DETAILED ACTION
Response to Amendment
This is a final office action in response to a communication filed on March 17, 2026. Claims 1-13 and 16-27 are pending in the application.
Status of Objections and Rejections
All objections and rejections from the previous office action are withdrawn in view of Applicant’s amendment.
New grounds of rejection under 35 U.S.C. §103 are necessitated by the amendments.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-8, 21-22, and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Ehsan (“Screen-Printed Graphene/Carbon Electrodes on Paper Substrates as Impedance Sensors for Detection of Coronavirus in Nasopharyngeal Fluid Samples,” 2021, Diagnostics, vol. 11, pgs. 1-12) in view of Jang (US 2010/0000441 A1), and further in view of Dong (US 11,022,610), supported by Muzyka (“Characterization of Graphite Oxide and Reduced Graphene Oxide Obtained from Different Graphite Precursors and Oxidized by Different Methods Using Raman Spectroscopy,” 2018, Materials, vol. 11, pgs. 1-15) as an evidence for claim 1.
Regarding claim 1, Ehsan teaches a sensor for detecting an analyte (the impedance sensor for detecting severe acute respiratory syndrome [SARS-CoV-2] in Figs. 1-2 [pg. 1, Abstract; pg. 2, para. 3]), comprising:
a porous, hydrophilic substrate (hydrophilic cellulose-based paper pad as the based substrate in Figs. 1-2 [pg. 3, para. 3; pg. 5, para. 3]);
a coating comprising graphene (graphene/carbon ink used to print the working electrode in Figs. 1e and 2 [pg. 3, para. 3]), the coating disposed throughout the porous, hydrophilic substrate (the graphene/carbon ink is embedded in the porous cellulose network [pg. 5, para. 3]);
a sensing area at which the coating at a surface of the sensor is functionalized with at least one molecule that provides for a binding interaction with the analyte (the circular working electrode in Figs. 1e and 2 is functionalized with a spike IgG antibody [pg. 4, para. 1: PBASE; pg. 5, para. 3]), wherein the graphene in the coating at the surface of the sensor comprise oxidized graphene, wherein the oxidized graphene comprises carboxyl functional groups (the oxidized graphene comprises both hydroxyl and carboxylic terminal groups [pg. 5, para. 3]); and
a contact area separate from the sensing area (the connecting pads and leading wires in Fig. 1c [pg. 3, para. 3]), the contact area comprising an electrode in operative arrangement with the sensing area (the connecting pads connect to the working electrode via the leading wires in Fig. 1e [pg. 3, para. 3]).
The limitation “to provide a signal indicative of an impedance” is a functional recitation. Apparatus claims cover what a device is, not what a device does (MPEP 2114(II)). 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 intended use, then it meets the claim. See MPEP 2114. In the instant case, Ehsan teaches a contact area and sensing area that are configured to perform the functional limitations above (the sensor is based on electrochemical impedance spectroscopy, see Figs. 2 and 4 [pg. 1, Abstract]).
Ehsan is silent to the limitation wherein the coating comprises a mixture of graphene nanoflakes and a conductive polymer, wherein the graphene nanoflakes in the coating at the surface of the sensor comprise oxidized graphene, wherein the oxidized graphene comprises carboxyl functional groups.
Jang teaches coatings comprising graphene nanoparticles including oxidized graphene nanoflakes (conductive inks that can contain oxidized or non-oxidized graphene nanoplatelets [GNPs] to meet property requirements of intended applications [0040, 0042, 0045]), wherein the oxidized graphene comprises carboxyl functional groups (as evidenced by Muzyka, the graphene oxide produced by the method in Jang [see 0054 in Jang and Method A in Table 1 in Muzyka] results in oxidized graphene with hydroxyl and carboxyl functional groups [see Fig. 5 and pg. 6, para. 1 in Muzyka]). Distributing the nanoflakes in a conductive polymer increases nanoflake dispersion, establishes nanocomposite structure, and maintains low resistivity (GNPs dispersed in PEDOT:PSS polymer [0044, 0049, 0061]), and the coating is water-based (oxidized NGPs and PEDOT:PSS diluted in water [0054, 0057, 0058]). Jang further teaches that this composition is inkjet printable, such that the coating can be printed in patterns via cost-effective methods [0027].
