Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 3, 4, 7, 9 – 11, 13, 15 – 17, 19 – 21, and 23 in the reply filed on 22 January 2026 is acknowledged.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07 January 2023 and 02 December 2024 were filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(4) because reference character “111” has been used to designate both “conduit” and “Gel surface facing aperture” (see page 34 line 14). Reference character “108” has been used to designated both “support compartment” and “cover aperture” (see page 36 line 23).
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(4) because reference characters "109" and "107" have both been used to designate “base aperture” (see page 36 line 24).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 4, 10, 13, 15 – 17, and 19 – 21 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 3 recites the limitation "the plane of the microfluidic network" in line 2. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, the examiner interprets this limitation to mean “a plane of the microfluidic network defined by a fluid flow direction.”
Claim 4 recites the limitation "the diameter of the aperture in the base" and “the diameter of the aperture in the cover” in line 4. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, the examiner interprets this limitation to mean “a diameter of the aperture in the base” and “a diameter of the aperture in the cover.”
Claim 10 recites the limitation “the boundary between the at least one support compartment and the at least one perfusion compartment” and “the boundary between the at least one support compartment and the conduit” in lines 3 and 5, respectively. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, the examiner interprets this limitation to mean “a boundary between the at least one support compartment and the at least one perfusion compartment” and “a boundary between the at least one support compartment and the conduit.”
Claim 13 recites the limitation "the support compartment" in line 2. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, the examiner interprets this limitation to mean “the at least one support compartment.”
Claim 15 is dependent on claim 14, which has been cancelled. The claim is rejected as incomplete, and is not being further considered on the merits.
Claim 16 recites the limitation "the exterior part of the base and/or the exterior part of the cover" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. For the purposes of examination, the examiner interprets this limitation to mean “an exterior part of the base and/or an exterior part of the cover.”
Claims 17 and 19 – 21 are rejected as being indefinite due to their dependence on claim 16.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
Claims 1, 3, 4, 7, 9, 10, 11 and 23 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Vulto et al (US 20220017846 A1).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
With regards to claim 1, Vulto et al teaches;
The claimed “at least one microfluidic network” has been read on the taught (Abstract, “A microfluidic device comprising a microfluidic network is described.”);
The claimed “a base, a microfluidic channel, and a cover” has been read on the taught (Abstract, “The device comprises a base, a microfluidic channel and a cover…”);
The claimed “at least one perfusion compartment inside the microfluidic channel” and “at least one support compartment inside the microfluidic channel” have been read on the taught ([0203], “As shown in the top view (FIG. 2), the circular capillary pressure barrier divides the microfluidic network in two sub-volumes. One sub-volume, in this embodiment the central volume within the capillary pressure barrier, comprises the strain compartment or cell culture chamber, and the second sub-volume defined by microfluidic channel (102) leading to and surrounding the first sub-volume.”; The sub-volume comprising the cell culture chamber reads on at least one support compartment. The second sub-volume defined by the microfluidic channel reads on at least one perfusion compartment.);
The claimed “the base and cover each comprise an aperture, thereby defining a conduit through the microfluidic channel” has been read on the taught ([0218], “Specifically, FIG. 10A shows an aperture in base (101) across which diaphragm (106) extends, with capillary pressure barrier (105) outside of the aperture. In this particular configuration, diaphragm (106) is aligned with inlet aperture (107)…”; The aperture in the base 101 reads on the base comprising an aperture. The inlet aperture 107 reads on an aperture in the cover.);
The claimed “the conduit is in fluidic contact with the at least one support compartment, and in fluidic contact with the at least one perfusion compartment through the at least one support compartment” has been read on the taught ([0204], “The formation of two sub-volumes in direct contact with one another without any intervening structure such as a wall or membrane is one of the key characteristics of the device and assay plate.”; See also Figure 1, reproduced below).
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With regards to claim 3, the device of claim is anticipated by Vulto et al.
The claimed “wherein the conduit is substantially orthogonal to the plane of the microfluidic network” has been read on the taught (See figure 1, reproduced on page 6, which shows the aperture orthogonal to microfluidic channel).
With regards to claim 4, the device of claim 1 is anticipated by Vulto et al.
