DETAILED ACTION
Table of Contents
I. Notice of Pre-AIA or AIA Status 3
II. Drawings and Specification 3
III. Claim Rejections - 35 USC § 112 4
A. Claims 1-13 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. 5
1. Claim 1 5
2. Claim 3 7
3. Claim 7 7
IV. Claim Rejections - 35 USC § 102 8
A. Claims 1-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2010/0327847 (“Leiber”). 8
B. Claims 7-9 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2017/0298429 (“Peng-429”), as evidenced by US 2012/0193236 (“Peng-236”) for only claim 8. 10
V. Claim Rejections - 35 USC § 103 14
A. Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Leiber in view of US 2016/0231307 (“Xie”). 14
B. Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Leiber in view of US 2015/0038378 (“Cheng”). 15
C. Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Peng-429 in view of US 2017/0059547 (“Feng”). 16
D. Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0298429 (“Peng-429”) in view of Leiber and as evidenced by US 2016/0254355 (“Koenig”) only for claim 2. 18
E. Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Peng-429, as evidenced by Peng-236, as applied to claims 7 and 8 above, and further in view of Leiber and Cheng 22
VI. Response to Arguments 23
Conclusion 25
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I. 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 .
II. Drawings and Specification
(1) Fig. 6 is objected to because the lines connecting each of the reference characters, 12 and 16, to the corresponding elements in Fig. 6 are not the same as 12 and 16 are pointing to in each of Figs. 1, 2A, 2B, 4, 5, and 7. In other words, reference character 12 in Fig. 6 should be pointing to the SiNx layer, and reference character 16 should be pointing to the electrode. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application.
(2) The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, each of the “first electrode” and the “second electrode” of the “second set of electrodes”, as currently added to claim 1, must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Further in this regard, it is noted that each of Figs. 1, 2A, 2B, 3, 5, 6, and 7 shows only the currently claimed “first set of electrodes 16, i.e. Au/Cr electrodes. It is further noted that in certain locations, the specification appears to mistakenly call the electrodes 16 both Au/Cr and Ag/AgCl most notably paragraph [0055], which states,
[0055] Measurement of experimental metrics includes, but is not limited to, electron tunneling current in plane to the graphene 14 acquired with the Au/Cr electrodes 16, in addition to the measurement of perpendicular ionic current with the Ag/AgCl electrodes 16. …
(Instant Specification: ¶ 55; emphasis added)
The two Au/Cr electrodes 16 shown in Figs. 1, 2A, 2B, 3, 5, 6, and 7 cannot simultaneously be two additional Ag/AgCl electrodes. And, as paragraph [0055] makes, clear, the Au/Cr electrodes perform a different function from the Ag/AgCl electrodes. As such, the specification should also be corrected.
(3) Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
III. 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.
A. Claims 1-13 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
1. Claim 1
Claim 1, as currently amended, reads,
[1] 1. (currently amended) A chip comprising:
[2] a silicon (Si) substrate;
[3] a silicon nitride (SiNx) layer on the Si substrate;
[4a] a graphene sheet comprising a nanopore,
[4b] the graphene sheet positioned atop the SiNx layer;
[5] a first set of electrodes coupled to the graphene sheet;
[6] a second set of electrodes, wherein a material of the first set of electrodes is different than a material of the second set of electrodes;
[7] a first liquid reservoir, wherein a first electrode in the second set of electrodes is coupled to the first liquid reservoir; and
[8] a second liquid reservoir, wherein a second electrode in the second set of electrodes is coupled to the second liquid reservoir.
First, as explained above, neither the first electrode or the second electrode of the second set of electrodes is shown in any of the figures of the Instant Application. Nor is either of the first and second liquid reservoir.
Second, the specification appears to state that the claimed “chip” and the reservoirs are separate entities, stating, e.g.,
[0024] FIG. 1 illustrates an annotated side elevational view of one example embodiment of the Si/SiNx chip with a GNR, GNP, and Au/Cr electrodes, according to the present application. Ag/AgCl electrodes are above and below the chip in this figure.
[0025] FIGS. 2A and 2B illustrate annotated side elevational views of the Si/SiNx chip of FIG. 1 with the Au/Cr electrodes encapsulated and the graphene and electrodes encapsulated, respectively. Ag/AgCl electrodes are above and below the chip in this figure.
