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 .
Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 22, 2026 has been entered.
Status of the Claims
Claims 1 and 4 have been amended; claims 18-28 are new; and claims 2-3 and 6-17 have been cancelled. Claims 1, 4-5, and 18-28 are currently pending and examined herein.
Status of the Rejection
New grounds of specification and claim objection are necessitated by the amendment.
New grounds of claim rejection under 35 U.S.C. 112(b) are necessitated by the amendment.
All 35 U.S.C. § 103 rejections from the previous office action for claims 1, and 4-5 are essentially maintained and modified in response to the amendment.
New grounds of rejection under 35 U.S.C. § 103 for new claims 18-28 are necessitated by the amendment as outlined below.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: new claim 19 recites sidewall(s); new claim 20 recites nanoscale protrusions and recesses; new claim 21 recites “increased effective sensing surface area”; and new claim 22 recites “electrochemical impedance spectroscоpy”. The instant specification does not mention “sidewall(s)”, “protrusions”, “recesses”; “increased effective sensing surface area”, and “electrochemical impedance spectroscоpy” at all.
Claim Objection
Claims 1, 4-5, 18-19, 21-22, 24, and 28 are objected to because of the following informalities:
Claim 1: please amend “the silicon nanowires” to -- the plurality of silicon nanowires--; “the ITO-coated silicon nanowires” to -- the plurality of ITO-coated silicon nanowires--.
Claim 4: please amend “the nano-coarse surface” to -- the nano-coarse surface morphology--; “the ITO-coated silicon nanowires” to -- the plurality of ITO-coated silicon nanowires--.
Claim 5: please amend “containing silanol group” to -- containing the silanol group --.
Claim 18: please amend “the silicon nanowires” to -- the plurality of silicon nanowires--.
Claim 19: please amend “the ITO-coated silicon nanowires” to -- the plurality of ITO-coated silicon nanowires--; sidewall” to –sidewalls--.
Claim 21: please amend “the interconnected nanoscale protrusions and recesses” to -- the plurality of interconnected nanoscale protrusions and recesses--.
Claim 22: please amend “impedimetric biosensing” to – the impedimetric biosensing--.
Claim 24: please amend “containing a silanol group” to -- containing [[a]] the silanol group --.
Claim 28: please amend “the silicon nanowires” to -- the plurality of silicon nanowires--.
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 18-26 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 18, claim 18 recites “a high aspect ratio”, The term “high” is a relative term which also renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In this instant claim, it is unclear what is the requirement of the aspect ratio to be considered as a high aspect ratio. Claims 19-26 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 18.
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, 4-5, and 18-28 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (Real-time impedimetric detection of cardiac troponin I using ITO-coated vertically aligned silicon nanowires, Materials Letters, 2022, 311, 131575, available online 23 December 2021) and in view of Vashist et al. (Immobilization of antibody and enzymes on 3-Aminopropyltriethoxysilane-functionalized bioanalytical platforms for biosensor and diagnostics, Chemical Reviews, 2014, 114, 11083-11130).
Regarding claim 1, Yang teaches a nanostructural sensing substrate (a sensitive nanoelectronic device [NED] composed of ITO-coated vertically aligned silicon nanowires [abstract; Fig.1]), comprising:
a silicon substrate (all VASiNWs were vertically aligned on the silicon substrate [section 3.2]; see Fig.1A);
a plurality of vertically aligned silicon nanowires disposed on the silicon substrate ( all vertically aligned silicon nanowires [VASiNWs] were vertically aligned on the silicon substrate [section 3.2]; see Fig.1A);
an indium tin oxide (ITO) film coating the plurality of silicon nanowires (ITO-coated vertically aligned silicon nanowires [abstract; Fig.1A]; a 400-nm layer of ITO was deposited on the top of VASiNWs [section 2.1]);
wherein the plurality of ITO-coated silicon nanowires define an exposed sensing area (APTMS was used to modify the surface of exposed sensing area of ITO-coated VASiNWs, followed by immobilizing cTnIAb on the APTMS-modified ITO-coated VASiNWs [section 2.3 and Fig.1]) having a nano-coarse surface morphology (Figs.1 and 2B-2C show the exposed sensing area comprises a plurality of interconnected nanoscale protrusions formed by the plurality of silicon nanowires and a plurality of recesses formed by the spaces without vertically aligned silicon nanowires; Fig.2B-2C shows a part of the nano-coarse surface morphology) with an average surface roughness (due to the presence of the plurality of interconnected protrusions and recesses, the nano-coarse surface morphology must have an average surface roughness); and
wherein the exposed sensing area is configured for impedimetric biosensing (Fig.1B shows NED impedimetric system in the detection of cTnI by CtnIAb-modified-ITO-coated-VASiNWs via microfluidic systems [caption of Fig.1; section 2.4]; thus, the exposed sensing area is configured for impedimetric biosensing).
Yang is silent to: wherein the average surface roughness Ra is in a range of 400~650 nm.
Yang further teaches cTnI antibody (cTnIAb) is immobilized on APTMS-modified-ITO-coated VASiNWs (section 2.3 and Fig.1A).
