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 2/16/2024 has been considered by the examiner.
Election/Restrictions
Applicant's election of Group I, Claims 1-9 and 24-26, without traverse in the reply filed on 06/24/2026 is acknowledged.
Claim Objection
Claims 2 and 25 are objected to because of the following informalities:
Claim 2: please amend “electrodes” to –the source and drain electrodes--.
Claim 25: please amend “drain-source a current signal” to –a drain-source [[a]] current signal--.
Appropriate correction is required.
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 1-6, 8-9, and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Seo et al. (Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor, ACS Nano, 2020, 14, 5135-5142), and in view of Hoffman et al. (US20170018626A1), Nah et al. (A wearable microfluidics-integrated impedimetric immunosensor based on Ti3C2Tx MXene incorporated laser-burned graphene for noninvasive sweat cortisol detection, Sensors and Actuators B: Chemical, 2021, 329, 129206), and Hummer et al. (US20220365066A1).
Regarding claim 1, Seo teaches a sensor for detecting virus particles (a FET-based biosensor for detecting COVID-19 causative virus [SARS-CoV-2] in human nasopharyngeal swab specimens [title, and Fig.1]), comprising:
a substrate (a SiO2/Si substrate [Fabrication of Graphene-based sensing devices on pg. 5140]; Figs. 1 and 3A shows a substrate of the FET biosensor) ;
a field effect transistor (FET), the FET including source and drain electrodes formed on the substrate (Fig.1 shows a FET including source and drain electrodes formed on the substrate); and
a two-dimensional virus sensing transduction material (VSTM) film (graphene sheet in Fig.1) formed on the FET (see Fig.1), the VSTM film configured to collect a sample collected from a subject (Fig.1 shows graphene film configured to collect a sample from COVID-19 patient), the VSTM film comprising graphene (graphene sheet in Fig.1) and having a probe (SARS-CoV-2 spike antibody in Fig.1) corresponding to the virus particles to be detected linked thereto (see Fig.1; detection of SARS-CoV-2 antigen protein is shown in Fig.4),
wherein a drain-source current response of the FET is representative of an amount of the virus particles in the sample (see Figs. 4B, 4E, and 4F).
Seo teaches wherein the VSTM film comprises graphene and is silent to wherein the VSTM film comprises MXene-graphene.
Hoffman teaches a FET sensor comprising a channel formed over and/or between the source and drain electrodes, wherein the channel material is a 2D material layer which may be composed of one or more of graphene, Molybdenum disulfide (MoS2), MoSe2, Phosphorene (black phosphorous), Silicene, Borophene, Tungsten disulfide (WS2), Boron Nitride, WSe2, Stanene (2D tin), Graphane, Germanane, Nickel HITP, Mxenes (Ti2C, (Ti0.5, Nb0.5), V2C, Nb2C, Ti3C2, Ti3CN, Nb4C3, Ta4C3), and/or transition metal dichalcogenides [para. 0346].
Nah teaches an immunosensor based on MXene/graphene as noninvasive sweat cortisol detection (title and abstract).
Hummer teaches detection of COVID-19 using MXene biosensors through interaction between SARS-CoV-2 virus and a probe (which is SARS-CoV-2 DNA biologically sensitive molecules 4250) immobilized on MXene sheen 4240 ([para. 0227-0228] and Figs. 42A and 42B).