[0052] In various embodiments, the assembled Si/SiNx chip 5, GNR 14 with GNP 20, and Au/Cr electrodes 16 (collectively referred to as the “chip mounted graphene” for simplicity) is transferred to a constructed microfluidic cassette containing ionic fluid of determined concentration, pH, and volume, as shown schematically in FIG. 8. …
[0053] In FIG. 8, the chip 5 is provided between two polymer channels bonded with two thin films of polymer in between. The chip is used to sequence DNA/RNA as it passes from one counter-current channel to the other.
[0054] In some embodiments, said microfluidic cassette, constructed from a range of materials including but not limited to thermoplastic polymers such as PDMS, may contain two distinct liquid reservoirs or “half-cells”, in between which may be positioned the chip-mounted graphene 14. Each Ag/AgCl electrode 16 is deposited in each half-cell of the microfluidic cassette, the chip 5 placed such that the electrodes 16 lie parallel to the flow of nucleic acids to be used for subsequent measurement of ionic current.
(Instant Specification: ¶¶ 24, 25, 52, 53, 54; emphasis added)
So the specification appears to indicate that the microfluidic cassette contains the claimed first and second liquid reservoir which form the half-cells when coupled with the respective first and second Ag/AgCl electrodes, which are not the Au/Cr electrodes 16 on the chip 5, as the paragraphs from the specification, above, make clear.
Based on the foregoing, it appears that the chip 5, to which the preamble of claim 1 is directed, is less than all of the elements to which claim 1 is directed since it also includes both the reservoirs and the second set of electrodes. As such, it is unclear if claim 1 is a chip or more than just a chip. The problem could be corrected by changing the preamble to reflect that claim 1 is drawn to more than just the chip, e.g., “A structure” or “A device”, etcetera.
Claims 2-6 and 12 are rejected for including the same indefinite feature by depending from claim 1 either directly or indirectly.
2. Claim 3
Claim 3 recites the limitation, “the one or more electrodes”. There is insufficient antecedent basis for this limitation in the claim. It is presumed that Applicant is referring, instead, to the “first set of electrodes” in claim 1.
3. Claim 7
Claim 7, as currently amended, reads,
7. (currently amended) A method comprising:
[1] providing a graphene monolayer;
[2] sculpting a graphene nanoribbon out of the graphene monolayer using electron-beam lithography;
[3] providing a nanopore in the graphene nanoribbon; and
[4a] providing a chip comprising:
[4b] a silicon (Si) substrate;
[4c] a silicon nitride (SiNx) layer on the Si substrate;
[4d] one or more electrodes; and
[4e] the graphene nanoribbon comprising the nanopore,
[4f] the graphene nanoribbon positioned atop the SiNx layer; and
[5] measuring, through the one or more electrodes, an ionic current.
New features [1]-[3] are directed to a process of making while, by contrast, feature [5] is directed to a process of using. As such, the statutory class of the invention in claim 7 is indefinite. See MPEP 2173.05(p)(II) directed to mixing of statutory classes in a single claim that renders the claim indefinite because it is unclear when infringement would occur. Here, it is unclear if infringement occurs when the process of making features [1]-[3] are performed or when the process of using feature [5] is performed. If party A makes the sensor chip but does not use it, and then sells the chemFET to party B who only uses it but did not make it, then neither party A nor party B infringes claim 7. Infringement of claim 7 could only occur if the same party both makes and uses the chemFET.
Claims 8-11 and 13 are rejected for including the same indefinite feature by depending from claim 7, either directly or indirectly.
IV. Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
A. Claims 1-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2010/0327847 (“Leiber”).
With regard to claim 1, Leiber discloses, generally in Figs. 1, 3A-3E, and 4,
1. (currently amended) [1] A chip comprising:
[2] a silicon (Si) substrate 30 [¶¶ 43, 45];
[3] a silicon nitride (SiNx) layer 32 or 34 on the Si substrate [¶¶ 43, 45];
[4a] a graphene sheet 44 [¶ 48] comprising a nanopore 20, 56 [“nanopore 20” (¶ 20) in Fig. 1, and “nanopore edge 56” (¶ 57) in Fig. 3F and shown but not labeled in Fig. 4],
[4b] the graphene sheet 44 positioned atop the SiNx layer 32 or 34;
[5] a first set of electrodes 40, 42 [¶ 47: “source and drain regions 40, 42” in Fig. 3C and D and S in Fig. 4] coupled to the graphene sheet 44;
[6] a second set of electrodes, wherein a material [e.g. “metal such as Ni, Ti/Pd, Pt” (¶ 47)] of the first set of electrodes 40, 42 is different than a material [“Ag/AgCl” in Fig. 4] of the second set of electrodes [“Ag/AgCl” in Fig. 4; ¶ 62];
[7] a first liquid reservoir 70 [¶¶ 60, 63; Fig. 4], wherein a first electrode [i.e. Ag/AgCl in 70] in the second set of electrodes is coupled to the first liquid reservoir 70; and
[8] a second liquid reservoir 72 [¶¶ 60, 63; Fig. 4], wherein a second electrode [i.e. Ag/AgCl in 72] in the second set of electrodes is coupled to the second liquid reservoir 72.
