Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/20/2026 has been entered.
Response to Amendment
The Amendment filed 01/20/2026 has been entered. Claims 1, 4, 6-10, and 13-22 remain pending in the application. Claims 16-22 are withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4, 6-10 and 13-15 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.
Regarding claim 1, claim 1 recites “the opening through the electrically conductive layer forming a bottom of the wall of the well” in lines 10-11. Since “a wall of a well with a bottom boundary defined by the substrate layer” is established in lines 8-9, it is unclear how the “opening” forms a bottom of the wall of the well. Is the bottom of the well formed by the substrate layer or the opening? If the opening is interpreted as a gap/hole, would the wall of the electrically conductive layer that forms the opening form the wall of the bottom of the wall of the well? Claims 4, 6-10 and 13-15 are rejected by virtue of their dependency on claim 1.
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, 4, 6-7, and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Bashir et al. (US 20120021918 A1) in view of Kinz-Thompson et al. (US 20130294972 A1; cited in the IDS filed 03/24/2022).
Regarding claim 1, Bashir teaches an apparatus (Figs. 1-6 and abstract, chemical sensor device 100) for sensing a molecule (interpreted as an intended use, see MPEP 2114; abstract teaches biochemical sensing and molecule detection), the structure comprising:
a substrate layer (Fig. 1, first passivation layer 107);
a sample interface layer (second passivation layer 109) having a sample interface side (side of element 109 towards the top, opposite of the side adjacent to element 108) and a substrate layer facing side (side of element 109 adjacent to element 108);
an electrically conductive layer (electrostatic lens electrode 108; wherein the electrode is interpreted as an electrically conductive layer since it can conduct electricity as an electrode) disposed between the substrate layer facing side of the sample interface layer and the substrate layer (Fig. 1, element 108 is between elements 109 and 107);
wherein the sample interface layer (109) and electrically conductive layer (108) each define a respective opening therethrough that, aligned, compose a wall of a well (Fig. 1 shows elements 108 and 109 have aligned respective openings that compose a wall of a well) with a bottom boundary defined by the substrate layer (Fig. 1 shows a bottom boundary of the wall of the well is defined by first passivation layer 107);
the opening through the electrically conductive layer forming a bottom of the wall of the well (Fig. 1 teaches the opening through element 108 forms a bottom of the wall of the well since element 108 is below element 109 and therefore is interpreted as part of the bottom wall of the well), and the electrically conductive layer (108), when energized with a given polarity relative to an electrically conductive element in a sample at the sample interface layer, producing an electric field from the electrically conductive layer through the well to the electrically conductive element (interpreted as a functional limitation of the electrostatic lens electrode 108; Figs. 2A-2D and paragraph [0055] teach a potential difference is applied to the electrostatic lens electrode and the gate to attract molecules, thus the electrostatic lens electrode 108 is structurally capable of being energized with a given polarity to produce an electric field to produce an electric field as claimed; note that “an electrically conductive element in a sample” is not positively recited structurally), the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer at the bottom of the wall of the well (interpreted as a functional limitation of the electrostatic lens electrode 108; Figs. 2A-2D and paragraph [0055] teach a potential difference is applied to the electrostatic lens electrode and the gate to attract molecules, thus the electrostatic lens electrode 108 is structurally capable of producing an electric field of a polarity as claimed to draw or attract the molecule from the top side of the second passivation layer 109, through the well and towards the electrostatic lens electrode 108, i.e. bottom of the wall of the well; note that “molecule” is not positively recited structurally);
an organic matter (Figs. 2A-2D, probe molecule 210; paragraph [0021] teaches probe molecules include DNA, LNA, PNA, RNA, aptamer, or proteins, which are organic matter), fixedly located in the well (Figs. 2A-2D and paragraph [0021] teaches the probe molecule is immobilized in the well), that is selected based on a property that enables the molecule to chemically couple thereto (paragraph [0055] teaches the probe molecule is for detection of the target analyte molecule, thus is capable of enabling the molecule to chemically couple thereto), wherein the molecule is DNA or RNA (note that “the molecule” is not positively recited structurally; paragraph [0023] teaches detection of RNA or DNA, thus the apparatus is capable of being used for sensing DNA or RNA); and
a voltage potential source (Fig. 2C and paragraph [0016] teaches a voltage controller, where a potential difference 213 is applied) configured to apply a voltage potential difference between the electrically conductive element and the electrically conductive layer (interpreted as a functional limitation, see MPEP 2114; Figs. 2C-2D and paragraph [0016] teaches a voltage controller, where a potential difference is applied; therefore, the voltage controller is structurally capable of applying a voltage potential difference between an electrically conductive element in a sample and the electrically conductive layer, i.e. electrostatic lens electrode 108, at a later time, such as when an electrically conductive element in a sample is between the areas of elements 108 and 103; note that “the electrically conductive element” is not positively recited structurally).
Bashir fails to teach:
wherein the substrate layer is a transparent material at visible and near-infrared wavelengths and the sample interface layer is an optically reflective layer for the visible and near-infrared wavelengths;
an optical sensor system, the optical sensor system having an arrangement to direct a wavelength to the well via the substrate layer and collect a response from the molecule via the substrate layer, the optically reflective layer limiting transmission of the wavelengths to the sample above the sample interface layer;
wherein the visible wavelengths range from about 400 nm to about 800 nm, and wherein the well is a zero-mode waveguide relative to the visible wavelengths;
wherein the organic matter is a complex comprising a DNA or RNA-processing enzyme to which the molecule binds.
