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 .
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitations uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitations are: “an optical coupling element” and “an optical detector” in claims 1 and 12.
Because these claim limitations are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, they are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have these limitations interpreted under
35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitations to avoid them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitations recite sufficient structure to perform the claimed function so as to avoid them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Objections
Claims 3 and 13 are objected to because of the following informalities:
a) in claim 3, line 6, “mental” should be replaced with – metal –.
b) as a first matter
37 C.F.R. 1.75 Claim(s).
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(c) One or more claims may be presented in dependent form, referring back to and further limiting another claim or claims in the same application. Any dependent claim which refers to more than one other claim ("multiple dependent claim") shall refer to such other claims in the alternative only. A multiple dependent claim shall not serve as a basis for any other multiple dependent claim. For fee calculation purposes under § 1.16, a multiple dependent claim will be considered to be that number of claims to which direct reference is made therein. For fee calculation purposes also, any claim depending from a multiple dependent claim will be considered to be that number of claims to which direct reference is made in that multiple dependent claim. In addition to the other filing fees, any original application which is filed with, or is amended to include, multiple dependent claims must have paid therein the fee set forth in § 1.16(j). Claims in dependent form shall be construed to include all the limitations of the claim incorporated by reference into the dependent claim. A multiple dependent claim shall be construed to incorporate by reference all the limitations of each of the particular claims in relation to which it is being considered.
Underlining by the Examiner.
Claim 3 requires
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However, claim 2, from which claim 3 depends, requires
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Thus, claim 3 is not a proper dependent claim as it does not fully further limit the subject matter of claim 2, but expands it with regard to the composition of the first electrode and of the second electrode.
c) in claim 13, line 6, “mental” should be replaced with – metal –.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
Note that dependent claims will have the deficiencies of base and intervening claims.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim 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:
a) claim 1 requires
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Also, Applicant’s originally filed specification paragraph [0126] states,
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However, Applicant’s Figure 1, presented below, which ”. . . . illustrates a schematic diagram of a nanopore-optical electronic device according to some embodiments of the present disclosure…” (see Applicant’s originally filed specification paragraph [0079]), shows a trans chamber over an unlabeled planar substrate, which supports a first electrode 106 and a second electrode 108, and a cis chamber underneath this planar substrate. Also, third electrode 110 and fourth electrode 112 are clearly spaced away from this planar substrate. Note the following in the MPEP
2173.03 Correspondence Between Specification and Claims [R-07.2022]
The specification should ideally serve as a glossary to the claim terms so that the examiner and the public can clearly ascertain the meaning of the claim terms. Correspondence between the specification and claims is required by 37 CFR 1.75(d)(1), which provides that claim terms must find clear support or antecedent basis in the specification so that the meaning of the terms may be ascertainable by reference to the specification. Glossaries of terms used in the claims are a helpful device for ensuring adequate definition of terms used in claims. If the specification does not provide the needed support or antecedent basis for the claim terms, the specification should be objected to under 37 CFR 1.75(d)(1). See MPEP § 608.01(o) and MPEP § 2181, subsection IV. Applicant will be required to make appropriate amendment to the description to provide clear support or antecedent basis for the claim terms provided no new matter is introduced, or amend the claim.
A claim, although clear on its face, may also be indefinite when a conflict or inconsistency between the claimed subject matter and the specification disclosure renders the scope of the claim uncertain as inconsistency with the specification disclosure or prior art teachings may make an otherwise definite claim take on an unreasonable degree of uncertainty. In re Moore, 439 F.2d 1232, 1235-36, 169 USPQ 236, 239 (CCPA 1971); In re Cohn, 438 F.2d 989, 169 USPQ 95 (CCPA 1971); In re Hammack, 427 F.2d 1378, 166 USPQ 204 (CCPA 1970).
Underlining added by the Examiner.
Applicant is requested to clarify how the claim 1 limitation “a cis-fluidic chamber and a trans-fluidic chamber in a planar substrate; . . . . [italicizing by the Examiner]” is to be understood. In particular, does the word “in” actually mean “over” or “underneath” or does “a planar substrate” actually mean a cuboid-shaped container? If Applicant is being his own lexicographer please heed MPEP 2173.05(a).
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b) claim 3 recites the limitation "the biomolecule" in line 4. There is insufficient antecedent basis for this limitation in the claim.
c) claim 3 requires
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However, claim 2, from which claim 3 depends, requires
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Claim 3 seems to diverge from claim 2 regarding the making and composition of the first electrode and of the second electrode. Applicant is requested to clarify whether the claim 3 phrase “wherein the first and second electrodes are electrochemically deposited with one or more metal materials” is meant to be encompassed by the claim 2 phrase “wherein the first electrode, the second electrode, the third electrode, and the fourth electrode are independently formed . . . .” Applicant is requested to clarify how the “mental [sic] materials” or claim 3 relate to the “gold, palladium, platinum, silver, or combinations thereof…” of claim 2.
c) claim 3 requires “and the nanogap is self-aligned with the first and second electrodes [italicizing by the Examiner]” It is not clear how understand this phrase. Applicant is requested to provide at least two examples of such self-alignment.
d) claim 5 requires “wherein the first electrode and the second electrode are orthogonal to the nano-fluidic channel and forms a self-aligned transverse tunneling junction with the nanogap on the planar substrate. [italicizing by the Examiner]” It is not clear how understand this clause. Applicant is requested to provide at least two examples of such self-alignment.
e) claim 12 requires
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Also, Applicant’s originally filed specification paragraph [0126] states,
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However, Applicant’s Figure 1, presented below, which ”. . . . illustrates a schematic diagram of a nanopore-optical electronic device according to some embodiments of the present disclosure…” (see Applicant’s originally filed specification paragraph [0079]), shows a trans chamber over an unlabeled planar substrate, which supports a first electrode 106 and a second electrode 108, and a cis chamber underneath this planar substrate. Also, third electrode 110 and fourth electrode 112 are clearly spaced away from this planar substrate. Note the following in the MPEP
2173.03 Correspondence Between Specification and Claims [R-07.2022]
The specification should ideally serve as a glossary to the claim terms so that the examiner and the public can clearly ascertain the meaning of the claim terms. Correspondence between the specification and claims is required by 37 CFR 1.75(d)(1), which provides that claim terms must find clear support or antecedent basis in the specification so that the meaning of the terms may be ascertainable by reference to the specification. Glossaries of terms used in the claims are a helpful device for ensuring adequate definition of terms used in claims. If the specification does not provide the needed support or antecedent basis for the claim terms, the specification should be objected to under 37 CFR 1.75(d)(1). See MPEP § 608.01(o) and MPEP § 2181, subsection IV. Applicant will be required to make appropriate amendment to the description to provide clear support or antecedent basis for the claim terms provided no new matter is introduced, or amend the claim.
