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 .
Claim Status
Claim 1-3 and 6-24 are pending with claims 1-3, 9-11 under examination and claims 6-8 and 12-24 withdrawn from consideration.
Claims 4-5 have been canceled.
Response to Amendment
Applicant’s amendments to the claims, received 01/21/2026, have overcome the 112(b) rejection(s) previously set forth in the Non-Final Office Action mailed on 9/17/2019. Accordingly, the 112(b) rejection(s) have been withdrawn.
Based on the amended claims and remarks received on 01/21/2026, the previous prior art rejection over Hung has been withdrawn and a new prior art rejection set forth (see below).
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Hung et al. (US 2007/0275455; already of record – hereinafter “Hung”), in view of Konry et al. (US 2017/0199173; already of record – hereinafter “Konry”) and Battrell et al. (US 2009/0181411 – hereinafter “Battrell”).
Regarding claim 1, Hung disclose a microfluidic device for analysis and isolation of a plurality of cells (Hung disclose a microfluidic device for capturing and performing an assay on cells, fig 3, [0006, 0060, 0078]), the device comprising:
a first layer comprising an array of microchambers or docking sites for storing and analyzing the plurality of cells in a liquid medium (Hung disclose an array of microchambers 58, 60 for capturing and performing an assay on cells in a medium, the array of wells connected by microfluidic channels formed in a first layer; figs. 3 & 5B, 13A-13H, [0020, 0022, 0058-0060, 0080]), each microchamber or docking site fluidically connected with a laterally connected collection channel (Hung disclose laterally connected collection channels 72a, 72b, 74 for liquid to flow into or out of the well; figs. 5B, 7A-D, 9B-E & 11, [0059]);
a second layer comprising a plurality of pneumatic channels, wherein the second layer overlays the first layer (Hung disclose pneumatic channels 84, 86 formed in a second layer of an upper and lower multilayer microfluidic device; figs. 3 5B, 9C-D “Pneumatically controlled channel”, & 11, [0022, 0024, 0058, 0059-0062, 0080]); and
a membrane, the membrane forming a valve disposed above each laterally connected collection channel (Hung disclose a membrane forming a valves 78, 80, 82, 104, 105, 106, 108, 112, 114, and 116 for controlling the flow of medium into and out of the microchambers 58, 60 and to switch the condition of the valve between its open and closed sates; figs. 3 & 5B, 7A-D, 9A-E, [0017-0018, 0020, 0022, 0035, 0059-0060, 0063-0065, 0080, 0082, 0088, 0100])
wherein in a closed configuration the membrane expands into and within the laterally connected collection channel thereby blocking fluid flow through the laterally connected collection channel (Hung; fig. 9E, [0035]);
wherein in an open valve configuration the membrane does not extend into the laterally connected collection channel (Hung; fig. 9D, [0035]);
wherein each valve is selectively actuatable through one of said pneumatic channels (Hung disclose valves 104, 105, 106, 108, 112, 114, and 116 are controlled by pneumatic valves 78, 80, 82 in the pneumatic channels 84, 86; figs. 3 & 5B, [0060, 0063-0065]), and
wherein actuation of one or more of said valves opens a pathway for removal of one of said plurality of cells from the microchamber or docking sites fluidically connected to the one or more valves through said laterally connected connection channel (Hung disclose when the assay is completed, cells may be removed from the wells by opening microvalve 82, closing valves 78, 80, and forcing medium through each passageway in an outlet-to inlet direction; figs. 5B, 7A-D, & 11, [0059-0060]).
Hung does not teach the cells are cell spheroids.
However, Konry teach the analogous art of a microfluidic device for the analysis and isolation of a plurality of cell spheroids (Konry; [0004]) comprising a plurality of microfluidic chambers (Konry; [0084]) valves (Konry; [0085]) and docking stations (Konry; [0085]) for actuation of one or more of said valves opens a pathway for removal of a cell from the microchamber or docking sites fluidically connected to the one or more valves (Konry; [0084-0085]) wherein the cell is a cell spheroid (Konry; [0076, 0084-0085]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to have modified the plurality of cells of Hung with the plurality of cell spheroids, as taught by Konry, because Konry teaches the cell spheroids are useful in the study of antitumor agents (Konry; [0094]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since Hung and Konry both teach microfluidic devices for use in cell culture assays.
