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 .
This is a FINAL REJECTION in response to applicant’s claim amendments and arguments filed December 19, 2025. Claims 1-20 are pending review in this correspondence.
Response to Amendment
Rejection of claims 1-10 and 12-14 as being unpatentable over Xu et al (US 2005/01967476 A1) in view of Yue et al (US 2007/0014695 A1) is withdrawn in view of applicant’s arguments to claim 1.
Rejection of claims 15-18 and 20 as being unpatentable over Xu et al (US 2005/01967476 A1) in view of Yue et al (US 2007/0014695 A1) is maintained in view of applicant’s arguments.
Rejection of claim 11 as being unpatentable over Xu et al (US 2005/01967476 A1) in and Yue et al (US 2007/0014695 A1) in view of Xu et al (Us 2005/0009004 A1) is withdrawn in view of applicant’s arguments to claim 1.
Rejection of claim 19 as being unpatentable over Xu et al (US 2005/01967476 A1) in and Yue et al (US 2007/0014695 A1) in view of Korpela (US 2003/0003023 A1) is maintained in view of applicant’s arguments to claim 15.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 15-18 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al (US 2005/0196746 A1) in view of Yue et al (US 2007/0014695 A1).
With respect to claim 15, first it is noted that Xu discloses in Para. 387 that the aspects of the invention can be combined and are not limited to a single embodiment.
Further, Xu discloses a system comprising:
a microfluidic device (device discussed in Fig. 13, Para. 0365) comprising:
A sample inlet (See Figs. 13A-D reproduced below);
An outlet channel (See Figs. 13A-D reproduced below); and
A substrate (See Figs. 13A-D reproduced below) comprising a set of chambers (microwells 1303) in fluid communication with the sample inlet, wherein each chamber (microwell 1303) of the set of chambers has a maximum cross-section at an opening into the chamber and wherein the opening defines an entry for material of a sample to enter the chamber (See Fig. 13A and Para. 0054 for discussion of how the upper opening of a well can be of any shape and can be of an irregular conformation; the walls of a well can extend upward from the lower surface of a well at any angle or in any way); and
An isolation mechanism comprising a space (area between the inlet and chamber opening depicted in Fig. 13A below) fluidly connected to the sample inlet to the openings having the maximum width of the set of the chambers and configured to apply an isolation layer covering the openings (See Paras. 0365 and 0035 for discussion of how the drops of compound solution are dispensed) having the maximum width of the set of chambers to seal the set of chambers (See Para. 0333 for discussion of sealing in the presence of complete solution superfusion of the upper chamber).
Xu fails to specifically state that the set of chambers comprises from 10,000 to 1,000,000 individual chambers. However, Para. 0188 teaches that the biochip has hydrophobic surface areas that can have any number of holes/microwells, from 1 to more than one thousand. Given that Xu states the chip can contain more than 1,000 microwells, it would encompass the cited limitations of 10,000 to 1,000,000. As set forth in MPEP 2144.05, in the case where the claimed range “overlap or lie inside ranges disclosed by the prior art”, a prima facie case of obviousness exists, In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Additionally, Xu fails to disclose that the isolation mechanism works to flow a continuous isolation layer through the space that is fluidly connected to the set of chambers.
Yue teaches sealing of a substrate for biological testing, wherein (See Figs. 38-39C). The substrate 3910 may comprise a base 3930 and a film layer covering the base to form the sample distribution network shown. In the exemplary embodiment, each sample chamber 3980 is in flow communication with a main fluid supply channel 3970 via a sample introduction (inlet) channel 3975 (See Para. 0148). Sample S (e.g., a biological sample) is introduced to the substrate 3910. The sample S may be pumped through the main fluid supply channel 3970, the introduction channels 3975, and into the sample chambers 3980 via pressure from a volume of oil (not shown in FIG. 39A), or other substance that is immiscible with the sample, that is pumped behind the sample S. As shown in FIG. 39A, the sample S that is introduced is sufficient to fill the sample chambers 3980, the introduction and venting channels 3975 and 3976, the venting chambers 3990, and the main fluid supply channel 3970 from the inlet of the substrate 3910 (at the right hand side in FIG. 39A) up to the plug 3900. The plug 3900 prevents the sample S from advancing past the plug 3900 until the sample S has a chance to fill the various chambers and channels, as shown in FIG. 39A (See Para. 0149). Once the substrate 3910 has been filled with sample S, as depicted in FIG. 39A, the plug 3900 may begin to dissolve, thus allowing any remaining supply of sample S to the substrate 3910 and the oil O behind it to flow in the main fluid supply channel 3970 past the location of the plug 3900, as shown in FIG. 39B. The oil O may continue to be supplied to the substrate 3910 such that it fills the main fluid supply channel 3970, the main fluid outlet channel 3972, the venting chambers 3992, and reaches the overfill chamber 3995, as shown in FIG. 39C. Due to the immiscibility of the oil O and sample S, once the oil fills the portions of the substrate 3910 described above and shown in FIG. 39C, the oil acts to seal the inlet and outlet of each of the sample chambers 3980, for example, so that further processing of the sample in the chambers 3980 may occur (See Para. 0150).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to supply the oil to the channels, inlet, and outlet in a continuous fashion, as taught by Yue, to the method of Xu, to ensure that all inlets/outlets of the microfluidic device and chamber are substantially sealed, so that further processing of the isolated particles/cells may occur (See Paras. 0148-0150 of Yue).
