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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-17, in the reply filed on 05/04/2026 is acknowledged.
Claim 18 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/04/2026.
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the “top layer of the disposable microfluidic chip contains two pipette inlets (0.4 mm diameter) above each chamber” (claim 4) and “wherein one inlet discharges the fluid into the disposable microfluidic chip and another inlet liberates the air out of the chamber” (claim 5) must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: In the specification, paragraph [0021], it is suggested to recite “DENV”, “HIV”, and “HCV” in an unabbreviated form to establish the acronyms. Appropriate correction is required.
Claim Objections
Claim 11 is objected to because of the following informalities: In line 1, it is suggested to recite “magnetic actuation platform of claim 10” as “automated platform of claim 10”. Appropriate correction is required.
Claim 17 is objected to because of the following informalities: it is suggested to recite “DENV”, “ZIKV”, “HIV”, and “HCV” in an unabbreviated form to establish the acronyms. Appropriate correction is required.
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 1-17 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 limitation "the clinical samples" (plural) in line 6. There is insufficient antecedent basis for this limitation in the claim. Claim 1 only establishes a singular “clinical sample” in line 2, and does not establish antecedent basis for multiple “clinical samples”. It is suggested to recite” the clinical samples” in line 6 as “the clinical sample”. Claims 2-17 are rejected by virtue of their dependency on claim 1.
Regarding claim 4, the limitation within the parenthesis, “(0.4 mm diameter)" in line 2, renders the claim indefinite because it is unclear whether the limitation(s) following the limitation within the parenthesis are part of the claimed invention or is a mere example of the diameter of the inlets. See MPEP § 2173.05(d). For examination purposes, the limitation of 0.4 mm diameter is interpreted as required structurally. Claim 5 is rejected by virtue of its dependency on claim 4.
Regarding claim 4, claim 4 recites “each chamber” in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. The limitation of “each chamber” appears to referring to multiple chambers, however claims 1-2 do not establish any chambers. Claim 5 is rejected by virtue of its dependency on claim 4.
Regarding claim 5, claim 5 recites “one inlet…another inlet” in lines 1-2. It is unclear if the one inlet and another inlet is the same or different from the “two pipette inlets” established in claim 4. For examination purposes, the one inlet and another inlet of claim 5 is interpreted as the same as the two pipette inlets of claim 4. It is suggested to recite “one inlet” as “one inlet of the two pipette inlets” and “another inlet” as “another inlet of the two pipette inlets”.
Regarding claim 5, claim 5 recites “the fluid” and “the air” in lines 1-2. There is insufficient antecedent basis for these limitations in the claim.
Regarding claim 5, claim 5 recites “the chamber” in line 3. It is unclear of “the chamber” is one of “each chamber” established in claim 4, or a different chamber. It is unclear which “chamber” is being referred to by “the chamber”.
Regarding claim 6, claim 6 recites “four chambers” in line 2. It is unclear if the “four chambers” is the same or different from “an inlet chamber; at least one washing buffer chamber; an amplification chamber; and an unconnected oval-shaped sensor chamber” established in claim 3. Does claim 6 require an additional four chambers other than the chambers recited in claim 3?
Regarding claim 9, claim 9 recites “the other chambers” in line 2. It is unclear which “chambers” is being referred to since claim 3 establishes “plurality of independent aqueous chambers…inlet chamber…at least one washing buffer chamber; an amplification chamber”. Is the “chambers” the inlet chamber, the at least one washing buffer chamber, and the an amplification chamber? Or is “chambers” referring to different chambers of the “plurality of independent aqueous chambers”?
Regarding claim 10, claim 10 recites “the magnetic actuation” in line 1. There is insufficient antecedent basis for this limitation in the claim. Note that claim 1 only establishes “magnetic actuation platform being activated…” and does not recite a step or process of “magnetic actuation”. Claims 11 and 14 are rejected by virtue of their dependency on claim 10.
Regarding claim 12, claim 12 recites “said platform” in line 1. It is unclear if “said platform” is referring to the “automated platform” or the “magnetic actuation platform”. For examination purposes, “said platform” is interpreted as the “automated platform”.