With regard to claims 2-5, Leiber further discloses,
2. (original) The chip of Claim 1, wherein the graphene sheet 44 comprises a monolayer graphene nanoribbon [¶ 34; ¶ 48: “For many applications, a generally rectangular ribbon-shaped or strip-shaped graphene channel region 44 can be preferred” (Figs. 1, 3C)].
3. (original) The chip of Claim 2, wherein
[1] the nanopore 20, 56 is centered in the monolayer graphene nanoribbon 44 [as shown in Fig. 1], and
[2] the monolayer graphene nanoribbon 44 is mounted to the one or more electrodes 40, 42, S, D [as shown in Figs. 3B-3E, and 4].
4. (original) The chip of Claim 2, wherein the monolayer graphene is configured for genetics sequencing [¶¶ 33, 35, 36; e.g. of DNA 22 (¶ 21) as shown in Fig. 4].
5. (original) The chip of Claim 1, wherein the graphene sheet 44 is positioned atop the SiNx layer 32 or 34 via Deep Ultraviolet (DUV) lithography or scanning thermal probe lithography.
As explained above, Leiber discloses that the graphene sheet 44 is positioned atop the SiNx layer 32 or 34.
The process of positioning the graphene sheet fails to have patentable weight for failing to require a structure. Note that a “product by process” claim is directed to the product per se, no matter how actually made, In re Hirao, 190 USPQ 15 at 17 (footnote 3). See also In re Brown, 173 USPQ 685; In re Luck, 177 USPQ 523; In re Fessmann, 180 USPQ 324; In re Avery, 186 USPQ 161; In re Marosi et al, 218 USPQ 289; and particularly In re Thorpe, 227 USPQ 964, all of which make it clear that it is the patentability of the final product per se which must be determined in a “product by process” claim, and not the patentability of the process, and that an old or obvious product produced by a new method is not patentable as a product, whether claimed in “product by process” claims or not. Note that Applicant has the burden of proof in such cases, as the above case law make clear.
B. Claims 7-9 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2017/0298429 (“Peng-429”), as evidenced by US 2012/0193236 (“Peng-236”) for only claim 8.
With regard to claim 7, Peng-429 discloses, generally in Fig. 4,
7. (currently amended) A method comprising:
[1] providing a graphene monolayer 104 [¶ 25, infra];
[2] sculpting a graphene nanoribbon 104 out of the graphene monolayer 104 using electron-beam lithography [¶ 25, infra];
[3] providing a nanopore in the graphene nanoribbon 104 [¶ 27: “Nanopore 110 through the stacked layers 106, 104, and 102 with sizes ranging from 0.5 nm to 100 nm can be made via TEM (transmission electron microscopy) drilling or other techniques.”]; and
[4a] providing a chip 100 [¶ 23; Fig. 1]comprising:
[4b] a silicon (Si) substrate 101 [¶ 24];
[4c] a silicon nitride (SiNx) layer 102 [¶ 24] on the Si substrate 101;
[4d] one or more electrodes 105a, 105b, 214, 215 [¶¶ 25, 38]; and
[4e] the graphene nanoribbon 104 comprising the nanopore 110,
[4f] the graphene nanoribbon 104 positioned atop the SiNx layer 102; and
[5] measuring, through the one or more electrodes 214, 215, an ionic current [using ammeter 225; ¶¶ 38-42].
With regard to feature [1] of claim 7, Peng-429 states that “the graphene layer 104 can be as thin as 0.335 nm (nanometers)” (¶¶ 22, 35). Koenig evinces that a monolayer of graphene is 0.34 nm thick (Koenig: ¶ 43). Therefore, it is held, absent evidence to the contrary, that the graphene layer that is 0.335 nm is a monolayer of graphene. As such, the burden of proof is shifted to Applicant to prove the contrary. (See MPEP 2112(I)-(V).)
