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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-6 and 8-9) in the reply filed on 17 April 2026 is acknowledged.
Claims 10-20 (Group II) are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 17 April 2026.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: Reference number 211 in Figure 2. Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) 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 Objections
Claim 1 is objected to because of the following informalities:
Line 15 of claim 1 recites “perform image analysis to detect trap locations and calculate droplet coordinates.” In earlier parts of the claims the traps and droplets are referred to as “a plurality of traps/droplets.” In order to maintain claim language consistency, Examiner recommends amending claim to recite, “perform image analysis to detect locations of the plurality of traps and calculate coordinates of the plurality of droplets” or an equivalent thereof.
Line 20 of claim 1 recites “triggering the illumination source…” Examiner recommends amending the claim to recite “trigger the illumination source…” in order to maintain consistency in the verb tense of the claim.
Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “a controller for controlling the microfluidic system” in claim 1.
Based on the specification of the instant application, “a controller” will be interpreted to be a computer system that is coupled to and controls the operation systems (par. 0074) for conducting a method (Fig. 8; par. 0075-0076), including but not limited to parts commonly associated with a computer systems such as a monitor, a computer/processor, user output and input devices, memory, and communication interfaces (Fig. 11; par. 0090-0092, 0101).
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 1-6 and 8-9 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 1 recites the limitation “a selected droplet located in a trap…” in line 8 of the claim. It is unclear if this is the same trap as the “respective ones of the plurality of traps…” in lines 4-5 of the same claim. Examiner recommends amending the claim to recite “a selected droplet located in the respective trap…” or an equivalent thereof to make it clear it is one of the traps of the plurality of traps.
Claim 1 recites the limitation “generate a path for the movement…” in line 16 of the claim. "A path" previously recited in line 12 of the same claim. It is unclear if this is the same path or a different path the motorized stage follows. Examiner believes these to be the same path and will be examined as such. Examiner recommends amending the claim to recite "the path" or an equivalent thereof.
Claims 2-6 and 8-9 are rejected based on their dependence to claim 1.
Claim Rejections - 35 USC § 103
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 1-4 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng, et. al. ("Photo-responsive fluorosurfactant enabled by plasmonic nanoparticles for light-driven droplet manipulation;" as cited in IDS and references made with respect to provided copy dated 9 April 2024) in view of Weitz, et. al. (US 20190118182 A1) and Wheeler, et. al. (US 20200016594 A1).
Regarding claim 1, Cheng teaches a photo-responsive surfactant to stabilize droplets for analysis in droplet microfluidics (Abstract). Cheng teaches a microfluidic-based droplet generator that is paired with an optical system (Fig. 3; pg. 21921-21922, section "Fabrication of the Microfluidic Droplet Generator"). Cheng teaches the microfluidic droplet generator comprises a flow-focusing channel on which water-in-oil (w/o) droplets are formed (Fig. 1c; pg. 21922, section "Generation and Manipulation of f-Au@SiO2-Stabilized Droplets," par. 01). Cheng teaches the microfluidic droplet generator creates droplets are stabilized by fluorinated gold−silica core−shell nanoparticles (NPs) (f-Au@SiO2) at an interface between an aqueous phase and fluorocarbon oil phase (pg. 21917, col. 2, section "Stabilization of Water-in-Oil Droplets by f-Au@SiO2") (each droplet stabilized by a photo-responsive fluorosurfactant based on plasmonic nanoparticles (NPs)).
Cheng teaches once droplets are formed by the droplet generator, droplets (a corresponding plurality of droplets) are inserted into a PDMS chamber with micrometer dimensions, with each droplet isolated from one another by HFE-7500 within the chamber (pg. 21922, section "Generation and Manipulation of f-Au@SiO2-Stabilized Droplets: Photothermal Response of Individual Droplets") (a microfluidic system, comprising: a microfluidic device, including: a flow channel).
Cheng teaches the optical setup comprises an inverted microscope (Tx2R, Nikon) that further comprises a sample stage (Fig. 3; pg. 21922, section "Generation and Manipulation of f-Au@SiO2-Stabilized Droplets: Optical Setup"). Cheng teaches the PDMS chamber is mounted to the sample stage of the optical setup (Fig. 3; pg. 21922, section "Generation and Manipulation of f-Au@SiO2-Stabilized Droplets: Photothermal Response of Individual Droplets") (a… stage coupled to the microfluidic device).
The optical setup further comprises a laser as the excitation source to create the photothermal effect that moved the isolated droplets (Fig. 3; pg. 21922, section "Generation and Manipulation of f-Au@SiO2-Stabilized Droplets: Optical Setup & Photothermal Response of Individual Droplets") (an illumination source configured to deliver illumination to the photo-responsive fluorosurfactant on a selected droplet). Cheng teaches the photothermal response of the f-Au@SiO2 on the w/o droplets by the laser generates a bubble that guides the droplets in a designated direction (Fig. 4; pg. 21920, col. 1, lines 20-22), the bubble generated due to heating from the photothermal response (pg. 21918, col. 1, section "Photothermal Response of w/o Droplets Stabilized by f-Au@SiO2", par. 01 of section) (to generate sufficient heat to cause bubble formation… to release the droplet) (the illumination source to release the selected droplets via bubble formation).