Ehsan and Jang are both considered analogous to the claimed invention because they are in the same field of oxidized graphene conductive coatings. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the oxidized graphene coating layer in Ehsan with a coating comprising a mixture of oxidized graphene nanoflakes distributed in a PEDOT:PSS conductive polymer, as taught in Jang, because the substitution would enable coating patterns via cost-effective inkjet printing, wherein the coating has increased nanoflake dispersion, nanocomposite structure, and low resistivity [0027, 0044, 0049, 0061 in Jang], while maintaining the hydroxyl and carboxyl functional groups required to functionalize the working electrode in Ehsan (oxidized graphene inherently comprises hydroxyl and carboxyl functional groups [pg. 5, para. 3 in Ehsan; pg. 6, para. 1 in Muzyka]). The coating in Jang would also disperse throughout the porous, hydrophilic substrate taught in Ehsan, as the coating is water-based [0054, 0057, 0058 in Jang].
Ehsan does not disclose wherein the at least one molecule is covalently bound to the oxidized graphene.
However, Dong teaches a sensor chip having an array of nanoposts coated with a noble metal and graphene oxide (GO) to detect target biomarker molecules ([Abstract]). The GO-Au nanoposts were functionalized with anti-ErbB2 molecules via EDC-NHS coupling chemistry (col. 11, ll. 51-53). The EDC reacted covalently with -COOH groups present at the GO nanosheets to form an intermediate O-acylisourea (col. 11, ll. 58-60). Thus, Dong teaches a molecule covalently bound to the oxidized graphene.
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 Ehsan by substituting the linking molecule PBASE with the DEC-NHS molecule as taught by Dong because EDC-NHC coupling chemistry is known in the prior art for being covalently immobilized on the graphene oxide for biomarker detection and 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. Here, the substitution of one known element for another would yield nothing more than predictable results. MPEP 2141(III)(B).
Regarding claim 2, modified Ehsan teaches the sensor of claim 1, and Ehsan further teaches wherein the porous, hydrophilic substrate comprises cellulose (cellulose based paper pad [pg. 2, para. 3]).
Regarding claim 3, modified Ehsan teaches the sensor of claim 1, and Ehsan further teaches wherein the porous, hydrophilic substrate is a cellulose paper (cellulose based paper pad [pg. 2, para. 3]).
Regarding claim 4, modified Ehsan teaches the sensor of claim 1, and further teaches wherein the coating comprising the mixture of graphene nanoflakes and the conductive polymer is a mixture comprising graphene nanoflakes distributed in the conductive polymer (the coating is a mixture comprising a graphene oxide nanoplatelet/PEDOT:PSS conductive polymer dispersion [0042, 0066 in Jang]).
Regarding claim 5, modified Ehsan teaches the sensor of claim 4, and further teaches wherein the graphene nanoflakes are homogenously distributed in the mixture (the graphene oxide nanoplatelets are well dispersed, producing a homogeneous suspension [0042, 0044 in Jang]).
Regarding claim 6, modified Ehsan teaches the sensor of claim 1, and further teaches wherein the conductive polymer comprises Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) (the coating is a mixture comprising graphene oxide nanoparticles distributed in a PEDOT:PSS conductive polymer [0044, 0049, 0061, 0066 in Jang]).
Regarding claim 7, modified Ehsan teaches the sensor of claim 1, and Ehsan further teaches wherein the at least one molecule is a protein (spike IgG antibody [pg. 4, para. 1; pg. 5, para. 3]).
Regarding claim 8, modified Ehsan teaches the sensor of claim 7, and Ehsan further teaches wherein the protein is an antibody (spike IgG antibody [pg. 4, para. 1; pg. 5, para. 3]).
