]).
Biro does not directly teach that the light source is configured to both heat and excite. However, Biro does teach a light source that heats (Pages 7-8, paragraph [0056]; Page 9, paragraph [0061]; Pages 9-10, paragraph [0063]) and a light source for fluorescent excitation (Page 14, paragraphs [0080]-[0081]). Biro teaches that these light sources can both be LEDs (Pages 9-10, paragraph [0063]; Page 14, paragraph [0080]-[0081]), meaning the same kind of light can perform both functions. Therefore, it would be obvious to one of ordinary skill in the art, based on these teachings, that a single light source can be configured to both heat and excite. This would amount to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)).
Biro does not teach that the lens module has a plurality of metalenses.
Khorasaninejad, in a reasonably pertinent field, teaches on metalenses and their use in focusing light (Page 6, column 2, paragraph 2; Page 7, column 1, paragraph 3).
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 Biro with the metalenses of Khorasaninejad. Since Khorasaninejad teaches on using metalenses to focus light, which is reasonably pertinent to the system of Biro, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to simple substitution of one known element for another to obtain predictable results (MPEP 2141(III)). Furthermore, metalenses provide benefits such as high efficiency, high numerical apertures, and the ability to miniaturize systems (Page 1, column 3, paragraph 1).
With regards to the limitations directed to the properties of the solution upon using/operating the system, the courts have held that the rearrangement of parts within a device is obvious when the arrangement does not specifically modify the operation of the device (In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950)). See MPEP 2144.04. Thus the arrangement of the solution, its contents, and what those contents do is obvious given Biro’s teachings on the system’s structure.
The courts have further held that “while features of apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function.” In re Screiber, 128 F.3d 1473, 1477-78, 44 USPQ2d 1429, 1431-32 (Fed. Cir. 1997). In addition, “[A]pparatus claims cover what a device is, not what a device does”. Hewlett-Packard Co.v.Bausch & Lomb Inc. 909, F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). Therefore, the operating uses, such as “a solution comprising a plurality of first nucleic acids (NAs) and a plurality of first fluorophores…amplifying the plurality of first NAs”, fail to define additional structural elements beyond providing heat/excitation light, detecting heat/excitation light, generating temperature/excitation signals, and reactions to the temperature signal, and do not further define the claimed system as a whole. Because the cited prior art teaches the structural elements of the claimed system, the claim is deemed obvious. See MPEP 2114.
Regarding instant claim 2, Biro, in view of Khorasaninejad, teaches the system of claim 1. Biro further teaches the system further comprising, wherein the controller is further configured to determine presence of the plurality of first NAs in the solution based on the first fluorescence signal (Figure 11).
Regarding instant claim 4, Biro, in view of Khorasaninejad teaches the system of claim 1. Biro further teaches wherein the light source comprises a blue light emitting diode (LED) (Page 9, paragraph [0061]), wherein the first excitation light has a blue range of wavelengths (Page 9, paragraph [0061]), wherein the second light is in a long wavelength infrared (LWIR) range (Page 11, paragraph [0070]), and wherein the third light has an orange range of wavelengths (Page 12, paragraph [0073]; Table 1).
With regards to the limitations directed to the properties of the solution upon using/operating the system, the courts have held that the rearrangement of parts within a device is obvious when the arrangement does not specifically modify the operation of the device (In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950)). See MPEP 2144.04. Thus the arrangement of the solution is obvious.
The courts have further held that “while features of apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function.” In re Screiber, 128 F.3d 1473, 1477-78, 44 USPQ2d 1429, 1431-32 (Fed. Cir. 1997). In addition, “[A]pparatus claims cover what a device is, not what a device does”. Hewlett-Packard Co.v.Bausch & Lomb Inc. 909, F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). Therefore, the operating uses e.g., “wherein the second light is in a long wavelength infrared (LWIR) range, and wherein the third light has an orange range of wavelengths” fails to define additional structural elements of the claimed system as a whole. Because the cited prior teaches the structural elements of the claimed system, namely that a detector is capable of detecting these wavelengths of light, the claim is deemed obvious. See MPEP 2114.