Regarding claim 12, claim 12 recites “an in-build surface heater” in lines 1-2. It is unclear if the in-build surface heater is the same or different from the “surface heater” established in claim 1. Additionally, claim 12 recites “said heater” in line 3. It is unclear if “said heater” is referring to the “in-build surface heater” of claim 12 or “surface heater” of claim 1.
Regarding claim 12, claim 12 recites “the temperature”, “the start”, and “the isothermal amplification procedure” in lines 2-4. There is insufficient antecedent basis for these limitations in the claim.
Regarding claim 14, claim 14 recites “magnetic actuation” in line 1. It is unclear if “magnetic actuation” is the same or different from “magnetic actuation” established in claim 10.
Regarding claim 14, claim 14 recites “the at least one magnetic bead movement from one chamber to another ” in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 15, claim 15 recites “the amplification chamber” in line 2. There is insufficient antecedent basis for this limitation in the claim.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 12, and 15-17 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Selden et al. (US 20170260567 A1; cited in the IDS filed 12/01/2022).
Regarding claim 1, Selden teaches an automated platform (abstract and [0022],[0122] teaches a microfluidic biochip that can performed automated steps) for the detection of a virus, bacteria, and/or other organism of interest from a clinical sample (interpreted as an intended use, see MPEP 2114; [0149],[0369], [0378] teaches interrogation of pathogens, such as bacteria in blood; [0119] teaches detection of DNA from human, bacterial, and viral clinical and research samples), said automated platform comprising:
a disposable microfluidic chip ([0015],[0119] teaches a biochip including microfluidic features; [0130] teaches the biochip is disposable) for receiving the clinical sample therethrough ([0017] teaches a chamber to receive a sample; [0119] teaches a sample is inserted into the biochip) for isolating, purifying and amplifying the virus, bacteria, and/or other organism of interest in the clinical samples ([0119] teaches purification, amplification, and separation, i.e. isolation, of human, bacterial, and viral clinical and research samples);
a magnetic actuation platform ([0132] and [0145] teach magnetic drive mechanisms to drive, i.e. actuate, fluids throughout the biochip; [0134] teaches magnetic subsystems); said magnetic actuation platform being activated to convey the clinical samples through said disposable microfluidic chip ([0132] and [0145] teach magnetic drive mechanisms to drive fluids throughout the biochip; therefore, the magnetic drive mechanisms is capable of being activated to convey samples through the biochip); and
a surface heater ([0144], “heating elements”; [0252] teaches heaters and heater plates) for heating the clinical samples ([0122]-[0123], [0198], [0252]).
Regarding claim 12, Selden further teaches wherein said platform comprises an in-built surface heater ([0144] teaches the biochip includes thermoplastic layers that contain heating elements, i.e. in-built surface heater) to control the temperature required for isothermal amplification (interpreted as an intended use, see MPEP 2114; [0125] teaches scripted process steps for amplification includes repeating cycling of temperatures, which includes 70 °C; therefore, the heater is capable of controlling a temperature required for isothermal amplification); wherein said heater is activated at the start of the isothermal amplification procedure to a temperature of 70 °C ± 2°C (interpreted as an intended use, see MPEP 2114; [0125] teaches scripted process steps for amplification includes repeating cycling of temperatures, which includes 70 °C; therefore, the heater is capable being activated at the start of an isothermal amplification procedure to a temperature of 70 °C).
Note that “to control the temperature required for isothermal amplification; wherein said heater is activated at the start of the isothermal amplification procedure to a temperature of 70 °C ± 2°C” is interpreted as an intended use or functional limitation. Note that an intended use and 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 intended use or functional limitations, then it meets the claim. See MPEP 2114. The apparatus of modified Selden is identical to the presently claimed structure. Modified Selden discloses the claimed surface heater that can heat at 70 °C as claimed and therefore, would have the ability to perform the use recited in the claim. See MPEP 2112.01 (I).