Given the teachings of Seo regarding the graphene-based FET for sensing SARS-CoV-2 virus through interaction between SARS-CoV-2 virus and ARS-CoV-2 spike antibody (probe) immobilized on the continuous graphene layer; the teachings of Hummer regarding sensing SARS-CoV-2 virus through interaction between SARS-CoV-2 virus and a probe (which is SARS-CoV2 DNA 4250) immobilized on MXene sheet; the teachings of Nah regarding the use of MXene/graphene hybrid film for sensing cortisol in sweat through interaction between analyte of cortisol and cortisol antibody (probe) immobilized on the MXene/graphene hybrid film; and the teachings of Hoffman regarding FET sensor comprising 2D material layer as the channel, wherein the 2D material may be composed of one or more of graphene,…, and MXene, 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 VSTM film (the graphene sheet) in Seo by adding a MXene layer on the graphene sheet to provide a continuous virus sensing transduction material (VSTM) film formed on the FET, and having the probe immobilized on the VSTM film, as taught by combined Seo, Hummer, Nah, and Hoffman, since MXene nanosheets would provide good electrical conductivity making them useful in electrochemical applications (the 1st paragraph in Col. 2 on page 2 in Nah); Hummer teaches the suitable alternative MXene as the VSTM for sensing COVID-19; Nah teaches the suitable alternative MXene/graphene as the sensing transduction material for biosensor; and Hoffman teaches wherein the 2D channel material of the FET sensor would be composed of one or more of graphene and MXenes.
Regarding claim 2, modified Seo teaches the virus sensor set forth in claim 1, and Seo teaches wherein electrodes of the FET and the VSTM film are directly on a surface of the substrate (see Fig.1).
The limitation “printed” is a product by process limitation. 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 instant case, Seo teaches wherein electrodes of the FET and the VSTM film are directly on a surface of the substrate (see Fig.1), and there is no evidence the step of the recited printing process imparts any additional structure on the FET that is not already present or substantially similar to that of modified Seo.
Regarding claim 3, modified Seo teaches the virus sensor set forth in claim 1, and “wherein the virus particles to be detected are SARS-COV-2 virus particles and/or influenza A (H1N1)” further limits the sample to be detected but fails to further limit the sensor apparatus. A claim is only limited by positively recited elements. Thus, "[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims." See MPEP 2115. Since the claim further limits the virus particles to be detected (material worked upon) but fails to limit the sensor (by a structure being claimed), the limitations of the claim have no patentable weight.
In the alternative, Examiner further notes that Seo does teach wherein the virus particles to be detected are SARS-COV-2 virus particles (title, abstract and Fig.1).
Regarding claim 4, modified Seo teaches the virus sensor set forth in claim 1, wherein the VSTM film comprises covalently bonded MXene-graphene hybrid continuous film (Seo teaches 2D material of graphene sheet which is a continuous film as shown in Fig.1; Hoffman also teaches the 2D material layer as the channel of the FET, wherein the 2D material layer may be composed one or more of graphene and Mxenes [see rejection of claim 1 above]; Nan teaches MXene-graphene hybrid film forming Ti-O-C bond, thus demonstrating the formation of a covalent bond between laser-burned graphene [LBG] and Ti3C2Tx MXene [the first paragraph in Col. 2 on pg. 5]; thus the VSTM film comprises a 2D material of MXene disposed on the 2D material of graphene to form covalently bonded MXene-graphene [Ti-O-C bond] hybrid continuous film).
Regarding claim 5, modified Seo teaches the virus sensor set forth in claim 1, and Seo is silent to further comprising a microfluid receiver associated with the VSTM film configured to collect the sample from the subject.
Seo teaches the test sample is placed on the VSTM film of the FET biosensor, as shown in Fig.1. Fig.2A shows the dimension of the VSTM film is L x W=100x100 µm2 (see caption of Fig.2).
Nah teaches a microfluid receiver associated with the VSTM film configured to collect the sample from the subject (Fig.2 shows the MXene/graphene of the sensor is integrated with a microfluidic channel made of PDMS, and sweat enter the channel from human skin [section 2.3]).
Given the teachings of Seo regarding the test sample is placed on the VSTM film of the FET sensor and the dimensions of the VSTM film are L x W=100x100 µm2, and the teachings of Nah regarding a microfluidic channel is disposed on the VSTM film of the sensor to receive the test sample, 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 sensor by providing a microfluidic reservoir/receiver disposed on the VSTM film of the sensor, as taught by combined Seo and Nah, since it would allow to collect the test sample to be detected by the VSTM film of the sensor (see Fig.1 in Seo and Fig.2 in Nah).