Kinz-Thompson teaches an apparatus for sensing a molecule (Fig. 1; abstract), the structure comprising: a substrate layer (substrate 120); a sample interface layer (side wall 110) having a sample interface side (top side of side wall 110 opposite of element 130) and a substrate layer facing side (bottom side of side wall 110 adjacent to element 130); an electrically conductive layer (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer) disposed between the substrate layer facing side of the sample interface layer and the substrate layer (Fig. 1 shows adhesion layer 130 is between elements 110 and 120); and wherein the sample interface layer and electrically conductive layer each define a respective opening therethrough that, aligned, compose a wall of a well (Fig. 1 shows an opening through elements 110 and 130 that are aligned and compose a wall of nano-well 101) with a bottom boundary defined by the substrate layer (Fig. 1 shows nano-well 101 with a bottom boundary defined by substrate 120). Kinz-Thompson teaches the substrate layer is a transparent material at visible and near-infrared wavelengths (paragraph [0026] teaches the substrate 120 is a transparent material, such as glass; therefore, the glass is transparent at visible and near-infrared wavelengths) and the sample interface layer is an optically reflective layer for the visible and near-infrared wavelengths (paragraph [0026] teaches side wall 101 is made from gold, wherein gold is a structurally material that is capable of optically reflecting visible and near-infrared wavelengths, i.e. optically reflective layer). Kinz-Thompson teaches an optical sensor system (Fig. 8), the optical sensor system having an arrangement to direct a wavelength to the well via the substrate layer (Figs. 1 and 8 and paragraph [0040], arrangement of the laser, collection optics, dichroic beam splitter, and objective, wherein a wavelength is directed to the well via the substrate layer 120) and collect a response from the molecule via the substrate layer (Figs. 8-9 and paragraphs [0040],[0042] teaches fluorescence is collected from a molecule from the apparatus), the optically reflective layer limiting transmission of the wavelengths to the sample above the sample interface layer (interpreted as a functional limitation of the optically reflective layer, see MPEP 2114; paragraph [0026] teaches side wall 101 is made from gold, wherein gold is a structurally material that is capable of optically reflecting wavelengths; therefore, the gold side wall is capable of limiting transmission of wavelengths as claimed). Kinz-Thompson teaches zero-mode waveguides (ZMWs) includes apertures in a metal film that allows for observation of single-molecule phenomena to allow light to be shown through the waveguide; thus ZMWs can provide improved signal-to-noise ratio of single-molecule fluorescence, permitting single fluorophore-labeled biomolecules to be observed in imaging buffers containing physiologically relevant, micromolar concentrations of fluorophore-labeled ligands (paragraphs [0004],[0044]).
Since Kinz-Thompson teaches an apparatus for sensing a molecule comprising a well, similar to Bashir, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the substrate layer and sample interface layer of Bashir to incorporate the teachings of a zero-mode waveguide structure comprising a transparent substrate and optically reflective sample interface layer, and an optical system of Kinz-Thompson (Figs. 1 and 8; paragraphs [0026], [0040],[0042]) to provide: wherein the substrate layer is a transparent material (i.e. glass) at visible and near-infrared wavelengths and the sample interface layer is an optically reflective layer (i.e. gold) for the visible and near-infrared wavelengths; an optical sensor system, the optical sensor system having an arrangement to direct a wavelength to the well via the substrate layer and collect a response from the molecule via the substrate layer, the optically reflective layer limiting transmission of the wavelengths to the sample above the sample interface layer; and wherein the visible wavelengths range from about 400 nm to about 800 nm. Doing so would have a reasonable expectation of successfully allowing for observation of single-molecule phenomena via light measurement, and improving signal-to-noise ratio of single-molecule fluorescence detection for observing the molecule as taught by Kinz-Thompson (paragraphs [0004],[0044]).
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. the claimed substrate layer is a transparent material, the claimed optically reflective layer, and the claimed optical sensor system) by known methods with no change in their respective functions (i.e. sensing and analyzing a molecule), and the combinations yielded nothing more than predictable results (i.e. providing the substrate layer as a transparent material, the sample interface layer as an optically reflective layer, and an optical sensor system would yield nothing more than the obvious and predictable result of allowing for observation of single-molecule phenomena via light measurement, and improving signal-to-noise ratio of single-molecule fluorescence detection for observing the molecule as taught by Kinz-Thompson, paragraphs [0004],[0044]). See MPEP 2143(A).
Modified Bashir fails to teach: wherein the well is a zero-mode waveguide relative to the visible wavelengths;
wherein the organic matter is a complex comprising a DNA or RNA-processing enzyme to which the molecule binds.
Kinz-Thompson teaches wherein the well is a zero-mode waveguide relative to the visible wavelengths (paragraph [0026] teaches the zero-mode waveguide, ZMW, includes the nano-well 101; thus, the nano-well 101 is a ZMW relative to the visible wavelengths). Kinz-Thompson teaches zero-mode waveguides (ZMWs) includes apertures in a metal film that allows for observation of single-molecule phenomena to allow light to be shown through the waveguide; thus ZMWs can provide improved signal-to-noise ratio of single-molecule fluorescence, permitting single fluorophore-labeled biomolecules to be observed in imaging buffers containing physiologically relevant, micromolar concentrations of fluorophore-labeled ligands (paragraphs [0004],[0044]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the well of modified Bashir to incorporate the teachings of a zero-mode waveguide structure of Kinz-Thompson (Fig. 1; paragraphs [0026], [0004],[0044]) to provide: wherein the well is a zero-mode waveguide relative to the visible wavelengths. Doing so would have a reasonable expectation of successfully allowing for observation of single-molecule phenomena via light measurement, and improving signal-to-noise ratio of single-molecule fluorescence detection for observing the molecule as taught by Kinz-Thompson (paragraphs [0004],[0044]).
Modified Bashir fails to teach: wherein the organic matter is a complex comprising a DNA or RNA-processing enzyme to which the molecule binds.
Bashir teaches an embodiment of providing the chemical sensor device with nucleic acids and/or replication enzymes such as polymerase, i.e. a DNA or RNA-processing enzyme, necessary for synthesis of complements to fragments to be sequenced (paragraph [0031]). Bashir teaches an embodiment to isolate, detect, sequence and/or amplify a target molecule; where a target DNA fragment is attracted toward the sensing region where an enzyme, for example DNA polymerase, synthesizes a complementary DNA fragment (paragraph [0062]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the organic matter of modified Bashir to incorporate the teachings of DNA or RNA-processing enzymes of Bashir (paragraphs [0031],[0062]) to provide: wherein the organic matter is a complex comprising a DNA or RNA-processing enzyme to which the molecule binds. Doing so would have a reasonable expectation of successfully isolating, detecting, sequencing and/or amplifying a target molecule as taught by Bashir (paragraphs [0031],[0062]).
