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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 21 May 2026 has been entered.
Response to Amendment
This is an office action in response to Applicant’s arguments and remarks filed on 21 May 2026. Claims 68-72 are pending in the application. Claims 55-67 have been previously canceled. Claims 68-72 are being examined herein.
Status of the Objections and Rejections
The objection to the drawings are withdrawn in view of submitted replacement drawings.
The rejections to claims 68-69 and 71-72 under 35 USC § 103 in view of Chiang, et. al. (US 20150275292 A1) in view of Hansen, et. al. (US 20110053151 A1) are withdrawn in view of amendments.
The rejection to claim 70 under 35 USC § 103 in view of Chiang, et. al. (US 20150275292 A1) in view of Hansen, et. al. (US 20110053151 A1) and in further view of Wiktor (US 20160339427 A1) is withdrawn in view of amendments.
Response to Arguments
Applicant’s arguments, see Remarks pages 10-11, filed 21 May 2026, with respect to the rejection(s) of claim(s) 68-69 and 71-72 under 35 USC § 103 in view of Chiang, et. al. (US 20150275292 A1) in view of Hansen, et. al. (US 20110053151 A1) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Battrell, et. al. (US 20090148933 A1) in view of Chiang, et. al. (US 20150275292 A1) and Ulmanella, et. al. ( US 20070280856 A1).
Applicant first disagrees that is would be obvious to modify Chiang in view of Hansen (pg. 10, par. 05-06). Applicant further adds the addition of a trough in the reactions chambers is not taught, disclosed, or suggested by Chiang with alone or in view of Hansen or Wiktor (pg. 10, par. 07 – pg. 11, par. 02).
Examiner agrees, Chiang either alone or in combination with the recited art do not teach, disclose, or suggest the presence of a trough in the reaction chambers.
Examiner notes the use of Chiang, et. al. (US 20150275292 A1) is still used but in a new context, specifically surrounding the micro-pores. Examiner notes Applicant provides no arguments directed at the use of Chiang that teach the elements specifically surrounding the micro-pores and product capture housing.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 68-72 are rejected under 35 U.S.C. 103 as being unpatentable over Battrell, et. al. (US 20090148933 A1) in view of Chiang, et. al. (US 20150275292 A1) and Ulmanella, et. al. ( US 20070280856 A1).
Regarding claim 68, a plurality of nucleic acid molecules in a sample). Battrell teaches the microfluidic device comprises (see Fig. 1-4 for the following):
A sample port (an inlet port)
A waste outlet (an outlet port)
A microfluidic circuit between the sample port and waste outlet (a cartridge fluidically coupling said inlet port and said outlet port and defining a space)
The microfluidic circuit comprising (a space containing) (see Fig. 1-4 for the following):
A series of chambers (lysis chamber of Fig. 1; bellows chambers for amplification of Fig. 2) interconnected by valves and channels, wherein each chamber contributes to the processing of the sample (lysis and amplification through melting, annealing, and extending) (par. 0180, 0182, 0192, 0194-0195) (multiple primary PCR reaction chambers fluidically coupled to said inlet port to receive material from said inlet port and produce primary PCR reaction chamber products from the material).
Detection chambers wherein the amplified nucleic acid products are detected based on capture agents (par. 0203-0204) (a product capture housing).
Battrell teaches the detection chambers further comprises chamber partially defined by a ceiling (an optical window 2104) and floor (a solid substrate) (par. 0269) and a series of pads 2102 (a plurality of product capture subdivisions) wherein each pad further comprises immobilized antibodies 2103 (Fig. 21; par. 0269). The series of pads can take on one of many geometries including an array 2204 as seen in Figure 22 (par. 0270) (a product capture housing enclosing a solid support with a plurality of product capture subdivisions configured in separate rows and columns).