With regard to feature [2] of claim 7, Peng-429 states,
[0025] To form the graphene layer 104, thin films of graphene can be formed by CVD (chemical vapor deposition) growth on metal, by exfoliation of bulk graphite, or by epitaxial grown on SiC (silicon carbide) by high temperature decomposition of its surface and sublimation of Si. Among these methods, graphene grown on copper can produce the largest film area (up to 30 inches in width). The underlying copper can be etched away by copper etchant and transferred to targeting substrate by using thermal release tape, PMMA (polymethyl methacrylate), or PDMS (polydimethylsiloxane). In this application, the graphene film/layer 104 can be transferred onto LPCVD Si3N4 layer 102 and be patterned through photolithography or ebeam lithography followed by reactive ion etching (RIE) based on O2 plasma. …
(Peng-429: ¶ 25; emphasis added)
This is all of the limitations of claim 7.
With regard to claims 9 and 11, Peng-429 further discloses,
9. The method of Claim 7, further comprising the step of providing a flow of an ionic fluid.
11. The method of Claim 9, wherein the ionic fluid is configured to stabilize nucleic acids for translocation and sequencing.
Peng-429 teaches that the ionic buffer 213 in the reservoirs 211 and 212 includes “free mobile ions” which reads on a “flow of an ionic fluid” within the broadest reasonable interpretation of the claim, as currently drafted.
With regard to the “stabilizing” of nucleic acids, Peng-429 states, that “the free mobile ions in the ionic buffer 213 will concentrate around the charged DNA molecule 217 to electrically screen any charge on the DNA”:
[0033] The DNA molecule 217 has charges on its molecular backbone 205 as well as different dipole moments for each of its DNA bases 218. When DNA molecule 217 is in ionic buffer, the free mobile ions in the ionic buffer 213 will concentrate around the charged DNA molecule 217 to electrically screen any charge on the DNA. The ions that screen the charged DNA are called counter-ions. As the counter ions are under thermal agitation, so the charged ions will spread out with a length scale, called Debye length, instead of tightly wrapping the DNA molecule 217.
(Peng-429: ¶ 33; emphasis added)
The function of the free mobile ions concentrating around the DNA molecule is taken to be stabilization, within the broadest reasonable interpretation in the claim, as currently drafted.
This is all of the limitations of claims 9 and 11.
Claim 8 reads,
8. The method of Claim 7, wherein the measuring step includes measuring a bimodal measurement of DNA or RNA nucleotide translocation by analyzing tunneling and ionic current simultaneously.
As explained above, Peng-429 uses ammeter 225, and therefore the flow of current through electrodes, 214 and 215, that are positioned in the reservoirs, 212 and 211, respectively, to measure the ionic current (Peng-429: ¶¶ 38-42; Fig. 7). Peng also, simultaneously measures a modulated current through the graphene transistor ammeter 220 between the claimed “one or more electrodes” 105a and 105b (Peng-429: abstract; ¶¶ 22, 35, 37, 38; Fig. 6).
It is held, absent evidence to the contrary, that the modulated current through the graphene transistor is a tunneling current. Evidence comes from Peng-236, which is the pre-grant publication of 13/359,729—incorporated by reference in its entirety into Peng-429 (Peng-429: ¶ 45).
Peng-236, like Peng-429, teaches a nucleic acid sequencing sensor having a nanometer-sized nanopore 206, 308 through a silicon nitride layer 202, 302 supported by a silicon substrate 201, 301 (Peng-236: Figs. 2A-2F, 3A-3B; ¶¶ 35-38), albeit not through a graphene layer, instead between electrodes 304a and 304b formed from metal layer 204 abutting the nanopore 206, 308 and forming a “tunneling junction” 205, 305 having the same spacing as the size of the nanopore, which may be as small as 0.4 nm which is the dimension of the electron beam used to pattern the metal layer (Peng-236: ¶¶ 30-31). Peng-236 explains that the flow of the nucleic acid through the nanopore 206, 308 generates a tunneling current between the electrodes 304a, 304b (Peng-236; abstract; ¶¶ 5-8, 30, 42-45).
Moreover, the configuration of the nucleic acid-sequencing graphene transistor chip and translocation of the nucleic acid through the nanopore of a monolayer of graphene between reservoirs is the same as in the Instant Application, having a nanopore size that can be even smaller than the 1 nm claimed in the Instant Application. Because the configuration of the device in Peng-429 is the same as that in the Instant Application, this provides additional evidence that the current measured by ammeter 220 in Peng-429 is a tunneling current.
