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 .
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: Label 722 in figures 7A and 7B. Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 31 is objected to because of the following informalities: in line 2 of the claim, the phrase “to generate a gas bubble vis electrolysis.” Examiner believes “vis” should instead read “via.” Appropriate correction is required.
Claim Interpretation
Examiner notes the orientation terms horizontal and vertical are relative to the orientation of the device. Because the fluid flow is driven by electrical means through the nanopores and nanochannels, the gravitational impact of fluid flow does not influence the device orientation. Therefore, wells that in one orientation appear horizontally side-by-side, when rotated 90° become vertically side-by-side without changing the scope of the claims.
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.
Claim 23 is 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.
Claim 23 recites the limitation "a liquid flow in at least one of the second nanoscale openings" in line 3 of the claim. There is insufficient antecedent basis for this limitation in the claim as a second nanoscale opening is not previously recited in either claim 1 or 23. Examiner believes “the second nanoscale opening” is referring to the nanochannel and will be examined as such. Further, only one nanochannel (second nanoscale opening) is recited in claim 1 and 23, therefore, the limitation “in at least one of the second nanoscale openings” also lacks the antecedent basis. Examiner will examine for only a singular nanochannel. Examiner recommends amending the claim to recite “a liquid flow in the nanochannel opening” or an equivalent thereof.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3-10, 15-16, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Boyanov, et. al. (US 20210156819 A1; claiming priority date of 23 Dec. 2019).
Regarding claim 1, Boyanov fluidic teaches a device with a plurality of nanoscale openings (Abstract) to be used as a sequencer device (par. 0010) (nanopore sequencing device). Boyanov teaches the sequencing device 10 comprises (Fig. 2A; par. 0070-0071):
a cis well (14) associated with a cis electrode (30)
a trans well (16) associated with a trans electrode (34)
a field effect transistor (FET) system 22 with associated cavities 15 and 21 fluidically connecting the cis well 14 to the trans well 16; it is understood FET system 22 comprises a sensing electrode and is supported by Boyanov in paragraphs 0104 and 0108 with Boyanov further supporting the sensor electrode of the FET system 22 is distinctly different than the trans electrode 34 (par. 0113) (a middle well associated with the sensing electrode) (wherein the middle well is… in fluid communication with the cis well and the trans well).
Boyanov teaches each of these components are embedded in a substrate 12 enclosing the device between the cis 14 and trans 16 well (Fig. 2A, 2B, 6A; par. 0083).The substrate further defines the FET system 22 between base substrate 62' (substrate) and end 38 (Fig. 6A, par. 0087-0088, 0097, 0119) and further comprises interior walls/interstitial regions 32 (Fig. 6A; par. 0088) being made of a dielectric material (par. 0066) (a substrate comprising a dielectric layer) (at least one sensing electrode on a surface of the dielectric layer) (wherein the middle well is positioned on the substrate) and second nanochannel opening 25 is defined by base substrate 62' (Fig. 2A, 6A; par. 0087) (wherein the nanochannel is formed on the surface of the substrate).
Boyanov further teaches a nanopore (a first nanoscale opening, 23) fluidically connecting the cis well (14) and the middle well (15, 21) (Fig. 2A; par. 0072) and a nanochannel (a second nanoscale opening 25) fluidically connecting the middle well (15, 21) and the trans well (16) (Fig. 2A; par. 0072).
Regarding claim 3, Boyanov teaches wherein the nanopore (first nanoscale opening 23) is positioned in and through a membrane (24) separating the cis well (14) and the middle well (15, 21) (Fig. 2A; par. 0076).
Regarding claim 4, Boyanov teaches the membrane 24 any suitable natural (lipid or lipid equivalent) or synthetic (solid state, silicon, graphene) material (par. 0050-0053, 0076) (wherein the membrane is formed of lipid, silicon, graphene, a solid-state material, a synthetic material, a biomimetic equivalent of lipid, or any combination thereof).
Regarding claim 5, Boyanov teaches second nanoscale opening 25 is defined as a nanopore (par. 0078) and a nanopore is a hollow structure that is embedded in the membrane and extends across the membrane (par. 0054) and the nanopore can be a biological nanopore like a polypeptide, polynucleotide, or a solid state nanopore, or a hybrid of both (par. 0056-0061) (wherein the nanopore is a hollow in a structure formed of one or more polynucleotides, one or more polypeptides, one or more types of biopolymers, one or more carbon nanotubes, one or more types of solid-state materials, or any combination thereof disposed in the membrane).
Regarding claim 6, Boyanov teaches second nanoscale opening 25 is defined as a nanopore (par. 0078) and the nanopore can be a biological nanopore like a polypeptide or polynucleotide (par. 0056-0059) (wherein the nanopore comprises biologically derived material).
Regarding claim 7, Boyanov teaches the second nanoscale opening 25 can specifically be a porin polypeptide nanopore (par. 0057) (wherein the nanopore comprises a porin).
