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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/30/2026 is being considered by the examiner.
Response to Amendment
The Amendment filed 04/10/2026 has been entered. Claims 1-2, 5, 8-14, 16-20, 22-25 and 29 remain pending in the application. Claims 24-25 are withdrawn. Claims 1-2, 5, 8-14, 16-20, 22-23 and 29 are being examined herein.
Status of Rejections
All rejections of claim 6 are obviated by Applicant’s cancellation.
The rejections under nonstatutory double patenting over U.S. Patent No. 9291567 in view of Spero et al. (WO 2018236833 A1) are being withdrawn in view of Applicant’s amendment.
The provisional rejections under nonstatutory double patenting over copending Application No. 17/265,292 in view of Spero et al. (WO 2018236833 A1) are being withdrawn in view of Applicant’s amendment.
The rejections under 35 U.S.C. 112(b) are being withdrawn in view of Applicant’s amendment.
New grounds of rejection of claim 12 under 35 U.S.C. 112(b) are necessitated by the amendment.
The rejection under 35 U.S.C. 103 are being withdrawn in view of Applicant’s amendment.
New grounds of rejection under 35 U.S.C. 103 are necessitated by the amendments.
Claim Objections
Claim 29 is objected to because of the following informalities:
claim 29, lines 1-2, “between a sample inlet, and a waste” should read “between a sample inlet and a waste”;
claim 29, lines 2-3, “each region's neighbouring region is either inlet proximal or waste proximal of the region” should read “each region's neighbouring region is either inlet proximal or waste proximal relative to the region.”
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.
Claim 12 and 29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 12 has been amended to recite the limitation “… wherein relief patterning of the substrate and/or first film …” in lines 1-2. It is unclear whether “relief patterning” is a process or a structure. Clarification is requested. If the Applicant intends to recite “relief patterning” as a structure, it is suggested the limitation to amended to recite a separate relief patterned region (Fig. 1).
Claim 29 recites the limitation " … wherein chamber extends between a sample inlet, and a waste …" in lines 1-3. It is unclear what the structure of “a waste” is (e.g., is it a waste port ,para. 0042, or waste reservoir, para. 0062?) Clarification is requested. For the purpose of examination, it is being interpreted as a waste port (para. 0042).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 5 and 23 rejected under 35 U.S.C. 103 as being unpatentable over Spero et al. (WO 2018236833 A1) in view of Fuchs et al. (US 20120244529 A1).
Regarding claim 1, Spero teaches a kit for forming a microfluidic chip (Fig. 1A, the chip includes 100 and 200, specifically the 100 shown in Fig. 23 is used; in addition Fig. 2B, 100 includes 150 140, 110, 130), the kit comprising:
a substrate (110) having a surface with topographical relief bearing at least 4 relief patterned regions (4 of the reaction chambers 105 in Fig. 23B), each defining a respective interface-pinning reaction vessel (reaction chamber 105, which has an array of microposts 122)(para. 0056) covering a footprint area with a surface area of at least 1.6 times the footprint area (para. 0061, the micropost array has microposts of 4 mm-diameter, a controlled density of 105 microposts/cm2 with 30 x higher or 100 x lower being reasonable range, and paras. 0011 and 0042, each micropost can have height between 1-100 mm; therefore, the surface area is at least 1.6 times. For example, for a micropost of 4 mm in diameter and 100 mm in height, its surface area is 1.27x 10-5 cm (which means 1.27x 10-5 cm surface area per micropost), and with a controlled density of 2 x 105 microposts/cm2 (which is 2 x 105 microposts/ footprint area in cm2), then that would yield 2.5 times of surface area per footprint area); and
a part (150) with a covering surface dimensioned for sealing against the substrate (110)(Figs. 2A and 2B)
where:
each region (reaction chamber 105) is separated from a neighbouring region by a segment of the surface (Fig. 23B);
each segment separates its region from the neighbouring region by a distance (Fig. 23B).
Spero teaches the footprint area, but Spero does not teach the specific dimensions of the footprint area and thus fails to teach the footprint area is 0.5 to 15 cm2.
However, Spero teaches the reaction chamber 105 can be any area/size (para. 0099). Additionally, Figs. 12-14, 23B and para. 0085 teaches chamber 105 are made in a 6-inch or 12-inch wafer, which has an area of 182cm2 and 730 cm2, respectively, and thus has sufficient area to make the modular active surface device 100 shown in Fig. 23B with reactor chambers 105 with area ranges in 0.5 to 15 cm2. Furthermore, Spero teaches wherein the area of reaction chamber 105 is a result-effective variable. Specifically, Spero teaches that the area of reaction chamber 105 is dependent on the end user’s requirement (para. 0099) in the context of processing biological material (e.g., biological assay) in microfluidics (abstract, para. 0049). 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 to have the reaction chambers with an area of 0.5 to 15 cm2 because it would have been within the ambit of one of ordinary skill in the art to arrive at through routine experimentation.
Spero teaches a microfluidic device (100 and 200)(Figs. 1A, 23B) for processing biological materials (para. 0004) for a variety of applications (paras. 0051 and 0105). Spero further teaches the size and features of modular active surface devices 100 (which comprises of 110)(Fig. 2B) is based on the requirements of the end user (para. 0099). Spero teaches the device can be used for assaying large amounts of biological material in a multiplexed format (para. 0068).