Note that the “molecule” and “electrically conductive element in a sample” are not positively recited structurally and the limitations of the sample interface layer and electrically conductive layer are interpreted as functional limitations of the claimed apparatus. The inclusion of the material or article, i.e. “molecule” and “electrically conductive element in a sample, worked upon by a structure, i.e. the sample interface layer and electrically conductive layer, being claimed does not impart patentability to the claims (see MPEP 2115).
Note that the limitations of “when energized with a given polarity…produces an electric field…to draw a molecule…” is interpreted as functional limitations of the claimed apparatus. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the functional limitations, then it meets the claim. See MPEP 2114. The apparatus of modified Bashir is identical to the presently claimed structure. Modified Bashir discloses the claimed substrate layer, sample interface layer, and electrically conductive layer (see above), and therefore, would have the ability to perform the functional limitations recited in the claim as discussed above. See MPEP 2112.01 (I).
Note that “visible wavelengths” is interpreted as a functional limitation of the substrate layer and optically reflective layer. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the functional limitations, then it meets the claim. See MPEP 2114. The apparatus of modified Bashir is identical to the presently claimed structure. Since modified Bashir teaches a transparent material, i.e. glass, the glass is structurally transparent at visible wavelengths range from about 400 nm to about 800 nm. Additionally, since modified Bashir teaches the optically reflective layer, i.e. gold, the optically reflective layer is a structurally material that is capable of optically reflecting the visible wavelengths range from about 400 nm to about 800 nm. Therefore, the structures of modified Bashir would have the ability to perform the functional limitations recited in the claim as discussed above. See MPEP 2112.01 (I).
Regarding claim 4, modified Bashir fails to teach wherein the sample interface layer, electrically conductive layer, and substrate layer define multiple wells, and wherein the sensor system is configured to sense a respective molecule in the multiple wells in a parallel manner.
Kinz-Thompson further teaches wherein the sample interface layer, electrically conductive layer, and substrate layer define multiple wells (paragraph [0027] teaches the device can include arrays or matrix of nano-wells separated by side walls 110), and wherein the sensor system is configured to sense a respective molecule in the multiple wells in a parallel manner (interpreted as a functional limitation of the sensor system, see MPEP 2114; paragraphs [0021],[0043] teaches measurement of fluorescence in different nano-wells, thus the sensor system is structurally capable of sensing a respective molecule in the wells in a parallel manner at a later time). Kinz-Thompson teaches analysis of molecules in each respective nano-well based on fluorescence (paragraph [0043]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus of modified Bashir to incorporate the teachings of multiple wells and analyzing multiple wells of Kinz-Thompson (paragraphs [0021],[0027],[0043]) to provide wherein the sample interface layer, electrically conductive layer, and substrate layer define multiple wells, and wherein the sensor system is configured to sense a respective molecule in the multiple wells in a parallel manner. Doing so would have a reasonable expectation of successfully improving throughput of analysis of multiple molecules in the same device as taught by Kinz-Thompson (paragraphs [0021],[0043]).
Regarding claim 6, while Bashir teaches a cylindrical sensing region (paragraph [0049]) and an opening above the sensing region having a cross-sectional dimension of 0.1 um to 50 um, i.e. 100 nm to 50,000 nm (paragraph [0019]), modified Bashir fails to teach: wherein the well is a cylindrically shaped hole of about 100nm to about 150nm in diameter and at least 100 nm in length.
Kinz-Thompson teaches the nano-well can have a diameter of 25-500 nm (paragraph [0027]) and a height, i.e. length, of 50-500 nm (paragraph [0027]).
Since Kinz-Thompson teaches the nano-well can have a diameter of 25-500 nm (paragraph [0027]) and a height, i.e. length, of 50-500 nm (paragraph [0027]), wherein the taught diameter range of 25-500 nm overlaps with the claimed diameter range of 100-150 nm and the taught length range of 50-500 nm overlaps with the claimed length range of at least 100 nm, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the wells of modified Bashir to provide wherein the well is a cylindrically shaped hole of about 100nm to about 150nm in diameter and at least 100 nm in length. I.e., it would have been prima facia obvious to have selected the overlapping portion of the range (i.e. diameter of 100-150 nm; length of at least 100 nm) from the taught diameter of 25-500 nm (Kinz-Thompson, paragraph [0027]) and a height, i.e. length, of 50-500 nm (Kinz-Thompson, paragraph [0027]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Regarding claim 7, modified Bashir further teaches wherein the transparent material includes fused silica, quartz, or glass (see above claim 1; the combination of Bashir with Kinz-Thompson teaches the transparent material is glass; Kinz-Thompson, paragraph [0026] teaches the substrate 120 is a transparent material, such as glass).
Regarding claim 13, while Bashir teaches one or more probe molecules immobilized on the surface of the sensing region or the surface of the first passivation layer (paragraph [0021]), modified Bashir fails to teach: wherein the organic matter is attached to an electrically non-conductive layer in the well through biotinylated polyethylene glycol silane-based functionalization of the substrate layer.
Kinz-Thompson further teaches wherein the organic matter (Fig. 1, target molecule 150) is attached to an electrically non-conductive layer in the well (Fig. 1 shows target molecule 150 attached to substrate 120 in the nano-well 101 via elements 125 and 126; paragraph [0026] teaches the substrate is glass, which is an electrically non-conductive layer; note that the BRI of “electrically non-conductive layer” includes the interpretation that the substrate layer is the electrically non-conductive layer) through biotinylated polyethylene glycol silane-based functionalization of the substrate layer (Fig. 1 and paragraph [0029] teaches target molecule 150 is attached to the glass substrate 120 through second functional molecule 125 comprising polyethylene glycol, wherein the second functional molecule includes a silane end group that is biotinylated, thus the substrate 120 is functionalized with biotinylated polyethylene glycol silane). Kinz-Thompson teaches a nano-well functionalized with at least one second molecule comprising a silane-PEG molecule, wherein the second molecule can further include a moiety, such as biotin, which is capable of binding a target biomolecule, which in turn can bind to a biomolecule of interest for single molecule fluorescence imaging analysis (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the organic matter of modified Bashir to incorporate the teachings of biotinylated polyethylene glycol silane-based functionalization of the substrate layer for attachment of an organic matter of Kinz-Thompson (Fig. 1; abstract; paragraphs [0026],[0029]) to provide wherein the organic matter is attached to an electrically non-conductive layer in the well through biotinylated polyethylene glycol silane-based functionalization of the substrate layer. Doing so would have a reasonable expectation of successfully functionalizing a desired organic matter to the substrate for proper analysis of a molecule as taught by Kinz-Thompson (Fig. 1; abstract; paragraphs [0026],[0029]).