Regarding claim 8, Boyanov teaches second nanoscale opening 25 is defined as a nanopore (par. 0078) and the nanopore can be a solid state nanopore (par. 0060) (wherein the nanopore comprises non-biologically derived material).
Regarding claim 9, Boyanov teaches the cis well 14, trans well 16, and middle cavities 15, 20 are all adjacent to one another (Fig. 2A). While Figure 2A depicts a vertical orientation, the device is fully capable of being rotated 90° to achieve the same structural and functional capabilities with a horizontal orientation because the fluid flow is driven by electrical means through the nanoscale openings and the gravitational impact of fluid flow does not influence the device orientation (par. 0012) (wherein at least the cis well or the trans well is positioned horizontally side-by-side with the middle well). A rotated version of Figure 2A is provided below.
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Regarding claim 10, Boyanov teaches the cis well 14, trans well 16, and middle cavities 15, 20 are all adjacent to one another (Fig. 2A). While Figure 2A depicts a vertical orientation, the device is fully capable of being rotated 90° to achieve the same structural and functional capabilities with a horizontal orientation because the fluid flow is driven by electrical means through the nanoscale openings and the gravitational impact of fluid flow does not influence the device orientation (par. 0012) (wherein at least the cis well and the trans well are positioned horizontally side-by-side with the middle well). A rotated version of Figure 2A is provided above.
Regarding claim 15, Boyanov teaches the cis well 14 can have a width of 1 mm (par. 0083) (wherein the cis well has a characteristic width of about 10 µm to about 10 mm).
Regarding claim 16, Boyanov teaches the trans well 16 has a width ranging from 10 µm to 1,000 µm (par. 0095) (wherein the trans well has a characteristic width of about 10 µm to about 10 mm).
Regarding claim 20, Boyanov teaches the second nanoscale opening 25 has an inner diameter ranging from 10 to 20 nm (par. 0075) (wherein the nanochannel is about 5 nm to about 200 nm wide).
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 2, 11-12, 19 and 24-29 are rejected under 35 U.S.C. 103 as being unpatentable over Boyanov, et. al. (US 20210156819 A1; claiming priority date of 23 Dec. 2019) as applied to claim 1 in view of So, et. al. (US 20170356038 A1).
Regarding claim 2, Boyanov teaches the limitation as applied to claim 1 regarding the use of a secondary nanoscale opening to use in addition to the nanopore (see claim 1 above). Boyanov teaches the second nanoscale opening 25 provides improved detection ability of the electrodes (par. 0107-0112).
Boyanov is silent to wherein the nanochannel does not comprise a through-hole in the substrate.
So teaches a nanopore-based sequencing chip for real-time analysis (Abstract) (nanopore sequencing device). So teaches device 800 comprises top 810, bottom 850, and nanopore 840 wafer that come together to form a bottom well (cis well) connected to a top well (middle well) through a nanopore and an upper microfluidic channel (trans well) connected to the top well (middle well) through a nanofluidic channel 830 (nanochannel) (Fig. 8) with each area comprising associated electrodes (Fig. 8, 11). So teaches each wafer portion further comprises a layer of dielectric material (par. 0048). As seen in Figure 8, So teaches the nanofluidic channel is not formed by going through the layered wafers, but instead formed as an elongated gap between the two wafers when sandwiched together (Fig. 8; par. 0050, 0055) (wherein the nanochannel does not comprise a through-hole in the substrate). So teaches forming and using a second nanofluidic opening in addition to the nanopore allows for additional sample control benefits such as controlling the flow rate, stretching the molecule, and serving as a filter (par. 0055) and this increased control allows for improved molecule analysis (par. 0056). So additionally teaches this method of chip formation allows for precise formation of the nanopore layer/wafer without interference from other layers/wafers and for the final integrated circuit layers/wafers to be bonded to the more customizable nanopore layer/wafer (par. 0048-0051).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the formation of the second nanoscale opening of Boyanov to not be formed from a through-hole in the substrate as taught by So because the sandwiched layers allow for easy customization to the nanopore layer without outer circuit layers interfering ultimately making the total device through the simple bonding of layers (So, par. 0048-0051) with a reasonable expectation of success. MPEP 2143(I)(G). The claimed limitations are obvious because all the claimed elements (secondary nanoscale opening in the form of a nanochannel) were known in the prior art and one skilled in the art could have modified structural formation steps, forming through-holes as layers are built as taught by Boyanov (Boyanov, Fig. 8A-8M), to instead forming individual layers and bonding each layer together to create a gap between layers as taught by So (So, par. 0048-0051) with no change in the respective function or goal (improved detection samples being sequenced, Boyanov par. 0107-0112, So par. 0055-0056) of the second nanoscale opening/nanochannel.
Regarding claim 11, Boyanov teaches the cis well 14, trans well 16, and middle cavities 15, 20 are all adjacent to one another (Fig. 2A). While Figure 2A depicts a vertical orientation, the device is fully capable of being rotated 90° to achieve the same structural and functional capabilities with a horizontal orientation because the fluid flow is driven by electrical means through the nanoscale openings and the gravitational impact of fluid flow does not influence the device orientation (par. 0012) (wherein the cis well is positioned horizontally side-by-side with the middle well). A rotated version of Figure 2A is provided below.