Modified Hung does not teach the membrane installed between the first layer and the second layer and separating the first layer from the second layer.
However, Battrell teach the analogous art of a microfluidic device for analysis (Battrell; fig. 1, [0039]) comprising a first fluidic layer (Battrell; figs. 5A-B, 7A-B, bottom “other layers”, [0104, 0119-0120]) and a second pneumatic layer that overlays the first fluidic layer (Battrell; figs. 5A-B, 7A-B, top “other layers”, [0104, 0119-0120]), and a membrane installed between the first layer and the second layer and separating the first layer from the second layer (Battrell; figs. 7A-B, #93 in “Adhesive” layer, [0104, 0119-0120]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the first layer, the second layer, and the membrane forming a valve of modified Hung with the membrane installed between the first layer and the second layer and separating the first layer from the second layer, as taught by Battrell, because Battrell teach the membrane installed between the first layer and the second layer and separating the first layer from the second layer allows eductive mixing of fluid in the first fluidic layer (Battrell; [0120]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since modified Hung and Battrell both teach pneumatic actuation of a membrane to control fluid flow.
Regarding claim 2, modified Hung teach the microfluidic device of claim 1 above, wherein the first layer further comprises a cell production module (Hung; [0021, 0051, 0079])
Modified Hung does not teach the cell production module is a cell spheroid production module wherein the cell spheroid production module comprises: a plurality of inlets for accepting solutions, cell suspensions, or oil; a plurality of microfluidic channels fluidically connected to said inlets, said plurality of microfluidic channels comprising an oil channel and one or more cell suspension channels; and a nozzle for forming aqueous microdroplets in oil, the nozzle comprising a nozzle inlet and a nozzle outlet, the nozzle inlet fluidically connected to said oil channel and at least one of said one or more cell suspension channels, and the nozzle outlet fluidically connected to said array of microchambers or docking sites.
However, Konry teach the analogous art of a cell production module as a cell spheroid production module (Konry; figs. 1A-1C, [0077]), wherein the cell spheroid production module comprises: a plurality of inlets for accepting solutions, cell suspensions, or oil (Konry; figs. 1A-1C, #10, #20, #25, #30, [0077, 0085, 0089, 0090]); a plurality of microfluidic channels fluidically connected to said inlets (Konry; figs. 1A-1C, channels connecting inlets 10/20/25/30 to nozzle 15 [0085, 0089]), said plurality of microfluidic channels comprising an oil channel and one or more cell suspension channels (Konry; figs. 1A-1C, [0085-0086, 0089-0090, 0092]); and a nozzle for forming aqueous microdroplets in oil (Konry; figs. 1A-1C, #15, [0085, 0089-0090]), the nozzle comprising a nozzle inlet and a nozzle outlet, the nozzle inlet fluidically connected to said oil channel and at least one of said one or more cell suspension channels (Konry; figs. 1A-1C, [0089-0090]), and the nozzle outlet fluidically connected to said array of microchambers or docking sites (Konry; [0085, 0089]).
It would have been obvious to one of ordinary skill in the art to have modified the cell production module of modified Hung with the cell spheroid production module, as taught by Konry, because Konry teaches the cell spheroids production module is useful in the study of antitumor agents (Konry; [0094]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since Hung and Konry both teach microfluidic devices for use in cell culture assays.
Regarding claim 3, modified Hung teach the microfluidic device of claim 1 above, wherein two, three, or four valves are fluidically connected to each microchamber or docking site (Hung disclose valves 104, 105, 106, 108, 112, 114, and 116 are controlled by pneumatic valves 78, 80, 82 in the pneumatic channels 84, 86; figs. 3 & 5B, 7A-D, [0060, 0063-0065]).
Regarding claim 9, modified Hung teach the microfluidic device of claim 1 above, further comprising, one or more cell spheroids disposed in a microchamber or docking site of the array (The modification of the plurality of cells of Hung with the plurality of cell spheroids, as taught by Konry, has previously been discussed in claim 1 above. Hung teach an array of microchambers 58, 60 for capturing and performing an assay on cells in a medium; figs. 3 & 5B, 13A-13H, [0058-0060]).