Regarding claim 6, modified Seo teaches the virus sensor set forth in claim 1, and “wherein the sample is collected from at least one of a bioaerosol, a solution, and a touch” further limits the sample to be detected but fails to further limit the sensor apparatus. A claim is only limited by positively recited elements. Thus, "[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims." See MPEP 2115. Since the claim further limits the sample to be detected (material worked upon) but fails to limit the sensor (by a structure being claimed), the limitations of the claim have no patentable weight.
In the alternative, Examiner further notes that Seo does teach wherein the sample is collected from a solution (the sample is collected from nasopharyngeal swab specimens from COVID-19 patients and the diagnosis of COVID-19 is performed using nasopharyngeal swabs suspended in universal transport medium [UTM] [abstract, Fig.1, section of Real-time detection of SARS-CoV-2 antigen protein on pg. 5140]).
Regarding claim 8, modified Seo teaches the virus sensor set forth in claim 1, and Seo teaches wherein the probe comprises an antibody corresponding to the virus particles to be detected and wherein the antibody linked to the VSTM film comprises SARS-COV-2 spike antibody (see “SARS-COV-2 spike antibody” in Fig.1 as the probe linked to the VSTM film, and the SARS-COV-2 spike antibody is an antibody corresponding to the virus particles [SARS-CoV-2 antigen protein] to be detected [see the detection results as shown in Fig.4]).
Regarding claim 9, modified Seo teaches the virus sensor set forth in claim 1, and Seo teaches wherein the probe comprises a SARS-COV-2 spike antibody corresponding to the virus particles (SARS-CoV-2 antigen protein) to be detected and wherein the SARS-COV-2 spike antibody linked to the VSTM film (see Figs. 1 and 4).
Seo is silent to wherein the probe comprises a deoxyribonucleic acid (DNA) corresponding to the virus particles to be detected and wherein the DNA linked to the VSTM film comprises SARS-COV-2 DNA.
Hummer teaches detection of COVID-19 using MXene biosensors [para. 0227-0228], wherein the probe comprises a deoxyribonucleic acid (DNA) corresponding to the virus particles to be detected and wherein the DNA linked to the VSTM film comprises SARS-COV-2 DNA ( biologically sensitive molecules probes 4230 are SARS-CoV2 DNA biologically sensitive molecules 4250. The SARS-CoV2 DNA biologically sensitive molecules 4250 layered onto the MXene 4240 [para. 0228]).
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 probe of SARS-COV-2 spike antibody with the probe of SARS-COV-2 DNA, as taught by Hummer, since Hummer teaches the suitable alternative probe of SARS-COV-2 DNA for the detection of COVID-19 [para. 0228].
Regarding claim 24, modified Seo teaches the virus sensor set forth in claim 1, and Seo teaches further comprising a resistance monitor system (2634B semiconductor analyzer [Keithley Instruments, Cleveland, OH] and a probe station [Sensing Measurement on pg.5141]) coupled to the FET for measuring the drain-source current response thereof representative of the amount of the virus particles in the sample (I is the detected real-time current [Sensing Measurement on pg.5141]; Fig.4 shows the measured drain-source current response thereof representative of the amount of the virus particles [SARS-CoV-2 antigen protein] in the sample).
Regarding claim 25, modified Seo teaches the virus sensor set forth in claim 24, and Seo teaches wherein the resistance monitor system comprises a detector circuit configured to measure a drain-source current signal (A drain-source bias voltage of about 10 mV was maintained during measurement. The detected electrical response signal is the drain-source current I [Sensing Measurement on pg.5141; Fig.4]; Fig.3c shows a drain-source current signal IDS vs VDS, thus the 2634B semiconductor analyzer comprises a detector circuit configured to measure a drain-source current signal IDS).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Seo, Hoffman, Nah and Hummer, as applied to claim 1 above, and further in view of Riazi et al. (Surface modification of a MXene by an aminosilane coupling agent, Advanced Materials Interfaces, 2020, 7, 1902008)
Regarding claim 7, modified Seo teaches the virus sensor set forth in claim 1, and Seo further teaches wherein the VSTM film is functionalized for virus detection using 1-pyrenebutyric acid N-hydroxysuccinimide ester for linking the corresponding probe (see caption of Fig.1). As outlined in the rejection of claim 1 above, the VSTM film is a MXene/graphene hybrid film.