Boyanov is silent to the trans well is positioned vertically adjacent to the middle well.
So teaches a nanopore-based sequencing chip for real-time analysis (Abstract) (nanopore sequencing device). So teaches device 800 comprises top 810, bottom 850, and nanopore 840 wafer that come together to form a bottom well (cis well) connected to a top well (middle well) through a nanopore and an upper microfluidic channel (trans well) connected to the top well (middle well) through a nanofluidic channel 830 (nanochannel) (Fig. 8) with each area comprising associated electrodes (Fig. 8, 11). So teaches each wafer portion further comprises a layer of dielectric material (par. 0048). As seen in Figure 8, So teaches the nanofluidic channel is formed as an elongated gap between the two wafers when sandwiched together (Fig. 8; par. 0050, 0055). Similarly, the device is fully capable of being rotated 90° to achieve the same structural and functional capabilities with a horizontal orientation because the fluid flow is driven by electrical means through the nanoscale openings and the gravitational impact of fluid flow does not influence the device orientation (par. 0037). This positions the upper microfluidic channel (trans well) vertically adjacent to the top well (middle well) (Fig. 8) (wherein the trans well is positioned vertically adjacent to the middle well). So teaches this final structural relationship between wells is a result of the chip production method, and So teaches this method of chip formation allows for precise formation of the nanopore layer/wafer without interference from other layers/wafers and for the final integrated circuit layers/wafers to be bonded to the more customizable nanopore layer/wafer (par. 0048-0051).
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It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the structural relationship of the wells of all being horizontally adjacent of Boyanov to instead position the trans well vertically beside the middle well as taught by So because the sandwiched layers allow for easy customization to the nanopore layer without outer circuit layers interfering ultimately making the total device through the simple bonding of layers (So, par. 0048-0051) with a reasonable expectation of success. MPEP 2143(I)(G). The claimed limitations are obvious because all the claimed elements (vertical trans well and horizontal cis well) were known in the prior art and one skilled in the art could have modified structural formation steps, building layers are up each other as taught by Boyanov (Boyanov, Fig. 8A-8M), to instead forming individual layers and bonding each layer together to create turn in the fluidic pathway to create a vertically attached trans well as taught by So (So, par. 0048-0051) with no change in the respective function or goal (improved detection samples being sequenced, Boyanov par. 0107-0112, So par. 0055-0056) of the nanopore sequencing device.
Regarding claim 12, Boyanov teaches cis well 14 is positioned adjacent to and above the cavities 15, 21 (middle well) (Fig. 2A) (the cis well is positioned vertically adjacent to the middle well). Boyanov teaches the trans well 15 is also beside cavities 15 and 21 (middle well).
Boyanov is silent to wherein the trans well is positioned horizontally side-by-side with the middle well.
So teaches a nanopore-based sequencing chip for real-time analysis (Abstract) (nanopore sequencing device). So teaches device 800 comprises top 810, bottom 850, and nanopore 840 wafer that come together to form a bottom well (cis well) connected to a top well (middle well) through a nanopore and an upper microfluidic channel (trans well) connected to the top well (middle well) through a nanofluidic channel 830 (nanochannel) (Fig. 8) with each area comprising associated electrodes (Fig. 8, 11). So teaches each wafer portion further comprises a layer of dielectric material (par. 0048). As seen in Figure 8, So teaches the nanofluidic channel is formed as an elongated gap between the two wafers when sandwiched together (Fig. 8; par. 0050, 0055). This positions the upper microfluidic channel (trans well) horizontally adjacent to the top well (middle well) (Fig. 8) (wherein the trans well is positioned horizontally side-by-side with the middle well). So teaches this final structural relationship between wells is a result of the chip production method, and So teaches this method of chip formation allows for precise formation of the nanopore layer/wafer without interference from other layers/wafers and for the final integrated circuit layers/wafers to be bonded to the more customizable nanopore layer/wafer (par. 0048-0051).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the structural relationship of the wells of all being vertically adjacent of Boyanov to instead position the trans well horizontally beside the middle well as taught by So because the sandwiched layers allow for easy customization to the nanopore layer without outer circuit layers interfering ultimately making the total device through the simple bonding of layers (So, par. 0048-0051) with a reasonable expectation of success. MPEP 2143(I)(G). The claimed limitations are obvious because all the claimed elements (horizontal trans well and vertical cis well) were known in the prior art and one skilled in the art could have modified structural formation steps, building layers are up each other as taught by Boyanov (Boyanov, Fig. 8A-8M), to instead forming individual layers and bonding each layer together to create turn in the fluidic pathway to create a horizontally attached trans well as taught by So (So, par. 0048-0051) with no change in the respective function or goal (improved detection samples being sequenced, Boyanov par. 0107-0112, So par. 0055-0056) of the nanopore sequencing device.