Regarding instant claim 11, Biro, in view of Khorasaninejad, teaches the system of claim 1. Biro further teaches wherein the plurality of first NAs comprise at least one of first RNAs and first DNAs, and wherein the solution comprises fluorophores that combine with the plurality of first NAs and fluoresce in response to receiving the first excitation light (Page 3, paragraphs [0037]-[0038], wherein a reaction chamber that can hold a solution with nucleic acids inherently teaches that any nucleic acids can be in the solution).
With regards to the limitations directed to the properties of the solution upon using/operating the system, the courts have held that the rearrangement of parts within a device is obvious when the arrangement does not specifically modify the operation of the device (In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950)). See MPEP 2144.04. Thus the arrangement of the solution is obvious.
The courts have further held that “while features of apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function.” In re Screiber, 128 F.3d 1473, 1477-78, 44 USPQ2d 1429, 1431-32 (Fed. Cir. 1997). In addition, “[A]pparatus claims cover what a device is, not what a device does”. Hewlett-Packard Co.v.Bausch & Lomb Inc. 909, F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). Therefore, the operating uses e.g., “wherein the solution comprises fluorophores that combine with the plurality of first NAs and fluoresce in response to receiving the first excitation light” fails to define additional structural elements of the claimed system as a whole. Because the cited prior teaches the structural elements of the claimed system, namely that a light source is capable of exciting, the claim is deemed obvious. See MPEP 2114.
Regarding instant claim 12, Biro, in view of Khorasaninejad, teaches the system of claim 1. Biro further teaches wherein the solution further comprises a plurality of second NAs and a plurality of second fluorophores, wherein the light source comprises a green LED and is further configured to emit a second excitation light towards the solution to heat and excite the solution for amplifying the plurality of second NAs (Page 12, paragraph [0073]), and wherein the detector is further configured to detect a fourth light emitted by the solution in response to the amplification of the plurality of second NAs by the second excitation light (Page 3, paragraph [0039]; Pages 11-12, paragraph [0070]; Page 14, paragraphs [0081]-[0082]).
With regards to the limitations directed to the properties of the solution housed within the reaction chamber upon using/operating the system, the courts have held that the rearrangement of parts within a device is obvious when the arrangement does not specifically modify the operation of the device (In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950)). See MPEP 2144.04. Thus the arrangement of solutions house within the reaction chamber is obvious.
The courts have further held that “while features of apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function.” In addition, “[A]pparatus claims cover what a device is, not what a device does”. Therefore, the operating uses, such as “solution further comprises a plurality of second NAs and a plurality of second fluorophores…the solution to heat the solution for amplifying the plurality of second NAs, and to excite the plurality of second NAs”, fail to define additional structural elements beyond providing heat/excitation light and detecting heat/excitation light, and do not further define the claimed system as a whole. Because the cited prior teaches the structural elements of the claimed system, namely the aspects of the light source and the detector, the claim is deemed obvious. See MPEP 2114.
Regarding instant claim 13, Biro, in view of Khorasaninejad, teaches the system of claim 12. Biro further teaches the system further comprising: a third pixel array configured to detect the fourth light and to generate a second fluorescence signal corresponding to the third light (Page 12, paragraph [0073]); and a controller configured to determine a concentration of the plurality of second NAs in the solution based on the second fluorescence signal (Figure 11).
Regarding instant claim 14, Biro, in view of Khorasaninejad, teaches the system of claim 13. Biro further teaches wherein the reaction chamber comprises a plurality of wells (Page 3, paragraph [0039]), one or more of the plurality of wells comprising the plurality of first NAs (Page 3, paragraph [0039]), wherein the second light comprises one or more fluorescent lights corresponding to the one or more of the plurality of wells (Page 24, paragraphs [0149] and [0150]), and wherein the first fluorescence signal comprises a two-dimensional image contrasting the one or more of the plurality of wells from other wells of the plurality of wells (Page 24, paragraph [0149]).
Regarding instant claim 15, Biro, in view of Khorasaninejad, teaches the system of claim 14. Biro further teaches the system further comprising: a controller configured to determine a concentration of the plurality of first NAs in the plurality of wells based on the two-dimensional image (Figure 11).