Regarding claim 15, Selden further teaches wherein an automated circuit board ([0122] teaches processing steps are performed by automated, computer-controlled scripts; [0134] teaches process control and computer subsystems; [0303] teaches a computer based controller to implement the script automatically; therefore, the platform that includes computer based controllers automated control of scripts are interpreted as an automated circuit board) controls the temperature of reagents enclosed in the amplification chamber of the microfluidic chip ([0122],[0303] teaches a computer based controller to automatically control subsystems; [0122] teaches automated computer-controlled scripts include heating samples within the thermal chambers, therefore is capable of controlling the temperature of reagents enclosed in an amplification chamber; [0123],[0125] teaches automated scripts for heating a chamber for an amplification reaction; [0156] teaches reagents for amplification reactions).
Regarding claim 16, Selden further teaches wherein multiple samples can be tested simultaneously (interpreted as an intended use, see MPEP 2114; [0127] and [0149] teaches processing multiple samples in parallel, therefore allowing for interrogation of a large number of pathogens and cellular processes simultaneously).
Regarding claim 17, note that “virus” of claim 1 and “DENY, ZIKV, HIV, coronavirus, and HCV” of claim 17 are not positively recited structurally and is interpreted as an intended use of the claimed system. A claim is only limited by positively recited elements; thus, inclusion of the material or article (“virus”; “DENY, ZIKV, HIV, coronavirus, and HCV”) worked upon by a structure (automated platform) being claimed does not impart patentability to the claims (see MPEP 2115).
Note that an intended use 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 intended uses, then it meets the claim. See MPEP 2114. The apparatus of Selden is identical to the presently claimed structure. Selden discloses the claimed disposable microfluidic chip, magnetic actuation platform, and surface heater (see above claim 1) as claimed and therefore, would have the ability to perform the use recited in the claim (i.e. detection of DENY, ZIKV, HIV, coronavirus, and HCV). See MPEP 2112.01 (I).
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.
Claims 2-11 and 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Selden as applied to claim 1 above, and further in view of Coarsey et al. (Coarsey C, Coleman B, Kabir MA, Sher M, Asghar W. Development of a flow- free magnetic actuation platform for an automated microfluidic ELISA. RSC Adv. March 12, 2019; 9(15):8159-8168; cited in the IDS filed 12/17/2023; also see Supplemental Information of Coarsey).
Regarding claim 2, Selden fails to teach: wherein the disposable microfluidic chip comprises three layers comprising: a top layer comprised of poly(methyl methacrylate) (PMMA) at a thickness of 750 um; a middle comprised of poly(methyl methacrylate) (PMMA) at a thickness of 1.5 mm; and a bottom layer comprised of poly(methyl methacrylate) (PMMA) at a thickness of 750 um.
Selden teaches the biochip comprises layers that contain microfluidic features ([0144]), and the biochip can incorporate additional layers ([0145]). Selden teaches the biochip may include multiple layers ([0154]-[0156]). Selden teaches the biochips can be fabricated by polymers, such as PMMA ([0152]). Selden teaches driving fluids through a biochip by a magnetic drive mechanism ([0132]).