Regarding claim 14, Bashir further teaches wherein the well forms the shape of a cylinder, truncated cone, or any polygonal prism (Fig. 1, shows a well above element 104 that is in a shape of a cylinder or a polygonal prism).
Regarding claim 15, Bashir teaches wherein the opening at the sample interface side of the sample interface layer (opening at the side of element 109 towards the top, opposite of the side adjacent to element 108) has a cross-sectional dimension of 0.1 um to 50 um, i.e. 100 nm to 50,000 nm (paragraph [0019]), modified Bashir fails to teach the opening has a diameter from about 20 nm to about 250 nm.
Since Bashir teaches the nano-well can have a cross-sectional dimension, i.e. diameter, of 0.1 um to 50 um, i.e. 100 nm to 50,000 nm (paragraph [0019]), wherein the taught diameter range of 100 nm to 50,000 nm overlaps with the claimed diameter range of 20 nm to about 250 nm (i.e. 100-250 nm), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the opening of Bashir to provide the opening has a diameter from about 20 nm to about 250 nm. I.e., it would have been prima facia obvious to have selected the overlapping portion of the range (i.e. 100-250 nm) from the taught diameter of 100 nm to 50,000 nm (paragraph [0019]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Claims 1, 4, 6-10, and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kinz-Thompson et al. (US 20130294972 A1; cited in the IDS filed 03/24/2022) in view of Rothberg et al. (US 20150141268 A1) and Hanes et al. (US 20180023134 A1).
Regarding claim 1, Kinz-Thompson teaches an apparatus (Fig. 1; abstract) for sensing a molecule (interpreted as an intended use, see MPEP 2114; abstract; Fig. 1 shows biomolecule of interest 160), the structure comprising:
a substrate layer (substrate 120);
a sample interface layer (side wall 110) having a sample interface side (top side of side wall 110 opposite of element 130) and a substrate layer facing side (bottom side of side wall 110 adjacent to element 130);
an electrically conductive layer (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer) disposed between the substrate layer facing side of the sample interface layer and the substrate layer (Fig. 1 shows adhesion layer 130 is between elements 110 and 120);
wherein the sample interface layer and electrically conductive layer each define a respective opening therethrough that, aligned, compose a wall of a well (Fig. 1 shows an opening through elements 110 and 130 that are aligned and compose a wall of nano-well 101) with a bottom boundary defined by the substrate layer (Fig. 1 shows nano-well 101 with a bottom boundary defined by substrate 120),
the opening through the electrically conductive layer forming a bottom of the wall of the well (Fig. 1 teaches the opening through adhesion layer 130 forms a bottom of the wall of the well since adhesion layer 130 is below element 110 and therefore is interpreted as part of the bottom wall of the well), and the electrically conductive layer (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer), when energized with a given polarity relative to an electrically conductive element in a sample at the sample interface layer, producing an electric field from the electrically conductive layer through the well to the electrically conductive element (interpreted as a functional limitation of the adhesion layer 130; Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, thus the titanium or metallic adhesion layer 130 is structurally capable of being energized with a given polarity to produce an electric field to produce an electric field as claimed since the layer is made of titanium or another metal, which is at least partially conductive; note that “an electrically conductive element in a sample” is not positively recited structurally), the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer at the bottom of the wall of the well (interpreted as a functional limitation of the adhesion layer 130; Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, thus the titanium or metallic adhesion layer 130 is structurally capable of producing an electric field of a polarity as claimed to draw or attract the molecule from the top side of the side wall 110, through the nano-well 101 and towards the adhesion layer 130, i.e. bottom of the wall of the well; note that “molecule” is not positively recited structurally);
wherein the substrate layer is a transparent material at visible and near-infrared wavelengths (paragraph [0026] teaches the substrate 120 is a transparent material, such as glass; therefore, the glass is transparent at visible and near-infrared wavelengths) and the sample interface layer is an optically reflective layer for the visible and near-infrared wavelengths (paragraph [0026] teaches side wall 101 is made from gold, wherein gold is a structurally material that is capable of optically reflecting visible and near-infrared wavelengths, i.e. optically reflective layer);
an optical sensor system (Figs. 1 and 8 and paragraph [0040], arrangement of the laser, collection optics, dichroic beam splitter, and objective), the optical sensor system having an arrangement (Figs. 1 and 8 and paragraph [0040], arrangement of the laser, collection optics, dichroic beam splitter, and objective) to direct a wavelength to the well via the substrate layer (interpreted as an intended use of the arrangement, see MPEP 2114; Figs. 1 and 8 and paragraph [0040], teach the arrangement of the laser, dichroic beam splitter, and objective directs a wavelength of light 180 to nano-well 101 via substrate 120) and collect a response from the molecule via the substrate layer (interpreted as an intended use of the arrangement, see MPEP 2114; Figs. 8-9 and paragraphs [0040],[0042] teaches fluorescence is collected from a molecule from the apparatus), the optically reflective layer limiting transmission of the wavelengths to the sample above the sample interface layer (interpreted as a functional limitation of the optically reflective layer, see MPEP 2114; paragraph [0026] teaches side wall 101 is made from gold, wherein gold is a structurally material that is capable of optically reflecting wavelengths; therefore, the gold side wall is capable of limiting transmission of wavelengths as claimed);
wherein the visible wavelengths range from about 400 nm to about 800 nm (note that “visible wavelengths” is interpreted as a functional limitation of the substrate layer and optically reflective layer; paragraph [0026] teaches the substrate 120 is a transparent material, such as glass; therefore, the glass is structurally transparent at visible wavelengths range from about 400 nm to about 800 nm; paragraph [0026] teaches side wall 101 is made from gold, wherein gold is a structurally material that is capable of optically reflecting the visible wavelengths range from about 400 nm to about 800 nm), and wherein the well is a zero-mode waveguide relative to the visible wavelengths (paragraph [0026] teaches the zero-mode waveguide, ZMW, includes the nano-well 101; thus, the nano-well 101 is a ZMW relative to the visible wavelengths);
an organic matter (Fig. 1, target molecule 150; paragraph [0029] teaches the target biomolecule can be streptavidin, i.e. organic matter), fixedly located in the well (Fig. 1 shows target molecule 150 is fixed in the nano-well 101 via elements 125 and 126), that is selected based on a property that enables the molecule to chemically couple thereto (paragraph [0030] teaches target biomolecule 150 can bind to the biomolecule of interest), wherein the molecule is DNA or RNA (note that “the molecule” is not positively recited structurally; paragraph [0026] teaches the biomolecule of interest includes DNA or RNA).