Regarding claim 19, Boyanov teaches the limitation as applied to claim 1 regarding the use of a secondary nanoscale opening to use in addition to the nanopore (see claim 1 above). Boyanov teaches the second nanoscale opening 25 provides improved detection ability of the electrodes (par. 0107-0112) and the second nanoscale opening with have dimensions larger than that of the first nanoscale opening (par. 0073-0075).
Boyanov is silent to wherein the nanochannel has a path length that is chosen to achieve a desired fluidic, ionic, and/or electrical resistance.
So teaches a nanopore-based sequencing chip for real-time analysis (Abstract) (nanopore sequencing device). So teaches device 800 comprises top 810, bottom 850, and nanopore 840 wafer that come together to form a bottom well (cis well) connected to a top well (middle well) through a nanopore and an upper microfluidic channel (trans well) connected to the top well (middle well) through a nanofluidic channel 830 (nanochannel) (Fig. 8) with each area comprising associated electrodes (Fig. 8, 11). As seen in Figure 8, So teaches the nanofluidic channel is not formed by going through the layered wafers, but instead formed as an elongated gap between the two wafers when sandwiched together (Fig. 8; par. 0050, 0055). So teaches forming and using a second nanofluidic opening in addition to the nanopore allows for additional sample control benefits such as controlling the flow rate, stretching the molecule, and serving as a filter (par. 0055-0056) (wherein the nanochannel has a path length that is chosen to achieve a desired fluidic… resistance). So teaches this increased control attributed to the nanofluidic channel allows for improved molecule analysis (par. 0056).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the length of the second nanoscale opening of Boyanov to be elongated for additional fluidic control as taught by So because the nanofluidic channel ability to contribute control to the fluidic flow of the device improves the molecular analysis abilities of the device (So, par. 0055-0056). The claimed limitations are obvious because all the claimed elements (secondary nanoscale opening in the form of a nanochannel) were known in the prior art and one skilled in the art could have modified structural formation steps, forming through-holes as layers are built as taught by Boyanov (Boyanov, Fig. 8A-8M), to instead forming individual layers and bonding each layer together to create a gap between layers as taught by So (So, par. 0048-0051) with no change in the respective function or goal (improved detection samples being sequenced, Boyanov par. 0107-0112, So par. 0055-0056) of the second nanoscale opening/nanochannel.
Regarding claim 24, Boyanov teaches the nanopore sequencing device 10 of claim 1 can be formed in plurality as an array 100 (Fig. 6A; par. 0080). In the array form Boyanov teaches a cis well 14 in fluid communication with a plurality of first nanoscale openings 23 each first nanoscale opening 23 associated with its own FET system (as described in claim 1) (a plurality of middle wells, wherein each middle well is associated with a respective sensing electrode) and cavities 15 and 21 (each middle well is in fluid communication with the cis well through a respective nanopore) and leading to a plurality of associated second nanoscale openings 25 that fluidically connect the trans well 16 (each middle well is in fluid communication with the trans well through a respective nanochannel) (Fig. 6A; par. 0080-0082, 0087, 0090).
Boyanov is silent to wherein the respective nanochannel is oriented parallel to the substrate surface.
So teaches a nanopore-based sequencing chip for real-time analysis (Abstract) (nanopore sequencing device). So teaches device 800 comprises top 810, bottom 850, and nanopore 840 wafer that come together to form a bottom well (cis well) connected to a top well (middle well) through a nanopore and an upper microfluidic channel (trans well) connected to the top well (middle well) through a nanofluidic channel 830 (nanochannel) (Fig. 8) with each area comprising associated electrodes (Fig. 8, 11). So teaches each wafer portion further comprises a layer of dielectric material (par. 0048). As seen in Figure 8, So teaches the nanofluidic channel is not formed by going through the layered wafers, but instead formed as an elongated gap between the two wafers when sandwiched together (Fig. 8; par. 0050, 0055) (wherein the respective nanochannel is oriented parallel to the substrate surface). So teaches the technique to making a singular nanopore and nanochannel can also be applied to create an array of nanopores and nanofluidic channels (Fig. 10B, par. 0038). So teaches forming and using a second nanofluidic opening in addition to the nanopore allows for additional sample control benefits such as controlling the flow rate, stretching the molecule, and serving as a filter (par. 0055) and this increased control allows for improved molecule analysis (par. 0056). So additionally teaches this method of chip formation allows for precise formation of the nanopore layer/wafer without interference from other layers/wafers and for the final integrated circuit layers/wafers to be bonded to the more customizable nanopore layer/wafer (par. 0048-0051).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the formation of the second nanoscale opening of Boyanov to not be formed from a through-hole in the substrate as taught by So because the sandwiched layers allow for easy customization to the nanopore layer without outer circuit layers interfering ultimately making the total device through the simple bonding of layers (So, par. 0048-0051) with a reasonable expectation of success. MPEP 2143(I)(G). The claimed limitations are obvious because all the claimed elements (secondary nanoscale opening in the form of a nanochannel formed in plurality with a plurality of nanopores) were known in the prior art and one skilled in the art could have modified structural formation steps, forming through-holes as layers are built as taught by Boyanov (Boyanov, Fig. 8A-8M), to instead forming individual layers and bonding each layer together to create a gap between layers parallel to the surface as taught by So (So, par. 0048-0051) with no change in the respective function or goal (improved detection samples being sequenced, Boyanov par. 0107-0112, So par. 0055-0056) of the second nanoscale opening/nanochannel and can further be applied to an array like structure to accommodate a plurality of individual nanopores and nanochannels (So, par. 0038).