Coarsey teaches an automated platform (abstract and Figs. 1-3 teaches a microfluidic immunoassay detection platform for automated microfluidic assays) for the detection of a virus, bacteria, and/or other organism of interest from a clinical sample (abstract; page 8167, “Conclusions”), said automated platform comprising: a disposable microfluidic chip (Figs. 1-3 teach a microfluidic chip, which is interpreted as “disposable” since the chip is structurally capable of being disposed) for receiving the clinical sample (page 8162, left column, first full paragraph teaches loading a sample into a reaction well of the microfluidic chip; therefore, the microfluidic chip is capable of receiving a clinical sample); a magnetic actuation platform (Fig. 3); said magnetic actuation platform being activated to convey samples through the disposable microfluidic chip (pages 8160-8161, section, “Platform automation and bead control”). Coarsey teaches wherein the disposable microfluidic chip comprises three layers (Fig. 2a; page 8160, section “Microfluidic chip design”) comprising: a top layer comprised of poly(methyl methacrylate) (PMMA) at a thickness of 750 um (Supplemental Information, Table 1, teaches Chips C or D with a top loading layer being 750 um thick); a middle comprised of poly(methyl methacrylate) (PMMA) at a thickness of 1.5 mm (page 8163, left column, first full paragraph teaches 1.5 mm PMMA well depth; Supplemental Information, Table 1, teaches Chips C or D with a middle well layer being 1.5 mm thick); and a bottom layer comprised of poly(methyl methacrylate) (PMMA) at a thickness of 750 um (Supplemental Information, Table 1, teaches Chips C or D with a bottom base layer being 750 um thick). Coarsey teaches the dimensions of the microfluidic chip allowed beads to travel through the chip with minimal bead loss, enabling reliable and optimized quantitation (page 8163, left column, first full paragraph). Coarsey teaches the chip is cost-effective, requires small reagent microfluidic volumes, provides quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (page 8167, “Conclusion”); and the highly versatile platform for magnetic bead-based assays can be developed for detection of viral and bacterial pathogens (page 8167, “Conclusion”).
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 disposable microfluidic chip of Selden to incorporate Selden’s teachings of biochips with multiple layers and fabricated from PMMA ([0145],[0154]-[0156], [0152]) and magnetic drive mechanisms to drive fluids ([0132]) and Coarsey’s teachings of an automated microfluidic chip with three PMMA layers of the claimed thicknesses (Figs. 1-3; page 8160, section “Microfluidic chip design”; page 8163, left column, first full paragraph; Supplemental Information, Table 1) to provide: wherein the disposable microfluidic chip comprises three layers comprising: a top layer comprised of poly(methyl methacrylate) (PMMA) at a thickness of 750 um; a middle comprised of poly(methyl methacrylate) (PMMA) at a thickness of 1.5 mm; and a bottom layer comprised of poly(methyl methacrylate) (PMMA) at a thickness of 750 um. Doing so would have a reasonable expectation of successfully optimizing the layers and dimensions of the microfluidic chip to enable desired materials to travel through the chip with minimal loss of materials such as beads, therefore enabling reliable and optimized quantitation (Coarsey, page 8163, left column, first full paragraph). Additionally, doing so would have a reasonable expectation of providing a cost-effective chip that requires small reagent microfluidic volumes and providing quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (Coarsey, page 8167, “Conclusion”) and improving versatility of the chip for detection of viral and bacterial pathogens (Coarsey, page 8167, “Conclusion”).
Regarding claim 3, Selden fails to teach: wherein the disposable microfluidic chip comprises plurality of independent aqueous chambers separated by a plurality of elliptical shaped valving chambers containing mineral oil which work as valves, the plurality of independent aqueous chambers comprising: an inlet chamber; at least one washing buffer chamber; an amplification chamber; and an unconnected oval-shaped sensor chamber.
Selden teaches the biochip includes a chamber to receive a sample and an amplification chamber ([0017]). Selden teaches the biochip includes various chambers, such as reaction chambers and detection regions ([0144]). Selden teaches flow control steps that includes washing ([0199]). Selden teaches a wash solution from a wash reagent chamber is introduced to a chamber ([0310]).