While Kinz-Thompson teaches biomolecules of interest may include those which associate with other molecules such as polymerases, enzymes, or ribozymes (paragraph [0026]), Kinz-Thompson fails to teach:
wherein the organic matter is a complex comprising a DNA or RNA-processing enzyme to which the molecule binds; and
a voltage potential source configured to apply a voltage potential difference between the electrically conductive element and the electrically conductive layer.
Rothberg teaches devices and systems capable of sequencing single nucleic acid molecules with high accuracy (paragraph [0161]), wherein a DNA polymerase, i.e. DNA processing enzyme, is immobilized or attached to a sample wall, such as the bottom of a sample well (paragraph [0161]). Rothberg teaches a sample well contains enzymes such as a polymerase needed for nucleic acid synthesis (paragraph [0161]). Rothberg teaches nucleic acid sequencing of a plurality of single-stranded target nucleic acid templates may be completed where multiple sample wells are available, wherein each sample well is contacted with appropriate reagents, such as polymerase (paragraph [0166]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the organic matter of Kinz-Thompson to incorporate the teachings of DNA or RNA-processing enzymes of Rothberg (paragraphs [0161],[0166]) to provide: wherein the organic matter is a complex comprising a DNA or RNA-processing enzyme to which the molecule binds. Doing so would have a reasonable expectation of successfully improving processing of a desired molecule such as DNA by providing an appropriate reagent to the well as taught by Rothberg (paragraphs [0161],[0166]).
Modified Kinz-Thompson fails to teach: a voltage potential source configured to apply a voltage potential difference between the electrically conductive element and the electrically conductive layer.
Hanes teaches systems for distributing molecules and complexes into reaction sites (abstract; Figs. 9-10), resulting in an increased density of loading and/or increased efficiency of loading than is seen with passive diffusion methods alone (paragraph [0005]). Hanes teaches the reaction sites can be nanoscale wells (paragraph [0156]). Hanes teaches the system (Fig. 10) comprises a zero-mode waveguide array comprising wells (Fig. 10). Hanes teaches a voltage potential source (Fig. 10, potentiostat) configured to apply a voltage potential difference between an electrically conductive element (DNA/polymerase) and an electrically conductive layer (Fig. 10, conducting layers of the waveguide) (paragraphs [0139]-[0140] teaches a voltage is applied). Hanes teaches applying a potential enables mobility of charged molecules in solution (paragraph [0140]; Figs. 9-10). Hanes teaches an embodiment in which the molecule of interest being driven toward the ZMW is DNA, and it will be appreciated that any charged molecule can be used in any of the configurations described herein when an electric potential is used as the driving force (paragraph [0151]).
Since Hanes teaches a system for analyzing molecules in a well, similar to Kinz-Thompson, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus of modified Kinz-Thompson to incorporate the teachings of a voltage potential source to apply a voltage potential difference to distributing molecules into reaction sites of Hanes (abstract; Figs. 9-10; paragraphs [0005],[0151],[0156]) to provide: a voltage potential source configured to apply a voltage potential difference between the electrically conductive element and the electrically conductive layer. Doing so would have a reasonable expectation of successfully improving driving or distributing desired molecules of interest towards a well for analysis as taught by Hanes (paragraphs [0005],[0151]).
Note that the “molecule” and “electrically conductive element in a sample” are not positively recited structurally and the limitations of the sample interface layer and electrically conductive layer are interpreted as functional limitations of the claimed apparatus. The inclusion of the material or article, i.e. “molecule” and “electrically conductive element in a sample, worked upon by a structure, i.e. the sample interface layer and electrically conductive layer, being claimed does not impart patentability to the claims (see MPEP 2115).
Note that the limitations of “when energized with a given polarity…produces an electric field…to draw a molecule…” is interpreted as functional limitations of the claimed apparatus. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the functional limitations, then it meets the claim. See MPEP 2114. The apparatus of modified Kinz-Thompson is identical to the presently claimed structure. Kinz-Thompson discloses the claimed substrate layer, sample interface layer, and electrically conductive layer (see above), and therefore, would have the ability to perform the functional limitations recited in the claim as discussed above. See MPEP 2112.01 (I).
Regarding claim 4, Kinz-Thompson further teaches wherein the sample interface layer, electrically conductive layer, and substrate layer define multiple wells (paragraph [0027] teaches the device can include arrays or matrix of nano-wells separated by side walls 110), and wherein the sensor system is configured to sense a respective molecule in the multiple wells in a parallel manner (interpreted as a functional limitation of the sensor system, see MPEP 2114; paragraphs [0021],[0043] teaches measurement of fluorescence in different nano-wells, thus the sensor system is structurally capable of sensing a respective molecule in the wells in a parallel manner at a later time).
Regarding claim 6, Kinz-Thompson further teaches wherein the wells (Figs. 1 and 6, nano-well 101) are cylindrically shaped holes (paragraphs [0027], [0037] teach the nano-wells have circular cross sections, i.e. cylindrically shaped holes). Kinz-Thompson fails to explicitly teach the cylindrically shaped hole of about 100nm to about 150nm in diameter and at least 100 nm in length.
Kinz-Thompson teaches the nano-well can have a diameter of 25-500 nm (paragraph [0027]) and a height, i.e. length, of 50-500 nm (paragraph [0027]).