A claim, although clear on its face, may also be indefinite when a conflict or inconsistency between the claimed subject matter and the specification disclosure renders the scope of the claim uncertain as inconsistency with the specification disclosure or prior art teachings may make an otherwise definite claim take on an unreasonable degree of uncertainty. In re Moore, 439 F.2d 1232, 1235-36, 169 USPQ 236, 239 (CCPA 1971); In re Cohn, 438 F.2d 989, 169 USPQ 95 (CCPA 1971); In re Hammack, 427 F.2d 1378, 166 USPQ 204 (CCPA 1970).
Underlining added by the Examiner.
Applicant is requested to clarify how the claim 12 limitation “a cis-fluidic chamber and a trans-fluidic chamber in a planar substrate; . . . . [italicizing by the Examiner]” is to be understood. In particular, does the word “in” actually mean “over” or “underneath” or does “a planar substrate” actually mean a cuboid-shaped container? If Applicant is being his own lexicographer please heed MPEP 2173.05(a).
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f) claim 13 requires “and the nanogap is self-aligned with the first and second electrodes . . . . [italicizing by the Examiner]” It is not clear how understand this phrase. Applicant is requested to provide at least two examples of such self-alignment.
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, 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, 10-12, 14, 16, 18, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Golovchenko et al. US 2006/0003458 A1 (hereafter “Golovchenko”) in view of Timothy Joyce US 2006/0019259 A1 (hereafter “Joyce”) and Mellor et al. US 8,802,838, B2 (hereafter “Mellor”).
Addressing claim 1, Golovchenko discloses a nanopore electronic device (see the title and Figure 1(b)), the nanopore electronic device comprising:
a cis-fluidic chamber and a trans-fluidic chamber in a planar substrate1 (see Figure 1(b));
a nano-fluidic channel connecting the cis-fluidic chamber and the trans-fluidic chamber (see Figure 6, noting therein “pore”, and Figure 10, noting therein “hole radius”. Also see paragraph [0025].);
a third electrode and a fourth electrode in the cis-fluidic chamber and the trans-fluidic chamber, respectively (the Examiner is construing the electrode clearly shown, but unlabeled, in the cis chamber in Figure 1(b) as this third electrode and is construing the electrode clearly shown and labeled “+” in the trans chamber in Figure 1(b) as this fourth electrode. Note also the following in paragraph [0080], “The electrode in the trans chamber is positively biased and connected to current sensing electronics, while the other electrode is connected to signal ground.”); and
a current-measuring circuit configured to measure an ionic current between the third electrode and the fourth electrode (this circuit may be inferred from “ionic current signal” in Figure 1(b) and from the graphs shown in Figure 1(c) in which the y-axis is labeled “Ionic current”. See also paragraphs [0013], [0082], and [0083].).
Golovchenko, though, does not disclose that the nanopore electronic device is a nanopore-optical electronic device,
a first electrode and a second electrode in the nano-fluidic channel, the first electrode and the second electrode forming a nanogap between the first electrode and the second electrode;
an optical coupling element configured to couple an electromagnetic beam with the nanogap;
an optical detector configured to detect an optical signal from the nanogap when a biomolecule translocates through the nanogap; and
a current-measuring circuit configured to measure a tunneling current between the first electrode and the second electrode.
Joyce discloses a nanopore-optical electronic device (see the title,
paragraph [0010], and Figures 6A, 6B, and 7),
a first electrode (7 in Figures 6A and 6B) and a second electrode (8 in Figures 6A and 6B) in the nano-fluidic channel (see Figures 6A and 6B and paragraph [0066] noting especially, “ When the optional substrate 8 is employed, the first electrode 7 and the second electrode 9 may be deposited on the substrate, or may comprise a portion of the substrate 8. In this embodiment of the invention, the nanopore 3 also passes through the optional substrate 8. Other embodiments of the invention may also be possible where the first electrode 7 and the second electrode 9 are positioned in the same plane (as opposed to one electrode being above or below the other) with or without the optional substrate 8. The use of multiple electrodes and/or substrates are also within the scope of the invention. [italicizing by the Examiner] ”), the first electrode and the second electrode forming a nanogap between the first electrode and the second electrode (see again Figures 6A and 6B, and paragraph [0066].);
an electromagnetic beam source (42 in Figure 6A) configured to expose the nanogap to an electromagnetic beam (Figure 6A and paragraph [0077]);
an optical detector (43 in Figure 6A) configured to detect an optical signal from the nanogap when a biomolecule translocates through the nanogap (Figure 6A and paragraph [0077]); and
a current-measuring circuit configured (11 in Figure 6A) to measure a tunneling current between the first electrode and the second electrode (see Figure 6A noting therein the circle with an arrow inside, which one of ordinary skill in the art would understand represents an electrical measurement meter. That at least tunneling current is to be measured is implied by Figures 7 and 8, and paragraphs [0082], [0085], [0087], and [0089]).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to replace the “Chip containing nanopore detector” in Golovchenko Figure 1(b) with the chip containing nanopore detector of Joyce
Figure 6A (the Joyce nanopore-optical electronic device as described above) because the nanopore electronic device of Golovchenko will then be a nanopore-optical electronic device that will allow multiple detection techniques, namely ionic blockage current, tunneling current, and optical detection, such as fluorescence detection, to simultaneously and independently monitor a biopolymer as it traverses the nanopore. See in this regard Joyce paragraphs [0004]-[0008], which briefly discusses various detection techniques commonly used in nanopore sensors. By allowing multiple detection techniques to be used simultaneously and independently monitor a biopolymer as it traverses the nanopore, complementary information about the biopolymer can be obtained and information from one technique can possibly be used to confirm information obtained by another technique.