Coarsey teaches an automated platform (abstract and Figs. 1-3 teaches a microfluidic immunoassay detection platform for automated microfluidic assays) for the detection of a virus, bacteria, and/or other organism of interest from a clinical sample (abstract; page 8167, “Conclusions”), said automated platform comprising: a disposable microfluidic chip (Figs. 1-3 teach a microfluidic chip, which is interpreted as “disposable” since the chip is structurally capable of being disposed) for receiving the clinical sample (page 8162, left column, first full paragraph teaches loading a sample into a reaction well of the microfluidic chip; therefore, the microfluidic chip is capable of receiving a clinical sample); a magnetic actuation platform (Fig. 3); said magnetic actuation platform being activated to convey samples through the disposable microfluidic chip (pages 8160-8161, section, “Platform automation and bead control”). Coarsey teaches wherein the disposable microfluidic chip (Figs. 1-3 and 6; page 8160, section, “Microfluidic chip design”) comprises plurality of independent aqueous chambers (Figs. 1-3 and 6 page 8160, section, “Microfluidic chip design” teach reagent wells) separated by a plurality of elliptical shaped valving chambers containing mineral oil which work as valves (Figs. 1-3 and 6 and page 8160, section, “Microfluidic chip design” teach elliptical mineral oil wells, which are interpreted to work as valves as shown in Figs. 1 and 6), the plurality of independent aqueous chambers comprising: an inlet chamber (Fig. 1, interpreted as the primary well); at least one washing buffer chamber (Fig. 1, interpreted as the well where beads are mixed with a second antibody); an amplification chamber (Fig. 1, interpreted as the well for assay color development); and an unconnected oval-shaped sensor chamber (Fig. 1 and page 8162, right column, teaches a larger oil retention well, which is interpreted as the right most oval-shaped sensor chamber; Fig. 1 and “Microfluidic chip design” teach elliptical mineral oil wells are separated by reagent wells, therefore the right most oval-shaped sensor chamber is interpreted as at least unconnected from the first reagent well since it is separated from the first reagent well via other aqueous reagent wells, elliptical mineral oil wells, and channels). Coarsey teaches the chip is cost-effective, requires small reagent microfluidic volumes, provides quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (page 8167, “Conclusion”); and the highly versatile platform for magnetic bead-based assays can be developed for detection of viral and bacterial pathogens (page 8167, “Conclusion”).
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 disposable microfluidic chip of Selden to incorporate Selden’s teachings of a biochip including a chamber to receive a sample, an amplification chamber, reaction chambers and detection regions, washing steps, and chambers for washing ([0017],[0144],[0199],[0310]) and Coarsey’s teachings of a microfluidic chip with a plurality of independent aqueous chambers separated by elliptical shaped valving chambers containing mineral oils and the chambers including inlet, washing, amplification, and sensor chambers (Figs. 1-3,6; page 8160, section, “Microfluidic chip design”) to provide: wherein the disposable microfluidic chip comprises plurality of independent aqueous chambers separated by a plurality of elliptical shaped valving chambers containing mineral oil which work as valves, the plurality of independent aqueous chambers comprising: an inlet chamber; at least one washing buffer chamber; an amplification chamber; and an unconnected oval-shaped sensor chamber. Doing so would have a reasonable expectation of successfully improving separation of chambers for microfluidic processing of samples and providing a cost-effective chip that requires small reagent microfluidic volumes, and providing quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (Coarsey, page 8167, “Conclusion”) and improving versatility of the chip for detection of viral and bacterial pathogens (Coarsey, page 8167, “Conclusion”).
Regarding claim 4, modified Selden fails to teach: wherein the top layer of the disposable microfluidic chip contains two pipette inlets (0.4 mm diameter) above each chamber.
Coarsey teaches the top layer of the disposable microfluidic chip contains two pipette inlets (0.4 mm diameter) above each chamber (page 8160, section, “Microfluidic chip design” teaches the top layer includes pipette inlets with 0.4 mm diameter for reagent loading and air escape while the wells are filled), which allows for easy access to each well for reagent loading and air escape while wells are filled (page 8160, section, “Microfluidic chip design”).
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 top layer of modified Selden to incorporate Coarsey’s teachings of each well having two pipette inlets for easy access to each well for reagent loading and air escape while wells are filled (page 8160, section, “Microfluidic chip design”) to provide: wherein the top layer of the disposable microfluidic chip contains two pipette inlets (0.4 mm diameter) above each chamber. Doing so would have a reasonable expectation of successfully improving access to each well for reagent loading and improving air escape while wells are filled (page 8160, section, “Microfluidic chip design”).
Regarding claim 5, modified Selden further teaches wherein one inlet discharges the fluid into the disposable microfluidic chip and another inlet liberates the air out of the chamber (see above claim 4; modified Selden in view of Coarsey provides the two pipette inlets, one for reagent loading and another for air escape; Coarsey, page 8160, section, “Microfluidic chip design”).
