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 1-5, 7, 10, 20-21, 23-24, 26, 33, 37, 74 and 101-103 are pending with claims 1-5, 7, 10, 20-21, 23-24, 26, 33, and 101-103 under examination and claims 37 and 74 withdrawn from consideration.
Claims 6, 8-9, 11-19, 22, 25, 27-32, 34-36, 38-73, and 75-100 have been canceled.
Response to Amendment
Based on the amended claims and remarks received on 12/10/2025, the previous prior art rejection over Abate has modified to address the amended claims (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 1-5, 7, 10, 20, 23-24, 26, and 101-103 are rejected under 35 U.S.C. 103 as being unpatentable over Amini et al. (US 2017/0128940; already of record – hereinafter “Amini”), and further in view of Steenblock et al. (US 2014/0179544; already of record – hereinafter “Steenblock”), or alternatively over Amini, in view of Steenblock, and further in view of Abate (US 2017/0022538; already of record – hereinafter “Abate”).
Regarding claim 1, Amini disclose a method for generating droplets (Amini; fig. 8, [0006, 0037, 0142-0152]), comprising:
flowing a third fluid comprising a plurality of cells into a first fluid (Amini; fig. 8, Step 1 “Ordered barcoded beads/lysis”, Step 2 “Ordered cell suspension”, [0143]), wherein the third fluid is miscible with the first fluid (Amini disclose the third fluid and first fluid merge, [0037, 0143, 0164]);
flowing in a channel of a microfluidic device the first fluid into a second fluid under stable jetting conditions to provide a jet of the first fluid in the second fluid (Amini; fig. 8, Jetted fluid from Step 1 and Step 2 flow into oil at Step 3 with the jet of the first fluid flowing into the oil fluid, [0143]),
wherein the jet of the first fluid does not spontaneously break into droplets in the second fluid (Amini disclose the microfluidic device is designed to generate droplets each containing a single cell and a single bead. The microchannel device is configured to separate, order, and focus streams of barcoded beads to one or more focusing positions within a channel flow field (Step 1). The microchannel device is configured to separate, order, and focus streams of cells to one or more focusing positions within a channel flow field (Step 2). The microchannel device receives an oil as another input (Step 3), and combines the ordered barcoded bead, the ordered cell, and an oil to generate droplets within a-double-undispersed-Poisson statistics, where each droplet contains one bead and one cell; fig. 8, [0143]. Accordingly, Amini disclose the ordered particles in the first fluid stream prevent the first fluid from spontaneously breaking into droplets in the second fluid resulting in the generation of droplets each with one bead and one cell, as shown in Step 4 of fig. 8; [0142-0143]. Further, Amini disclose adjusting the flow rate of bead fluid so that every droplet encapsulated one bead wherein the jet of the first fluid does not spontaneously break into droplets in the second fluid; fig. 9 and [0171]), and
wherein the first fluid is immiscible with the second fluid (Amini disclose the merged stream of beads and cells is then contacted with an oil or other immiscible fluid to create a droplet containing the beads and cells; [0037, 0165]); and
introducing a plurality of particles into the first fluid upstream of the jet, thereby causing the plurality of particles to flow into the jet, thereby triggering break-up of the jet and encapsulation of the plurality of particles and cells in a plurality of monodispersed droplets of the first fluid in the second fluid (Amini; figs. 4 & 8, Step 1, the microchannel device is configured to separate, order, and focus streams of barcoded beads to one or more focusing positions within a channel flow field. The bead triggers breakup of the jet to generate droplets containing one bead and one cell in Step 4; [0018, 0142-0143]),
wherein the plurality of particles comprises rigid particles or hydrogel particles (Amini; [0159]).
Amini does not explicitly disclose the droplets are monodispersed droplets.
However, Steenblock teach the analogous art of a method for generating droplets (Steenblock; fig. 1, #102, [0072]), wherein the droplets are monodispersed droplets (Steenblock; [0133]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method for generating droplet of Amini with the method for generating monodispersed droplets, as taught by Steenblock, because Steenblock teach the method for generating monodispersed droplets creates a highly uniform size of droplets (Steenblock; [0133]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since Amini and Steenblock both teach microchannel flow focusing to generate an emulsion of droplets.
If it is deemed that modified Amini does not teach wherein the jet of the first fluid does not spontaneously break into droplets in the second fluid, Abate teach the analogous art of a method for generating monodispersed droplets (Abate disclose methods for generating monodispersed droplets having extremely uniform size; figs. 1-4, 6, 11-12, 14, [0124, 0394, 0403, 0405]), wherein a first jet of a first fluid does not spontaneously break into droplets in a second fluid (Abate teach a drop maker may operate close to the dripping-to-jetting transition such that, in the absence of a cell, 8 µm drops are formed and when a cell is present the disturbance created in the flow will trigger the breakup of the jet, forming drops 25 µm in diameter; figs. 1-4, 6, & 14, [0166]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method for generating monodispersed droplets of modified Amini with the method wherein the jet in the first fluid does not spontaneously break into droplets in the second fluid, as taught by Abate, because Abate teach the presence of the cell creates a disturbance in the flow that will trigger the breakup of the jet to form uniform droplets in diameter which can be sorted from non-spontaneously formed droplets having a smaller uniform diameter when a cell is absent; [0166]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since modified Amini and Abate both teach microfluidic devices for generating monodispersed droplets by jetting a first fluid into a second fluid.
