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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/3/2024 has been considered by the examiner.
Claim Objection
Claim 1 is objected to because of the following informalities:
Claim 1: please amend “the fold film” in line 9 to -- the [[f]]gold film --.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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.
Regarding claim 1, claim 1 recites “a semi-continuous film” in lines 4 and 11, and “very small nanostructures with some 3D clustering” in line 5, which render the claim indefinite because the terms “semi-continuous” and “very small” are relative terms. The terms “semi-continuous” and “very small” are not defined by the claim, and the specification does not provide a standard for ascertaining the required degree, and one of ordinary skill in the art would not be reasonably appraised of the scope of the invention. Furthermore, it is unclear what does “a fill fraction” in line 5 refer to. The specification does not provide the definition of fill fraction and additional clarification on how to ascertain that term. Since it is not an ordinary or customary term, it is unclear if it refers to a packing fraction or a porosity of the gold film, or a surface area ratio of the surface area of the graphene layer having the gold nanostructures to the total surface area of the graphene layer. Claim 2 is further rejected by virtue of its dependence upon and because it fails to cure the deficiencies of indefinite claim 1.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over Jian et al. (CN111999360A, English translation), in view of Yuan et al. (Gold nanoparticles decorated on single layer graphene applied for electrochemical ultrasensitive glucose biosensor, Journal of Electroanalytical Chemistry, 2019, 855, 113495), Chen et al. (Fabrication of gold nanoparticles on bilayer graphene for glucose electrochemical biosensing, J. Mater. Chem., 2011, 21, 7604), Scandurra et al. (Dewetted gold nanostructures onto exfoliated graphene paper as high efficient glucose sensor, Nanomaterials, 2019, 9, 1794), and Justino et al. (Study of the effects of surface pKa and electron transfer kinetics of electroactive 4-nitrothiophenol/4-mercaptobenzoic acid binary SAM on the simultaneous determination of epinephrine and uric acid, Journal of electroanalytical chemistry, 2013, 703, 158-165).
Regarding claim 1, Jian teaches a method of making a composite film electrode (a method of making a graphene-based non-enzyme glucose sensor [para. 0008]; claim 4), comprising:
providing a substrate having a graphene layer on top of a copper layer (a graphene film grown on the surface of the copper substrate [para. 0010]); and
drying an initial composite film electrode to obtain the composite film electrode (after coating the two-dimensional layered structure compound, drying the sample coated with the two-dimensional layered structure compound [para. 0054]).
Jian further teaches a nanostructure layer on a top surface of the graphene layer (a two-dimensional layered structure compound scattered on the surface of the graphene film and a copper nanoparticle outer layer [para. 0010]).
Jian does not teach the following limitations: (1) depositing a gold film comprising gold nanostructures on the graphene layer to obtain an initial sensor, wherein the gold film is a semi-continuous film having a fractal structure with very small nanostructures with some 3D clustering, wherein the gold film has a fill fraction of about 80%; (2) immersing the initial sensor in a solution of absolute ethanol and 4-nitrothiophenol (4-NTP) to obtain an initial composite film electrode having the 4-NTP adsorbed onto a top surface of the gold film; and (3) the composite film electrode being a semi-continuous film having a fractal structure.
Yuan teaches a glucose biosensor comprising gold nanoparticles (AuNPs) decorated on single layer graphene (Au/SLG) (abstract and Scheme 1). The average size of the AuNPs is 8 nm (the first paragraph in Col. 2 on page 3). The SEM image of Au/SLG on GCE in Fig.1 shows a semi-continuous AuNP film having a fractal structure (i.e., similar shape of different regions/areas of the well dispersed AuNPs) with very small nanostructures (i.e., average size of the AuNPs is 8 nm) with some 3D clustering (some relatively large clustering is shown in Fig.1; AuNPs are 3D) (section 3.2).