Regarding claim 25, Modified Boyanov teaches the plurality of first nanoscale openings 23 are embedded in a respective plurality of membranes 24 separating the plurality of cavities 15, 20 from the cis well 14 (Boyanov, Fig. 6A) (wherein the respective nanopore is positioned in and through a respective membrane separating each of the middle wells and the cis well).
Regarding claim 26, Modified Boyanov teaches wherein the array of first 23 and second 25 nanoscale openings can lead to a common trans well 16 (Boyanov, par. 0080, 0087) (wherein the trans well is a common trans channel in fluid communication with the plurality of middle wells through respective nanochannels).
Regarding claim 27, Modified Boyanov teaches wherein the array of first 23 and second 25 nanoscale openings are connected to a common cis well 14 (Boyanov, Fig. 6A, par. 0080) (wherein the cis well is a common cis channel in fluid communication with the plurality of middle wells through respective nanopores).
Regarding claim 28, Modified Boyanov teaches the plurality of first nanoscale openings 2 and associated parts can be arranged in many different patterns including a series of rows and columns (Boyanov, par. 0090) (wherein the middle wells are arranged in an ordered array).
Regarding claim 29, Modified Boyanov teaches the density of the nanopore sequencing device can create and array up to 1,000,000 first nanoscale openings 23 (par. 0091). Because each first nanoscale opening 23 is associated with its own cavities, if there are up to 1,000,000 first nanoscale openings 23, there are an associated up to 1,000,000 cavities (wherein the device comprises at least 1,000,000 middle wells).
Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Boyanov, et. al. (US 20210156819 A1; claiming priority date of 16 Feb. 2018) as applied to claim 1 in view of Xie (US 20160231307 A1).
Regarding claim 13, Boyanov teaches cavities 15 and 21 between first 23 and second 25 nanoscale openings vary in width (Fig. 2A).
Boyanov is silent to wherein the middle well has a characteristic width of about 5 µm to about 200 µm.
Xie teaches a nanopore sensor disposed between two fluid reservoirs with a fluid path (Abstract). Xie teaches a nanopore sensing device 100 comprising a cis reservoir 102 with electrode 15, a trans reservoir 104 with electrode 13, a nanopore 12 and fluidic path 105 fluidically connecting the cis 102 to the trans 104 reservoir with a transudative element 7 (a general embodiment seen in Fig. 5 with further embodiments of the fluidic path 105 seen in Fig. 13-15B). Xie teaches wherein the geometric requirements of the fluidic passage are influenced by the resistance requirements based on the geometric properties of the nanopore, meaning the aspect ratio of the nanopore to the fluidic path must be optimized to reach a resistance ratio (Fig. 7; par. 0109-0110) with other geometric properties like the fluidic path length and concentration of the ionic solution further impacting width requirements (Fig. 8; par. 0122-0123).
Since this particular parameter is recognized as a result-effective variable (i.e. a variable which achieves a recognized result), the determination of the optimum or workable ranges of said variable can be characterized as routine experimentation. See MPEP 2144.05 (II)(A). Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention for the middle well has a characteristic width of about 5 µm to about 200 µm.
Regarding claim 14, Boyanov teaches cavities 15 and 21 between first 23 and second 25 nanoscale openings vary in width (Fig. 2A).
Boyanov is silent to wherein the middle well has a characteristic depth of about 5 µm to about 200 µm.
Xie teaches a nanopore sensor disposed between two fluid reservoirs with a fluid path (Abstract). Xie teaches a nanopore sensing device 100 comprising a cis reservoir 102 with electrode 15, a trans reservoir 104 with electrode 13, a nanopore 12 and fluidic path 105 fluidically connecting the cis 102 to the trans 104 reservoir with a transudative element 7 (a general embodiment seen in Fig. 5 with further embodiments of the fluidic path 105 seen in Fig. 13-15B). Xie teaches wherein the geometric requirements of the fluidic passage are influenced by the resistance requirements based on the geometric properties of the nanopore, meaning the aspect ratio of the nanopore to the fluidic path must be optimized to reach a resistance ratio (Fig. 7; par. 0109-0110) with other geometric properties like the fluidic path length and concentration of the ionic solution further impacting depth requirements (Fig. 8; par. 0122-0123).