Regarding instant claim 16, Biro teaches a system for nucleic acid (NA) amplification (Page 1, paragraph [0006]), the system comprising: a light source configured to emit a light based on a control signal towards a solution comprising a plurality of first nucleic acids (NAs) and a plurality of first fluorophores, to heat the solution for amplifying the plurality of first NAs (Pages 7-8, paragraph [0056]; Page 9, paragraph [0061]; Pages 9-10, paragraph [0063]), and a light source configured to emit a light based on a control signal towards a solution comprising a plurality of first nucleic acids (NAs) and a plurality of first fluorophores, to excite the solution for amplifying the plurality of first NAs (Pages 7-8, paragraph [0056]; Page 9, paragraph [0061]; Pages 9-10, paragraph [0063]; Page 14, paragraphs [0080]-[0081]); a reaction chamber configured to house the solution (Page 3, paragraph [0038]); a detector configured to detect a second light emitted by the solution in response to heating by the excitation light and a third light emitted by the solution in response to amplification of the plurality of first NAs by the excitation light, and to generate a temperature signal corresponding to the second light and a fluorescence signal corresponding to the third light (Page 3, paragraph [0039]; Pages 11-12, paragraph [0070]); a lens module configured to focus the second and third lights onto the detector (Page 13, paragraph [0074]); and a controller configured to generate the control signal to pulse the excitation light based on the temperature signal (Page 1, paragraph [0007]; Pages 3-4, paragraph [0039]; Page 11, paragraph [0070]; Page 17, paragraph [0101]; Pages 17-18, paragraph [0103]; Figure 11), the control signal having a variable pulse width and being based on the temperature signal and a target temperature of the solution (Page 11, paragraph [0070]; Page 17, paragraph [0101]; Pages 17-18, paragraph [0103]), wherein the controller is further configured to determine presence of the plurality of NAs in the solution based on the fluorescence signal (Figure 11).
Biro does not directly teach that the light source is configured to both heat and excite. However, Biro does teach a light source that heats (Pages 7-8, paragraph [0056]; Page 9, paragraph [0061]; Pages 9-10, paragraph [0063]) and a light source for fluorescent excitation (Page 14, paragraphs [0080]-[0081]). Biro teaches that these light sources can both be LEDs (Pages 9-10, paragraph [0063]; Page 14, paragraph [0080]-[0081]), meaning the same kind of light can perform both functions. Therefore, it would be obvious to one of ordinary skill in the art, based on these teachings, that a single light source can be configured to both heat and excite. This would amount to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)).
Biro does not teach that the lens module has a plurality of metalenses.
Khorasaninejad, in a reasonably pertinent field, teaches on metalenses and their use in focusing light (Page 6, column 2, paragraph 2; Page 7, column 1, paragraph 3).
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 Biro with the metalenses of Khorasaninejad. Since Khorasaninejad teaches on using metalenses to focus light, which is reasonably pertinent to the system of Biro, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to simple substitution of one known element for another to obtain predictable results (MPEP 2141(III)). Furthermore, metalenses provide benefits such as high efficiency, high numerical apertures, and the ability to miniaturize systems (Page 1, column 3, paragraph 1).
With regards to the limitations directed to the properties of the solution housed within the reaction chamber upon using/operating the system, the courts have held that the rearrangement of parts within a device is obvious when the arrangement does not specifically modify the operation of the device. Thus the arrangement of solutions house within the reaction chamber is obvious.
The courts have further held that “while features of apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function.” In addition, “[A]pparatus claims cover what a device is, not what a device does”. Therefore, the operating uses e.g., “solution being configured to emit a light in response to heating by the first excitation light and to emit a third light in response to amplification of the plurality of first NAs” fails to define additional structural elements of the claimed reaction chamber or the claims system as a whole. Because the cited prior teaches the structural elements of the claimed system, the claim is deemed obvious. See MPEP 2114.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Biro et al. (US20180361379A1; previously cited) and Khorasaninejad (Metalenses: Versatile multifunctional photonic components, Science, October 2017, 358, 1-8), as applied to claims 1, 2, 4-6, and 11-16, and further in view of Lichtman (Fluorescence microscopy, Nature Methods, November 2005, 2, 910-919; previously cited).