Vashist teaches immobilization of antibodies and enzymes on APTES-functionalized surface for biosensors and diagnostics (title, TOC graph, and scheme 2). Several different techniques can be used for probing the surface roughness before and after silanization and bioconjugation (the 3rd paragraph in Col. 1 on page 11088). Protein/enzyme molecules can be attached to different interfaces with various mechanisms and forces acting between protein and surface, including hydrophobic, electrostatic, and van der Waals forces. Surface roughness also affects adsorption and the morphology of adsorbed protein (the first paragraph in section 3.5 on page 11102). Thus, Vashist teaches the surface roughness of the sensing area affects adsorption and the morphology of adsorbed protein.
Given the teachings of Vashist regarding the surface roughness of the sensing area affecting adsorption and morphology of adsorbed protein, and the teachings of Yang regarding cTnI antibody (cTnIAb) is immobilized on the APTMS-modified-ITO-coated VASiNWs for the detection of CTnI, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the surface roughness of the ITO-coated VASiNWs would also affect adsorption and morphology of adsorbed protein, which is cTnIAb in Yang.
As the adsorption and the morphology of adsorbed protein are variables that can be modified, among others, by adjusting the surface roughness of the exposed sensing area where proteins/antibodies are adsorbed/immobilized, the precise surface roughness of the nano-coarse surface morphology of the ITO-coated-VASiNWs 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 average surface roughness Ra in a range of 400~650 nm 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 average surface roughness Ra of the exposed sensing area of the ITO-coated VASiNWs of Yang to obtain the desired average surface roughness of 400 ~650 nm and accordingly the desired amount and morphology of the protein/antibody immobilized on the sensing area for detection of cTnI in human blood sera with good sensitivity. “[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.).
Regarding claim 4, modified Yang teaches the nanostructural sensing substrate of claim 1, and Yang teaches wherein the nano-coarse surface morphology of the ITO-coated silicon nanowires is further modified with a small molecule containing a silanol group (APTMS was used to modify the surface of exposed sensing area of ITO-coated-VASiNWs [section 2.3]. The disclosed APTMS containing a silanol group and is also the same as that in this instant application, as evidenced by instant claim 5 below).
Regarding claim 5, modified Yang teaches the nanostructural sensing substrate of claim 4, and Yang teaches wherein the small molecule containing the silanol group is 3-aminopropyl trimethoxysilane (APTMS) (APTMS was used to modify the surface of exposed sensing area of ITO-coated-VASiNWs [section 2.3]).
Regarding claim 18, modified Yang teaches the nanostructural sensing substrate of claim 1, and Yang teaches wherein the silicon nanowires have a high aspect ratio (Fig.2B shows the VASiNWs with a length of 2 µm, and Fig.2C shows the the VASiNWs with a length of 2.5 µm [section 3.2]; Based on the scale bar shown in Figs. 2B and 2C, the diameter of the VASiNWs is less than 0.25 µm, yielding an aspect ratio of length/diameter> 2.5/0.25=10, thus the disclosed VASiNWs have a high aspect ratio of length/diameter).
Regarding claim 19, modified Yang teaches the nanostructural sensing substrate of claim 18, and Yang teaches wherein the nano-coarse surface morphology is present on both sidewalls and top surfaces of the ITO-coated silicon nanowires (Fig.1 shows the surface of the exposed sensing area of the ITO-coated silicon nanowires include both sidewalls and top surfaces of the ITO-coated silicon nanowires).
Regarding claim 20, modified Yang teaches the nanostructural sensing substrate of claim 19, wherein the nano-coarse surface morphology comprises a plurality of interconnected nanoscale protrusions and recesses (as outlined in the rejection of claim 1 above, the nano-coarse surface morphology of the exposed sensing area comprises a plurality of interconnected nanoscale protrusions formed by the plurality of silicon nanowires and a plurality of recesses formed by the spaces without the vertically aligned silicon nanowires, as shown in Figs.1 and 2B).
Regarding claim 21, modified Yang teaches the nanostructural sensing substrate of claim 20, and Yang teaches wherein the plurality of interconnected nanoscale protrusions and recesses collectively define an increased effective sensing surface area (see Fig. 1; note that the surface of exposed sensing area of the ITO-coated-VASiNWs was functionalized [section 2.3], thus the plurality of interconnected nanoscale protrusions and recesses collectively define an increased effective sensing surface area to be functionalized).
Regarding claim 22, modified Yang teaches the nanostructural sensing substrate of claim 21, and Yang teaches wherein the exposed sensing area is configured for impedimetric biosensing using electrochemical impedance spectroscоpy (Fig.1B shows NED impedimetric system in the detection of cTnI by CtnIAb-modified-ITO-coated-VASiNWs via microfluidic systems [caption of Fig.1; section 2.4]; Impedance measurements were performed using the E4980A precision LCR meter [Agilent Technologies] in frequency sweep mode and operated at 2 mV from 20 Hz to 2 MHz [section 2.4]. Note that the disclosed E4980A precision LCR meter [Agilent Technologies] is the same as the impedance analyzer used in this instant application, as evidenced by “Impedance measurements are performed using the E4980A precision LCR meter (Agilent Technologies) in frequency sweep mode and operated at 2 mV from 20 Hz to 2 MHz” [para. 0041] in PG-Pub of this instant specification. Thus, the exposed sensing area is configured for the impedimetric biosensing using electrochemical impedance spectroscоpy).