The nanopore-optical electronic device of Golovchenko as modified by Joyce, though, does not have “an optical coupling element configured to couple an electromagnetic beam with the nanogap; . . . .”, although it does have, as indicated above, “an electromagnetic beam source (42 in Figure 6A) configured to expose the nanogap to an electromagnetic beam (Figure 6A and paragraph [0077]); . . . .”
Mellor discloses an ultra-high- coupling element throughput opti-nanopore DNA readout platform comprising an optical coupling element configured to couple an electromagnetic beam with the nanogap. See the title, and Figure 9 and col. 15:27-55, noting therein the following optical coupling elements Beam Expander 322, optical fiber 320, mirror 321, and microscope objective 314. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to provide one or more of the optical coupling element disclosed by Mellor in the nanopore-optical electronic device of Golovchenko as modified by Joyce because this allows the electromagnetic beam to be focused with or upon the nanogap as desired. For example, Mellor discloses, “The laser beam is slightly expanded at the focal point of objective 314, to allow a larger illumination area. The expansion of the beam is accomplished by slightly diverging the incoming expanded laser beam at the entrance to microscope objective 314. By moving one of the lenses on the beam expander 322 with respect to the other one, the beam is slightly defocused at the focal point of objective 314 and achieves a larger illumination area (~10 µm).” See Mellor col. 15:36-43.
Addressing claim 6, for the additional limitation of this claim recall the following from the rejection of underlying claim 1, “Mellor discloses an ultra-high- coupling element throughput opti-nanopore DNA readout platform comprising an optical coupling element configured to couple an electromagnetic beam with the nanogap. See the title, and Figure 9 and col. 15:27-55, noting therein the following optical coupling elements Beam Expander 322, optical fiber 320, mirror 321, and microscope objective 314. [italicizing added]” Note that a microscope objective is understood by the Examiner to include at least one lens.
Addressing claim 8, Golovchenko as modified by Joyce and Mellor discloses at least having the optical signal be fluorescence. See Mellor col. 4:7-12.
Addressing claim 10, for the additional limitation of this claim note the following in Golovchenko paragraph [0009], “In various embodiments, the polymer is a nucleic acid (e.g., single- or double-stranded DNA or RNA), a protein, a synthetic polymer, or a polysaccharide.”
Addressing claim 11, for the additional limitation of this claim recall the following from the rejection of underlying claim 1, “It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to replace the “Chip containing nanopore detector” in Golovchenko Figure 1(b) with the chip containing nanopore detector of Joyce Figure 6A (the Joyce nanopore-optical electronic device as described above) because the nanopore electronic device of Golovchenko will then be a nanopore-optical electronic device that will allow multiple detection techniques, namely ionic blockage current, tunneling current, and optical detection, such as fluorescence detection, to simultaneously and independently monitor a biopolymer as it traverses the nanopore. [highlighting added]”
Addressing claim 12, Golovchenko discloses a nanopore electronic device (see the title and Figure 1(b)), the nanopore electronic device comprising:
a cis-fluidic chamber and a trans-fluidic chamber in a planar substrate2 (see Figure 1(b));
a nano-fluidic channel connecting the cis-fluidic chamber and the trans-fluidic chamber (see Figure 6, noting therein “pore”, and Figure 10, noting therein “hole radius”. Also see paragraph [0025].);
a third electrode and a fourth electrode in the cis-fluidic chamber and the trans-fluidic chamber, respectively (the Examiner is construing the electrode clearly shown, but unlabeled, in the cis chamber in Figure 1(b) as this third electrode and is construing the electrode clearly shown and labeled “+” in the trans chamber in Figure 1(b) as this fourth electrode. Note also the following in paragraph [0080], “The electrode in the trans chamber is positively biased and connected to current sensing electronics, while the other electrode is connected to signal ground.”); and
a current-measuring circuit configured to measure an ionic current between the third electrode and the fourth electrode (this circuit may be inferred from “ionic current signal” in Figure 1(b) and from the graphs shown in Figure 1(c) in which the y-axis is labeled “Ionic current”. See also paragraphs [0013], [0082], and [0083].).
Golovchenko, though, does not disclose that the nanopore electronic device is a nanopore-optical electronic device,
a first electrode and a second electrode in the nano-fluidic channel, the first electrode and the second electrode forming a nanogap between the first electrode and the second electrode;
an optical coupling element configured to couple an electromagnetic beam with the nanogap;
an optical detector configured to detect an optical signal from the nanogap when a biomolecule translocates through the nanogap; and
a current-measuring circuit configured to measure a tunneling current between the first electrode and the second electrode.