Spero teaches the substrate (110) has isolated reaction chambers 105 (vessels) instead of a single flow-through chamber that includes the vessels (reaction chambers 105)(Fig. 23B), and thus Spero fails to teach the part (150) with a covering surface dimensioned for sealing against the substrate to enclose a single flow-through chamber that includes the vessels, and consequently fails to teach and the chamber includes each region and each separating segment.
However, Fuchs teaches a microfluidic device for analyzing biological samples (Fuchs, abstract) in a multiplexed format. Fuchs teaches the device comprises a single flow-through chamber including an inlet that is connected to a plurality of reaction channels (reaction vessels), which are connected to an outlet (Fig. 1C, para. 0055). Fuchs teaches device allows for the multiplexed format such that a single sample can enter device through the inlet and be assayed in different conditions in different reaction channels.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the isolated reaction chambers 105 taught by Spero to include a single flow-through chamber that includes an inlet that is connected to the reaction vessels (reaction chambers 105), which are connected an outlet as taught by Fuchs in order to perform multiplexed assays using a single sample with a reasonable expectation of success (Fuchs, abstract and para. 0055) (MPEP 2143)(I)(G).
The teachings of Spero as modified by Fuchs would yield the part (150) with a covering surface dimensioned for sealing against the substrate to enclose a single flow-through chamber (Fuchs, Fig. 1C, modified Spero has one inlet that branches into/connects each of the chambers 105, which connected into a single outlet, the space between the inlet and the outlet is the single flow-through chamber. The inlet, chambers 105 and outlets are all fluidically connected, and thus a single enclosed space, which is a chamber); and the chamber includes each region and each separating segment (the single flow-through chamber includes the chambers 105 of Spero and the segments separating chambers 105).
Modified Spero further teaches each region (chamber 105) is separated from each neighbouring region by segments of the surface (the regions between reaction chambers 105) that have a ratio of surface area to footprint that is no more than 1.1 (the regions between reaction chambers 105 do not have microposts and thus the ratio is closer to 1)(Fig. 23B).
Spero does not explicitly teach each segment separates the neighbouring regions by a distance that is greater than at least one of: 0.1 mm; or 5% of a mean of the extents of the neighbouring regions in the planar directions.
However Spero teaches wherein the dimensions of the regions between reaction chambers 105 is a result-effective variable. Specifically, Spero teaches that the size and features of modular active surface devices 100 (the regions between reaction chambers 105 is feature of 100) depends on the end user’s requirement (para. 0099 and Fig. 23B). 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 to have the dimensions of the regions between reaction chambers 105 between the reaction chamber to be greater than at least one of: 0.1 mm; or 5% of a mean of the extents of the neighbouring regions in the planar directions because it would have been within the ambit of one of ordinary skill in the art to arrive at through routine experimentation.
Regarding claim 2, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 1.
Modified Spero fails to explicitly teach wherein each region's footprint (the area of reaction chamber 105) extends at least 0.1 mm, and at most 50 mm, in both each of two normal planar directions.
However Spero teaches wherein the area (and thus the length and width) of reaction chamber 105 a result-effective variable. Specifically, Spero teaches that the area (length and width) of reaction 105 is depends on the end user’s requirement (para. 0099). 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 to have the reaction chambers with an length and width to be at least 0.1 mm, and at most 50 mm and be within the area limitation of claim 1 because it would have been within the ambit of one of ordinary skill in the art to arrive at through routine experimentation.
Regarding claim 5, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 1. Modified Spero further teaches each region (reaction chamber 105, which has an array of microposts) has a surface area that is 2-50 times its footprint area (para. 0061, the micropost array has microposts of 4 mm-diameter, a controlled density of 105 microposts/cm2 with 30 x higher or 100 x lower being reasonable range; and paras. 0011 and 0042, each micropost can have height between 1-100 mm, and thus the surface area is 2-50 times its footprint area. For example, for a micropost of 4 mm in diameter and 100 mm in height, its surface area is 1.27x 10-5 cm (which means 1.27x 10-5 cm surface area per micropost), and with a controlled density of 2 x 105 microposts/cm2 (which is 2 x 105 microposts/ footprint area in cm2), then that would yield 2.5 times of surface area per footprint area) because it would have been within the ambit of one of ordinary skill in the art to arrive at through routine experimentation.
Regarding claim 23, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 1. Modified Spero further teaches the kit according to claim 1 assembled to form the chip (Spero, Fig. 2A -2B).
Claims 8-13, 16-17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Spero et al. (WO 2018236833 A1) in view of Fuchs et al. (US 20120244529 A1) as applied to claim 1 above, and further in view of Lawi et al. (“A Microfluidic Cartridge System for Multiplexed Clinical Analysis.” JALA Charlottes Va. 2009 December 1; 14(6): 407–412).
Regarding claim 8, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 1. Modified Spero further teaches wherein the chamber (modified Spero has a single flow-through chamber that includes an inlet that is connected to the reaction chambers 105, which are connected an outlet) has at least one ingress (fluid ports 112, in modified Spero, the inlet is connected to each of the reaction chamber 105 through its fluid port 112) from a microfluidic network (212) of the chip (cartridge 200 and modular active surface devices 100)(Fig. 1A) that includes the substrate (110) and the part (150)(Fig. 1A, 2B, modular active surface devices 100 is configured to be integrated into fluidic cartridge 200)
Spero further teaches cartridge 200 can be of different configurations (Figs. 20, 21 and paras. 0099-0100); however, modified Spero does not explicitly teaches the microfluidic network comprising at least two microfluidic channels coupling two different reservoirs with the ingress.