Based on all of the foregoing evidence, the burden of proof is shifted to Applicant to prove the contrary, i.e. that the measured current through ammeter 220 is not a tunneling current. (See MPEP 2112(I)-(V).)
This is all of the limitations of claim 8.
V. Claim Rejections - 35 USC § 103
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 of this title, 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.
A. Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Leiber in view of US 2016/0231307 (“Xie”).
Claim 6 reads,
6. (original) The chip of Claim 1, wherein the nanopore is 1 nm.
With regard to claim 6, Leiber states, “For many applications, a nanopore diameter less than about 10 nm or less than about 5 nm is preferred, with a diameter of between about 1.5 nm and about 2 nm preferred for ssDNA sensing.” (Leiber: ¶ 55)
Leiber does not give a pore diameter of specifically 1 nm.
Xie teaches that it is known to use a nanopore diameter of 1 nm in graphene in a graphene-based bioFET, specifically for DNA sequencing (¶¶ 94, 157).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use a nanopore diameter of 1 nm in the graphene nanoribbon channel 44 in Leiber, because 1 nm is close to 1.5 nm disclosed in Leiber and is known to be suitable for the same purpose of sequencing DNA, as taught in Xie.
Based on the foregoing, the claimed nanopore diameter of 1 nm is obvious absent evidence showing it achieves unexpected results relative to the prior art range. See In re Woodruff, 16 USPQ2d 1935, 1937 (Fed. Cir. 1990). See also In re Boesch, 205 USPQ 215 (CCPA) (discovery of optimum value of result effective variable in known process is ordinarily within skill of art).
B. Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Leiber in view of US 2015/0038378 (“Cheng”).
Claim 12 reads,
12. (new) The chip of Claim 1,
[1] wherein the material of the first set of electrodes comprises gold/chromium (Au/Cr),
[2] wherein the material of the second set of electrodes comprises silver (Ag)/silver chloride (AgCl).
The prior art of Leiber, as explained above, teaches each of the features of claim 1.
As explained above, (1) Leiber discloses feature [2] of claim 12.
Leiber discloses that the first set of electrodes 40, 42, S, D are, e.g., Ni, Ti/Pd, Pt, but does not teach Au/Cr.
Cheng, like Leiber, teaches a graphene nanoribbon transistor used as a biosensor (Cheng: title, abstract, Figs. 1, 2). Cheng teaches that the first set of electrodes 102, 104 that correspond to the source and drain electrodes of Leiber, are made from Au/Cr (¶ 43 and Fig. 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use Au/Cr as the first set of electrodes 40, 42, S, D in Leiber because it would be the substitution of one known electrode material for another known electrode material suitable for forming the source and drain regions to a graphene nanoribbon transistor used for sensing biological materials. As such, the selection of Au/Cr amount to obvious material choice. (See MPEP 2144.07)
C. Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Peng-429 in view of US 2017/0059547 (“Feng”).
Claim 10 reads,
10. (original) The method of Claim 9, wherein the ionic fluid is a butylmethylimidazolium chloride (BMIM-Cl) solvent.
The prior art of Peng-429, as explained above, teaches each of the features of claims 7 and 9.
Peng-429 does not provide the composition of the “ionic buffer 213” in the reservoirs 211, 212.
Feng, like Peng-429, teaches a nucleic acid (e.g. DNA 18) sequencing sensor having a nanometer-sized nanopore 12 (Feng: ¶ 174) through a two-dimensional (2D) semiconductor channel material supported on a silicon nitride layer, in turn supported by a silicon substrate (Feng: Figs. 1, 2a, 2b; ¶¶ 35-38). The 2D semiconductor is MoS2 rather than a graphene layer, although graphene layers are also investigated (Feng: ¶¶ 132-137). Also like Peng-429, the DNA is sequenced by using ionic current and tunneling measurements given the configuration of the electrodes and ammeters AT and Ai, as shown in Fig. 1 (¶¶ 2, 3, 185, 190). Feng further teaches the use of room temperature ionic liquids (RTILs) 4a in the reservoirs 3a (Feng: ¶¶ 161-162, 199-200). The RTILs are used as solvents for the nucleic acids, e.g. DNA, to control the viscosity of the RTIL and thereby slowing the translocation speed of the nucleic acid through the nanopore, which, in turn, improves detection accuracy and reliability (Feng: ¶¶ 21-30, 50, infra). Among the preferred RTILs are 1-butyl-3methylimidazolium cations having, a counter ion of e.g. chlorine (Feng: ¶¶ 21-30, 50). Of note, Feng states the following:
[0021] In an embodiment of the invention, the first conducting liquid comprises a room temperature ionic liquid (RTIL).