Joyce discloses a nanopore-optical electronic device (see the title,
paragraph [0010], and Figures 6A, 6B, and 7),
a first electrode (7 in Figures 6A and 6B) and a second electrode (8 in Figures 6A and 6B) in the nano-fluidic channel (see Figures 6A and 6B and paragraph [0066] noting especially, “ When the optional substrate 8 is employed, the first electrode 7 and the second electrode 9 may be deposited on the substrate, or may comprise a portion of the substrate 8. In this embodiment of the invention, the nanopore 3 also passes through the optional substrate 8. Other embodiments of the invention may also be possible where the first electrode 7 and the second electrode 9 are positioned in the same plane (as opposed to one electrode being above or below the other) with or without the optional substrate 8. The use of multiple electrodes and/or substrates are also within the scope of the invention. [italicizing by the Examiner] ”), the first electrode and the second electrode forming a nanogap between the first electrode and the second electrode (see again Figures 6A and 6B, and paragraph [0066].);
an electromagnetic beam source (42 in Figure 6A) configured to expose the nanogap to an electromagnetic beam (Figure 6A and paragraph [0077]);
an optical detector (43 in Figure 6A) configured to detect an optical signal from the nanogap when a biomolecule translocates through the nanogap (Figure 6A and paragraph [0077]); and
a current-measuring circuit configured (11 in Figure 6A) to measure a tunneling current between the first electrode and the second electrode (see Figure 6A noting therein the circle with an arrow inside, which one of ordinary skill in the art would understand represents an electrical measurement meter. That at least tunneling current is to be measured is implied by Figures 7 and 8, and paragraphs [0082], [0085], [0087], and [0089]).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to replace the “Chip containing nanopore detector” in Golovchenko Figure 1(b) with the chip containing nanopore detector of Joyce
Figure 6A (the Joyce nanopore-optical electronic device as described above) because the nanopore electronic device of Golovchenko will then be a nanopore-optical electronic device that will allow multiple detection techniques, namely ionic blockage current, tunneling current, and optical detection, such as fluorescence detection, to simultaneously and independently monitor a biopolymer as it traverses the nanopore. See in this regard Joyce paragraphs [0004]-[0008], which briefly discusses various detection techniques commonly used in nanopore sensors. By allowing multiple detection techniques to be used simultaneously and independently monitor a biopolymer as it traverses the nanopore, complementary information about the biopolymer can be obtained and information from one technique can possibly be used to confirm information obtained by another technique.
The nanopore-optical electronic device of Golovchenko as modified by Joyce, though, does not have “an optical coupling element configured to couple an electromagnetic beam with the nanogap; . . . .”, although it does have, as indicated above, “an electromagnetic beam source (42 in Figure 6A) configured to expose the nanogap to an electromagnetic beam (Figure 6A and paragraph [0077]); . . . .”
Mellor discloses an ultra-high- coupling element throughput opti-nanopore DNA readout platform comprising an optical coupling element configured to couple an electromagnetic beam with the nanogap. See the title, and Figure 9 and col. 15:27-55, noting therein the following optical coupling elements Beam Expander 322, optical fiber 320, mirror 321, and microscope objective 314. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to provide one or more of the optical coupling elements disclosed by Mellor in the nanopore-optical electronic device of Golovchenko as modified by Joyce because this allows the electromagnetic beam to be focused with or upon the nanogap as desired. For example, Mellor discloses, “The laser beam is slightly expanded at the focal point of objective 314, to allow a larger illumination area. The expansion of the beam is accomplished by slightly diverging the incoming expanded laser beam at the entrance to microscope objective 314. By moving one of the lenses on the beam expander 322 with respect to the other one, the beam is slightly defocused at the focal point of objective 314 and achieves a larger illumination area (~10 µm).” See Mellor col. 15:36-43.
In sum, Golovchenko as modified by Joyce and Mellor discloses the nanopore-optical electronic device to be used in the method of Applicant’s claim 12.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to perform the steps of “providing a sample solution comprising a biomolecule in the cis-fluidic chamber; providing a first bias between the third electrode and the fourth electrode across the nano-fluidic channel; providing a second bias across the first electrode and the second electrode across the nanogap; concurrently measuring: a tunneling current between the first electrode and the second electrode, an ionic current between the third electrode and the fourth electrode when the biomolecule translocates through the nanogap, and an optical signal from the nanogap when the biomolecule translocates through the nanogap; . . . .”, because these steps are just a matter of using the nanopore-optical electronic device of Golovchenko as modified by Joyce and Mellor.
As for the claim 12 limitation “. . . .; and correlating the tunneling current, the ionic current, and the optical signal to determine a sequence of the biomolecule…” it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to perform this step because (1) Golovchenko discloses, “This method enables alternative probing mechanisms and applications including the study of molecular structure, e.g., conformation, and sequencing.[italicizing by the Examiner]”(see Golovchenko paragraph [0026]), and (2) as stated above, earlier in this claim rejection, “By allowing multiple detection techniques to be used simultaneously and independently monitor a biopolymer as it traverses the nanopore, complementary information about the biopolymer can be obtained and information from one technique can possibly be used to confirm information obtained by another technique.”
Addressing claim 14, for the additional limitation of this claim recall the following from the rejection of underlying claim 12, “Mellor discloses an ultra-high- coupling element throughput opti-nanopore DNA readout platform comprising an optical coupling element configured to couple an electromagnetic beam with the nanogap. See the title, and Figure 9 and col. 15:27-55, noting therein the following optical coupling elements Beam Expander 322, optical fiber 320, mirror 321, and microscope objective 314. [italicizing added]” Note that a microscope objective is understood by the Examiner to include at least one lens.
Addressing claim 16, Golovchenko as modified by Joyce and Mellor discloses at least having the optical signal be fluorescence. See Mellor col. 4:7-12.
Addressing claim 18, for the additional limitation of this claim note the following in Golovchenko paragraph [0009], “In various embodiments, the polymer is a nucleic acid (e.g., single- or double-stranded DNA or RNA), a protein, a synthetic polymer, or a polysaccharide.”
Addressing claim 19, for the additional limitation of this claim recall the following from the rejection of underlying claim 12, “It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to replace the “Chip containing nanopore detector” in Golovchenko Figure 1(b) with the chip containing nanopore detector of Joyce Figure 6A (the Joyce nanopore-optical electronic device as described above) because the nanopore electronic device of Golovchenko will then be a nanopore-optical electronic device that will allow multiple detection techniques, namely ionic blockage current, tunneling current, and optical detection, such as fluorescence detection, to simultaneously and independently monitor a biopolymer as it traverses the nanopore. [highlighting added]”
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Golovchenko in view of Joyce and Mellor as applied to claims 1, 6, 8, 10-12, 14, 16, 18, and 19 above, and further in view of Barth et al. US 2005/0014162 A1 (hereafter “Barth”).