However, Lawi teaches a microfluidic cartridge for performing multiplexed assays. Lawi further teaches the cartridges comprises a chamber (fluid handling component, FHC) has at least one ingress (reaction chamber valve ports, Fig. 3) from a microfluidic network of a chip (FHC and reagent storage component, RSC), the microfluidic network comprising at least two microfluidic channels (the channel that connects the reservoir containing the sample to each of the reaction chamber valve port in the FHC and the channel that connects the reservoir containing the substrate reagent TMB to each of the reaction chamber valve port in the FHC) coupling two different reservoirs (two of the reservoirs in the RSC- the reservoir containing the sample and the reservoir containing the substrate reagent, Fig. 3 and p. 2 under “Cartridge System”) with the ingress (interpreted as the at least one ingress)(reaction chamber valve ports in the fluid handling component, Fig. 3). Lawi teaches one of the reservoirs for storing a sample and one is for reagent substrate (p.2, “Cartridge System”) and consequently providing the sample and reagent to the reaction chamber from the reaction chamber valve ports (ingresses) for the multiplexed assays (Figs. 3-4 and p. 2, “Fluid Handling”).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified 212 (microfluidic network) of the fluidic cartridge 200 taught by Spero to include at least two microfluidic channels coupling two different reservoirs with the reaction chamber valve ports (the least one ingress/ fluid ports 112) taught by Lawi in order to provide the sample and reagent necessary for the multiplexed assays with a reasonable expectation of success (Lawi, Figs 3-4, and p.2, “Cartridge System” and “Fluid Handling”) (MPEP 2143)(I)(G).
Regarding claim 9, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 8. Modified Spero further teaches wherein the microfluidic network comprises two subnetworks (one subnetwork comprising the channel that connects the reservoir containing the sample to the fluid port 112 of each of the chambers 105; and the second subnetwork comprising the channel that connects the reservoir containing the substrate reagent to fluid port 112 of each of the chambers 105)(see claim 8 and also Lawi, Fig. 3 and p. 2 under “Cartridge System”): a marking network equipped for performing a marking process within the chamber (interpreted as a functional limitation, the channel that connects the reservoir containing the substrate reagent TMB is structurally capable of performing a marking process); and a prep network equipped for treating a test sample (interpreted as a functional limitation, the channel that connects the reservoir containing the sample is structurally capable of treating a test sample).
Regarding claim 10, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 8. Spero further teaches wherein the part (150) is a first film (PET substrate)(para. 0068), and the covering surface is a side of the first film (the bottom side of 150 is the covering surface, Fig. 2B).
Regarding claim 11, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 10. Modified Spero further teaches wherein
Regarding claim 12, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 10.
Modified Spero does not explicitly teach wherein the relief patterning of the substrate and/or first film defines at least one microfluidic blister for retaining a liquid.
However, Spero teaches the modular active surface device 100 can be delivered to the user (to be integrated with cartridge 200, para. 0100) and then surface modifications can be performed in the field, and blister packs are used to store and to release a surface modification chemical to achieve modification of any surface in reaction chambers 105 (paras. 0105-0106).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modified the chip (cartridge 200 and device 100) to include relief patterning that defines at least one microfluidic blister for retaining a liquid in order to release a surface modification chemical to achieve surface modification of any surface in reaction chambers 105 with a reasonable expectation of success (Spero, paras. 0105-0106) (MPEP 2143)(I)(G).
Regarding claim 13, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 10. Modified Spero further teaches wherein the substrate (110) is a second film (Fig. 2B); the kit further comprises a third film (140); and at least one of the first, second or third films, has at least one through-bore (para. 0053, substrate 110 has fluid ports 112) via for coupling two microfluidic networks when stacked (Figs. 1A, 2B, para. 0055, and also see above).
Regarding claim 16, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 1.
Modified Spero fails to teach the kit further comprising supplies of at least 3 probes.
Modified Spero teaches a modular microfluidic device for multiplex assays (para. 0068) with eight reaction chambers 105 (Fig. 23B). Spero further teaches any surface in reaction chambers 105, including the microposts 122, can be modified to promote binding of a target analyte or modified like a microarray (para. 0105). Furthermore Lawi teaches a microfluidic device for multiplex assays with six reaction chambers (Lawi, Fig. 3). Lawi further teaches a surfaces in the reaction chambers precoated with probes (myoglobin protein, RNA, BSA) to perform multiplex assay for detecting different analytes (Lawi, p. 3 “Fluid Distribution Component”).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the surface of each of the chamber 105 taught by Spero with a probe taught by Lawi in order to perform multiplex assays with a reasonable expectation of success (Spero, para. 0068 and 0121 and Lawi, Fig. 3 and p. 3 “Fluid Distribution Component”) (MPEP 2143)(I)(G).
The teachings of modified Spero would yield the kit further comprising supplies of at least 3 probes, with each probes functionalizing to one of the reaction chamber 105.