The claimed “the aperture in the base is substantially aligned with the aperture in the cover” has been read on the taught ([0218], “Specifically, FIG. 10A shows an aperture in base (101) across which diaphragm (106) extends, with capillary pressure barrier (105) outside of the aperture. In this particular configuration, diaphragm (106) is aligned with inlet aperture (107)…”).
With regards to claim 7, the device of claim 1 is anticipated by Vulto et al.
The claimed “wherein any one or both of the aperture in the base and the aperture in the cover has a rim which is configured to pin a fluid with the at least one support compartment” has been read on the taught ([0117], “…the capillary pressure barrier is selected from a rim or ridge…”; [0204], “FIG. 3 provides a close up view of the vertical cross section of a part of the microfluidic network, showing the capillary pressure barrier (105) on the base layer and diaphragm (106).”; The capillary pressure barrier on the base layer and diaphragm reads on the aperture in the base having a rim.).
With regards to claim 9, the device of claim 1 is anticipated by Vulto et al.
The claimed “wherein the at least one support compartment is defined at least in part by any one or more of; […] one or more capillary pressure barriers located in the microfluidic channel” has been read on the taught ([0115], “In one example, the capillary pressure barrier comprises or consists of a rim or ridge of material protruding from an internal surface of the microfluidic channel…”; [0203], “One sub-volume, in this embodiment the central volume within the capillary pressure barrier…”).
With regards to claim 10, the device of claim 9 is anticipated by Vulto et al.
The claimed “wherein one capillary pressure barrier of the one or more of the capillary pressure barriers defines at least in part the boundary between the at least one support compartment and the at least one perfusion compartment” has been read on the taught ([0204], “The formation of two sub-volumes in direct contact with one another without any intervening structure such as a wall or membrane is one of the key characteristics of the device and assay plate.”; [0061], “wherein the microfluidic channel comprises a sub-volume defined at least in part by the diaphragm and by a capillary pressure barrier in the microfluidic channel.”).
With regards to claim 11, the device of claim 1 is anticipated by Vulto et al.
The claimed “wherein the at least one support compartment and/or the at least one perfusion compartment are each fluidically connected to one or more respective inlets and/or one or more respective outlets” has been read on the taught ([0099], “The microfluidic channel may be provided with one or more additional fluid inlets, and one or more outlets or vents, as required for any particular use of the microfluidic network of the microfluidic device.”; [0206], “In this embodiment a central strain compartment is connected to four media inlets (104)…”).
With regards to claim 23, the device of claim 9 is anticipated by Vulto et al.
The claimed “wherein the one or more capillary pressure barriers each comprise: a ridge of material protruding from an internal surface of the microfluidic channel” has been read on the taught ([0115], “In one example, the capillary pressure barrier comprises or consists of a rim or ridge of material protruding from an internal surface of the microfluidic channel…”).
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 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 13, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Vulto et al (US 20220017846 A1) in view of Moritz et al (US 20110306122 A1).
With regards to claim 13, the device of claim 1 is anticipated by Vulto et al.
However, Vulto et al does not explicitly disclose wherein the support compartment does not include a membrane for supporting a layer of cells.
In the analogous art of cell culturing devices, Moritz et al teaches;
“A cell culture device including at least one support compartment, with two apertures intersecting the support compartment” has been read on the taught ([0044], “…the conduit 9 penetrates the entire body 2 in an essentially perpendicular direction from the first surface 3 to the second surface 4… The conduit 9 comprises a culture compartment 17 that is situated close to the second surface 3 of the body 2.”; See also Figure 7, which shows an open top, an open bottom.);
The claimed “wherein the support compartment does not include a membrane for supporting a layer of cells” has been read on the taught (Abstract, “A hanging drop plate…”; See also figure 8, reproduced below, which shows the liquid hanging from the aperture without a membrane.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device taught by Vulto et al with the hanging drop device as taught by Moritz et al, for the benefit of enabling 3D cell cultures and forming microtissues ([0002], “The hanging drop (HD-) technology has shown to be a universal method to enable 3D cell culture… As there is no substrate available on which the cells can adhere, they accumulate at the bottom of the drop and form a microtissue.”).