[0022] In an embodiment of the invention, the room temperature ionic liquid (RTIL) has a viscosity (cP1) at room temperature from about 100 centipoises (cP) to about 500 centipoises (cP), for instance from about 100 cP to about 300 cP.
[0023] In an embodiment of the invention, the room temperature ionic liquid (RTIL) is selected from an essentially pure RTIL, optionally mixed with an organic solvent, or a mixture of a water-miscible RTIL in water with a water content from about 5 to about 50 wt %.
[0024] In an embodiment of the invention, the room temperature ionic liquid (RTIL) is selected from a group based on the anion nature: (a) systems based on AlCl3 and organic salts such as 1-butyl-3-methylimidazolium chloride, [bmim][Cl]; ….
[0026] In an embodiment of the invention, the room temperature ionic liquid (RTIL) includes N,N-dialkylimidazolium cations such as dibutyl, dioctyl, dinonyl, didecylimidazolium, 1-Butyl-3-methyl and 1-ethyl-3-methylimidazolium cations ([bmim]+ and [emim]+).
[0028] In an embodiment of the invention, the room temperature ionic liquid (RTIL) comprises 1-Butyl-3-methyl and 1-ethyl-3-methyl imidazolium cations.
[0030] In an embodiment of the invention, the room temperature ionic liquid (RTIL) is preferably 1-butyl-3-methylimidazolium hexafluorophosphate (BminPF.sub.6) but in principle RTILs that have high viscosity but have cations that bind preferentially to A, T, G, U or C nucleotides could provide additional benefit in specificity such as described in Zhang et al., 2012, Ionic liquids with metal chelate anions, Chemical Communications 48: 2334-2336. These properties could be further exploited to amplify the small differences in bases.
[0050] An advantageous characteristic of the invention is to provide a system where the viscosity of the conducting fluids can be tuned according to the needs and the analyte to be characterized. The viscosity gradient system exploits room temperature ionic liquid (preferably 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6)) as solvent, allowing slowing down DNA translocation speed. This allows adjusting the speed of translocation and thus improving detection accuracy and reliability.
(Feng: ¶¶ 21-24, 26, 28, 30, and 50; emphasis added)
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use BMIM-Cl as the ion buffer 213 for the nucleic acid in the cis reservoir 211 in Peng-429, in order to beneficially control the viscosity of the ionic buffer 213, thereby slowing the translocation speed of the nucleic acid through the nanopore 110, which, in turn, improves detection accuracy and reliability, as taught in Feng (Feng: ¶¶ 21-30, 50, supra).
This is all of the features of claim 10.
D. Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0298429 (“Peng-429”) in view of Leiber and as evidenced by US 2016/0254355 (“Koenig”) only for claim 2.
Claim 1 reads,
1. (currently amended) [1] A chip comprising:
[2] a silicon (Si) substrate;
[3] a silicon nitride (SiNx) layer on the Si substrate;
[4a] a graphene sheet comprising a nanopore,
[4b] the graphene sheet positioned atop the SiNx layer;
[5] a first set of electrodes coupled to the graphene sheet;
[6] a second set of electrodes, wherein a material of the first set of electrodes is different than a material of the second set of electrodes;
[7] a first liquid reservoir, wherein a first electrode in the second set of electrodes is coupled to the first liquid reservoir; and
[8] a second liquid reservoir, wherein a second electrode in the second set of electrodes is coupled to the second liquid reservoir.
With regard to claim 1, Peng-429 discloses, generally in Figs. 1A, 2A-2B, and 3
1. (currently amended) [1] A chip 100 [¶ 23; Fig. 1] comprising:
[2] a silicon (Si) substrate 101 [¶ 24];
[3] a silicon nitride (SiNx) layer 102 [¶ 24] on the Si substrate 101;
[4a] a graphene sheet 104 [¶ 25] comprising a nanopore 110 [¶¶ 22, 23, 27-20],
[4b] the graphene sheet 104 positioned atop the SiNx layer 102 [¶ 25];
[5] a first set of electrodes 105a, 105b [¶ 25] coupled to the graphene sheet 104;
[6] a second set of electrodes 214, 215 [¶ 32; Fig. 3], wherein a material of the first set of electrodes 105a, 105b [e.g. Ti/Pd/Au (¶ 25)] is different than a material of the second set of electrodes 214, 215;
[7] a first liquid reservoir 211 [¶ 32; Fig. 3], wherein a first electrode 215 in the second set of electrodes is coupled to the first liquid reservoir 211; and
[8] a second liquid reservoir 212 [¶ 32; Fig. 3], wherein a second electrode 214 in the second set of electrodes is coupled to the second liquid reservoir 212.