Regarding claim 17, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 16. Modified Spero further teaches wherein the supplies are provided by functionalizing each of the vessels with a respective one and only one of the at least 3 probes (see claim 16 above).
Regarding claim 20, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 1.
Modified Spero fails to the kit further comprising at least one marking liquid the marking liquid comprising one or more of: a developer; a conjugated detection antibody with a target-specific binding moiety; a wash buffer; a hybridization solution; formaldehyde; and a PCR product contained within a microfluidic chamber of a chip formed with at least the substrate and the covering surface.
Spero teaches a microfluidic device (100 and 200) for processing biological materials (para. 0003). Spero teaches the device can be used for a variety of applications (paras. 0050 and 0105), including performing assays in a multiplexed format (para. 0068). Spero teaches the device comprises modular active surface device 100, which includes a substrate (110) and a cover (150); wherein the device 100 is integrated into a chip (cartridge 200 and device 100)(Fig. 1A, 2B and para. 0010). Spero further teaches cartridge 200 can be of different configurations (Figs. 20, 21 and paras. 0099-0100). Spero further teaches liquid and pellet reagents and reagent in blister pack can be provided with device 100 (paras. 0106-0109)
Modified Spero does not disclose what the reagents are, and thus fails to teach the kit further comprising at least one marking liquid the marking liquid comprising one or more of: a developer; a conjugated detection antibody with a target-specific binding moiety; a wash buffer; a hybridization solution; formaldehyde; and a PCR product contained within a microfluidic chamber of a chip formed with at least the substrate and the cover.
However, Lawi teaches a microfluidic cartridge for performing multiplexed assays (Abstract). Lawi further teaches the cartridges comprises the fluid handing component FHC that includes a and a cover (Fig. 3 and “Fluid Distribution Component”); wherein the FHC is combined with a reagent storage component RSC (microfluidic chamber) into a cartridge (chip)(p. 2, “System Overview”). Lawi teaches the RSC (microfluidic chamber) includes individual reagent compartments (Fig. 3). Lawi further the cartridge comprising at least one marking liquid the marking liquid comprising a developer (TMB); a conjugated detection antibody with a target-specific binding moiety (HRP-antibody or oligonucleotide probe) and a wash buffer (p. 2, Cartridge System and Electrochemical Sensor and Detection Mechanism); contained within a microfluidic chamber (RSC) of a chip (cartridge) formed with at least the substrate and the cover (FHC).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the cartridge 200 (of the chip) taught by Spero to include a microfluidic chamber with reagent compartments to hold marking liquid including a developer (TMB), a conjugated detection antibody with a target-specific binding moiety (HRP-antibody or oligonucleotide probe), a wash buffer as taught by to Lawi in order to perform multiplex assays with a reasonable expectation of success (Lawi, abstract) (MPEP 2143)(I)(G).
The teaching of modified Spero would yield the kit further comprising at least one marking liquid the marking liquid comprising one or more of: a developer; a conjugated detection antibody with a target-specific binding moiety; a wash buffer; a hybridization solution; formaldehyde; and a PCR product contained within a microfluidic chamber (the microfluidic chamber with reagent compartment taught by Lawi) of a chip formed with at least the substrate (110) and the covering surface (150) (the chip comprises 100 and 200; and 110 and 150 are part of 100, Spero, Fig. 2A, 2B).
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Spero et al. (WO 2018236833 A1) in view of Fuchs et al. (US 20120244529 A1) as applied to claim 1 above, and further in view of Schaff et al. (US 10197480 B2).
Regarding claim 14, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 1. Spero further teaches wherein at least one of the substrate (110) and the part (150) is transparent to an inspection wavelength (para. 0011, active surface layer 110 is made of PDMS, which is optically transparent); the chip produced by sealing the surface (the surface of 110 containing microposts) and the covering surface (the surface of the part)(Fig. 2A and 2B) permits inspection of the vessels through the transparent material (para. 0065).
Spero teaches the device is configured for optically interacting external light source and transparency is a determining characteristic of selection of material (para. 0006 and 0065). Modified Spero does not explicitly the transparent material is sealed to a material that is reflective or opaque to the inspection wavelength, to improve imaging of the vessels (reaction chambers 105).
Schaff teaches microfluidic cartridges. Schaff teaches a lower element of the cartridge is opaque and an upper element and side elements of the cartridge are transparent such that illumination from a side of the cartridge causes light to scattering off sample and enhances contrast (a transparent material is sealed to a material that is reflective or opaque to the inspection wavelength) (Schaff, claim 35).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified substrate 150 taught by Spero with a material that is reflective or opaque to the inspection wavelength in order to enhances contrast with a reasonable expectation of success (Schaff, claim 35) (MPEP 2143)(I)(G).
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Spero et al. (WO 2018236833 A1) in view of Fuchs et al. (US 20120244529 A1) as applied to claim 1 and further in view of Spero et al. (US 20180229237, hereinafter “ ’237 ”) .
Regarding claim 29, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 1.
Modified Spero teach wherein the chamber extends between a sample inlet and a waste (outlet) (interpreted as a waste port as discussed above in the 35 U.S.C. 112(b) section. “Waste” is interpreted as an intended use. The outlet in modified Spero meets the structural limitation of the intended use).