Jian and Yuan are considered analogous art to the claimed invention because they are in the same field of electrochemical glucose sensor using a composite graphene electrode. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composite film electrode and the method of making the composite film electrode in Jian by substituting the nanostructure layer on the top surface of the graphene layer in Jian with a gold film that is a semi-continuous film having a fractal structure with very small nanostructures with some 3D clustering deposited on the graphene layer, as taught by Yuan, since AuNP would be stable, and have larger surface-to-volume ratio and outstanding conductivity, modifiability, and biocompatibility than other metal nanoparticles (the 2nd paragraph in section 1 of Yuan). The simple substitution of one known element for another (i.e., AuNPs nanostructure for another nanostructure) is likely to be obvious when predictable results are achieved (i.e., detection of analyte such as glucose) [MPEP § 2143(I)(B)]. Furthermore, the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art [MPEP § 2144.07].
Modified Jian still does not teach the following limitations: (1) wherein the gold film has a fill fraction of about 80%; (2) immersing the initial sensor in a solution of absolute ethanol and 4-nitrothiophenol (4-NTP) to obtain an initial composite film electrode having the 4-NTP adsorbed onto a top surface of the gold film; and (3) the composite film electrode being a semi-continuous film having a fractal structure.
Chen teaches a glucose electrochemical biosensor comprising gold nanoparticles scattered well on a top surface of graphene, and the loading amount of AuNPs can be controlled (abstract). Section 3.2 details the control of the loading amount of the AuNPs on graphene. Fig.5 shows the relationship between the reduction peak currents of the bound GOD and the amount of the graphene-AuNPs hybrid. With an increase in the loading amount of the graphene-AuNPs hybrid from 0.75 µg to 3.75 µg, the reduction peak currents enhanced nearly linearly. The reduction peak currents decreased while the amount of the graphene-AuNPs hybrid was more than 3.75 µg (the last paragraph in Col.1 of section 3.3 on page 7608). It was obviously that AuNPs played an important role in the improvement of the GOD adsorption. The homogenized AuNPs on graphene and the carboxyl groups that are present on their surface, help more GOD molecules to bind to the hybrid electrode (the first paragraph in Col. 2 of section 3.3 on page 7607). Thus, Chen teaches the loading amount of AuNPs on the top surface of the graphene affects the adsorption of GOD and accordingly the detection result of the glucose electrochemical biosensor (Firstly, AuNPs could facilitate electron transfer between immobilized GOD and the electrode. Secondly, because the AuNPs obtained the unique properties to provide a suitable microenvironment for GOD immobilization retaining its biological activity, the activity of GOD could be maintained for more than 4 months. Thirdly, due to the homogenized AuNPs on graphene, more GOD molecules could bind to the hybrid electrode [the first paragraph in Col. 1 on page 7610]).
Scandurra teaches a highly efficient glucose sensor comprising AuNPs on graphene (abstract), and further teaches the amount of gold present in the form of nanostructures on the sensor surface determines the electrode response. In fact, gold is not just a catalyst, but participate in the oxidation reaction of glucose. The apparent lower response of the electrode can be attributed to the lower gold content (the 2nd paragraph in section 3.5 on page 10).
Since the formed gold film is a semi-continuous film of AuNPs, the fill fraction of AuNPs on the graphene layer affects the loading amount of AuNPs on the graphene layer. As the fill fraction of AuNPs increases, the loading amount of AuNPs also increases. Given the teachings of Chen regarding the loading amount of Au on the graphene layer affecting the adsorption of GOD and accordingly the detection result of the glucose electrochemical biosensor; and the teachings of Scandurra regarding the amount of gold present in the form of nanostructures on the graphene sensor surface determines the electrode response, the claimed filling fraction of the gold film also affects the detection result/response of the glucose electrochemical biosensor. Thus, the claimed filling fraction of the gold film is a result effective variable.
As the detection result/response of glucose electro-chemical sensor is a variable that can be modified, among others, by adjusting the filling fraction of the gold film on a top surface of the graphene layer, the precise filling fraction of the Au would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed filling fraction of 80% of Au cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the filling fraction of Au in modified Jian to obtain the desired 80% filling fraction of Au and accordingly the desired peak current for the detection of the glucose as taught by Chen and Scandurra. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Modified Jian still does not teach the following limitations: (2) immersing the initial sensor in a solution of absolute ethanol and 4-nitrothiophenol (4-NTP) to obtain an initial composite film electrode having the 4-NTP adsorbed onto a top surface of the gold film; and (3) the composite film electrode being a semi-continuous film having a fractal structure.