Since Kinz-Thompson teaches the nano-well can have a diameter of 25-500 nm (paragraph [0027]) and a height, i.e. length, of 50-500 nm (paragraph [0027]), wherein the taught diameter range of 25-500 nm overlaps with the claimed diameter range of 100-150 nm and the taught length range of 50-500 nm overlaps with the claimed length range of at least 100 nm, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the wells of Kinz-Thompson to provide where the cylindrically shaped hole of about 100nm to about 150nm in diameter and at least 100 nm in length. I.e., it would have been prima facia obvious to have selected the overlapping portion of the range (i.e. diameter of 100-150 nm; length of at least 100 nm) from the taught diameter of 25-500 nm (paragraph [0027]) and a height, i.e. length, of 50-500 nm (paragraph [0027]) (In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); see MPEP 2144.05 (I)).
Regarding claim 7, Kinz-Thompson further teaches wherein the transparent material includes fused silica, quartz, or glass (paragraph [0026] teaches the substrate 120 is a transparent material, such as glass).
Regarding claim 8, Kinz-Thompson further teaches wherein the sample interface layer is a metal (paragraph [0026] teaches side wall 101 is made from gold). Modified Kinz-Thompson fails to teach the apparatus of claim 1 further comprising an electrically non-conductive layer positioned between the sample interface layer and the electrically conductive layer, wherein the electrically non-conductive layer defines a respective opening aligned with the opening of the sample interface layer and the opening of the electrically conductive layer.
Rothberg teaches a device capable of performing biomolecule detection and/or analysis, such as single-molecule nucleic acid sequencing, wherein the device includes a sample well (abstract). Rothberg teaches a sample well may be formed as a nanohole and may be formed as a zero-mode waveguide having a cylindrical shape (paragraph [0208]). Rothberg teaches an embodiment of the device (Fig. 3-7F) comprising a sample interface layer (3-230), substrate layer (3-235), and an electrically conductive layer (Fig. 3-7F and paragraph [0225], first layer 3-232 which is a semiconducting or conducting material) between the sample interface layer and substrate layer (Fig. 3-7F). Rothberg teaches the sample interface layer is a metal (paragraph [0225], first layer 3-230 which is a conductor or semiconductor; paragraph [0298] teaches top layer 3-230 is a conductive metal; paragraph [0364] teaches conductive material 3-230), and further comprising an electrically non-conductive layer (Fig. 3-7F and paragraph [0225], second layer 3-234 which is an insulator or dielectric, i.e. electrically non-conductive layer) positioned between the sample interface layer (3-230) and the electrically conductive layer (3-232), wherein the electrically non-conductive layer defines a respective opening aligned with the opening of the sample interface layer and the opening of the electrically conductive layer (Fig. 3-7F shows aligned openings of elements 3-230, 3-234, 3-232). Rothberg teaches conductive materials include gold and aluminum (paragraph [0364]). Rothberg teaches multi-layer materials used for forming a sample well may be selected to suppress excitation radiation from propagating beyond the sample well and multi-layer structure into the bulk specimen (paragraph [0225]).
Since Rothberg teaches wells for sensing a molecule, similar to Kinz-Thompson, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus of modified Kinz-Thompson to incorporate the teachings of multi-layer materials used to for a sample well of Rothberg (Fig. 3-7F; paragraphs [0225],[0298],[0364]) to provide: the apparatus of claim 1 further comprising an electrically non-conductive layer positioned between the sample interface layer and the electrically conductive layer, wherein the electrically non-conductive layer defines a respective opening aligned with the opening of the sample interface layer and the opening of the electrically conductive layer. Doing so would have a reasonable expectation of successfully improving insulation of the electrically conductive layer and suppressing excitation radiation from propagating beyond a sample well as taught by Rothberg (paragraph [0225]).
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. and the claimed electrically non-conductive layer) by known methods with no change in their respective functions (i.e. sensing and analyzing a molecule in a well while insulating the electrically conductive layer), and the combinations yielded nothing more than predictable results (i.e. providing the claimed electrically non-conductive layer would yield nothing more than the obvious and predictable result of enabling molecule sensing and analysis within a well while insulating the electrically conductive layer). See MPEP 2143(A).
Regarding claim 9, modified Kinz-Thompson fails to teach wherein the electrically non-conductive layer is made of a material including silicon dioxide, aluminum oxide, or silicon nitride.
Rothberg teaches an insulating layer may comprise an oxide, such as silicon dioxide (paragraph [0298]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the electrically non-conductive layer of modified Kinz-Thompson to incorporate the teachings of an silicon dioxide insulating layer of Rothberg (paragraph [0298]) to provide wherein the electrically non-conductive layer is made of a material including silicon dioxide, aluminum oxide, or silicon nitride. Doing so would have a reasonable expectation of successfully insulating desired layers of the apparatus.
Regarding claim 10, Kinz-Thompson further teaches wherein the metal includes platinum, gold, silver, titanium, aluminum, or combination thereof (paragraph [0026] teaches side wall 101 is made from gold).
Regarding claim 13, Kinz-Thompson further teaches wherein the organic matter (Fig. 1, target molecule 150) is attached to an electrically non-conductive layer in the well (Fig. 1 shows target molecule 150 attached to substrate 120 in the nano-well 101 via elements 125 and 126; paragraph [0026] teaches the substrate is glass, which is an electrically non-conductive layer; note that the BRI of “electrically non-conductive layer” includes the interpretation that the substrate layer is the electrically non-conductive layer) through biotinylated polyethylene glycol silane-based functionalization of the substrate layer (Fig. 1 and paragraph [0029] teaches target molecule 150 is attached to the glass substrate 120 through second functional molecule 125 comprising polyethylene glycol, wherein the second functional molecule includes a silane end group that is biotinylated, thus the substrate 120 is functionalized with biotinylated polyethylene glycol silane).
Regarding claim 14, Kinz-Thompson further teaches wherein the well forms the shape of a cylinder, truncated cone, or any polygonal prism (Fig. 1 and paragraphs [0027], [0037] teach the nano-wells have circular cross sections, i.e. cylindrically shaped holes).