Spero teaches a microfluidic system comprising reaction chambers (regions) for biological assays, wherein the chambers includes surface topography such as pillars (paras. 0006 and 0049).
Spero in view of Fuchs teaches the reaction chambers 105 (regions) are all connected between one inlet and one outlet (claim 1) in order to perform multiplexed assay with a single sample. Fuchs further teaches in the Fig. 1C that the device is channels (regions) are arrayed in a parallel configuration. Consequently, modified Spero but does not teach that the regions are arrayed in series, such that each region's neighbouring region is either inlet proximal or waste proximal of the region.
However, Fuchs teaches the device for multiplexed assay can be performed in a parallel or a serial configuration (Fuchs, para. 0054 and 0055). Furthermore, ‘237 teaches a microfluidic system for biological assays comprising reaction chambers (regions) with surface topography such as pillars (‘273, paras. 0006 and 0049). ‘237 further teaches the system comprises multiple flow cell units (reaction chambers) that are arranged in parallel or in series (‘237, Fig. 9 and 10 and para. 0133) for analysis of parallel or series configuration, respectively (‘237, paras. 0135, 0205).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the configuration of the reaction chambers 105 in the single flow-through chamber to be arrayed in series as taught by ‘237 (Fig. 9 and 10 and para. 0133) and Fuchs (para. 0054-0055) because one of ordinary skill in the art would accordingly have recognized the a reaction chamber configuration in series would result in the predictable result of providing a configuration for multiplexed assay (‘237 and Fuchs, para. 0054-0055).
In the case where Applicant intends for the “waste” to be a reservoir instead of a port, the following rejection is put forth.
Modified Spero teach wherein chamber extends between a sample inlet and an outlet, but does not teach explicitly the outlet is connected to a waste reservoir, and thus fails to teach wherein chamber extends between a sample inlet and a waste.
However, Fuchs teaches a waste reservoir that is connected between the channels and the outlet for storing generated waste that are potentially biohazardous for ease of disposal (Fig. 1 and para. 0063).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the single flow-through chamber taught by modified Spero to include a waste reservoir as taught by Fuchs in order to store generated waste that are potentially biohazardous for ease of disposal (Fuchs, para. 0063)
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Spero et al. (WO 2018236833 A1) in view of Fuchs et al. (US 20120244529 A1) and further in view of Lawi et al. (“A Microfluidic Cartridge System for Multiplexed Clinical Analysis.” JALA Charlottes Va. 2009 December 1; 14(6): 407–412) as applied to claim 16 above, and further in view of Walsh et al. (“Microfluidics with fluid walls.” Nature Communications Vol. 8, Article number 81, 2017.)
Regarding claim 19, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 16. Spero further teaches wherein the supply is provided, carried by a liquid in a fluid-tight container (blister pack)(para. 0106).
Modified Spero further teaches any surface in reaction chambers 105 can be modified with protein or DNA (biomolecule) probes to promote binding of a target analyte (Spero, para. 0105 and Lawi, p. 3 “Fluid Distribution Component”). Spero teaches surface modification is homogeneous (Spero, para. 0105).
Spero teaches the blister pack is used to release a surface modification chemical (para. 0106) to modify surfaces of reaction chamber 105 (para. 0105), but does not specify a fluid flow control method use for releasing the chemical, nor the property or volume of the chemical that would allow for spreading the chemical across and sufficiently cover the reaction chamber 105 (region) in a self-limiting way, and thus does not explicitly teach the liquid (chemical) having a contact angle and viscosity allowing for spontaneous spreading of the liquid across the region, and a volume sufficient to cover the region, but insufficient volume to overcome interface pinning, whereby the liquid, if it meets any part of the region, is self-limited to substantially covering that region.
However, Walsh teaches fluid-flow-control method that utilizes interfacial forces to pin liquids to substrates to constraint a volume of liquid to specific regions (Walsh, Abstract and Introduction). Walsh further teaches interfacial pinning is dependent fluid volume, contact angle and hydrodynamic resistance (which is dependent on viscosity)(Walsh, Results) .
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the fluid flow control method taught by Spero to incorporate the use of interfacial forces as taught by Walsh in order to spread the chemical across and sufficiently cover the reaction chamber 105 in a self-limiting way to perform homogeneous surface modification with a reasonable expectation of success (Walsh, Abstract and Introduction) (MPEP 2143)(I)(G). In addition, Walsh teaches wherein the contact angle, volume and viscosity of the liquid (chemical) is a result-effective variable. Specifically, Walsh teaches interfacial pinning is dependent fluid volume, contact angle and hydrodynamic resistance (which is dependent on viscosity)(Walsh, Results). Since these particular parameters is recognized as result-effective variables (i.e. a variable which achieves a recognized result), the determination of the optimum or workable ranges of said variables 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 to have the liquid (chemical) to have a contact angle and viscosity allowing for spontaneous spreading of the liquid across the region, and a volume sufficient to cover the region, but insufficient volume to overcome interface pinning, whereby the liquid, if it meets any part of the region, is self-limited to substantially covering that region.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Spero et al. (WO 2018236833 A1) in view of Fuchs et al. (US 20120244529 A1) and further in view of Lawi et al. (“A Microfluidic Cartridge System for Multiplexed Clinical Analysis.” JALA Charlottes Va. 2009 December 1; 14(6): 407–412) as applied to claim 20 above, and further in view of Berenguel-Alonso et al. (“Rapid Prototyping of a Cyclic Olefin Copolymer Microfluidic Device for Automated Oocyte Culturing.” SLAS Technology. Volume 22, Issue 5, October 2017, Pages 507-517),
Regarding claim 22, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 20. Modified Spero further teaches the developer is 3,3',5,5'-tetramethylbenzidine (TMB, see claim 20).