Regarding claim 6, modified Selden further teaches: wherein the plurality of independent aqueous chambers comprises four chambers (see above claim 3; Selden in combination with Coarsey teaches the inlet chamber, at least one washing buffer chamber, amplification chamber, and unconnected oval-shaped sensor chamber, i.e. four chambers).
Regarding claim 7, modified Selden fails to teach: wherein the at least one washing buffer chamber comprises a first washing buffer chamber and a second washing buffer chamber.
Coarsey teaches wherein the at least one washing buffer chamber comprises a first washing buffer chamber and a second washing buffer chamber (Supplemental Information, page 6, Chip Loading Diagram S4, teaches wash buffer PBS in chambers 1a and 1c). Coarsey teaches beads were moved through a washing phase, mixed with a secondary antibody, and after a final rinsing stage, the beads are moved to a final reaction well (Fig. 1). Coarsey teaches wash steps to remove oil encapsulation and enhance assay reactions (page 8165, right column, first paragraph).
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 at least one washing buffer chamber of modified Selden to incorporate Coarsey’s teachings of two washing buffer chambers (Fig. 1; Supplemental Information, page 6, Chip Loading Diagram S4) to provide: wherein the at least one washing buffer chamber comprises a first washing buffer chamber and a second washing buffer chamber. Doing so would have a reasonable expectation of successfully improving washing a sample for enhanced assay reactions and detection.
Regarding claim 8, modified Selden fails to teach: wherein the plurality of elliptical shaped valving chambers comprises a first valving chamber, a second valving chamber, and a third valving chamber.
Coarsey teaches wherein the plurality of elliptical shaped valving chambers (Fig. 1; page 8160, section, “Microfluidic chip design”, elliptical mineral oil wells; Supplemental Information, page 6, Chip Loading Diagram S4) comprises a first valving chamber, a second valving chamber, and a third valving chamber (Fig. 1 and Supplemental Information, page 6, Chip Loading Diagram S4, interpreted as any three of the four elliptical mineral oil wells 2e, 2d, 2c, 2b). Coarsey teaches between the diamond reaction phase wells, ovals containing oil prevent any cross-contamination of the reaction (page 8162, left column).
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 plurality of elliptical shaped valving chambers of modified Selden to incorporate Coarsey’s teachings of at least three elliptical mineral oil wells (Figs. 1 and Supplemental Information, page 6, Chip Loading Diagram S4) to provide: wherein the plurality of elliptical shaped valving chambers comprises a first valving chamber, a second valving chamber, and a third valving chamber. Doing so would have a reasonable expectation of successfully improving separation of the aqueous chambers and preventing cross-contamination between the chambers (Coarsey, page 8162, left column).
Regarding claim 9, modified Selden fails to teach: wherein the unconnected oval-shaped sensor chamber is separated from the other chambers.
Coarsey teaches the unconnected oval-shaped sensor chamber is separated from the other chambers (Fig. 1 and page 8162, right column, teaches a larger oil retention well, which is interpreted as the right most oval-shaped sensor chamber; Fig. 1 and “Microfluidic chip design” teach the elliptical mineral oil wells are separated by reagent wells, therefore the right most oval-shaped sensor chamber is interpreted as at least separated from the other wells since there is a physical separation via other wells and channels).
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 disposable microfluidic chip of Selden to incorporate Coarsey’s teachings of a microfluidic chip with a plurality of independent aqueous chambers separated by elliptical shaped valving chambers containing mineral oils and the chambers including inlet, washing, amplification, and sensor chambers (Figs. 1-3,6; page 8160, section, “Microfluidic chip design”) to provide: wherein the unconnected oval-shaped sensor chamber is separated from the other chambers. Doing so would have a reasonable expectation of successfully improving separation of chambers for microfluidic processing of samples and providing a cost-effective chip that requires small reagent microfluidic volumes, and providing quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (Coarsey, page 8167, “Conclusion” and improving versatility of the chip for detection of viral and bacterial pathogens (Coarsey, page 8167, “Conclusion”).