Regarding claim 10, modified Hung teach a system comprising the microfluidic device of claim 1 (The microfluidic device of claim 1 has previously been discussed above) and a cell production device (Hung; [0021, 0051, 0079]).
Modified Hung does not teach the cell production device is a separate cell spheroid production device comprising: a plurality of inlets for accepting solutions, cell suspensions, or oil; a plurality of microfluidic channels fluidically connected to said inlets, said plurality of microfluidic channels comprising an oil channel and one or more cell suspension channels; and a nozzle for forming aqueous microdroplets in oil, the nozzle comprising a nozzle inlet and a nozzle outlet, the nozzle inlet fluidically connected to said oil channel and at least one of said one or more cell suspension channels, and the nozzle outlet fluidically connected to an outlet; wherein said outlet is capable of providing the plurality of cell spheroids from said cell spheroid production device through a fluidic coupling to said array of microchambers or docking sites of the microfluidic device.
However, Konry teaches the analogous art of a cell production device as a separate cell spheroid production device (Konry; figs. 1A-1C, [0077]) comprising: a plurality of inlets for accepting solutions, cell suspensions, or oil (Konry; figs. 1A-1C, #10, #20, #25, #30, [0077, 0085, 0089, 0090]); a plurality of microfluidic channels fluidically connected to said inlets (Konry; figs. 1A-1C, channels connecting inlets 10/20/25/30 to nozzle 15 [0085, 0089]), said plurality of microfluidic channels comprising an oil channel and one or more cell suspension channels (Konry; figs. 1A-1C, [0085-0086, 0089-0090, 0092]); and a nozzle for forming aqueous microdroplets in oil, the nozzle comprising a nozzle inlet and a nozzle outlet (Konry; figs. 1A-1C, #15, [0085, 0089-0090]), the nozzle inlet fluidically connected to said oil channel and at least one of said one or more cell suspension channels (Konry; figs. 1A-1C, [0089-0090]), and the nozzle outlet fluidically connected to an outlet (Konry; figs. 1A-1C, [0085, 0089]); wherein said outlet is capable of providing the plurality of cell spheroids from said cell spheroid production device through a fluidic coupling to said array of microchambers or docking sites of the microfluidic device (Konry; figs. 1A-1C, [0084-0085, 0087]).
It would have been obvious to one of ordinary skill in the art to have modified the cell production module of modified Hung with the separate cell spheroid production module, as taught by Konry, because Konry teaches the separate cell spheroids production module is useful in the study of antitumor agents (Konry; [0094]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since Hung and Konry both teach microfluidic devices for use in cell culture assays.
Regarding claim 11, modified Hung teach a system comprising the microfluidic device of claim 1 (The microfluidic device of claim 1 has previously been discussed above) and a controlled pneumatic pressure source connected to one or more of said pneumatic channels, the pressure source capable of selectively actuating one or more of said valves (Hung teach pneumatic valves 78, 80, 82 in the pneumatic channels 84, 86 are activated by fluid pressure from stations 15 and 16; figs. 3 & 5B, [0060, 0063-0066]).
Response to Arguments
Applicant’s arguments filed on 01/21/2026 have been considered but are moot because the arguments are towards the amended claims and do not apply to the current grounds of rejection. However, because the examiner is using the same prior art in the rejection, then the examiner will address applicant’s remarks in order to promote compact prosecution.
Applicants argue on pages 7-8 of their remarks that Hung does not teach the amended limitation “a membrane installed between the first layer and the second layer”. The examiner agrees with applicant’s argument. However, upon further consideration, a new ground(s) of rejection is made in view of Battrell which disclose the amended limitations.
Citations to art
In the above citations to documents in the art, an effort has been made to specifically cite representative passages, however rejections are in reference to the entirety of each document relied upon. Other passages, not specifically cited, may apply as well.
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 extension fee 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 date of this final action.
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/C.A.T./Examiner, Art Unit 1798
/BENJAMIN R WHATLEY/Primary Examiner, Art Unit 1798