Modified Spero teaches the substrate (110) is PDMS (para. 0011) and thus fails to teaches that the substrate is a cyclic olefin copolymer.
Modified Spero teaches the substrate is PDMS and thus fails to teaches that wherein the substrate is composed of a cyclic olefin copolymer. Modified Spero further fails to teach the developer is 3,3',5,5'-tetramethylbenzidine.
However, Berenguel-Alonso teaches fabricating microfluidic device using cyclic olefin copolymers (COC). Berenguel-Alonso further teaches COCs have emerges as alternative to PDMS in production of microfluidic devices because COCs has the advantage of low fabrication costs, all at the prototyping and mass production scale (Abstract, Introduction and Conclusion).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the material of 110 comprising PDMS with COC taught by Berenguel-Alonso in order to have low fabrication costs at the prototyping and mass production scale with a reasonable expectation of success (Berenguel-Alonso, Abstract, Introduction and Conclusion) (MPEP 2143)(I)(G).
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Spero et al. ( WO 2018236833 A1) in view of Fuchs et al. (US 20120244529 A1) and further in view of Lawi et al. (“A Microfluidic Cartridge System for Multiplexed Clinical Analysis.” JALA Charlottes Va. 2009 December 1; 14(6): 407–412) as applied to claim 17 above, and further in view of Berenguel-Alonso et al. (“Rapid Prototyping of a Cyclic Olefin Copolymer Microfluidic Device for Automated Oocyte Culturing.” SLAS Technology. Volume 22, Issue 5, October 2017, Pages 507-517), further in view of Laib et al. (Immobilization of Biomolecules on Cycloolefin Polymer Supports, Anal. Chem. 2007, 79, 6264-6270), further in view of O’Neil et al. “Characterization of Activated Cyclic Olefin Copolymer: Effects of Ethylene/Norbornene Content on the Physiochemical Properties.” Analyst. 2016 November 28; 141(24): 6521–6532), and further in view of Hermanson (2013, Bioconjugate Techniques (Third Edition). Chapter 15 Immobilization of Ligands on Chromatography Supports).
Regarding claim 18, modified Spero teaches all of the elements of the current invention as stated above with respect to claim 17.
Modified Spero teaches the substrate (110) is PDMS (para. 0011) and thus fails to teaches that the substrate is composed of a cyclic olefin copolymer.
However, Berenguel-Alonso teaches fabricating microfluidic device using cyclic olefin copolymers (COC). Berenguel-Alonso further teaches COCs have emerges as alternative to PDMS in production of microfluidic devices because COCs has the advantage of low fabrication costs at the prototyping and mass production scale (Abstract, Introduction and Conclusion).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the material of 110 comprising PDMS with COC taught by Berenguel-Alonso in order to have low fabrication costs at the prototyping and mass production scale with a reasonable expectation of success (Berenguel-Alonso, Abstract, Introduction and Conclusion) (MPEP 2143)(I)(G).
Furthermore, modified Spero also fails to teach the functionalization is consistent with formation by oxygen plasma surface activation, reaction with cyanogen bromide, and binding of the probe.
However, modified Spero teaches any surface in reaction chambers 105, including the microposts 122, can be modified with protein or DNA (biomolecule) probes to promote binding of a target analyte (Spero, para. 0105 and Lawi, p. 3 “Fluid Distribution Component”). In addition, Laib teaches on modifying probes immobilization of biomolecules on COC surfaces. Laib further teaches COC is hydrophobic and the surface need to be activated and hydrophilized, without destroying their optical properties, by low-pressure gas plasma (e.g. O2 plasma) to introduce functional groups for immobilization of biomolecules (p. 6264 right col. to p. 6265, left col.). In Addition, O’Neil teaches O-2 plasma treatment of COC introduces hydroxyl groups to the COC surface (O’Neil, p. 9). Moreover, Hermanson teaches bioconjugation technique for covalently conjugating biomolecules to solid supports. Hermanson further teach -OH group on a support can be activated by cyanogen bromide to modified biomolecule through amine (pp. 664-666, Fig. 15.61 and 15.62 ; amine is commonly present in biomolecules, e.g., lysine in proteins and DNA oligos with an amine spacer, and commonly used for modification).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the functionalization method taught by modified Spero with a method of functionalization that is consistent with formation by oxygen plasma surface activation of COCs (Laib, p. 6264 right col. to p. 6265, left col., and O’Neil, p. 9), reaction with cyanogen bromide, and binding of the probe (Hermanson, pp. 664-666, Fig. 15.61 and 15.62) in order to modify the surfaces in reaction chambers 105 to promote binding of a target analyte without destroying COC’s optical properties with a reasonable expectation of success (Spero, para. 0105 and Lawi, p. 3 “Fluid Distribution Component”, Laib, pp. 6264-6264) (MPEP 2143)(I)(G).