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Fig. 13 (reproduction)
With respect to claim 16, the combination of Xu and Yue teaches a venting system configured to vent air bubbles (See Fig. 13A of Xu reproduced below; section depicted leads to an outflow conduit; See Para. 0272 of Xu for general discussion of said conduit). Regarding the limitation “configured to vent air bubbles” this limitation is directed to the function of the apparatus and/or the manner of operating the apparatus, all the structural limitations of the claim has been disclosed by Xu and the apparatus of Xu is capable of venting bubbles at the location shown. As such, it is deemed that the claimed apparatus is not differentiated from the apparatus of Xu (see MPEP §2114). It should further be noted that Yue teaches the incorporation of venting channels and venting chambers (2976 and 3990, respectively; See Fig. 38 and Para. 0148).
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672
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Fig. 13A (reproduced)
With respect to claim 17, the combination of Xu and Yue teaches that that the isolation layer comprises an oil (See Paras. 0148-0150 of Yue).
With respect to claim 18, the combination of Xu and Yue teaches that the substrate is optically transparent (See Para. 0168 of Xu for discussion of how the ion transport measuring means or surface surrounding the ion transport measuring means can be made of silica, glass, quartz, silicon; Para. 0275 discusses that the upper chamber piece ca be made of one or more plastics, one or more polymers, glass, wherein glass and transparent polymers are preferred transparent materials).
With respect to claim 20, the combination of Xu and Yue teaches a workstation comprising an imaging platform, wherein the imaging platform comprises an imager for detecting a set of emission wavelengths of light (See Para. 0131 of Xu for the discussion detectable labels such as, but not limited to, photometric, colorimetric, radioactive or morphological such as changes of cell morphology that are detectable, such as by optical methods; it could surmise that the incorporation of optical methods of detection in various forms would imply the incorporation of an imager and associated system).
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al (US 2005/0196746 A1) and Yue et al (US 2007/0014695 A1) in view of Korpela (US 2003/0003023 A1).
Refer above for the combined teachings of Xu and Yue.
With respect to claim 19, Xu fails to disclose a workstation comprising a stage supporting the substrate, wherein the stage is thermally coupled with a heater for heating the substrate. Although Yue teaches that the substrate is designed to be brought into contact with a thermal block of a PCR device for sealing and thermocycling (See Para. 0139), there is no specific discussion of a heater.
Korpela teaches preferred applications for the method of the invention in in situ PCR applications (See Para. 0090), wherein the vessel tray can be placed into specially designed thermocyclers (See Para. 0111). In PCR reactions elevated temperature are utilized and, in these cases, increase of vapor and air pressure tends to pull used vessel covers of the mouth of the vessel. Combination of the above-described use of negative pressure with minimization of air space inside the vessel to be closed is particularly advantageous when performing, for instance, PCR reactions and other amplification reactions in which elevated temperatures and small volumes of liquids are used (See Para. 0089).
It would have been obvious to one of ordinary skill in the art at the time of filing to incorporate the addition of a heater designed to be in physical contact with the biochip of combined Xu and Yue, as taught by Korpela, for the purpose of performing PCR reactions and other amplification reactions under more optimized conditions (See Paras. 0089 of Korpela) and as part of another specific use for the device of combined Xu and Yue.
Allowable Subject Matter
Claims 1-14 are allowed.
The following is an examiner’s statement of reasons for allowance: The closest cited prior art of reference is to Xu et al (US 2005/0196746 A1) which teaches a method of providing a microfluidic device comprising a sample inlet, an outlet channel, and a substrate comprising a set of chambers in fluid communication with the sample inlet, wherein each chamber has a maximum cross-section at an opening into the chamber and wherein the opening defines an entry for material of a sample to enter the chamber, and receiving a sample into the sample inlet. However, Xu fails to disclose, teach, or suggest the step of flowing a continuous isolation layer through a space that is fluidly connected to the set of chambers, further wherein the continuous isolation layer covers the openings having the maximum cross-section of the set of chambers as a continuous layer and seals the set of chambers. Rather, Xu teaches in Para. 0035 the step of applying a compound solution as droplets that are dispensed over the microwells containing the cells, and dispensed in such a way that the solution does not flow into neighboring microwells. Additionally, the secondary reference to Yue does not teach, suggest, or disclose that the continuous isolation layer covers the openings having the maximum cross-section of the set of chambers as a continuous layer. Rather, Yue reports a different mechanism. Yue reports a substrate for biological testing in which oil is pumped behind a sample through a main fluid supply channel 3970, introduction channels 3975, and into sample chambers 3980 (Paras. 0148-0150). In Yue, the oil flows through the main fluid supply channel and fills the channel network to seal the chambers at the narrow introduction channels 3975 and venting channels 3976. Yue explicitly states that "the oil acts to seal the inlet and outlet of each of the sample chambers 3980" (Para. 0150). The sealing occurs at the introduction and venting channel junctions, not by covering the maximum cross-section openings of the chambers themselves. The oil seals the chambers by filling these narrow channel pathways, not by forming a continuous layer that covers the wide chamber openings. Yue's approach is structurally and functionally distinct from a covering layer over chamber openings.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Response to Arguments
Applicant's arguments filed December 19, 2025 have been fully considered but they are not persuasive:
APPLICANT ARGUES: “Xu does not teach, suggest, or disclose flowing a continuous isolation layer through a space fluidly connected to the chambers, wherein the isolation layer covers the openings having the maximum cross-section of the chambers as a continuous layer. Xu reports an ion transport measurement device having microwells with a flow-through upper chamber design. As acknowledged in the Office Action, at page 5, Xu only discloses discontinuous droplet dispensing of compound solution to individual microwells, not a continuous isolation layer flowing through a connected space.