With regard to feature [6] of claim 1 and claim 12,
[6] … wherein a material of the first set of electrodes is different than a material of the second set of electrodes;
Peng-429 states that (1) the first set of electrodes 105a, 105b are “metal pads” made from, e.g., Ti/Pd/Au (¶ 25) and (2) the second set of electrodes 214, 215 are “electrochemical electrodes” (¶ 40), thereby suggesting that they are made from different materials, Peng-429 nonetheless does not give a material for the electrochemical electrodes 214, 215 and therefore does not explicitly teach that they are made from materials other than Ti/Pd/Au.
Leiber, like Peng-429, teaches a graphene-based transistor including a graphene nanoribbon channel with a nanopore for nucleotide, e.g. DNA and RNA, sequencing. As explained above in rejecting claim 1 over Leiber, Leiber teaches Ag/AgCl electrodes in each of the two reservoirs on opposite sides of the graphene nanoribbon channel to provide an electrical driving force to m (Leiber: ¶ 62-63; Fig. 4). This is, i.e. the driving of the DNA or RNA through the nanopore, one of the two purposes for the electrochemical electrodes 214, 215 in Peng-429 by applying a voltage bias to the electrodes 214, 215 using the voltage source 216 (Peng-429: ¶ 38).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use Ag/AgCl electrodes for the electrochemical electrodes 214, 215 in Peng-429 because Peng-429 is merely silent to the composition of the electrodes 214, 215 such that one having ordinary skill in the art would use known electrodes suitable for the same purpose of driving DNA and RNA through a nanopore in graphene, such as the Ag/AgCl electrodes taught in Leiber. As such, the selection of Ag/AgCl electrode amounts to obvious material choice. (See MPEP 2144.07.)
This is all of the limitations of claim 1.
With regard to claim 2, Peng-429 further discloses,
2. (original) The chip of Claim 1, wherein the graphene sheet 104 comprises a monolayer graphene nanoribbon [as shown in Figs. 2A-2C].
Peng-429 states that “the graphene layer 104 can be as thin as 0.335 nm (nanometers)” (¶¶ 22, 35). Koenig evinces that a monolayer of graphene is 0.34 nm thick (Koenig: ¶ 43). Therefore, it is held, absent evidence to the contrary, that the graphene layer that is 0.335 nm is a monolayer of graphene. As such, the burden of proof is shifted to Applicant to prove the contrary. (See MPEP 2112(I)-(V).)
With regard to claims 3 and 4, Peng-429 further discloses,
3. (original) The chip of Claim 2, wherein
[1] the nanopore 110 is centered in the monolayer graphene nanoribbon 104 [as shown in Fig. 2A], and
[2] the monolayer graphene nanoribbon 104 is mounted to the one or more electrodes 105a, 105b [as shown in Figs. 1A and 2A-2B].
4. (original) The chip of Claim 2, wherein the monolayer graphene 104 is configured for genetics sequencing [as shown in Fig. 3; ¶ 31].
Claim 5 reads,
5. (original) The chip of Claim 1, wherein the graphene sheet is positioned atop the SiNx layer via Deep Ultraviolet (DUV) lithography or scanning thermal probe lithography.
As explained above, Peng-429 discloses that the graphene sheet 104 is positioned atop the SiNx layer 102 (¶ 25).
The process of positioning the graphene sheet fails to have patentable weight for failing to require a structure. Note that a “product by process” claim is directed to the product per se, no matter how actually made, In re Hirao, 190 USPQ 15 at 17 (footnote 3). See also In re Brown, 173 USPQ 685; In re Luck, 177 USPQ 523; In re Fessmann, 180 USPQ 324; In re Avery, 186 USPQ 161; In re Marosi et al, 218 USPQ 289; and particularly In re Thorpe, 227 USPQ 964, all of which make it clear that it is the patentability of the final product per se which must be determined in a “product by process” claim, and not the patentability of the process, and that an old or obvious product produced by a new method is not patentable as a product, whether claimed in “product by process” claims or not. Note that Applicant has the burden of proof in such cases, as the above case law make clear.