Response to Arguments
Applicant’s arguments, see p. 6, filed 04/10/2026, with respect to the Restriction Requirement have been fully considered and are not persuasive.
The Applicant argues that neither Spero nor Fuchs teaches “a single chamber having at least 4 relief-patterned regions, each defining a respective interface pinning reaction vessel (IPRV).” In particular, the Applicant argues that the references fails to teach each IPRV has a footprint area of 0.5 to 15 cm2 . The Applicant further argues that “no separate and distinct pinning is provided by the structure of Spero or Fuchs with a single flow-through chamber”. In addition, the Applicant appears to be also be arguing that the structure of Spero and/or Fuchs cannot provide pinning as the claim requires.
The examiner respectfully disagrees. As discussed in the OA of 01/13/2026, a footprint area of 0.5 to 15 cm2 is obvious over the teachings of Spero. Spero teaches a flexible, modular platform for fabricating microfluidic devices that allow a user to select the size, dimensions and features of a device (para. 0099) for various processing (e.g., mixing operations, binding operations, and cell processing operations, para. 0009) of biological materials (para. 0051), and the chambers 105 are mass-produced in a 6-in or 12-in wafer (Fig. 23A ad para. 0075) with area of ~182 cm2 and ~730 cm2. Therefore, it is within the context of a microfluidic-scale reaction chamber that is mass produced by a wafer that Spero teaches that the area of chamber 105 can be any size (para. 0099). Based on Spero’s teachings, it is the objective of a user/ POSITA to determine the area of a reaction chamber (result-effective variable) that would satisfy his/her application’s the requirements such as sample volume, reagent concentration, binding efficiency, etc. (typical requirements a POSTIA would consider), and thus the determination of the area of the reaction chamber would involve routine experimentation. Furthermore, of a footprint area is 0.5 to 15 cm2 would have been within the ambit of POTSIA to arrive at through routine experimentation as discussed in the OA of as evident by Malic et al (Polymer-based microfluidic chip for rapid and efficient immunomagnetic capture and release of Listeria monocytogenes, Lab Chip. 2015 Oct 21;15(20):3994-4007)(provided by the Applicant’s IDS of 12/13/2022), which discloses a chamber populated with pillars within a microfluidic device, wherein the chamber has an area of 30 x 17 mm (5.1 cm2). Therefore this argument is unpersuasive.
With regards to the argument relating to “no separate and distinct pinning is provided by the structure of Spero or Fuchs with a single flow-through chamber”, Spero in view of Fuchs does teach 4 separate relief patterned regions (4 of the reaction chambers 105; Spero, Fig. 23B ) in a single flow-through chamber (Spero as modified by Fuchs’ single flow-through chamber) as discussed pp. 3-4 in the OA of 01/13/2026. It is unclear in what aspect of the analysis the Applicant disagrees with. To further clarify the examiner’s position, a chamber is an enclosed space, and a flow-through chamber is interpreted as an enclosed space with an inlet and an outlet for fluid to flow through. Fuchs, Fig. 1C teaches an apparatus with an inlet fluidically connected to multiple channels which are fluidically connected to an outlet. Since the inlet, outlet and channels are all fluidically connected, the space extends between the inlet and outlet is a single enclosed space, and thus Fuchs does teach in Fig. 1C a single flow-through chamber. In the same way, the teachings of Spero in view of Fuchs teaches a single flow-through chamber that includes an inlet that is connected to the separate reaction vessels (reaction chambers 105/ relief patterned regions), which are connected an outlet”. Therefore, this argument is unpersuasive.
In terms of interface pinning, “interface-pinning” is an intended use of the vessel (claim 1, line 3). The structure taught by Spero meets the limitation of the intended use since the structure of Spero (array of microposts) provides high surface area that is structurally capable of interface-pinning with an appropriate volume/ viscosity of the liquid. See also MPEP 2114 (II). Therefore, this argument is unpersuasive.
Applicant’s arguments, see pp. 6-8, filed 04/10/2026, with respect to the Double Patenting have been fully considered. The nonstatutory double patenting rejection over claim 8 of U.S. Patent No. US 9291567 B2 in view of Spero (WO 2018236833 A1) has been withdrawn in view of Applicant’s amendment.
With regard to the Applicant’s arguments that claim 8 of US 9291567 and claim 1 of the instant are patentably distinct because of their different intended uses, the arguments are unpersuasive. The Applicant argues that the pillar array for ‘567 is intended for SPR while the topographical relief bearing of the instant is not. In particular, the Applicant argues that claim 8 of ‘567 recites the pillar arrays “suitable for plasmonic resonance reading” which requires the pillar arrays to be “very regular in shape and depth.” The Applicant further argues that the instant invention involves flowing liquid through the chamber and allows for densification of dye elements, and that claim 1 recites “several things that PP claim 8 does not.
The examiner respectfully disagrees. Claim 1 of the instant does not preclude having topographical relief bearing is “very regular in shape and depth” or suitable for plasmonic resonance reading. Therefore the argument is not persuasive. In addition, claim 1 does not recites a limitation requiring “flowing liquid through the chamber and allows for densification of dye elements.” Therefore the argument is not persuasive. The Applicant also does not state specifically what the “several things that PP claim 8 does not teach” are, nor provides any specific supposed errors in the examiner's action relating to the “several things”. Therefore the argument is not persuasive.