Regarding claim 15, Kinz-Thompson further teaches wherein the opening at the sample interface side of the sample interface layer (opening of nano-well 101 at the top side of side wall 110 opposite of element 130) has a diameter from about 20 nm to about 250 nm (paragraph [0027] teaches the nano-well has a diameter of 200-250 nm).
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Bashir in view of Kinz-Thompson as applied to claim 1 above, and further in view of Rothberg et al. (US 20150141268 A1).
Regarding claim 8, while Bashir teaches passivation layers can include aluminum (paragraph [0020]), and that the passivation layers can include layers comprising insulating materials, such as an insulator deposited on a semiconductor layer (paragraph [0020]), modified Bashir fails to teach: wherein the sample interface layer is a metal, and further comprising an electrically non-conductive layer positioned between the sample interface layer and the electrically conductive layer, wherein the electrically non-conductive layer defines a respective opening aligned with the opening of the sample interface layer and the opening of the electrically conductive layer.
Rothberg teaches a device capable of performing biomolecule detection and/or analysis, such as single-molecule nucleic acid sequencing, wherein the device includes a sample well (abstract). Rothberg teaches a sample well may be formed as a nanohole and may be formed as a zero-mode waveguide having a cylindrical shape (paragraph [0208]). Rothberg teaches an embodiment of the device (Fig. 3-7F) comprising a sample interface layer (3-230), substrate layer (3-235), and an electrically conductive layer (Fig. 3-7F and paragraph [0225], first layer 3-232 which is a semiconducting or conducting material) between the sample interface layer and substrate layer (Fig. 3-7F). Rothberg teaches the sample interface layer is a metal (paragraph [0225], first layer 3-230 which is a conductor or semiconductor; paragraph [0298] teaches top layer 3-230 is a conductive metal; paragraph [0364] teaches conductive material 3-230), and further comprising an electrically non-conductive layer (Fig. 3-7F and paragraph [0225], second layer 3-234 which is an insulator or dielectric, i.e. electrically non-conductive layer) positioned between the sample interface layer (3-230) and the electrically conductive layer (3-232), wherein the electrically non-conductive layer defines a respective opening aligned with the opening of the sample interface layer and the opening of the electrically conductive layer (Fig. 3-7F shows aligned openings of elements 3-230, 3-234, 3-232). Rothberg teaches conductive materials include gold and aluminum (paragraph [0364]). Rothberg teaches multi-layer materials used for forming a sample well may be selected to suppress excitation radiation from propagating beyond the sample well and multi-layer structure into the bulk specimen (paragraph [0225]).
Since Rothberg teaches wells for sensing a molecule, similar to Bashir, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus of modified Bashir to incorporate the teachings of multi-layer materials used to for a sample well of Rothberg (Fig. 3-7F; paragraphs [0225],[0298],[0364]) and the teachings of passivation layers include aluminum (Bashir, paragraph [0020]) and that the passivation layers can include layers comprising insulating materials, such as an insulator deposited on a semiconductor layer of Bashir (paragraph [0020]), to provide wherein the sample interface layer is a metal, and further comprising an electrically non-conductive layer positioned between the sample interface layer and the electrically conductive layer, wherein the electrically non-conductive layer defines a respective opening aligned with the opening of the sample interface layer and the opening of the electrically conductive layer. Doing so would have a reasonable expectation of successfully improving insulation of the electrically conductive layer and suppressing excitation radiation from propagating beyond a sample well as taught by Rothberg (paragraph [0225]).
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. the claimed the sample interface layer is a metal, such as aluminum and/or gold, and the claimed electrically non-conductive layer, such as an insulator layer) by known methods with no change in their respective functions (i.e. sensing and analyzing a molecule in a well while insulating the electrically conductive layer), and the combinations yielded nothing more than predictable results (i.e. providing the claimed the sample interface layer is a metal and the claimed electrically non-conductive layer would yield nothing more than the obvious and predictable result of enabling molecule sensing and analysis within a well while insulating the electrically conductive layer). See MPEP 2143(A).
Regarding claim 9, while Bashir teaches passivation layers can include layers comprising insulating materials, such as an insulator deposited on a semiconductor layer (paragraph [0020]), modified Bashir fails to teach: wherein the electrically non-conductive layer is made of a material including silicon dioxide, aluminum oxide, or silicon nitride.
Rothberg teaches an insulating layer may comprise an oxide, such as silicon dioxide (paragraph [0298]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the electrically non-conductive layer of modified Bashir to incorporate the teachings of an silicon dioxide insulating layer of Rothberg (paragraph [0298]) to provide wherein the electrically non-conductive layer is made of a material including silicon dioxide, aluminum oxide, or silicon nitride. Doing so would have a reasonable expectation of successfully insulating desired layers of the apparatus.
Regarding claim 10, while Bashir teaches passivation layers can include aluminum (paragraph [0020]), modified Bashir fails to teach wherein the metal includes platinum, gold, silver, titanium, aluminum, or combination thereof.
Rothberg teaches the sample interface layer is a metal (paragraph [0225], first layer 3-230 which is a semiconducting or conducting material; paragraph [0298] teaches top layer 3-230 is a conductive metal; paragraph [0364] teaches conductive material 3-230). Rothberg teaches the sample interface layer (Fig. 3-7F, first layer 3-230) is a conductive material (paragraph [0364]), wherein conductive materials include Au, Al, Ti, TiN, Ag, and alloys or combination layers thereof (paragraph [0364]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the metal of modified Bashir to incorporate the teachings of materials for a sample interface layer such as Au, Al, Ti, TiN, and/or Ag of Rothberg (paragraph [0364]) and the teachings of passivation layers including aluminum of Bashir (paragraph [0020]) to provide wherein the metal includes platinum, gold, silver, titanium, aluminum, or combination thereof. Doing so would have reasonable expectation of successfully providing desired conductivity to the metal.
Furthermore, the claimed limitations are obvious because all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements (i.e. the metal includes platinum, gold, silver, titanium, aluminum, or combination thereof) by known methods with no change in their respective functions (i.e. sensing and analyzing a molecule in a well), and the combinations yielded nothing more than predictable results (i.e. providing the metal includes platinum, gold, silver, titanium, aluminum, or combination thereof would yield nothing more than the obvious and predictable result of enabling molecule sensing and analysis within a well and providing desired conductivity to the metal). See MPEP 2143(A).