Battrell teaches the detection chambers accommodate a fluid stream 2101 through the chamber, wherein the fluid stream flows above the floor of the detection chamber to interact with the series of pads before leaving the detection chamber to the waste outlet (Fig. 21; par. 0269) (said product capture housing comprising… a fluid channel to permit material to pass from said inlet port through a column of the product capture subdivisions, and to said outlet port, wherein the (fluid channel is) located above… the solid support). Battrell further teaches the sample pad (represented by 502 in Fig. 5) are coated with capture antibodies 503 that form a tether with amplified nucleic acid product to attach with paramagnetic bead 501 for detection (Fig. 5; par. 0230-0231) (and wherein one or more of the primary PCR reaction chamber products are further reacted to create array products which are detected). Note, since the capture pads can have an array geometry, the captured nucleic acid products bound to microbeads creates detectable products that follow said array geometry (array products). Battrell teaches the microfluidic circuit operates by moving the sample from the sample port, through the lysis chamber, through the amplification chambers, and finally to the detection chamber before moving to the waste outlet (Fig. 4) (wherein one or more of the rows and columns of separate product capture subdivisions receive material which has passed through one of said multiple primary PCR reaction chambers).
Battrell is silent to wherein each of said multiple primary PCR reaction chambers comprises a trough.
Ulmanella teaches a microfluidic device comprising a plurality of chambers for testing biological samples wherein the chambers comprise physical modifications (Abstract). Ulmanella teaches microfluidic chambers 20 can include physical modifications such as grooves 35 at a surface of the chamber (Fig. 3; par. 0078). While Figure 3 of Ulmanella depict multiple grooves 35, Ulmanella teaches any number of grooves can be used (par. 0081) such as a singular groove on a surface (wherein each of said multiple primary PCR reaction chambers comprises a trough). Ulmanella teaches such physical modifications such as grooves within microfluidic chambers provide a cost effective way to improve fluid movement through chamber such as preventing bubble formation (par. 0009) through the physical manipulation of the sample meniscus (par. 0012).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the PCR reaction chambers of Battrell to further include a physical modification like grooves (trough) as taught by Ulmanella because the physical modification physically manipulate the sample meniscus to efficiently fill a microfluidic chamber (Ulmanella, par. 0012) with a reasonable expectation of success. MPEP 2143(I)(G). Furthermore, the claimed limitations are obvious because all the claimed elements (microfluidic chambers and physical modifications to said chambers) were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination yields nothing more than predictable results (a microfluidic chamber with improved filling efficiency). MPEP 2143(I)(A).
Modified Battrell is silent to with each separate product capture subdivision comprising an array of a plurality of individual hydrophilic micro-pores, wherein each of said individual hydrophilic micro-pores is separated by hydrophobic surfaces, and wherein each of said individual hydrophilic micro-pores has opposed first and second open ends with the first end having a large diameter and the second end having a diameter which is smaller than that of the first end, said product capture housing comprising a plurality of fluid channels, wherein the plurality of fluid channels (pass material) into contact with the array of micro-pores in those subdivisions, wherein the plurality of fluid channels are located above and below the solid support, and the array products (which) are detected in the micro-pores.
Chiang teaches a honeycomb tube comprising a fluidic path leading to a chamber with a plurality of wells that can perform multiplexing assays such as for nucleic acids (Abstract, par. 0002, 0046). Chiang teaches the honeycomb tube 100 is a cartridge and comprises a fluidic inlet 110 connected to a fluidic outlet 112 (Fig. 1A-B; par. 0061) (an inlet port) (an outlet port) (a cartridge fluidically coupling said inlet port and said outlet port and defining a space). Between the inlet 110 and outlet 112 of the honeycomb tube 100 is a fluidic path 114 with a pre-amplification chamber 122 and a well chamber 118 embedded in a planar frame 102 with a first planar substrate 104, second planar substrate 106, and a well substrate 120 that make up the cartridge (Fig. 1A-B; par. 0061-0062).