Regarding claim 10, Selden fails to teach: wherein the magnetic actuation is executed by at least one small magnet which is enclosed with stepper motor and able to move bidirectionally on stepper motor linear slide rails.
Coarsey teaches magnetic actuation is executed by at least one small magnet which is enclosed with stepper motor and able to move bidirectionally on stepper motor linear slide rails (pages 8160-8161, section “Platform automation and bead control” and Fig. 3 teaches magnets enclosed with a stepper motor that moves in forward and backwards directions on linear slide rails). Coarsey teaches the magnetic actuator allows for automatically moving microparticles through the microfluidic chip (page 8160, section “Platform automation and bead control”). Coarsey teaches the chip is cost-effective, requires small reagent microfluidic volumes, provides quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (page 8167, “Conclusion”); and the highly versatile platform for magnetic bead-based assays can be developed for detection of viral and bacterial pathogens (page 8167, “Conclusion”).
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 disposable microfluidic chip of Selden to incorporate Coarsey’s teachings of a magnetic actuator for automatically moving microparticles through the microfluidic chip (pages 8160-8161, section “Platform automation and bead control” and Fig. 3; page 8167, “Conclusion”) to provide: wherein the magnetic actuation is executed by at least one small magnet which is enclosed with stepper motor and able to move bidirectionally on stepper motor linear slide rails. Doing so would have a reasonable expectation of successfully improving automation of movement of desired particles in the chip and therefore improving microfluidic processing of samples and providing a cost-effective chip that requires small reagent microfluidic volumes, and providing quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (Coarsey, page 8167, “Conclusion”) and improving versatility of the chip for detection of viral and bacterial pathogens (Coarsey, page 8167, “Conclusion”).
Regarding claim 11, modified Selden fails to teach: wherein the stepper motor linear slide rails are connected to the stepper motor by a power output wire.
Coarsey teaches the magnetic actuator allows for automatically moving microparticles through the microfluidic chip (page 8160, section “Platform automation and bead control”; Fig. 3). Coarsey teaches the stepper motor linear slide rails are connected to the stepper motor by a power output wire (Fig. 3). Coarsey teaches the chip is cost-effective, requires small reagent microfluidic volumes, provides quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (page 8167, “Conclusion”); and the highly versatile platform for magnetic bead-based assays can be developed for detection of viral and bacterial pathogens (page 8167, “Conclusion”).
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 disposable microfluidic chip of Selden to incorporate Coarsey’s teachings of a magnetic actuator for automatically moving microparticles through the microfluidic chip (pages 8160-8161, section “Platform automation and bead control” and Fig. 3; page 8167, “Conclusion”) to provide: wherein the stepper motor linear slide rails are connected to the stepper motor by a power output wire. Doing so would have a reasonable expectation of successfully providing power to the magnetic actuation platform and improving automation of movement of desired particles in the chip, improving microfluidic processing of samples, and providing a cost-effective chip that requires small reagent microfluidic volumes, and providing quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (Coarsey, page 8167, “Conclusion”) and improving versatility of the chip for detection of viral and bacterial pathogens (Coarsey, page 8167, “Conclusion”).
Regarding claim 13, modified Selden fails to teach: wherein the sensor chamber and the amplification chamber are filled with a reagent and the surface heater is attached to both chambers.
Selden teaches the biochip includes all reagents needed to process a sample ([0021]). Selden teaches various chambers comprising reagents ([0144]). Selden teaches a PCR reaction mix that is heated in a thermal cycling chamber ([0024]). Selden teaches thermal chambers are heated to heat samples ([0122]). Selden teaches a PCR amplification reaction including changing the temperature of a chamber ([0125]). Selden teaches a chamber with a fluid and reaction is heated ([0198]). Selden teaches heating the chip to establish and maintain temperature uniformity ([0252]).
Coarsey teaches various chambers filled with a reagent (Fig. 1 teaches antibody-coated superparamagnetic beads, i.e. reagent, is filled and transported through the reagent wells and mineral oil wells). Coarsey teaches the chip is cost-effective, requires small reagent microfluidic volumes, provides quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (page 8167, “Conclusion”); and the highly versatile platform for magnetic bead-based assays can be developed for detection of viral and bacterial pathogens (page 8167, “Conclusion”).