Addressing claim 2, Golovchenko discloses that the third and fourth electrodes are formed of AgCl. See Golovchenko paragraph [0023]. Joyce discloses “[0069] The first electrode 7 may comprise a variety of electrically conductive materials. Such materials include electrically conductive metals and alloys of tin, copper, zinc, iron, magnesium, cobalt, nickel, and vanadium. Other materials well known in the art that provide for electrical conduction may also be employed. [italicizing by the Examiner]” Joyce also discloses “[0070] The second electrode 9 may comprise the same or similar materials as described above for the first electrode 7.”
Barth discloses an apparatus and method for threading a biopolymer through a nanopore. This apparatus in one embodiment comprises a set of electrodes 6 and 6’ and another set of electrodes 9 and 9’ for moving, separating, or threading biopolymers. See the title, Figures 1A and 1B, and paragraph [0034]. Barth further discloses “[0038] The first electrode set 6,6' and the second electrode set 9,9' may comprise a variety of electrically conductive materials. Such materials include electrically conductive metals and alloys of platinum, iridium, palladium, gold, mercury, mercury calomel, tin, copper, zinc, iron, magnesium, cobalt, nickel, and vanadium and various combinations thereof. Other materials well known in the art that provide for electrical conduction may also be employed. [italicizing by the Examiner]” In light of Barth, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have in the nanopore-optical electronic device of Golovchenko as modified by Joyce and Mellor the first electrode, the second electrode, the third electrode, and the fourth electrode be independently formed of gold, palladium, platinum, silver, or combinations thereof, because it is prima facie obvious as simple substitution of one known element for another to obtain predictable result. See MPEP 2143(I)(B). One of ordinary skill in the art would be able to select suitable metal or metal compounds from which to make the first electrode, the second electrode, the third electrode, and the fourth electrode based on factors such as electrical conductivity, chemical inertness to electrolyte solution and biopolymer in the cis-fluidic chamber and trans-fluidic chamber, expected working voltage and/or current range, and ease and cost of manufacturing the electrodes.
Claims 3-5 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Golovchenko in view of Joyce and Mellor as applied to claims 1, 6, 8, 10-12, 14, 16, 18, and 19 above, and further in view of Xiao et al. US 2018/0259475 A1 (hereafter “Xiao”) and Stuart Lindsay US 2010/0084276 A1 (hereafter “Lindsay”) and Wang et al., Nanopore chip with self-aligned transverse tunneling junction for DNA detection,” Biosensors and Bioelectronics 193 (2021) 113552 (hereafter “Wang”).
Addressing claim 3, as a first matter the Examiner notes that the claim 3 limitation “wherein the first and second electrodes are electrochemically deposited with one or more metal materials within the nano-fluidic channel and under feed-back control, . . . . [italicizing by the Examiner]” is a product-by-process limitation. As such, it is not limited to the manipulation of the recited steps, only the structure implied by the steps. Also, once a product appearing to be substantially identical is found and a prior art rejection is made, the burden shifts to the Applicant to show an nonobvious difference. See MPEP 2113. As best can be determined by the Examiner there is no material difference between the first and second electrodes of the nanopore-optical electronic device of Golovchenko in view of Joyce and Mellor and those that are electrochemically deposited with one or more metal materials within the nano-fluidic channel and under feed-back control.3 In addition, note that if electrochemical deposition were to be used to form the first electrode and the second electrode it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to do so under feedback control because (1) Lindsay discloses using software to control the electrochemical deposition rate and duration in order to optimize the forming of tunneling sensing electrodes of a nanopore electronic device. See in Lindsay the Abstract, Figures 1A, 2, and 21, and paragraphs [0003], [0065], [0071], and [0153]-[0161]; and (2) Wang discloses “a new strategy based on feedback-controlled electrochemical processes in a confined nanoscale space to construct nanopore
devices with self-aligned transverse tunneling junctions, all embedded on a nanofluidic chip.” See the Abstract. These feedback-controlled electrochemical processes allow precise gap size control (3.1 Precise gap size control via electrochemical deposition; page 3) and “ . . . . integrate precisely aligned transverse electrodes tuned to detect DNA translocation…”(see 4. Conclusions).
As for the claim 3 limitation “wherein: the one or more mental materials comprise silver (Ag), nickel (Ni), cobalt (Co), Ni alloy, Co alloy, gold, palladium, platinum, iridium, or an alloy thereof, or a combination thereof, . . . .”, recall the following from the rejection of claim 2, ‘ “. . . . The first electrode set 6,6' and the second electrode set 9,9' may comprise a variety of electrically conductive materials. Such materials include electrically conductive metals and alloys of platinum, iridium, palladium, gold, mercury, mercury calomel, tin, copper, zinc, iron, magnesium, cobalt, nickel, and vanadium and various combinations thereof. Other materials well known in the art that provide for electrical conduction may also be employed. [italicizing by the Examiner]” ‘
As for the claim 3 limitations “a distance between the first and second electrodes is between 1 nm and 100 nm, and the nanogap is self-aligned with the first and second electrodes and has a narrowest bottleneck in a path between the cis-fluidic chamber and the trans-fluidic chamber…”, Xiao discloses “[a] DNA sequencing device, and related method, which include a nanopore having a maximum width dimension of no greater than about 50 nm, and a pair of electrodes having a spacing of no greater than about 2 nm, the electrodes being exposed within the nanopore to measure a DNA strand passing through the nanopore.[italicizing by the Examiner]” See the Xiao Abstract. In the Xiao Figure 2 embodiment and the nanogap is self-aligned with the first and second electrodes and has a narrowest bottleneck in a path between the cis-fluidic chamber and the trans-fluidic chamber. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have in the nanopore-optical electronic device of Golovchenko as modified by Joyce, Mellor, and Barth a distance between the first and second electrodes is between 1 nm and 100 nm, and the nanogap is self-aligned with the first and second electrodes and has a narrowest bottleneck in a path between the cis-fluidic chamber and the trans-fluidic chamber as taught by Xiao because Xiao discloses
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It will be noted that one of ordinary skill in the art would recognize from this disclosure that the nanogap spacing is thus a result-effective variable and so having the distance between the first and second electrodes be another value between 1 nm and 100 nm than about say 2 nm is prima facie obvious as routine optimization (MPEP 2144.05 (II)) based on the diameter of the biopolymer strand to be analyzed.