With regards to claim 16, the device of claim 1 is anticipated by Vulto et al.
However, Vulto et al does not explicitly disclose wherein the device further comprises at least one enclosure that at least partially covers the exterior part of the base and/or exterior part of the cover.
In the analogous art of cell culturing devices, Moritz et al teaches;
The claimed “at least one enclosure that at least partially covers the exterior part of the base and/or the exterior part of the cover” has been read on the taught ([0049], “…the same cover plate 22 can be used as shell underneath the hanging drop plate 1 or as a cap on top of it.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device taught by Vulto et al with the cover as taught by Moritz et al, for the benefit of preventing evaporation of the liquid ([0050], “…it is preferred to cover the hanging drop plate 1 on the top and bottom side in order to avoid unacceptable evaporation of the liquid in the liquid volume 6 or in the conduit 9.”).
With regards to claim 17, the device of claim 16 is obvious over Vulto et al in view of Moritz et al.
Vulto et al does not explicitly disclose the limitations of claim 17.
Moritz et al further teaches;
The claimed “wherein all or part of the at least one enclosure is removeable” has been read on the taught ([0050], “Such a "sandwich" of two cover plates 22 and one hanging drop plate 1 between them is the smallest unit preferably formed for storage, cultivation or incubation, and safe transport of a hanging drop plate, whether it is loaded with liquid volumes and cells and/or molecules or not (see FIG. 5).”; One of ordinary skill in the art will recognize that use of the sandwich for cultivation requires the covers to be removable, so that the cultivated cells can later be harvested.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device of Vulto et al with the cover as taught by Moritz et al, for the benefit of preventing evaporation of the liquid ([0050], “…it is preferred to cover the hanging drop plate 1 on the top and bottom side in order to avoid unacceptable evaporation of the liquid in the liquid volume 6 or in the conduit 9.”).
Claims 19 – 21 are rejected under 35 U.S.C. 103 as being unpatentable over Vulto et al (US 20220017846 A1) in view of Moritz et al (US 20110306122 A1) as applied to claim 16 above, and further in view of Collins (US 20210055283 A1).
With regards to claim 19, the device of claim 16 is obvious over Vulto et al in view of Moritz et al.
Moritz et al additionally teaches channel connecting the hanging droplets, as read on the taught ([0068], “FIG. 10B shows a variant with an open top inlet compartment that is fluidly connected to two or more conduits for supplying a 384 drop array with liquid dispensed from a 96 tip dispenser head.”).
However, neither Vulto et al nor Moritz et al explicitly disclose wherein the at least one enclosure defines a connecting channel connecting the conduits of at least two microfluidic networks of the plurality of microfluidic networks via their respective apertures in the base and/or in the cover.
In the analogous art of cell culturing devices, Collins teaches;
The claimed “the at least one enclosure defines a connecting channel connecting the conduits of at least two microfluidic networks via their respective apertures in the cover” has been read on the taught ([0034], “…there are provided methods for microfluidic lid with channels for dropping fluids arranged in a non-intersecting format on the top for perfusion fluidics and on the bottom for circulation fluidics.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device of Vulto et al in view of Moritz et al with the lid including channels as taught by Collins. According to MPEP 2143(I)(A), combining prior art elements according to known methods to yield predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Vulto et al in view of Moritz et al teach the microfluidic cell culture device and an enclosure. The prior art of Collins teaches an enclosure with a connecting channel. One of ordinary skill in the art could have combined these two elements according to known methods, and in combination, the cell culture device cultures cells in droplets, and the enclosure covers connects the microfluidic networks— each element performing the same function as it does separately. One of ordinary skill in the art would have found the combination to yield the predictable result of a cell culture device which can share fluids via connecting channels in the enclosure.
With regards to claim 20, the device of claim 17 is obvious over Vulto et al in view of Moritz et al.
However, this combination does not explicitly disclose wherein the at least one enclosure comprises one or more fluid inlets and/or fluid outlets.