Regarding instant claim 3, Biro, in view of Khorasaninejad, teaches the system of claim 1, as analyzed in the above 103 rejection. Biro further teaches that the system may comprise a mirror for guiding light (Page 13, paragraph [0074]).
Neither Biro nor Khorasaninejad teaches that the mirror is configured to pass-through the first excitation light and to direct the second and third lights toward the lens module.
Lichtman, in a reasonably pertinent field, teaches a dichroic mirror that can pass-through some wavelengths of light and reflect others, allowing for specific directionality of light beams (Figure 3).
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 Biro with the dichroic mirror of Lichtman. Since Lichtman teaches on the overlap of excitation light and light produced from that excitation (e.g. fluorescence), which is reasonably pertinent the system of Biro where fluorescence is being detected, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because dichroic mirrors can separate excitation light from emission light (Lichtman, Page 915, column 2, paragraph 1).
Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Biro et al. (US20180361379A1; previously cited) and Khorasaninejad (Metalenses: Versatile multifunctional photonic components, Science, October 2017, 358, 1-8), as applied to claims 1, 2, 4-6, and 11-16, further in view of Endrich (Practical usage of Panasonic GRIDEYE sensor v2.0 – Part 1, 2017, 166-171; previously cited) and Narendran (A Study of CMOS Cameras, 2000, 1-6; previously cited).
Regarding instant claim 5, Biro, in view of Khorasaninejad, teaches the system of claim 1, as analyzed in the above 103 rejection. Biro further teaches wherein the detector (Page 11, paragraph [0070]: “In some embodiments, detector 202 is a combination of the thermal infrared sensing device and the fluorescence detection subsystem.”) comprises: a thermopile array configured to detect the second light and to generate the temperature signal corresponding to the second light (Page 11, paragraph [0069]: a thermopile array); and a CMOS camera configured to detect the third light and to generate the first fluorescence signal corresponding to the third light (Page 12, paragraph [0073]: a CMOS camera).
Neither Biro nor Khorasaninejad teaches that a thermopile array and a CMOS camera comprise a pixel array.
In a general teaching, Endrich provides evidence that a thermopile array contains a pixel array (Page 167: “These high precision sensors, based on advanced MEMS technology, have absolute temperature detection, achieved on a two dimensional area of 8X8 “pixels”; Page 168: “The detected signals of the 64 pixels (in 8x8 organization)).
In another general teaching, Narendran provides evidence that a CMOS camera contains a pixel array (Page 1, Introduction).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, that the thermopile array of Biro would comprise a pixel array as evidenced by Endrich because both Biro and Endrich teach on thermopile arrays. Similarly, it would have been obvious to one of ordinary skill in the art that the CMOS camera of Biro would comprise a pixel array as evidenced by Narendran because both Biro and Narendran teach on CMOS cameras. Given the provided evidence, one of ordinary skill in the art would combine the teachings with a reasonable expectation of success.
Regarding instant claim 6, Biro teaches the system of claim 5, as analyzed in the above 103 rejection.
Biro further teaches wherein the temperature signal is an average of intensities of light detected by each one of pixels across the first pixel array, and wherein the first fluorescence signal is an average of intensities of light detected by each one of pixels across the second pixel array (Page 11, paragraph [0069]: a thermopile array; Page 12, paragraph [0073]: a CMOS camera).
Since the signals being an average of intensities represents what the pixel arrays are doing rather than what the system is, this claim represents a conclusionary statement that does not have an effect on the structure of the system. Therefore, the signals being average of intensities is considered an inherent property of the system of Biro.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Biro et al. (US20180361379A1; previously cited) and Khorasaninejad (Metalenses: Versatile multifunctional photonic components, Science, October 2017, 358, 1-8), as applied to claims 1, 2, 4-6, and 11-16, further in view of Rogalski (Challenges of small-pixel infrared detectors: a review, Reports on Progress in Physics, March 2016, 79, 1-43; previously cited), Pancheri (SPAD Image Sensor With Analog Counting Pixel for Time-Resolved Fluorescence Detection, IEEE Transactions on Electron Devices, October 2013, 60, 3442-3449; previously cited), and Myrick (US 20230266291, effective filing date 4/14/2014; previously cited).
Regarding instant claim 7, Biro teaches the system of claim 5, as analyzed in the above 103 rejection.