Since this particular parameter is recognized as a result-effective variable (i.e. a variable which achieves a recognized result), the determination of the optimum or workable ranges of said variable can be characterized as routine experimentation. See MPEP 2144.05 (II)(A). Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention for the middle well has a characteristic depth of about 5 µm to about 200 µm.
Claims 17-18 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Boyanov, et. al. (US 20210156819 A1; claiming priority date of 16 Feb. 2018) as applied to claim 1 in view of Xie (US 20260146988 A1; claiming priority date of 17 July 2020).
Regarding claim 17, Boyanov teaches the limitation as applied to claim 1 regarding the use of a secondary nanoscale opening to use in addition to the nanopore (see claim 1 above). Boyanov teaches the second nanoscale opening 25 provides improved detection ability of the electrodes (par. 0107-0112) and the second nanoscale opening with have dimensions larger than that of the first nanoscale opening (par. 0073-0075).
Boyanov is silent to wherein the nanochannel has a tortuous path.
Xie teaches a nanopore sensing device using nanopores and fluidic paths between two chambers (Abstract). Xie teaches the device comprises a first chamber 3 (cis well) and a second chamber 4 (trans well) fluidically connected by a nanopore 23 embedded in membrane 22 and fluidic passage 20 (Fig. 1). Xie teaches nanopore 23 first leads to well 31 and well 31 leads to a narrower fluidic resistor portion 150 (Fig. 2; par. 0059). Xie teaches wherein the fluidic resistor portion 150 takes on a tortuous path (Fig. 5; par. 0083) (wherein the nanochannel has a tortuous path). Xie teaches the addition of the fluidic resistor path 150 when paired with a voltage divider allows electric potentials to be monitored as molecules move across the nanopore (par. 0007). The geometry of the fluidic resistor path directly effecting the resistor benefits (par. 0085). Xie teaches the tortuous path allows for sufficient length to achieve desired fluidic resistance of the path while minimizing footprint on the device itself and thus size of the overall sensing device (par. 0083).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the second nanoscale opening of Boyanov to be an elongated, tortuous path as taught by Xie because the geometry of the resistor fluidic path influences the fluidic resistance and therefore sensing ability of the nanopore and a tortuous pattern allows for the path length to increase while minimizing the foodprint of the path on the overall device (Xie, 0084-0085). The claimed limitations are obvious because all the claimed elements (secondary nanoscale opening in the form of a nanochannel) were known in the prior art and one skilled in the art could have modified shape of the second nanoscale with no change in the respective function or goal (improved detection samples being sequenced, Boyanov par. 0107-0112, So par. 0007, 0085) of the second nanoscale opening/nanochannel.
Regarding claim 18, Modified Boyanov in view of Xie teaches the tortuous fluidic resistor path 150 can take on a plurality of different shapes including but not limited to a rectangular wave (Xie, Fig. 5), curved shapes, or spiral shapes (Xie, par. 0083-0084) (wherein the tortuous path comprises a rectangular wave shape, a sine wave shape… a spiral shape, or any combination thereof).
Regarding claim 21, Boyanov teaches the limitation as applied to claim 1 regarding the use of a secondary nanoscale opening to use in addition to the nanopore (see claim 1 above). Boyanov teaches the second nanoscale opening 25 provides improved detection ability of the electrodes (par. 0107-0112) and the second nanoscale opening with have dimensions larger than that of the first nanoscale opening (par. 0073-0075).
Boyanov is silent to wherein the nanochannel has a footprint with a length of between about 5 µm and about 500 µm.
Xie teaches a nanopore sensing device using nanopores and fluidic paths between two chambers (Abstract). Xie teaches the device comprises a first chamber 3 (cis well) and a second chamber 4 (trans well) fluidically connected by a nanopore 23 embedded in membrane 22 and fluidic passage 20 (Fig. 1). Xie teaches nanopore 23 first leads to well 31 and well 31 leads to a narrower fluidic resistor portion 150 (Fig. 2; par. 0059). Xie teaches wherein the fluidic resistor portion 150 takes on a tortuous path (Fig. 5; par. 0083) to create an overall cross-section of 10 to 100 µm (par. 0087) (wherein the nanochannel has a footprint with a length of between about 5 µm and about 500 µm). Xie teaches the addition of the fluidic resistor path 150 when paired with a voltage divider allows electric potentials to be monitored as molecules move across the nanopore (par. 0007). The geometry of the fluidic resistor path directly effecting the resistor benefits (par. 0085). Xie teaches the tortuous path allows for sufficient length to achieve desired fluidic resistance of the path while minimizing footprint on the device itself and thus size of the overall sensing device (par. 0083).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the second nanoscale opening of Boyanov to be an elongated, tortuous path with a footprint length between 5 to 500 µm as taught by Xie because the geometry of the resistor fluidic path influences the fluidic resistance and therefore sensing ability of the nanopore and a tortuous pattern allows for the path length to increase while minimizing the foodprint of the path on the overall device (Xie, 0084-0085). The claimed limitations are obvious because all the claimed elements (secondary nanoscale opening in the form of a nanochannel) were known in the prior art and one skilled in the art could have modified shape of the second nanoscale with no change in the respective function or goal (improved detection samples being sequenced, Boyanov par. 0107-0112, So par. 0007, 0085) of the second nanoscale opening/nanochannel.