The well substrate 120, embedded in the planar frame 102 (par. 0071) and comprises an array of through-holes (Fig. 1A-B; par. 0062) (a product capture housing enclosing a solid support). Because the well substrate 120 can accommodate up to 1000 or more wells (through-holes) (par. 0062), primer material can be individually deposited into a well (Fig. 3A; par. 0080), and the primary goal of the device is to perform multiplexing assays (par. 0105), the wells within the well substrate 120 can further be divided can be set to perform different assays in replicate (par. 0129). As seen in Figure 12, each square represents a subdivision in a specificized row and column of the larger well substrate 120, and each subdivision further comprises a plurality of individual wells/through-holes. Further, each well can be coated in a hydrophilic material and the planer surface separating the wells can be coated in a hydrophobic material (par. 063) (with a plurality of product capture subdivisions configured in separate rows and columns, with each separate product capture subdivision comprising an array of a plurality of individual hydrophilic micro-pores) (wherein each of said individual hydrophilic micro-pores is separated by hydrophobic surfaces).
Turning to Figure 2H to take a closer look at the wells (through-holes), the through-holes have a first (top) side that is wider in diameter than the second (bottom side) (cone shape) and open on both sides so "processing fluids can be exposed to both sides of the well-substrate" (par. 0078-0079) (and wherein each of said individual hydrophilic micro-pores has opposed first and second open ends with the first end having a large diameter and the second end having a diameter which is smaller than that of the first end). The well substrate 120 that holds the wells as depicted in Figure 2H has at least one fluid path on one side of the wells and a second fluid path on the second side of the wells (par. 0078) and all parts of the well are connected to the fluidic inlet 110 and outlet 112 (Fig. 1A-B) (said product capture housing comprising a plurality of fluid channels to permit material to pass from said inlet port through a column of the product capture subdivisions into contact with the array of micro-pores in those subdivisions, and to said outlet port, wherein the plurality of fluid channels are located above and below the solid support). The pre-amplification chamber 116 can include chemicals to produce a chemical reaction with the sample fluid before entering the well substrate 120 for analysis (par. 0091) (and wherein one or more of the primary reaction chamber products are further reacted to create array products which are detected in the micro-pores). Chiang teaches these particular elements of the well substrate (the array of through-holes, hydrophilic and hydrophobic coatings, cone-shaped through holes, detection within through-hole array) serve the primary goal of increasing throughput through multiplexing (par. 0002).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the detection chambers of modified Battrell to be an array of cone-shaped through-holes (micro-pores) with specific coating for detection as taught by Chiang because these elements of the product capture housing allows for increase in throughput through multiplexing (Chiang, par. 0002) with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 69, modified Battrell teaches a plurality of valves at multiple locations throughout the microfluidic circuit (as indicated by a circle with an "X" in the circle in the Figures, Battrell) (Battrell, Fig. 4). Some examples of the valves include valves for introducing a rehydration and wash buffer to a magnetic bead reservoir upstream the detection chamber and further includes valves leading to and away from the detection chamber from the amplifications chambers, through the detections chambers, and finally to the waste outlet (Battrell, Fig. 3, 4) (one or more valves for selectively introducing or removing reagents and/or reactants into or out of said product capture housing… through said outlet port).
Regarding claim 70, modified Battrell teaches a thermal interface at the bellow chambers, adjacent to the detection chambers, for the amplification process (Fig. 2, 4). Battrell taches the thermal interface comprises thermoelectric cooling (TEC) blocks in a heating arrangement (Battrell, par. 0193, 0195) (one or more heating elements in said cartridge proximate to said product capture housing).
Regarding claim 71, Battrell teaches a microfluidic cartridge system and methods of use for the analysis of nucleic acids in clinical samples (Abstract) (a method for preparing a system for identifying a plurality of nucleic acid molecules in a sample).
Battrell in view of Chiang and Ulmanella teach the system of claim 68 as seen in the above outline (providing the system of claim 68).