Regarding claim 23, modified Yang teaches the nanostructural sensing substrate of claim 22, and Yang teaches wherein the exposed sensing area is modified with a small molecule containing a silanol group (APTMS was used to modify the surface of exposed sensing area of ITO-coated-VASiNWs [section 2.3]. The disclosed APTMS containing a silanol group and is also the same as that in this instant application, as evidenced by instant claim 24 below).
Regarding claim 24, modified Yang teaches the nanostructural sensing substrate of claim 23, wherein the small molecule containing the silanol group is 3-aminopropyl trimethoxysilane (APTMS) (APTMS was used to modify the surface of exposed sensing area of ITO-coated-VASiNWs [section 2.3]).
Regarding claims 25-26, modified Yang teaches the nanostructural sensing substrate of claim 24, and the limitations “wherein the exposed sensing area is configured to immobilize a cardiac troponin I antibody” (of claim 25) and “wherein the cardiac troponin I antibody is immobilized via an aminosilane-based surface modification” (of claim 26) are functional limitation of the exposed sensing area. 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, Yang teaches the exposed sensing area is functionalized by APTMS/EDC-NHS/cTnI antibody for detection of cTnI (section 2.3), thus the exposed sensing area is configured to immobilize a cardiac troponin I antibody via an aminosilane-based surface modification. Examiner further notes that Yang does teach wherein the exposed sensing area is configured to immobilize a cardiac troponin I antibody (CTnI antibody [section 2.3 and Fig.1]) via an aminosilane-based surface modification (APTMS [section 2.3 and Fig.1]).
Regarding claim 27, modified Yang teaches the nanostructural sensing substrate of claim 1, and Yang teaches wherein the ITO film is electrically conductive (ITO is inherently electrically conductive).
Regarding claim 28, modified Yang teaches the nanostructural sensing substrate of claim 1, Yang teaches wherein the ITO film is disposed directly on the silicon nanowires without an intermediate conductive layer (Fig.1A shows ITO is directly disposed on the vertically aligned silicon nanowire without an intermediate conductive layer).
Response to Arguments
Applicant's arguments, see Remarks Pgs. 4-7, filed 1/22/2026, with respect to the 35 U.S.C. § 103 rejections have been fully considered.
Applicant’s Argument #1:
Regarding independent claim 1, Applicant argues at pages 4-6 that claim 1 defines the sensing substrate by the existence of an exposed sensing area having a nano-coarse surface morphology characterized by Ra = 400-650 nm. The claimed Ra range is recited as a structural characteristic of the sensing surface, not as a parameter to be optimized. Yang fails to disclose any surface roughness values, ranges, or structural surface states of the ITO-coated nanowires. Absent such disclosure, Yang does not teach or inherently result in the specific Ra-defined surface morphology as recited in the amended claim 1. Vashist fails to teach that a sensing surface having a nano-coarse morphology characterized by Ra = 400-650 nm constitutes a distinct structural state. Vashist fails to disclose any Ra values, ranges, or thresholds, nor does it disclose ITO-coated silicon nanowires having such a surface morphology. Accordingly, Vashist fails to supply the missing structural teaching absent from Yang. The result-effective variable doctrine applies where the prior art recognizes a parameter as result-effective and discloses workable ranges such that optimization would have been routine. Here, neither Yang nor Vashist disclose any Ra values, ranges, or thresholds for ITO-coated silicon nanowire sensing surfaces. Without disclosure of such ranges, there is no basis to conclude that the claimed Ra-defined surface morphology represents routine optimization of a known variable.
Examiner’s Response #1:
Applicant’s arguments have been fully considered, but are not persuasive. As outlined in the new grounds of rejection for the amended claim 1 above, Yang does teach an exposed sensing area having a nano-coarse surface morphology formed by the plurality of interconnected nanoscale protrusions (formed by the plurality of VASiNWs) and recesses formed by the spaces without VASiNWs, and it has a surface roughness. But Yang does not disclose that the average surface roughness is in the claimed range of 400 to 650 nm. Since Vashist teaches the surface roughness of the sensing area affecting adsorption and morphology of adsorbed protein on the APTES-functionalized surface, and Yang teaches cTnI antibody (cTnIAb) is immobilized on APTMS-modified-ITO-coated VASiNWs, thus the surface roughness of the ITO-coated VASiNWs affects the adsorption and morphology of adsorbed cTnIAb on the APTES-functionalized ITO-coated VASiNWs, thus the surface roughness of the ITO-coated VASiNWs is a result effective variable. MPEP 2144.05(III)(c) states: if the prior art does recognize that the variable affects the relevant property or result, then the variable is result-effective. Id. (‘A recognition in the prior art that a property is affected by the variable is sufficient to find the variable result-effective.’). Thus, the result-effective variable analysis is applicable to the amended claims.
Conclusion
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/SHIZHI QIAN/Examiner, Art Unit 1795