Addressing claim 4, as a first matter the Examiner notes that the claim 4 limitation “wherein the first and second electrodes being electrochemically deposited with one or more metal materials within the nano-fluidic channel and under feed-back control comprises a pulsed electrochemical deposition with a pulse width of 50 ms or less and a rest period of about 2 seconds between pulses… [italicizing by the Examiner]” is a product-by-process limitation. As such, it is not limited to the manipulation of the recited steps, only the structure implied by the steps. Also, once a product appearing to be substantially identical is found and a prior art rejection is made, the burden shifts to the Applicant to show an nonobvious difference. See MPEP 2113. As best can be determined by the Examiner there is no material difference between the first and second electrodes of the nanopore-optical electronic device of Golovchenko in view of Joyce and Mellor and those that are electrochemically deposited with one or more metal materials within the nano-fluidic channel and under feed-back control as claimed.
Addressing claim 5, for the additional limitation of this claim see Golovchenko Figure 6A and Xiao Figures 1 and 2 (which was turned to in the rejection of underlying claim 3 for the “a narrowest bottleneck” limitation).
Addressing claim 13, as for the claim 13 limitations “wherein the first and second electrodes are electrochemically deposited with one or more metal materials within the nano-fluidic channel and under feed-back control, thereby forming the nanogap with a single path for the biomolecule to translocate from the cis-fluidic chamber to the trans-fluidic chamber, . . . .”, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to so form the first and second electrodes because
Joyce discloses,” [0069] The first electrode 7 may comprise a variety of electrically conductive materials. Such materials include electrically conductive metals and alloys of tin, copper, zinc, iron, magnesium, cobalt, nickel, and vanadium. Other materials well known in the art that provide for electrical conduction may also be employed. When the first electrode 7 is deposited on or comprises a portion of the solid substrate 8, it may be positioned in any location relative to the second electrode 9. [italicizing by the Examiner]” Also, “[0070] The second electrode 9 may comprise the same or similar materials as described above for the first electrode 7. As discussed above, its shape, size and positioning may be altered relative to the first electrode 7 and the nanopore 3…”;
Lindsay discloses using software to control the electrochemical deposition rate and duration in order to optimize the forming of tunneling sensing electrodes of a nanopore electronic device. See in Lindsay the Abstract, Figures 1A, 2, and 21, and paragraphs [0003], [0065], [0071], and [0153]-[0161]; and
(3) Wang discloses “a new strategy based on feedback-controlled electrochemical processes in a confined nanoscale space to construct nanopore devices with self-aligned transverse tunneling junctions, all embedded on a nanofluidic chip.” See the Abstract. These feedback-controlled electrochemical processes allow precise gap size control (3.1 Precise gap size control via electrochemical deposition; page 3) and “ . . . . integrate precisely aligned transverse electrodes tuned to detect DNA translocation…”(see 4. Conclusions).
As for the claim 13 limitation “wherein: the one or more mental materials comprise silver (Ag), nickel (Ni), cobalt (Co), Ni alloy, Co alloy, gold, palladium, platinum, iridium, or an alloy thereof, or a combination thereof, . . . .”, Barth discloses an apparatus and method for threading a biopolymer through a nanopore. This apparatus in one embodiment comprises a set of electrodes 6 and 6’ and another set of electrodes 9 and 9’ for moving, separating, or threading biopolymers. See the title, Figures 1A and 1B, and paragraph [0034]. Barth further discloses “[0038] The first electrode set 6,6' and the second electrode set 9,9' may comprise a variety of electrically conductive materials. Such materials include electrically conductive metals and alloys of platinum, iridium, palladium, gold, mercury, mercury calomel, tin, copper, zinc, iron, magnesium, cobalt, nickel, and vanadium and various combinations thereof. Other materials well known in the art that provide for electrical conduction may also be employed. [italicizing by the Examiner]” In light of Barth, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have in the nanopore-optical electronic device of Golovchenko as modified by Joyce and Mellor the first electrode, the second electrode, the third electrode, and the fourth electrode be independently formed of gold, palladium, platinum, silver, or combinations thereof, because it is prima facie obvious as simple substitution of one known element for another to obtain predictable result. See MPEP 2143(I)(B). One of ordinary skill in the art would be able to select suitable metal or metal compounds from which to make the first electrode, the second electrode, the third electrode, and the fourth electrode based on factors such as electrical conductivity, chemical inertness to electrolyte solution and biopolymer in the cis-fluidic chamber and trans-fluidic chamber, expected working voltage and/or current range, and ease and cost of manufacturing the electrodes
As for the claim 13 limitations “a distance between the first and second electrodes is between 1 nm and 100 nm, and the nanogap is self-aligned with the first and second electrodes and has a narrowest bottleneck in a path between the cis-fluidic chamber and the trans-fluidic chamber…”, Xiao discloses “[a] DNA sequencing device, and related method, which include a nanopore having a maximum width dimension of no greater than about 50 nm, and a pair of electrodes having a spacing of no greater than about 2 nm, the electrodes being exposed within the nanopore to measure a DNA strand passing through the nanopore.[italicizing by the Examiner]” See the Xiao Abstract. In the Xiao Figure 2 embodiment and the nanogap is self-aligned with the first and second electrodes and has a narrowest bottleneck in a path between the cis-fluidic chamber and the trans-fluidic chamber. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have in the nanopore-optical electronic device of Golovchenko as modified by Joyce, Mellor, and Barth a distance between the first and second electrodes is between 1 nm and 100 nm, and the nanogap is self-aligned with the first and second electrodes and has a narrowest bottleneck in a path between the cis-fluidic chamber and the trans-fluidic chamber as taught by Xiao because Xiao discloses
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It will be noted that one of ordinary skill in the art would recognize from this disclosure that the nanogap spacing is thus a result-effective variable and so having the distance between the first and second electrodes be another value between 1 nm and 100 nm than about say 2 nm is prima facie obvious as routine optimization (MPEP 2144.05 (II)) based on the diameter of the biopolymer strand to be analyzed.