Claim 6 reads,
6. (original) The chip of Claim 1, wherein the nanopore is 1 nm.
The prior art of Peng-429, as explained above, discloses each of the features of claim 1.
Peng-429 states that the “[n]anopore 110 through the stacked layers 106, 104, and 102 with sizes ranging from 0.5 nm to 100 nm can be made via TEM (transmission electron microscopy) drilling or other techniques” (¶ 27, last sentence). Moreover, Leiber teaches that the nanopore for DNA sequencing can be from 1.5 to 2.0 nm (supra).
In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); MPEP 2144.05(I)). In such a situation, Applicant must show that the particular ranges are critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range. See In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). (See MPEP 2144.05(III)(A); emphasis added.)
E. Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Peng-429, as evidenced by Peng-236, as applied to claims 7 and 8 above, and further in view of Leiber and Cheng
Claim 13 reads,
13. (new) The method of Claim 8,
[1] wherein the one or more electrodes comprises the gold/chromium (Au/Cr) electrodes and silver (Ag)/silver chloride (AgCl) electrodes,
[2] wherein the tunneling current is measured using the Au/Cr electrodes, and wherein the ionic current is measured using the Ag/AgCl electrodes.
The prior art of Peng-429 as evidenced by Peng-236, as explained above, discloses each of the features of claims 7 and 8.
With regard to feature [2] of claim 13, as explained under the rejection of claim 1 over Peng-429 in view of Leiber, above, the use of Ag/AgCl electrodes for the second set of electrodes 214, 215 in Peng-429 is obvious in view of Leiber. That explanation is incorporated here.
With regard to feature [1] of claim 13, Peng-429 states that the first set of electrodes 105a, 105b are “metal pads” made from, e.g., Ti/Pd/Au (¶ 25) and does not, therefore teach Au/Cr.
As explained above, Cheng teaches a graphene nanoribbon transistor used as a biosensor (Cheng: title, abstract, Figs. 1, 2). Cheng teaches that the first set of electrodes 102, 104 that correspond to the first set of electrodes 105a, 105b of Peng-429, are made from Au/Cr (¶ 43 and Fig. 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to use Au/Cr as the first set of electrodes 105a, 105b of Peng-429 because it would be the substitution of one known electrode material for another known electrode material suitable for forming the source and drain regions to a graphene nanoribbon transistor used for sensing biological materials. As such, the selection of Au/Cr amount to obvious material choice. (See MPEP 2144.07)
This is all of the limitations of claim 13.
VI. Response to Arguments
Applicant’s amendment to claim 7 overcomes the objection to the drawings and the rejection under 35 USC 112(b). However, the amendment to claim 1 generates new objections to the drawings, and the amendment to claim 7 generates a new rejection under 35 USC 112(b) (supra).
Applicant’s arguments filed 03/05/2026 have been considered but they are not fully persuasive.
While Examiner agrees that Peng-429, alone, does not teach all of the features of claim 1, Examiner respectfully disagrees that Peng-429 fails to disclose the vast majority of the limitations of claims 1, as shown above. In fact, Peng-429 teaches all of the limitations of claim 1 except for the material of the first set of electrodes 105a, 105b being different from the material of the second electrodes 214, 215. The new reference, Leiber is relied on for this teaching (supra). Applicant fails to indicate why the features indicated in the rejection of claim 1 over Peng-429 in view of Leiber, are not disclosed in Peng-429.
Applicant argues that Peng-429 does not disclose all of the features of claim 7, as amended. Examiner respectfully disagrees and maintains that Peng-429 discloses all of the limitations of claim 7 for the reasons explained in the rejection. Applicant failed to meet its requirement that a monolayer of graphene is other than 0.335 nm thick, thereby proving that the graphene layer 104 in Peng-429 is a monolayer. Applicant failed to consider that Peng-429 explicitly states that the graphene nanoribbon is patterned, i.e. sculpted, using e-beam lithography (¶ 25), as quoted from Peng-429 in the rejection above. The formation of the nanopore 110 is unambiguously disclosed in Peng-429. As such, Applicant’s arguments are inconsistent with the explicit disclosure in Peng-429.
Applicant’s arguments with respect to the rejection of any other claims have been considered but are moot because the new grounds 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.
Based on the foregoing, Applicant’s arguments are not found persuasive.
Conclusion
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 date of this final action.
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Signed,
/ERIK KIELIN/
Primary Examiner, Art Unit 2814