Yue does not remedy the deficiencies of Xu.
Yue does not teach, suggest, or disclose that the continuous isolation layer covers the openings having the maximum cross-section of the set of chambers as a continuous layer. Yue reports a different mechanism. Yue reports a substrate for biological testing in which oil is pumped behind a sample through a main fluid supply channel 3970, introduction channels 3975, and into sample chambers 3980 (Yue, paragraphs [0148]-[0150]). In Yue, the oil flows through the main fluid supply channel and fills the channel network to seal the chambers at the narrow introduction channels 3975 and venting channels 3976. Yue explicitly states that "the oil acts to seal the inlet and outlet of each of the sample chambers 3980" (Yue, paragraph [0150]). The sealing occurs at the introduction and venting channel junctions, not by covering the maximum cross-section openings of the chambers themselves. The oil seals the chambers by filling these narrow channel pathways, not by forming a continuous layer that covers the wide chamber openings. Yue's approach is structurally and functionally distinct from a covering layer over chamber openings.
Additionally, the claims recite that the continuous isolation layer flows "through a space that is fluidly connected to the set of chambers." The isolation material flows through this space and forms a continuous layer covering the chamber openings at their maximum cross-section. In contrast, Yue's oil flows through a main supply channel and then through narrow introduction channels to reach the chambers. The oil does not flow through a space that is directly and openly connected to the maximum-width chamber openings.
The combination of Xu and Yue fails to arrive at the claimed invention because neither reference, alone or in combination, teaches an isolation layer that covers the openings having the maximum cross-section of the chambers as a continuous layer.
Further, applying Yue's approach to Xu's device would not yield a predictable result because the structures are incompatible. Xu's Figure 13 depicts microwells 1303 that open directly into a flow-through upper chamber used for ion transport measurement. Yue's sealing mechanism relies on oil filling connecting channels between chambers and a main channel. Xu does not have such connecting channels i.e., the microwells of Xu open directly into the upper chamber space. A skilled artisan seeking to combine these references would not have a reasonable expectation of success in achieving the claimed continuous covering layer because Yue's approach depends on a channel that Xu's device does not possess” (See Pgs. 5-6 of applicant’s remarks/arguments).
EXAMINER’S RESPONSE: While the examiner agrees with applicant’s assertions about Xu and Yue not adequately disclosing the method of claim 1, wherein the set of processes comprises flowing a continuous isolation layer through a space that is fluidly connected to the set of chambers, further wherein the continuous isolation layer covers the openings having the maximum cross-section of the set of chambers as a continuous layer and seals the set of chambers, the examiner disagrees with applicant’s assertions as it pertains to the system of claim 15. Applicant should note that the recitation of the 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 use (i.e. flowing a continuous isolation layer), then it meets the metes and bounds of the claim. With regard to claim 15, applicant should note that Para. 0035 of Xu discusses how cells are flowed through an upper channel for deposition into the transport measuring holes within the microwells that access the channel. Additionally, compound drops are dispensed directly over the ion transport measuring sites but are applied such that the compound solution does not flow into neighboring microwells. Thus, it is clear from this description that a fluid, including compound solution, would be capable of being flowed through the previously mentioned chamber channel to form a continuous isolation layer that cover openings having a maximum cross-section of the set of chambers, rather than being dispensed as droplets from above the plate. Yu was merely provided to demonstrate an application of a sealing fluid being flowed through a system (through channels) to cover openings to chambers. Xu has already addressed the capability of the system being used in that fashion, which is what is required for intended use recitations. Applicant might consider the incorporation of language that more clearly defines the structure that is encompassed by the recited isolation mechanism.
Furthermore, it is noted that Korpela was incorporated to address the limitations of claim 19, not those of claim 15, and as such, applicant’s arguments that Korpela fails to remedy the cited deficiencies of Xu and Yue as it pertains to claim 15 is moot.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRITTANY I FISHER whose telephone number is (469)295-9182. The examiner can normally be reached IFP.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Lin can be reached at (571) 272-8902. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRITTANY I FISHER/Examiner, Art Unit 1796 April 3, 2026
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