Claims 7 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Golovchenko in view of Joyce and Mellor as applied to claims 1, 6, 8, 10-12, 14, 16, 18, and 19 above, and further in view of Liu et al. CN 113533294 A based on an EPO machine-generated English language translation (hereafter “Liu”).
Addressing claim 7, Golovchenko as modified by Joyce and Mellor does not disclose “. . . ., wherein the optical coupling element further comprises a polarizer.”
Liu discloses “[t]ime-domain, space domain and spectral domain single molecule characterization device based on nano-gap electrode pair.” “The invention relates to the field of optoelectronic technology, in particular to a single molecule characterization
device based on a nano-gap electrode pair in time domain, space domain and spectral domain.” See page 1. “The device uses a confocal system for excitation to achieve an improvement in spatial resolution. The femtosecond laser 5 outputs the femtosecond laser through the single-mode polarization maintaining fiber 2b and enters the pulse
selector 6 after passing through the collimating beam expander 3b. . . . . The quarter wave plate 9 is modulated into circularly polarized light (or other required
polarized light). [italicizing by the Examiner]” See Liu page 5. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the optical coupling element of the nanopore-optical electronic device of Golovchenko as modified by Joyce and Mellor further comprise a polarizer as taught by Liu because (1) the optical arraignment of Liu is already similar to that of the nanopore-optical electronic device of Golovchenko as modified by Joyce and Mellor in that it also comprises at least one lens, at least one mirror, a laser, and a beam expander (see the second full paragraph on page 5 (“in order to . . . .”), and (2) Liu discloses, “In order to improve the time resolution and spatial resolution of tunnel current detection, the device can also realize optical coupling tunneling current detection through femtosecond laser pump-detection… [italicizing by the Examiner]” (see the second full paragraph on page 5), “The excitation of femtosecond laser stimulates the barrier change of the tunnel junction, forming a rapid change, and then through the tunnel junction single-molecule analyzer 24 to detect the electrical signal of the tunneling electrode quickly and accurately, and realize the time resolution of tunnel current detection. Significant increase in the rate… [italicizing by the Examiner]” (see the second full paragraph on page 5), and “Under excitation detection, the resolution of the spatial domain is improved. [italicizing by the Examiner]” (see the fourth full paragraph on page 5)”
Addressing claim 15, Golovchenko as modified by Joyce and Mellor does not disclose “. . . ., wherein the optical coupling element further comprises a polarizer.”
Liu discloses “[t]ime-domain, space domain and spectral domain single molecule characterization device based on nano-gap electrode pair.” “The invention relates to the field of optoelectronic technology, in particular to a single molecule characterization
device based on a nano-gap electrode pair in time domain, space domain and spectral domain.” See page 1. “The device uses a confocal system for excitation to achieve an improvement in spatial resolution. The femtosecond laser 5 outputs the femtosecond laser through the single-mode polarization maintaining fiber 2b and enters the pulse
selector 6 after passing through the collimating beam expander 3b. . . . . The quarter wave plate 9 is modulated into circularly polarized light (or other required
polarized light). [italicizing by the Examiner]” See Liu page 5. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the optical coupling element of the nanopore-optical electronic device of Golovchenko as modified by Joyce and Mellor further comprise a polarizer as taught by Liu because (1) the optical arraignment of Liu is already similar to that of the nanopore-optical electronic device of Golovchenko as modified by Joyce and Mellor in that it also comprises at least one lens, at least one mirror, a laser, and a beam expander (see the second full paragraph on page 5 (“in order to . . . .”), and (2) Liu discloses, “In order to improve the time resolution and spatial resolution of tunnel current detection, the device can also realize optical coupling tunneling current detection through femtosecond laser pump-detection… [italicizing by the Examiner]” (see the second full paragraph on page 5), “The excitation of femtosecond laser stimulates the barrier change of the tunnel junction, forming a rapid change, and then through the tunnel junction single-molecule analyzer 24 to detect the electrical signal of the tunneling electrode quickly and accurately, and realize the time resolution of tunnel current detection. Significant increase in the rate… [italicizing by the Examiner]” (see the second full paragraph on page 5), and “Under excitation detection, the resolution of the spatial domain is improved. [italicizing by the Examiner]” (see the fourth full paragraph on page 5)”
Claims 9 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Golovchenko in view of Joyce and Mellor as applied to claims 1, 6, 8, 10-12, 14, 16, 18, and 19 above, and further in view of Lindsay.
Addressing claim 9, Golovchenko as modified by Joyce and Mellor does not disclose “wherein the first electrode and the second electrode further comprise a surface modification layer including polyethylene glycol thiol (PEG-thiol), alkyl thiol, cysteine, 4(5)-(2- mercaptoethyl)-1 H-imidazole-2-carboxamide, or a combination thereof.”
Lindsay discloses a nanopore electronic device comprising: a cis-fluidic chamber and a trans-fluidic chamber in a planar substrate; a nano-fluidic channel connecting the cis-fluidic chamber and the trans-fluidic chamber; a first electrode and a second electrode in the nano-fluidic channel, the first electrode and the second electrode forming a nanogap between the first electrode and the second electrode; and a third electrode and a fourth electrode in the cis-fluidic chamber and the trans-fluidic chamber. See in Lindsay the Abstract, Figures 1A, 2, and 21, and paragraphs [0003], [0065], and [0071]. Lindsay further discloses having the first electrode and the second electrode further comprise a surface modification layer including an alkyl thiol or 4(5)-(2- mercaptoethyl)-1 H-imidazole-2-carboxamide. See paragraphs [0069] and [0180]. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the first electrode and the second electrode in the nanopore-optical electronic device of Golovchenko as modified by Joyce and Mellor further comprise a surface modification layer including an alkyl thiol or 4(5)-(2- mercaptoethyl)-1 H-imidazole-2-carboxamide as taught by Lindsay because Lindsay discloses that a first affinity element may then be connected to the first electrode and a second affinity element may then be connected to the second electrode, which will enhance the ability of the nanopore-optical electronic device to recognize DNA bases. See in Lindsay paragraphs [0017]-[0021], [0104], and [0180].