Response to Arguments
Applicant’s arguments, see page 7, filed 01/20/2026, with respect to the rejection under 35 U.S.C. 112(b) have been fully considered and are persuasive. The rejection under 35 U.S.C. 112(b) of 10/20/2025 has been withdrawn.
Applicant's arguments, see pages 7-9, filed 01/20/2026, with respect to the rejections under 35 U.S.C. 103 over Bashir in view of Kinz-Thompson have been fully considered but they are not persuasive.
In response to applicant’s argument that Bashir fails to teach “the opening through the electrically conductive layer forming a bottom of the wall of the well” and “an electric field draws a molecule form the sample towards the electrically conductive layer at the bottom of the wall of the well” (Remarks, pages 7-9), the examiner disagrees.
Bashir teaches the opening through the electrically conductive layer forming a bottom of the wall of the well (Fig. 1 teaches the opening through element 108 forms a bottom of the wall of the well since element 108 is below element 109 and therefore is interpreted as part of the bottom wall of the well); and the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer at the bottom of the wall of the well (interpreted as a functional limitation of the electrostatic lens electrode 108; Figs. 2A-2D and paragraph [0055] teach a potential difference is applied to the electrostatic lens electrode and the gate to attract molecules, thus the electrostatic lens electrode 108 is structurally capable of producing an electric field of a polarity as claimed to draw or attract the molecule from the top side of the second passivation layer 109, through the well and towards the electrostatic lens electrode 108, i.e. bottom of the wall of the well; note that “molecule” is not positively recited structurally).
Additionally, the limitations of “the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer at the bottom of the wall of the well” are interpreted as interpreted as a functional limitation of the claimed electrically conductive layer. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the functional limitations, then it meets the claim. See MPEP 2114. The apparatus comprising the electrically conductive layer of Bashir is identical to the presently claimed structure. Bashir teaches the electrically conductive layer (Fig. 1, electrostatic lens electrode 108; wherein an electrode is interpreted as an electrically conductive layer) and therefore, would have the ability to perform the functional limitations recited in the claim as discussed above. See MPEP 2112.01 (I). Additionally, note that the “molecule” and “electrically conductive element in a sample” are not positively recited structurally and the limitations of the electrically conductive layer are interpreted as functional limitations of the claimed apparatus. The inclusion of the material or article, i.e. “molecule” and “electrically conductive element in a sample, worked upon by a structure, i.e. the electrically conductive layer, being claimed does not impart patentability to the claims (see MPEP 2115).
It is suggested to incorporate further structural limitations to differentiate the claims from the prior art.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “the bottom of the well, performs an optical role for the light entering from underneath the bottom of the well, while also attracting the molecule into the bottom of the well form the opposite, fluid side of the well…advantage of altering the optical properties of the Zero Mode Waveguide, thereby improving optical signal capture from the molecule”, Remarks, pages 8-9) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant's arguments, see pages 9-11, filed 01/20/2026, with respect to the rejections under 35 U.S.C. 103 over Kinz-Thompson in view of Rothberg and Hanes have been fully considered but they are not persuasive.
In response to applicant’s argument that Kinz-Thompson fails to teach “the opening through the electrically conductive layer forming a bottom of the wall of the well” and “an electric field draws a molecule form the sample towards the electrically conductive layer at the bottom of the wall of the well” since Kinz-Thompson’s adhesive layer is not an electrically conductive layer (Remarks, pages 8-9), the examiner disagrees.
Kinz-Thompson teaches: an electrically conductive layer (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer; since adhesion layer 130 includes titanium or another metal, the layer is interpreted as electrically conductive since it comprises conductive elements such as titanium or metal); the opening through the electrically conductive layer forming a bottom of the wall of the well (Fig. 1 teaches the opening through adhesion layer 130 forms a bottom of the wall of the well since adhesion layer 130 is below element 110 and therefore is interpreted as part of the bottom wall of the well); and the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer at the bottom of the wall of the well (interpreted as a functional limitation of the adhesion layer 130; Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, thus the titanium or metallic adhesion layer 130 is structurally capable of producing an electric field of a polarity as claimed to draw or attract the molecule from the top side of the side wall 110, through the nano-well 101 and towards the adhesion layer 130, i.e. bottom of the wall of the well; note that “molecule” is not positively recited structurally).
Additionally, the limitations of “the electric field sufficient to draw the molecule, the molecule being of polarity opposite from the given polarity, from the sample at the sample interface side through the well toward the electrically conductive layer at the bottom of the wall of the well” are interpreted as interpreted as a functional limitation of the claimed electrically conductive layer. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the functional limitations, then it meets the claim. See MPEP 2114. The apparatus of modified Kinz-Thompson is identical to the presently claimed structure. Kinz-Thompson discloses the claimed substrate layer, sample interface layer, and electrically conductive layer (see above rejection of claim 1 under 35 U.S.C. 103), and therefore, would have the ability to perform the functional limitations recited in the claim as discussed above. See MPEP 2112.01 (I). Specifically, Kinz-Thompson teaches an electrically conductive layer (Fig. 1 and paragraph [0026] teaches adhesion layer 130 is a titanium layer or another metal, i.e. electrically conductive layer), which is a titanium or metal layer, therefore is electrically conductive and can be energized as claimed at a later time. Additionally, note that the “molecule” and “electrically conductive element in a sample” are not positively recited structurally and the limitations of the sample interface layer and electrically conductive layer are interpreted as functional limitations of the claimed apparatus. The inclusion of the material or article, i.e. “molecule” and “electrically conductive element in a sample, worked upon by a structure, i.e. the sample interface layer and electrically conductive layer, being claimed does not impart patentability to the claims (see MPEP 2115).
It is suggested to incorporate further structural limitations to differentiate the claims from the prior art.
In response to applicant’s arguments regarding claims 8-10 (Remarks, pages 11-12), the examiner disagrees for the same reasons as discussed above regarding claim 1.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HENRY H NGUYEN whose telephone number is (571)272-2338. The examiner can normally be reached M-F 7:30A-5:00P.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached at (571) 270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
Prosecution Insights