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 automated platform of modified Selden to incorporate Selden’s teachings of chambers with reagents, heating chambers, and heating the chip to maintain temperature uniformity ([0021], [0024], [0122],[0125],[0144],[0198],[0198]) and Coarsey’s teachings of chambers filled with reagents (Fig. 1) to provide: wherein the sensor chamber and the amplification chamber are filled with a reagent and the surface heater is attached to both chambers. Doing so would have a reasonable expectation of successfully improving sample processing with an appropriate reagent and improving control of temperature in the chambers.
Regarding claim 14, modified Selden fails to teach wherein magnetic actuation is coordinated by an automated circuit board and the at least one magnetic bead movement from one chamber to another.
Coarsey teaches magnetic actuation is coordinated by an automated circuit board (pages 8160-8161, section “Platform automation and bead control” teaches a microprocessor, such as a PCB, for software control of the magnetic actuation of the microfluidic chip) and the at least one magnetic bead movement from one chamber to another (pages 8161-8162, section “M-ELISA with mechanical actuation platform” teaches the beads were moved between wells, i.e. chambers). Coarsey teaches the chip is cost-effective, requires small reagent microfluidic volumes, provides quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (page 8167, “Conclusion”); and the highly versatile platform for magnetic bead-based assays can be developed for detection of viral and bacterial pathogens (page 8167, “Conclusion”).
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 disposable magnetic actuation platform of modified Selden to incorporate Coarsey’s teachings of a magnetic actuator with a PCB for automatically moving microparticles through wells of the microfluidic chip (pages 8160-8161, section “Platform automation and bead control”; pages 8161-8162, section “M-ELISA with mechanical actuation platform”; Fig. 3; page 8167, “Conclusion”) to provide: wherein magnetic actuation is coordinated by an automated circuit board and the at least one magnetic bead movement from one chamber to another. Doing so would have a reasonable expectation of successfully improving automation of movement of desired particles between chambers of the chip, improving microfluidic processing of samples, providing a cost-effective chip that requires small reagent microfluidic volumes, and providing quick assay turnaround and quantitative results, and therefore is beneficial for potential point of care applications (Coarsey, page 8167, “Conclusion”) and improving versatility of the chip for detection of viral and bacterial pathogens (Coarsey, page 8167, “Conclusion”).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Chen et al. (US 20120141989 A1) teaches a microfluidic chip for detecting a pathogen (abstract; Fig. 1), the chip including a sample loading chamber, purification/thermal lysis/ RT-LAMP reaction chamber, and waste chamber (Fig. 1). Chen teaches a magnetic bead is able to hybridize to a purification recognized fragment ([0030],[0037],[0038]). Chen teaches an isothermal amplification module of the microfluidic chip includes an array-type micro-heaters and temperature sensor to generate a temperature distribution with high thermal uniformity within the thermal lysis/LAMP reaction chamber ([0045]). Chen teaches a magnet and adjustable magnetic stage can be engaged and slided into a pocket during the purification process ([0045]). Chen teaches high specificity of the invention for samples including Dengue virus and Hepatitis B virus ([0084]).
Neely et al. (US 20130244238 A1) teaches a system for detection of analytes (abstract). Neely teaches aliquoting the assays into the separate detection chambers; these individual detection chambers are then disconnected from the reagent strip and from each other, and progress through the system separately. Because the reagent module is separated and discarded, the smallest possible sample unit travels through the instrument, conserving internal instrument space; and by splitting up each assay into its own unit, different incubation times and temperatures are possible as each multiplexed assay is physically removed from the others and each sample is individually manipulated ([0436]).
Crooks et al. (US 20150355132 A1) teaches paper fluidic devices for detecting analytes (abstract). Crooks teaches connection and disconnection between channels and reservoirs can be controlled, which allows for chemical sensing and detection assays that require multiple steps ([0109]).
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.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
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