Applicant’s arguments, see p.8 , filed 04/10/2026, with respect to the rejection under 35 U.S.C. 112(b) have been fully considered and are persuasive. Therefore, the rejection of 1/13/2026 has been withdrawn. However, a new ground of rejection of claim 12 under 35 U.S.C. 112(b) is necessitated by the amendment.
Applicant’s arguments, see pp. 8-12, filed 04/10/2026, with respect to the rejections under 35 U.S.C. 103 have been fully considered and are not persuasive.
In the arguments presented on page 8 of the amendment, the applicant argues that Spero does not imply, disclose, teach or suggest chambers 105 have the surface areas of 0.5 to 15 cm2.
The examiner agrees the footprint area (the area of chamber 105) is 0.5 to 15 cm2 might not be anticipated by Spero; however, the examiner respectfully disagrees that it is not obvious over Spero’s teaching that the footprint area is 0.5 to 15 cm2. Spero teaches a flexible, modular platform for fabricating microfluidic devices that allow user to select the size, dimensions and features of a device (para. 0099) for various processing (e.g., mixing operations, binding operations, and cell processing operations, para. 0009) of biological material (para. 0051), and the chambers 105 are mass-produced in a 6-in or 12-in wafer (0075) with area of ~182 cm2 and ~730 cm2. Therefore, it is within the context of a microfluidic-scale reaction chamber that is mass produced by a wafer that Spero teaches that the area of chamber 105 can be any size (para. 0099). Based on Spero’s teachings, it is the objective of a user/ POSITA to determine the area of a reaction chamber (result-effective variable) that would satisfy his/her application’s the requirements such as sample volume, reagent concentration, binding efficiency, etc. (typical requirements a POSTIA would consider), and thus the determination of the area of the reaction chamber would involve routine experimentation. Furthermore, of a footprint area is 0.5 to 15 cm2 would have been within the ambit of POTSIA to arrive at through routine experimentation as evident by Malic et al (Polymer-based microfluidic chip for rapid and efficient immunomagnetic capture and release of Listeria monocytogenes, Lab Chip. 2015 Oct 21;15(20):3994-4007)(provided by the Applicant’s IDS of 12/13/2022), which discloses a chamber populated with pillars within a microfluidic device, wherein the chamber has an area of 30 x 17 mm (5.1 cm2). Therefore this argument is unpersuasive.
In the arguments presented on pp. 9-11 of the amendment, the Applicant argues that Spero in view of Fuchs does not teach the structure of a single flow-through chamber that includes the vessels. In particular, the Applicant argues that Fuchs does not teach a single flow-through chamber in Fig. 1C, para. 0055, and that the structure of modified Spero is not a single flow-through chamber.
The examiner respectfully disagrees. A chamber is an enclosed space, and a flow-through chamber is interpreted as an enclosed space with an inlet and an outlet for a fluid to flow through. Fuchs in Fig. 1C teaches an apparatus with an inlet fluidically connected to multiple channels which are fluidically connected to an outlet. Since the inlet, outlet and channels are all fluidically connected, the space extends between the inlet and outlet is a single enclosed space, and thus Fuchs does teach in Fig. 1C a single flow-through chamber. In the same way, the teachings of Spero in view of Fuchs teaches “a single flow-through chamber that includes an inlet that is connected to the reaction vessels (reaction chambers 105), which are connected an outlet”. Therefore, the argument is not persuasive.
In the arguments presented on p. 11, 3rd paragraph, the Applicant argues that “Fig. 23B shows the same surface is provide between chambers 105 as within.”
The examiner respectfully disagrees. Spero teaches mask 140 provides the surface between chambers 105 (Figs. 14, 15 and 23B, Para. 079). Therefore this argument is unpersuasive.
In the arguments presented on p. 11, 4th paragraph, the Applicant argues that Spero does not teach the claimed separation and the claimed separation cannot be arrived from routine experimentation.
The examiner respectfully disagrees. As states in p. 17 of OA 01/13/2026, Spero does teach separation between chambers 105 (regions), and separation between chambers 105 are clearly shown in Fig. 23B. As discussed above, Spero teaches a flexible, modular platform for fabricating microfluidic devices that allow user to select the size, dimension and features of a device. Therefore, the user (a POTISA) needs to select/determine various dimensions of the device, including the dimensions of the regions between reaction chambers 105 based on the requirements of the assays, and thus the dimensions of the regions between reaction chambers 105 is a result-effective variable. As such, the dimensions of the regions between reaction chambers 105 the separation between two assay chambers within a microfluidic device of larger than 0.1 mm or 5% of a mean of the extents of the neiqhbouring region can be arrived through routine experimentation. Therefore, this argument is unpersuasive.
In the arguments presented on p. 11-12, the Applicant argues the Office has not demonstrate a prima facie case of obviousness because the structure taught by Spero does not achieve interface pinning.
The examiner respectfully disagree. “[I]nterface-pinning” is an intended use of the vessel (claim 1, line 3). The structure taught by Spero meets the limitation of the intended use since the structure is structurally capable of interface-pinning with an appropriate volume/ viscosity of the liquid. See also MPEP 2114 (II). Therefore, this argument is unpersuasive.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/M.L.C./Examiner, Art Unit 1758
/MATTHEW D KRCHA/Primary Examiner, Art Unit 1796
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