Regarding claim 2, modified Amini teach the method of claim 1 above, wherein the plurality of particles is introduced into the jet of the first fluid in a disordered configuration (Amini; fig. 9, [0171]).
Regarding claim 3, modified Amini teach the method of claim 1 above, wherein the plurality of particles comprises rigid particles (Amini; [0159]).
Regarding claim 4, modified Amini teach the method of claim 1 above, wherein the plurality of particles is introduced into the jet of the first fluid in an ordered configuration (Amini; figs. 4 & 8, Steps 1 & 2, the microchannel device is configured to separate, order, and focus streams of barcoded beads to one or more focusing positions within a channel flow field. The bead triggers breakup of the jet to generate droplets containing one bead and one cell in Step 4; [0018, 0142-0143]).
Regarding claim 5, modified Amini teach the method of claim 4 above, wherein the plurality of particles is introduced into the jet of the first fluid in a packed configuration (Amini teach barcoded beads, cells, and reagents are merged into droplets; fig. 8, [0143, 0159, 0164]. The examiner notes that paragraph [0050] of applicants printed publication describes a packed configuration as “the particles may include reagents for biochemical functionalization of particles and high-throughput pairing of particles with analytes, e.g., reagents or cells. For example, cells may be paired with particles functionalized with barcodes and/or nucleic acid synthesis reagent”. Accordingly, Amini disclose a packed configuration).
Regarding claim 7, modified Amini teach the method of claim 4 above, wherein the plurality of particles is ordered via inertial ordering (Amini; figs. 4 & 8, [0006, 0018, 0142]).
Regarding claim 10, modified Amini teach the method of claim 1 above, wherein each droplet of the plurality of monodispersed droplets comprises one, and not more than one, particle (The modification of the method for generating droplet of Amini with the method for generating monodispersed droplets, as taught by Steenblock, has previously been discussed in claim 1 above. Amani teach one bead and one cell per droplet; fig. 8, [0143]).
Regarding claim 20, modified Amini teach the method of claim 1 above, wherein the first fluid or the third fluid comprises a polymerizable component (Amini; [0159, 0163]).
Regarding claim 23, modified Amini teach the method of claim 1 above, wherein the third fluid comprises one or more reagents (Amini; [0163-0164]).
Regarding claim 24, modified Amini teach the method of claim 1 above, comprising merging one or more droplets with the jet prior to break-up of the jet (Amini; fig. 8, [0143]).
Regarding claim 26, modified Amini teach the method claim 1 above, wherein the plurality of particles is encapsulated at a rate of 1Hz to 100kHz (Amini; [0174, 0177, 0180, 0183, 0186]).
Regarding claim 101, modified Amini teach the method of claim 3 above, wherein the rigid particles comprise glass, silica, metal, or a combination thereof (Amini disclose magnetic beads; [0159]).
Regarding claim 102, modified Amini teach the method of claim 1 above, wherein the plurality of particles comprises hydrogel particles (Amini disclose hydrogel beads; [0159]).
Regarding claim 103, modified Amini teach the method of claim 102 above, wherein the hydrogel particles comprise a hydrogel selected from the group consisting of agarose, alginate, a polyethylene glycol (PEG), a polyacrylamide (PAA), and a combination thereof (Amini; [0159]).
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Amini, in view of Steenblock, and further in view of Zhang et al. (US 2011/0223314; already of record – hereinafter “Zhang”).
Regarding claim 21, modified Amini teach the method of claim 20 above, comprising the polymerizable component.
Modified Amini does not teach exposing the monodispersed droplets to conditions sufficient to polymerize the polymerizable component.
However, Zhang teach the analogous art of a method for generating droplets (Zhang; fig. 3, [0031]) comprising a polymerizable component (Zhang; fig. 3, #75, “prepolymer-encased droplet), wherein the droplets are exposed to conditions sufficient to polymerize the polymerizable component (Zhang; fig. 3, #50, [0031]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method for generating monodispersed droplets of modified Amini to comprise a UV light source sufficient to polymerize the prepolymer-encasing, as taught by Zhang, because Zhang teaches the UV light sources causes polymerization of the prepolymer layer and encapsulation to form microcapsules 80 (Zhang; fig. 3, [0031]). One of ordinary skill in the art would have expected this modification could have been performed with a reasonable expectation of success since modified Amini and Zhang both teach methods for forming droplets comprising particles, wherein the droplets are formed by jetting a first fluid into a second fluid.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Amini, in view of Steenblock, and further in view of Abate (US 2017/0022538; already of record – hereinafter “Abate”).