Addressing claim 17, Golovchenko as modified by Joyce and Mellor does not disclose “wherein the first electrode and the second electrode further comprise a surface modification layer including polyethylene glycol thiol (PEG-thiol), alkyl thiol, cysteine, 4(5)-(2- mercaptoethyl)-1 H-imidazole-2-carboxamide, or a combination thereof.”
Lindsay discloses a nanopore electronic device comprising: a cis-fluidic chamber and a trans-fluidic chamber in a planar substrate; a nano-fluidic channel connecting the cis-fluidic chamber and the trans-fluidic chamber; a first electrode and a second electrode in the nano-fluidic channel, the first electrode and the second electrode forming a nanogap between the first electrode and the second electrode; and a third electrode and a fourth electrode in the cis-fluidic chamber and the trans-fluidic chamber. See in Lindsay the Abstract, Figures 1A, 2, and 21, and paragraphs [0003], [0065], and [0071]. Lindsay further discloses having the first electrode and the second electrode further comprise a surface modification layer including an alkyl thiol or 4(5)-(2- mercaptoethyl)-1 H-imidazole-2-carboxamide. See paragraphs [0069] and [0180]. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to have the first electrode and the second electrode in the nanopore-optical electronic device of Golovchenko as modified by Joyce and Mellor further comprise a surface modification layer including an alkyl thiol or 4(5)-(2- mercaptoethyl)-1 H-imidazole-2-carboxamide as taught by Lindsay because Lindsay discloses that a first affinity element may then be connected to the first electrode and a second affinity element may then be connected to the second electrode, which will enhance the ability of the nanopore-optical electronic device to recognize DNA bases. See in Lindsay paragraphs [0017]-[0021], [0104], and [0180].
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Golovchenko in view of Joyce and Mellor as applied to claims 1, 6, 8, 10-12, 14, 16, 18, and 19 above, and further in view of Reid et al. US 2015/0057948 A1 (hereafter Reid),
Addressing claim 20, Golovchenko as modified by Joyce and Mellor does not disclose “wherein the correlating the tunneling current, the ionic current, and the optical signal to determine a sequence of the biomolecule comprises analyzing the tunneling current, the ionic current, and the optical signal by utilizing a machine learning algorithm to determine the sequence of the biomolecule, wherein the machine learning algorithm is a support vector machine.”
Reid discloses, “A time-ordered series of measurements of a polymer made during translocation of the polymer through a nanopore are analysed. The measurements are dependent on the identity of k-mers in the nanopore, a k-mer being k polymer units of the polymer, where k is a positive integer. The method involves deriving, from the series of measurements, a feature vector of time-ordered features representing characteristics of the measurements; and determining similarity between the derived feature vector and at least one other feature vector.” See the Reid Abstract.
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to utilizing a machine learning algorithm to determine the sequence of the biomolecule, wherein the machine learning algorithm is a support vector machine because Reid further discloses, “Given a training set of feature vectors of known class, standard statistical and machine-learning classification techniques may be used to predict the class of a new feature vector. For instance, a decision tree classifier (for example, but not limited, to C4.5. Quinlan, J. R. (1993) C4.5: Programs for Machine Learning. Morgan Kaufmann Publishers) can learn that particular positions of the reference-aligned feature vector are above a particular value for one class only. So-called black box methods such as neural networks, random forests and support vector machines may be used to make predictions of class membership, while not necessarily generating interpretable rules. In an alternative method, Bayesian networks may be implemented, where expert knowledge may also be incorporated.” See Reid paragraph [0272].
Put another way, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the application to utilize a machine learning algorithm to determine the sequence of the biomolecule, wherein the machine learning algorithm is a support vector machine because it is prima facie obvious as applying a known computational technique to a known device ready for improvement to yield predictable results. See MPEP 2143(I)(D).
Other Relevant Prior Art
The International Search Report for international application no. PCT/US2022/049816 cites an article by Wang et al. as a “X” document against
claims 1-6 and 8-11 of that application and as a Y” document against claims 6 and 7; and cites CN 113533294 A as a “Y” document against claims 6 and 7. The corresponding Written Opinion deems claims 6 and 7 to have novelty, but deems claims 1-5 and 8-11 to lack novelty over Wang. Claims 1-11 are deemed to lack an inventive step. The article by Wang et al. is the Wang reference used to reject claims 3-5 and 13 above under
35 U.S.C. 103. CN 113533294 A is the Liu reference used to reject claims 7 and 15 above under 35 U.S.C. 103.
The EPO Communication for application no./patent no. 22893711.6 - 1001 / 4434306 PCT/US2022049816 cites WO 2021/111987 A1, dated 2.08.2025, as a ‘X” document against claims 1-14 of that application and as a "Y” document against clam 15, and cites an article by Liang et al. as a “Y” document against claim 15.
US 20220291194 A1 is an English language equivalent to WO 2021/111987 A1.
WO 2021/111987 A1 together with the article by Liang et al. are at best redundant with respect to the prior art applied above under 35 U.S.C. 103.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER STEPHAN NOGUEROLA whose telephone number is (571)272-1343. The examiner can normally be reached on Monday - Friday 9:00AM-5:30 PM EST.
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/ALEXANDER S NOGUEROLA/ Primary Examiner, Art Unit 1795
1 Note that the phrase “in a planar substrate;” in light of Applicant’s Figure 1 can be understood to mean either – respectively underneath and over a planar substrate; -- or – in a cuboid-shaped container --. See the rejection of claim 1 under 35 U.S.C. 112(b) above.
2 Note that the phrase “in a planar substrate;” in light of Applicant’s Figure 1 can be understood to mean either – respectively underneath and over a planar substrate; -- or – in a cuboid-shaped container --. See the rejection of claim 1 under 35 U.S.C. 112(b) above.
3 Note that Joyce discloses, “Metal electrodes are formed by evaporation or other deposition means on the opposing surfaces of the SiN.sub.3 membrane.” See Joyce paragraph [0101].
Prosecution Insights