In the analogous art of cell culturing devices, Collins teaches;
The claimed “wherein the at least one enclosure comprises one or more fluid inlets and/or fluid outlets” has been read on the taught ([0033], “…there are provided methods for manifold with circular or rectangular shallow pillars to press the O-ring area of the manifold with rapidly connecting microfluidic lid.”; The rapidly connecting microfluidic lid reads on the fluid inlets and/or fluid outlets.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device of Vulto et al in view of Moritz et al with the lid including fluidic inlets and outlets as taught by Collins. According to MPEP 2143(I)(A), combining prior art elements according to known methods to yield predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Vulto et al in view of Moritz et al teach the microfluidic cell culture device and an enclosure. The prior art of Collins teaches an enclosure with ports. One of ordinary skill in the art could have combined these two elements according to known methods, and in combination, the cell culture device cultures cells in droplets, and the enclosure covers connects the microfluidic networks— each element performing the same function as it does separately. One of ordinary skill in the art would have found the combination to yield the predictable result of a cell culture device which allows for the introduction of fluids without requiring the removal of the enclosure.
With regards to claim 21, the device of claim 20 is obvious over Vulto et al in view of Moritz et al and further in view of Collins.
Vulto et al in view of Moritz et al does not explicitly disclose wherein the one or more fluid inlets are connected to the one or more fluid outlets outside of the microfluidic network, optionally through a pump, thereby enabling an at least partially circulating flow.
Collins further teaches;
The claimed “wherein the one or more fluid inlets are connected to the one or more fluid outlets outside of the microfluidic network, optionally through a pump, thereby enabling an at least partially circulating flow” has been read on the taught ([0014], “…there are provided methods for recirculating fluids within a well or reactor through pumps, manifold fitted with O-rings to a microfluidic lid fitted with dispensers/suckers.”; [0017], “…there are provided methods to couple a recirculation system and a perfusion system as a single fluidic system using air pumps/valves or liquid pumps/valves or combinations.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the microfluidic device of Vulto et al in view of Moritz et al with the lid including circulating flow as taught by Collins. According to MPEP 2143(I)(A), combining prior art elements according to known methods to yield predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Vulto et al in view of Moritz et al teach the microfluidic cell culture device and an enclosure. The prior art of Collins teaches an enclosure with ports. One of ordinary skill in the art could have combined these two elements according to known methods, and in combination, the cell culture device cultures cells, and the enclosure connects the microfluidic networks— each element performing the same function as it does separately. One of ordinary skill in the art would have found the combination to yield the predictable result of a cell culture device which allows for the circulation of fluids without requiring the removal of the enclosure.
Allowable Subject Matter
The claims filed 22 January 2026 are not allowable in their current state. However, the examiner believes that the disclosure of the current application encompasses potentially allowable subject matter. Vulto et al 2022 (US 20220017846 A1) explicitly teaches the use of a membrane in the bottom of the support compartment. While hanging drop methods for cell proliferation are well-known in the art, including devices which use capillary pressure barriers (See Olivier, EP 2811012 A1), these devices typically involve a top support for the droplet when combined with microfluidic channels in fluid communication with the droplet (See Fattinger et al, US 20140106395 A1). Likewise, devices which suspend a droplet without a top or bottom support do not include channels which allow for fluid exchange with the suspended droplet (See Moritz et al, US 20110306122 A1).
The examiner believes that a microfluidic device which uses capillary pressure barriers to suspend a droplet between a top and bottom aperture; wherein no membrane, gel, or other support is present in the aperture; and which uses capillary pressure barriers to allow fluidic contact with a perfusion compartment may be allowable over the prior art—provided that the rejections in view of Vulto et al 2022 could be overcome with an exception under 102(b)(2). The examiner is not able to provide amendments, but can be contacted for an interview to further prosecution.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Olivier (EP 2811012 A1) teaches a microfluidic hanging droplet plate using capillary pressure barriers.
Fattinger et al (US 20140106395 A1) teaches a microfluidic hanging droplet plate using capillary pressure barriers.
Hsu et al (US 20130084634 A1) teaches a microfluidic hanging drop cell culturing device connected to a microfluidic network.
Vulto et al (US 20150238952 A1) teaches the use of capillary pressure barriers in microfluidic devices.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON CLAIRE GERHARD whose telephone number is (571)270-0945. The examiner can normally be reached M-F, 9:00 - 5:30pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALISON CLAIRE GERHARD/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797