Regarding claim 33, modified Amini teach the method of claim 1 above, wherein the plurality of particles is introduced into the jet of the first fluid in a disordered configuration, resulting in a polydispersed emulsion comprising a population of monodispersed-particle containing droplets (Amini; fig. 9, [0171]).
Modified Amini does not teach wherein the method comprises sorting the monodispersed-particle containing droplets to separate them from other droplets in the polydispersed emulsion.
However, Abate teach the analogous art of a method for generating monodispersed droplets (Abate disclose methods for generating monodispersed droplets having extremely uniform size; figs. 1-4, 6, 11-12, 14, [0124, 0394, 0403, 0405]), wherein the method comprises sorting the monodispersed-particle containing droplets to separate them from other droplets in the polydispersed emulsion (Abate disclose sorting droplets; [0163-0192]. The examiner notes that paragraph [0063, 0188] of applicant’s printed publication describes a disordered configuration as “resulting in a polydispersed emulsion including a population of monodispersed-particles containing droplets and a population of polydispersed droplets that do not contain particles … the method can include a step of sorting the monodispersed-particle containing droplets to separate them from other droplets in the polydispersed emulsion, e.g., based on a size difference of the monodispersed-particle containing droplets relative to non-particle containing droplets”. Accordingly, Abate disclose a disordered configuration comprising a population of monodispersed-particles containing droplets and a population of polydispersed droplets that do not contain particles).
Response to Arguments
Applicant’s arguments filed on 12/10/2025 have been fully considered.
Applicant argues on pages 6-13 that the prior art does not teach the amended claim limitation “wherein the jet of the first fluid does not spontaneously break into droplets in the second fluid”. Applicant cites various examples of Amini including figs. 10, 12A, 13A, and 15A, and argue that the jet of Amini does spontaneously break into droplets, even without an applied perturbation such as introduction of particles. The examiner respectfully disagrees. First, applicant’s arguments are towards embodiments not previously cited or referenced in the Non-Final Office Action mailed on 08/12/2025. The Office Action only refers to figs. 8 & 9 of Amini for teaching the claimed invention. Second, applicant’s argument are towards the amended limitations and do not apply to the current grounds of rejection. Third, the examiner has modified the rejection over Amini in view of Steenblock and contents Amini does teach the argued limitations. Specifically, Amini disclose the microfluidic device is designed to generate droplets each containing a single cell and a single bead. The microchannel device is configured to separate, order, and focus streams of barcoded beads to one or more focusing positions within a channel flow field (Step 1). The microchannel device is configured to separate, order, and focus streams of cells to one or more focusing positions within a channel flow field (Step 2). The microchannel device receives an oil as another input (Step 3), and combines the ordered barcoded bead, the ordered cell, and an oil to generate droplets within a-double-undispersed-Poisson statistics, where each droplet contains one bead and one cell; fig. 8, [0143]. Accordingly, Amini disclose the ordered particles in the first fluid stream prevent the first fluid from spontaneously breaking into droplets in the second fluid resulting in the generation of droplets each with one bead and one cell, as shown in Step 4 of fig. 8; [0142-0143]. Further, Amini disclose adjusting the flow rate of bead fluid so that every droplet encapsulated one bead, wherein the jet of the first fluid does not spontaneously break into droplets in the second fluid; fig. 9 and [0171]. Still further, if it is deemed that modified Amini does not teach wherein the jet of the first fluid does not spontaneously break into droplets in the second fluid, Abate teach the analogous art of a method for generating monodispersed droplets (Abate disclose methods for generating monodispersed droplets having extremely uniform size; figs. 1-4, 6, 11-12, 14, [0124, 0394, 0403, 0405]), wherein a first jet of a first fluid does not spontaneously break into droplets in a second fluid (Abate teach a drop maker may operate close to the dripping-to-jetting transition such that, in the absence of a cell, 8 µm drops are formed and when a cell is present the disturbance created in the flow will trigger the breakup of the jet, forming drops 25 µm in diameter. In other words, the presence of the cell creates a disturbance in the flow that will trigger the breakup of the jet to form uniform droplets in diameter which can be sorted from non-spontaneously formed droplets having a smaller uniform diameter when a cell is absent; figs. 1-4, 6, & 14, [0166]).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CURTIS A THOMPSON whose telephone number is (571)272-0648. The examiner can normally be reached on M-F: 7:00 a.m. - 5:00 p.m..
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/C.A.T./Examiner, Art Unit 1798
/BENJAMIN R WHATLEY/Primary Examiner, Art Unit 1798