Battrell teaches the sample pad (represented by 502 in Fig. 5, Battrell) are coated with capture antibodies 503 that form a tether with amplified nucleic acid product to attach with paramagnetic bead 501 for detection (Battrell, Fig. 5; par. 0230-0231). Battrell teaches the capture antibodies are applied prior to total device assembly (Battrell, par. 203) (applying capture oligonucleotide primers or probes… of the product capture subdivisions on the solid support within said product capture housing).
Battrell is silent to the primer/probe being applied to the micro-pores of the product capture subdivisions and whereby the capture oligonucleotide primers or probes are retained within the micro-pores.
Chiang teaches a method for preparing the well substrate 120 with a primer using a printing pin (Fig. 2H, 3A; par. 0078-0080). Chiang teaches nucleic acid primer material or probe is loaded and dried or sealed into the well for amplification and/or detection of a specific target (Fig. 2H, 3A; par. 0029, 0079-0080, 0093-0094) (applying capture oligonucleotide primers or probes to the micro-pores of the product capture subdivisions on the solid support within said product capture housing, whereby the capture oligonucleotide primers or probes are retained within the micro-pores).
Chiang teaches these particular elements of the well substrate (the array of through-holes, hydrophilic and hydrophobic coatings, cone-shaped through holes, detection within through-hole array) serve the primary goal of increasing throughput through multiplexing (par. 0002).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the preparation of the detection chambers of modified Battrell to include an array of cone-shaped through-holes (micro-pores) with specific coatings applied before use as taught by Chiang because these elements of the product capture housing allows for increase in throughput through multiplexing (Chiang, par. 0002) with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 72, Battrell teaches a microfluidic cartridge system and methods of use for the analysis of nucleic acids in clinical samples (Abstract) (a process of identifying a plurality of nucleic acid molecules in a sample).
Battrell in view of Chiang and Ulmanella teach the system and system preparation method of claim 71 as seen in the above outline for applying capture antibodies to the microfluidic PCR device before use (Battrell, par. 0203) (a sample using the system prepared by the method of claim 71, wherein, following said applying capture oligonucleotide primers or probes to the micro-pores).
Battrell teaches the microfluidic circuit assays have three stages of extract, amplify, and detect (Battrell, par. 0173) and operates by moving the sample from the sample port, through the lysis chamber, through the amplification chambers, and finally to the detection chamber before moving to the waste outlet (Battrell, Fig. 4) (conducting reactions in said system). Battrell teaches after amplification of the nucleic acids in the sample, the sample moves to the detection chamber wherein the capture antibody 503 coating the sample pads 502 interact and bind with tags on the nucleic acid 505, 506, 504, 507 to create a tether to bind with a magnetic bead 501 for detection (Battrell, Fig. 5; par. 0230-0231) (detecting the presence of target nucleic acid molecules in the sample… based on said conducting the reactions).
Battrell is silent to the detecting being in the micro-pores.
Chiang teaches the primers/probed are loaded into the wells on the well substrate 120 and are sealed or dried into the wells before being liquified later during the reaction (par. 0080). Chiang teaches once the well substate 120 is loaded with probes/primers 134, the honeycomb tube cartridge is then strategically filled with the sample fluid and a series of reagents and heated to promote a reaction (Fig. 4A-D"; par. 0081-0086). The honeycomb cartridge 100 is then inserted into the sensor assembly for testing/measuring the assay, specifically PCR (par. 0087-0090) (detecting the presence of target nucleic acid molecules in the sample in the micro-pores based on said conducting the reactions).
Chiang teaches these particular elements of the well substrate (the array of through-holes and detection within through-hole array) serve the primary goal of increasing throughput through multiplexing (par. 0002).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the detection process of modified Battrell to include an array of cone-shaped through-holes (micro-pores) with specific coatings for detection as taught by Chiang because these elements of the product capture housing allows for increase in throughput through multiplexing (Chiang, par. 0002) with reasonable expectation of success. MPEP 2143(I)(G).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADISON T HERBERT whose telephone number is (571)270-1448. The examiner can normally be reached Monday-Friday 8:30a-5:00p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached at (571) 270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/M.T.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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