Biro does not teach wherein the first pixel array comprises a cooled infrared photodetector or an uncooled infrared photodetector, and wherein the second pixel array comprises at least one of an avalanche photodiode (APD), a quanta image sensor (QIS), and a single-photon avalanche diode (SPAD).
Rogalski, in a reasonably pertinent field, teaches wherein a pixel array comprises an uncooled infrared photodetector (Page 1, Abstract).
Furthermore, Pancheri, in a reasonably pertinent field, teaches wherein a pixel array comprises a single-photon avalanche diode (SPAD) (Page 3442, Abstract).
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 pixel arrays of Biro with detectors of Rogalski and Pancheri. Since the detectors of Rogalski are configured for infrared detection and the detector of Pancheri is configured for fluorescence detection, which are both reasonably pertinent to pixel arrays detecting infrared light and fluorescent light, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because both of these detectors could be combined with the system of Biro to carry out the functions of detecting light and generating temperature signals and fluorescent signals, respectively.
In another teaching, Myrick, in a reasonably pertinent field, teaches systems comprising sensors and sensing methods which can be highly sensitive, relatively inexpensive and small and which are suitable for use together with multiple functions, such as imaging, analyte detection and analyte differentiations (Abstract), wherein the analytes may comprise e.g., nucleic acids (DNA) (Pages 38 and 39, paragraph [0293]). Myrick, like Biro, teaches wherein the system may encompass lab-on-a-chip integration (Pages 2 and 3, paragraph [0018]), wherein said system may comprise plasmonic arrays that can be functionally compactly assembled onto integrated many-pixel imagers (Pages 2 and 3, paragraph [0018]) and used in multiplex sensing. See also Page 4, paragraph [0033] and Page 15, paragraph [0161]. Myrick teaches that the system may comprise of multiple detector zones comprising pixel zones wherein the amount of light applied to each pixel is measured to determine the present or absence of analyte at each detection zone (Page 4, paragraph [0033]). Myrick further discuss avalanche photodiodes in the detectors (Pages 6 and 7, paragraph [0099]). Myrick teaches that avalanche diodes such as SPADs can have signals gains and function at high temperatures (Pages 6 and 7, paragraph [0099]; Page 8, paragraph [0110]) and further operate to produce electropotential redox data for each pixel and its associated sensor surface (Page 13, paragraph [0149]).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the claimed invention to modify the pixel array of the detector of Biro to encompass an avalanche photodiode or single-photon avalanche diode in a lab-on-a-chip integration system as taught by Myrick. The ordinary artisan would have been motivated to do so for the advantage of increasing sensitivity and variability of the pixel array and detector in the system as suggested Myrick.
Response to Arguments
Applicant's arguments filed February 2nd, 2026 have been fully considered but they are not persuasive.
The Applicant first summarizes the Examiner’s previous art rejections (Page 9 of the Remarks filed February 2nd, 2026). The Applicant states that claim 1 has been amended to include certain features of claim 8, such that claim 1 now recites “a lens module having a plurality of metalenses, and configured to focus the second and third lights onto the detector; and…” (Page 9 of the Remarks filed February 2nd, 2026). The Applicant states that claim 16 has been similarly amended (Page 9 of the Remarks filed February 2nd, 2026). The Applicant argues that the cited references do not appear to disclose the feature of a lens module having a plurality of metalenses (Pages 9-10 of the Remarks filed February 2nd, 2026). The Applicant argues that, given this lack of disclosure, there is no reason why one or ordinary skill in the art would have combined the disclosures of the cited references to arrive at the claimed embodiments of claims 1 and 16, and therefore these claims would not have been obvious over the art of record (Page 10 of the Remarks filed February 2nd, 2026). The Applicant further argues that because claims 2-16 depend from claim 1, they are also not obvious over the art of record given the amendments to claim 1 (Page 10 of the Remarks filed February 2nd, 2026).
In response to these arguments, it is noted that the limitation of “plurality of metalenses” is taught by Khorasaninejad, which has been included in combination with Biro. As such, the arguments are not applicable given this teaching.
Conclusion
All claims stand rejected.
THIS ACTION IS MADE FINAL. 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.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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