Justino teaches the use of a gold electrode modified by 4-nitrothiophenol/4-mercaptobenzoic acid binary self-assembled monolayer (4NTP/4MBA SAM) for the simultaneous determination of epinephrine (EP) and uric acid (UA). To functionalize gold electrode with 4NTP single SAM, a gold electrode is immersed in a 1.0 mM solution of 4NTP in ethanol for 24h (the 2nd paragraph in section 2.2). Fig.5a shows that the voltammogram from the gold electrode modified with 4NTP SAM is better than that obtained from the bare gold electrode, and successfully identifies the two peaks for EP and UA, respectively (the first paragraph in Col. 2 in section 3.4).
Given the electrochemical sensor of this instant application is intended to be used for selectively detecting sugar (such as glucose), alcohol, and/or organic compound (such as urea) ([paras. 0002, 0045, 0058] of the specification), and the teachings of Justino regarding modification of gold electrode by a 4-NTP SAM and the gold electrode modified by 4-NTP SAM exhibited highly sensitivity/selectivity for the oxidation of EP and UA in the presence of AA, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composite film electrode and the method of making the composite film electrode in modified Jian by immersing the initial sensor in a solution of 4-NTP in ethanol to obtain an initial composite film electrode having the 4-NTP SAM adsorbed onto a top surface of the gold film, as taught by Justino, since the 4-NTP SAM would improve the selectivity and sensitivity of the sensor as shown in Fig.5a in Justino. Furthermore, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results [MPEP 2143(I)(A)]. Also, applying a known technique (i.e., functionalization of the gold electrode with 4-NTP SAM taught by Justino) to a known device (i.e., an electrochemical sensor for selectively detecting analyte) ready for improvement to yield predictable results is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143 (I)(D)).
Given the teachings of Jian as modified by Yuan above regarding the semi-continuous gold film having a fractal structure, and the teachings of Justino above regarding functionalizing the gold film with the 4-NTP SAM, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the formed initial composite film electrode is also a semi-continuous film having a fractal structure since the monolayer thickness of the absorbed 4-NTP SAM is very small and the absorbed 4-NTP SAM would not alter the structure of the underneath gold film.
Given the teachings of Jian regarding drying the initial composite film electrode, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to adopt the drying step in Jian to dry the initial composite film electrode in modified Jian to obtain the composite film electrode as a semi-continuous film having a fractal structure. Applying a known technique (i.e., drying a composite film electrode taught by Jian) to a known device (i.e., a composite film electrode in modified Jian) ready for improvement to yield predictable results is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143(I)(D)).
Note: Examiner interprets “a fill fraction” as a surface area ratio of the surface area of the graphene layer having the gold nanostructures to a total area of the graphene layer.
Regarding claim 2, modified Jian teaches the method of claim 1, wherein the gold film has a thickness of about 7.5 nm (according to the definition of the term “about” in [para. 0030] of the specification of this instant application, the term "about" refers to a ±10% variation from the nominal value unless otherwise indicated or inferred, therefore the claimed “about 7.5 nm” means a range from 7.5x0.9=6.75 nm to 7.5x1.1=8.25 nm. Jian as modified by Yuan above teaches the gold film of the well dispersed AuNPs having a size of 8 nm (the first paragraph in Col. 2 on page 3 in Yuan), falls within the claimed range of 6.75 nm to 8.25 nm).
Conclusion
The prior arts made of record and not relied upon are considered pertinent to applicant's disclosure: Yao et al. (Nanomaterial-enabled wearable sensors for healthcare, Advanced Healthcare Materials, 2018, 7, 1700889) teaches nanomaterials can be patterned into horseshoe, filamentary serpentine or fractal shapes to better accommodate the strain. Fan et al. (Fractal design concepts for stretchable electronics, Nature Communications, 2014, 5, 3266) teaches fractal structure of materials for electrophysiological sensors that simultaneously offer advanced electronic function and compliant mechanics (Fig.3c shows gold nanomembrane having a fractal structure).
Paria et al. ( US20250157600A1) teaches a pathogen detection system includes a pathogen sensor comprising a plasmonically active pathogen sensing area that comprises a hybrid structure of electrically conductive surface and metal nanofractals. Baig et al. (US20160235347A1) teaches a WE of an artificial sensor comprising a fractal Au nanostructure.
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/SHIZHI QIAN/Examiner, Art Unit 1795