Regarding claim 22, Modified Boyanov in view of Xie teaches the overall cross-section of 10 to 100 µm for the fluidic resistor path 150 (Xie, par. 0087) and a corresponding path length of 1 to 10 µm for the fluidic resistor path 150 (Xie, par. 0086) (wherein the path length of the nanochannel is about 1.5 to about 50 times the length of the nanochannel footprint).
Claim 23 rejected under 35 U.S.C. 103 as being unpatentable over Boyanov, et. al. (US 20210156819 A1; claiming priority date of 16 Feb. 2018) as applied to claim 1 in view of Cantley, et. al. ("Voltage gated inter-cation selective ion channels from graphene nanopores" 2019).
Regarding claim 23, Boyanov teaches the limitation as applied to claim 1 regarding the use of a secondary nanoscale opening to use in addition to the nanopore (see claim 1 above). Boyanov teaches the second nanoscale opening 25 provides improved detection ability of the electrodes (par. 0107-0112).
Boyanov is silent to the device further comprising at least one bubble generator, at least one pressure pulse generator, or any combination thereof to control a liquid flow in at least one of the second nanoscale openings.
Cantley teaches the use of nanobubbles to selectively control the ionic flux across a nanopore (Abstract). Cantley teaches a solid-state nanochannel/nanopore with a gold electrode applied to the solid-state surface within an electrolyte solution with a voltage applied across the device (pg. 9856, col. 2, par. 03) to ultimately from a nanobubble along the nanopore surface (pg. 9858, col. 1) (further comprising at least one bubble generator… to control a liquid flow in at least one of the second nanoscale openings). Cantley teaches this method allows for selective ion-transport through the nanopore (pg. 9859, "Conclusions") which in turn allows for selective control in ionic flux that more closely mimics biological systems (pg. 9856, col. 1, par. 01 - col. 2, par. 01).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the device nanopore sequencing device of Boyanov to further include a way to generate a gas bubble at the nanoscale opening as taught by Cantley because gas bubbles allow for selective control of ions through the nanoscale opening (Cantley, pg. 9856, col. 1, par. 01 - col. 2, par. 01) with reasonable expectation of success.
Claim 30 and 32 rejected under 35 U.S.C. 103 as being unpatentable over Boyanov, et. al. (US 20210156819 A1; claiming priority date of 16 Feb. 2018) and So, et. al. (US 20170356038 A1) as applied to claim 23 in further view of Cantley, et. al. ("Voltage gated inter-cation selective ion channels from graphene nanopores" 2019).
Regarding claim 30, Boyanov teaches the limitation as applied to claim 1 regarding the use of a secondary nanoscale opening to use in addition to the nanopore (see claim 1 above). Boyanov teaches the second nanoscale opening 25 provides improved detection ability of the electrodes (par. 0107-0112).
Boyanov is silent to wherein the device further comprises a gas bubble generator configured to generate a gas bubble to modulate or block a flow of current, ions, and /or fluid in the respective nanochannel.
Cantley teaches the use of nanobubbles to selectively control the ionic flux across a nanopore (Abstract). Cantley teaches a solid-state nanochannel/nanopore with a gold electrode applied to the solid-state surface within an electrolyte solution with a voltage applied across the device (Fig. 1a; pg. 9856, col. 2, par. 03) to ultimately from a nanobubble along the nanopore surface (pg. 9858, col. 1) (wherein the device further comprises a gas bubble generator configured to generate a gas bubble to modulate or block a flow of current, ions… in the respective nanochannel). Cantley teaches this method allows for selective ion-transport through the nanopore (pg. 9859, "Conclusions") which in turn allows for selective control in ionic flux that more closely mimics biological systems (pg. 9856, col. 1, par. 01 - col. 2, par. 01).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the device nanopore sequencing device of Boyanov to further include a way to generate a gas bubble at the nanoscale opening as taught by Cantley because gas bubbles allow for selective control of ions through the nanoscale opening (Cantley, pg. 9856, col. 1, par. 01 - col. 2, par. 01) with reasonable expectation of success.
Regarding claim 32, Modified Boyanov in view of Cantley teaches a solid-state nanochannel/nanopore with a gold electrode applied to the solid-state surface to generate the gas bubble (Cantley; Fig. 1a; pg. 9856, col. 2, par. 03) (wherein the gas bubble generator comprises an electrode on the bottom of the nanochannel configured to generate the gas bubble via electrolysis or electrode wetting). It is understood this gold electrode is separate from and operates separate from the FET system of Boyanov (see claim 1).