Regarding claim 21, modified Ehsan teaches a method of detecting an analyte (method for detecting SARS-CoV-2 spike protein [pg. 1, Abstract in Ehsan]), comprising:
exposing the sensor of claim 1 (see rejection of claim 1 above) to a sample (sample is dropped onto the sensor surface [see Fig. 2; pg. 5, para. 1 in Ehsan]);
measuring an impedance of the exposed sensor (quantitative measurements of the sample were performed with EIS in Figs. 4-6 [pg. 4, para. 2-pg. 5, para. 1; pg. 7, para. 2; pg. 8, para. 3; pg. 10, para. 1 in Ehsan]); and
comparing the measured impedance of the sensor to a reference impedance of the sensor to determine a presence of the analyte in the sample (the impedance of a sample positive for COVID-19 is compared to a negative sample in Fig. 6 to differentiate the presence of SARS-CoV-2 [pg. 10, para. 1 in Ehsan]).
Regarding claim 22, modified Ehsan teaches the sensor of claim 1, and Ehsan further teaches wherein the contact area is separated from the sensing area by a passivation layer (the non-exposed area of the strip sensor is covered with insulator ink [pg. 3, para. 3]).
Regarding claim 24, modified Ehsan teaches the sensor of claim 22, and Ehsan further teaches wherein the passivation layer is on exposed areas of the sensor other than the contact area and the sensing area (the insulator ink is electrically insulating [pg. 3, para. 3], such that the working electrode and the connecting pads in Fig. 1 would not be covered to maintain their function).
Regarding claim 25, modified Ehsan teaches the sensor of claim 1. The limitation “graphene nanoflakes doped with the conductive polymer” is considered a product-by-process limitation, as the claim is interpreted to align with the embodiment of Fig. 3, wherein the mixing of graphene and PEDOT-PSS results in P-doped graphene. The determination of patentability is based upon the product or apparatus structure itself. Patentability does not depend on its method of production or formation. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. See In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (see MPEP § 2113).
In the alternative, modified Ehsan teaches the process of making the mixture of graphene nanoflakes and conductive polymer that would result in the claimed doped graphene (ultrasonic energy is used to disperse graphene platelets in polymer suspension [0044 in Jang], which is a suitable mixing method to arrive at p-doped graphene ink as evidenced by [0037] in the instant specification).
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Ehsan in view of Jang and Dong, as applied to claim 8, and further in view of Mazloum-Ardakani (“Two kinds of electrochemical immunoassays for the tumor necrosis factor α in human serum using screen-printed graphite electrodes modified with poly(anthranilic acid),” 2014, Microchimica Acta, vol. 181, pgs. 917-924).
Regarding claim 9, modified Ehsan teaches the sensor of claim 8, but is silent to the limitation wherein the antibody is an antibody for a cytokine.
Mazloum-Ardakani teaches an electrochemical impedance-based immunoassay [pg. 917, Abstract], wherein a graphite working electrode is functionalized with the monoclonal antibody anti-tumor necrosis factor α (TNF-α) (see steps a-e in Scheme 1 [pg. 918, col. 1, para. 4]), such that the cytokine TNF-α can be detected as a protein biomarker [pg. 917, Abstract]. Mazloum-Ardakani further teaches that TNF-α detection enables immunological studies in several diseases including rheumatoid arthritis, psoriasis, HIV, diabetes, and cancer [pg. 917, col. 2, para. 1; pg. 918, col. 1, para. 3].
Modified Ehsan and Mazloum-Ardakani are both considered analogous to the claimed invention because they are in the same field of electrochemical impedance-based sensors. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the spike IgG antibodies in modified Ehsan with anti-TNF-α antibodies, as taught in Mazloum-Ardakani, such that the antibody protein provides for a binding interaction with the target antigen, because the substitution would enable immunological studies in several diseases ([pg. 917, col. 2, para. 1; pg. 918, col. 1, para. 3] in Mazloum-Ardakani). Furthermore, the claimed device differs from modified Ehsan by the substitution of some components (spike IgG antibodies) with other components (anti-TNF-α antibodies) whose functions were known in the prior art. One of ordinary skill in the art could substitute one known element for another to yield predictable results (MPEP 2143(I)(B)).