Seo is silent to wherein the probe linker is an aminosilane.
Riazi teaches surface functionalization of MXene with [3-(2-aminoethylamino)-propyl]trimethoxysilane (AEAPTES).
Since the VSTM film comprises MXene disposed on graphene (see rejection of claim 1 above), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to functionalize the top MXene by an aminosilane coupling agent such as AEAPTES, as taught by Riazi, since the silane coupling agent bonds to MXene surface both physically and chemically (abstract in Riazi).
Allowable Subject Matter
Claim 26 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter.
Regarding claim 26, modified Seo teaches the virus sensor set forth in claim 25, and Seo teaches the use of a 2634B semiconductor analyzer to measure the I-V curve (see Fig.3) and IDS at a fixed VDS for different concentration of the SARS-CoV-2 antigen protein in the sample (see Figs. 4-6). Seo is silent to wherein the detector circuit comprises an auto-balancing bridge impedance measurement circuit and a voltage divider resistance measurement circuit.
An auto-balancing bridge impedance measurement circuit is typically used in LCR (Inductance, Capacitance, Resistance) meters and impedance analyzers. For example, Agilent (Agilent Impedance measurement handbook, A guide to measurement technology and techniques, 4th Edition, June 17, 2009) teaches impedance measurement instruments (chapter 2.0) comprising auto-balancing bridge measurement circuit for measurements up to 110 MHz (see Figs. 2-1 and 2-2 and section 2.0). In some cases, measurement needs exist for evaluating impedance characteristics at large test signal voltages beyond the maximum oscillator output level of the instrument. For auto-balancing bridge instruments, output voltage enhancement is possible if the test signal is amplified as shown in Fig.5-43. A voltage divider is also required so that the input voltage of the Hp terminal is the same as the output voltage of the Hc terminal (Section 5-12). Although auto-balancing bridge circuit and voltage divider have been used in impedance analyzer, the combination is not used for DC I-V measurements because measuring current-voltage sweeps usually requires straightforward DC sourcing rather than AC signal balancing. Given the teachings of Seo regarding the measurements of I-V sweeps (see Fig.3) and current at a fixed drain-source voltage (section of Sensing instrument), one of ordinary skill in the art would use a straightforward DC sourcing rather than AC signal balancing for measuring a DC I-V curve or a DC current at a fixed voltage.
As allowable subject matter has been indicated, applicant's reply must either comply with all formal requirements or specifically traverse each requirement not complied with. See 37 CFR 1.111(b) and MPEP § 707.07(a).
Conclusion
The prior arts made of record and not relied upon are considered pertinent to applicant's disclosure: Hoffman (US20170053908A1) teaches a bioFET comprising a channel layer made of a 2D material comprising one or more of graphene and MXenes. Goldsmith et al. (US20220155289A1) teaches a FET including a channel made of 2D material composed of one or more of graphene and MXenes [para. 0498]. Chang et al. (US20110309334A1) teaches a graphene-based FET. Gu et al. (Three-dimensional porous Ti3C2Tx MXene-Graphene hybrid films for glucose biosensing, ACS Applied Nano Materials, 2019, 2, 6537-6545) teaches MXene-Graphene hybrid films for glucose biosensing. Zhou et al. (Super-tough MXene-functionalized graphene sheets, Nature communications, 2020, 11, 2027) teaches MXene nanosheets to functionalize rGO through Ti-O-C covalent bonding to obtain MXene-rGO sheet. Li et al. (Interfacial and electronic properties of heterostructures of MXene and graphene, Physical Review B, 2019, 99, 085429) teaches monolayer MXene-graphene heterostructure (Fig.1, abstract, and section II.A).
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/SHIZHI QIAN/Primary Examiner, Art Unit 1795
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