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Boyanov, et. al. (US 20210156819 A1; claiming priority date of 16 Feb. 2018), So, et. al. (US 20170356038 A1), and Cantley, et. al. ("Voltage gated inter-cation selective ion channels from graphene nanopores" 2019) as applied to claim 30 above, and further in view of Paul, et. al. (Single-bubble dynamics in nanopores: Transition between homogeneous and heterogeneous nucleation; 2020).
Regarding claim 33, Modified Boyanov in view of Cantley teaches the limitations as applied to claim 30 (see above) in regard to the benefits of including a gas bubble generator with a nanofluidic opening in order to control ionic flux/flow through the nanofluidic opening.
Modified Boyanov is silent to wherein the gas bubble generator comprises a resistive heater underneath the nanochannel configured to generate the gas bubble.
Paul teaches the application of Joule heating to create a singular bubble within a nanoscale space (Abstract). Paul teaches the addition of a nanobubble when added to a nanoscale space blocks ion transport through the nanopore (pg. 2, col. 2, par. 01). Paul teaches one method of generating singular bubble is through Joule heating in the wall/membrane of the nanopore generating heat in the membrane wall to heat the solution (pg. 2, col. 2, "III. Theoretical Analysis" - pg. 3, col. 1, par. 01) (wherein the gas bubble generator comprises a resistive heater underneath the nanochannel configured to generate the gas bubble). Paul teaches this method leads successive bubble formation of non-permanent air bubbles within the nanoscale opening with the effect of blocking ion flow through the nanoscale opening (pg. 8, col. 2, "IV. Results and Discussion" par. 01).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the electrode bubble generation method of modified Boyanov in view of Cantley to instead by generated by resistive heating as taught by Paul because it was recognized that resistive heating provides a method of repeatably generating non-permanent bubbles in nanoscale opening to influence ionic-flow through the nanoscale opening (Paul, pg. 8, col. 2, "IV. Results and Discussion" par. 01). The simple substitution from one known element (electrode-based bubble formation) for another (resistive heat-based bubble formation) is likely to be obvious when predictable results (continuous bubble formation within a nanoscale opening) are achieved. MPEP 2143(I)(B).
Claim 34-35 rejected under 35 U.S.C. 103 as being unpatentable over Boyanov, et. al. (US 20210156819 A1; claiming priority date of 16 Feb. 2018), So, et. al. (US 20170356038 A1), and Cantley, et. al. ("Voltage gated inter-cation selective ion channels from graphene nanopores" 2019) as applied to claim 30 above, and further in view of Aizel (US 20130175171 A1).
Regarding claim 34, Modified Boyanov teaches the limitation as applied to claim 30 (see above). Modified Boyanov in view of Cantley teaches bubbles when paired with a nanoscale opening result in selective control of ions through the opening (pg. 9859, "Conclusions"). It is understood, if bubbles are formed to slow/control the ionic flow, the bubbles must also be removed to re-open full flow through the nanoscale opening.
Modified Boyanov is silent to a gas bubble annihilator.
Aizel teaches a separation device comprising a series of chambers and at least one nanofluidic channel (Abstract). Aizel teaches a silicon substrate with 8 with a cap 13, the silicon substrate 8 comprises a series of chambers and connected by nanofluidic channels 3 (Fig. 9A-9C) wherein separation is achieved through the nanofluidic channels through the application of a voltage across the channels (par. 0009). Aizel teaches cap 13 comprises an actuator to enable flexural strain-ability (par. 0127) to de-pressurize trapped air bubble from channel 5 (par. 0126-0127) (further comprises a gas bubble annihilator). Aizel teaches the unwanted air bubbles can lead to clogging and need to be purged from the system (par. 0010).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the device nanopore sequencing device of modified Boyanov to further include a gas bubble annihilator because unwanted air bubbles can lead to clogging and need to be purged from the system (par. 0010) with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 35, Modified Boyanov in view of Aizel teaches the cap 13 comprises an actuator to enable flexural strain-ability (par. 0127) to de-pressurize trapped air bubble from channel 5 (Aizel, par. 0126-0127) (wherein the gas bubble annihilator comprises an actuator).
Allowable Subject Matter
Claim 31 is objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding claim 31, modified Boyanov in view of Cantley as applied to claim 30 teaches a gold electrode applied to a surface of a nanoscale opening to generate a gas bubble to control ionic flow through the nanopore (Cantley; Fig. 1a; pg. 9856, col. 2, par. 03). However, the gold electrode of Cantley is significantly different from the FET system 22 between base substrate 62' and end 38 of Boyanov (Boyanov, Fig. 6A, par. 0087-0088, 0097, 0119). Because of the vastly different structure and operation of the gold electrode (Cantley) and the FET system (Boyanov) there is no teaching, motivation, or suggestion to modify or substitute the FET system to also have the ability to generate a gas bubble like the gold electrode, and vice versa.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Xia, et. al. (US 20230349884 A1) teaches nanoscale device for sensing an analyte as it passes through the nanoscale openings from one chamber to a next chamber (Abstract).
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/M.T.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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