Regarding claim 10, modified Ehsan teaches the sensor of claim 9, and further teaches wherein the antibody is an antibody for a cytokine and the cytokine is TNF-α (anti-TNF-α antibodies are antibodies for the cytokine TNF-α [pg. 917, col. 2, para. 1; pg. 917, col. 1, para. 4 in Mazloum-Ardakani]).
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Ehsan in view of Jang and Dong, as applied to claim 22, and further in view of Maattanen (“A low-cost paper-based inkjet-printed platform for electrochemical analyses,” 2013, Sensors and Actuators B: Chemical, vol. 177, pgs. 153-162).
Regarding claim 23, modified Ehsan teaches the sensor of claim 22, but is silent to the limitation wherein the passivation layer comprises polydimethylsiloxane (PDMS).
Maattanen teaches a sensor for detecting an analyte (the three-electrode platform in Fig. 1 is used as an electrochemical cell [pg. 153, Abstract]), comprising a paper substrate (coated paper in Fig. 1), a sensing area at which a coating is functionalized (gold ink is printed on the paper substrate to form a working electrode, and a PDMS layer defines a reaction area for a drop of analyte in Fig. 1 [pg. 154, col. 2, para. 2; pg. 155, col. 1, para. 1]. The working electrode is further functionalized with a self-assembled monolayer in the reaction area [pg. 155, col. 1, para. 1]), and a contact area separate from the sensing area (see the gray connection points for probes that is separate from the reaction area with analyte in Fig. 1) by a passivation layer (the PDMS layer is the passivation layer that separates the sensing area of the working electrode from the probe contacts in Fig. 1 of Maattanen [pg. 155, col. 1, para. 1 in Maattanen]). Maattanen further teaches that using PDMS as the passivation layer material provides high wetting/non-wetting contrast for confining electrolyte to the electrodes in the sample area while maintaining fast annealing times [pg. 155, col. 1, para. 1; pg. 161, col. 1, para. 1].
Modified Ehsan and Maattanen are both considered analogous to the claimed invention because they are in the same field of paper-based electrochemical sensors. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the insulator ink passivation layer material in modified Ehsan with a PDMS passivation layer material, as taught in Maattanen, because the substitution would provide high wetting/non-wetting contrast for confining electrolyte to the electrodes in the sample area while maintaining fast annealing times [pg. 155, col. 1, para. 1; pg. 161, col. 1, para. 1 in Maattanen]. Furthermore, the claimed device differs from modified Ehsan by the substitution of some components (the insulator ink in modified Ehsan) with other components (the PDMS in Maattanen) whose functions were known in the prior art. One of ordinary skill in the art could substitute one known element for another to yield predictable results (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).
Claims 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Ehsan in view of Jang and Dong, and further in view of Zhang (US 2018/0100853).
Regarding claim 26-27, Ehsan in view of Jang and Dong discloses all limitations of claim 1, but fails to teach wherein the at least one molecule is covalently bound to the oxidized graphene by means of a carboxamide (claim 26) or wherein the carboxamide is formed by an amine group of the at least one molecule and a carboxyl functional group of the oxidized graphene (claim 27).
However, Zhang teaches a capture device including a graphene-oxide layer on the substrate, and a polymer coupled with the graphene-oxide and a receptor that is capable of binding with a target ([Abstract]). The substrate and be a particle ([Abstract]), and these nanoparticles can be coated with graphene-oxide nanosheets via carboxamide covalent bonds formed by EDC/NHS chemistry and modified with APTES, which leads to substantially improved stability (¶65). APTES results in amine groups on the nanoparticles that can react with the carboxylic acid groups of the GO (¶65).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilizing the EDC/NHS chemistry as taught by Zhang to covalently bound the linking molecules to the oxide graphene by means of a carboxamide formed by an amine group of the linking molecule and the carboxyl functional group of the oxidized graphene because the EDC/NHS chemistry modified with APTES would lead to substantially improve stability (¶65). Here, 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).
Response to Arguments
Applicant’s arguments have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. In the instant rejection, the prior art, Dong and Zhang, are relied on to teach the newly added limitations and claims.
Conclusion
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 extension fee 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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/C. SUN/Primary Examiner, Art Unit 1795
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