Cheng teaches the optical setup further comprises a high-speed camera to capture images of the bubble formation at the droplet (Fig. 3; pg. pg. 21918, col. 1, section "Photothermal Response of w/o Droplets Stabilized by f-Au@SiO2", par. 01 of section) (a camera positioned to capture images of the plurality of droplets).
Cheng is silent to the microfluidic device including a plurality of traps and the corresponding plurality of droplets located in respective ones of the plurality of traps and therefore all associated events that occur in the trap (bubble formation, droplet release, image capture, etc.).
Cheng is also silent to a controller for controlling the microfluidic system, the controller being configured to: control the camera to capture images of the trapped droplets; perform image analysis to detect trap locations and calculate droplet coordinates; generate a path for the movement of the motorized stage based on those coordinates; determine droplet properties to select droplets for release; generate a release pattern of the droplets for release; and triggering the illumination source to release the selected droplets via bubble formation.
Weitz teaches a microfluidic device to contain droplets within chambers wherein those droplets can be analyzed an imaged (Abstract). Weitz teaches a microfluidic device comprises a first 11 and second 12 location separated by flow path 22 and flow path 21 wherein flow path 21 comprises a chamber 30 (Fig. 1N) wherein the flow of and path droplets take is based on flow/hydrodynamic resistance (par. 0038). Weitz teaches the microfluidic device can comprise a sequential flow path with a series of collections chambers 51, 52, 53, 54, etc. (Fig. 4A; par. 0065, 70) (a microfluidic device, including; a flow channel with a plurality of traps). Weitz teaches collection chambers are sized and shaped based on what is collected and how many of said object is collected (par. 0043); therefore, each chamber can be configured to a single droplet (a corresponding plurality of droplets located in respective ones of the plurality of traps). Weitz teaches the physical isolation of microfluidic entities (droplets) allow for improved analysis of the isolated entities (par. 0003-0005).
Weitz teaches once droplets are trapped within a collection chamber, droplets can be analyzed and imaged within the collection chamber (par. 0057) (a camera positioned to capture images of the plurality of droplets in the plurality of traps). Weitz teaches droplets can be released from the chambers through a plurality of methods, such as a patterned released based on a pre-selected feature (par. 0058). Weitz teaches this preselected feature can be determined from an automated system comprising a camera connected to a computer, with one such release mechanism being formation of a bubble from a laser to release said droplet from a collection chamber (par. 0061) (a controller for controlling the microfluidic system, the controller being configured to:) with a program that selects which collection chamber to release based on a set criteria (par. 0058) (control the camera to capture images of the trapped droplets) (determine droplet properties to select droplets for release) (generate a release pattern of the droplets for release) (triggering the illumination source to release the selected droplets via bubble formation).
While it is not explicitly stated, the embodiments of the device of Weitz, specifically that a computer and associated program and be used to control the release of a droplet from the collection chamber (par. 0058) and that one such release method involves positioning a laser to produce a bubble to release specific droplet within a specific collection chamber (par. 0061), one of ordinary skill in the art can logically conclude that one such feature of the computer program for releasing captured droplets (a controller for controlling the microfluidic system, the controller being configured to) is fully capable to perform image analysis to detect trap locations and calculate droplet coordinates in order to correctly position the laser for droplet release.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to substitute the phase/solution-based isolation of droplets in the chamber as taught by Cheng to instead use physically isolated chamber as taught by Cheng because the physical isolation allows for improved analysis of the droplets of interest without disturbing surround droplets with predictable results. The claimed limitations are obvious because the simple substitution of one known element (phase-based droplet isolation, Cheng) for another (physical traps/chambers, Weitz) is likely to be obvious when predictable results (isolation of droplets from one another) are achieved. MPEP 2143(I)(B).
Further, it would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to combine the optical and microfluidic system of Cheng to further include a computer and computer-based programs to control processing features surrounding the imaging and releasing of collected droplets because it allows for automation of the system (Weitz, par. 0058) and automation reduces the natural variations caused by human operators along with other predictable results. The claimed limitations are obvious because the combination of the microfluidic and optical system of Cheng with the computer and computer programs of Weitz yields the predictable result of automation of the system where processing steps are controlled by computer programs. MPEP2143(I)(A).
Modified Cheng is still silent to a controller for controlling the microfluidic system, the controller being configured to: generate a path for the movement of the motorized stage based on those coordinates.
Wheeler teaches a microfluidic system that pairs a microfluidic device on a stage with an imaging system and a control system for controlling the microfluidic system as a whole (Abstract). Wheeler teaches a microfluidic device 40 with an internal space between a top and bottom plate (a flow path) wherein a droplet can be moved to a virtual microwell (par. 0129). Wheeler teaches the microfluidic device 40 is placed on motorized stage 32 that is part of the imaging system 30 for moving the microfluidic device 40 (Fig. 1; par. 0122) (a motorized stage coupled to the microfluidic device for movement of the microfluidic device along a path). Wheeler teaches a control system 3, comprising a computer, control board, and program/system which controls the motorized stage 32 to manage droplet movement on the microfluidic device 40 (par. 0125-0126). Wheeler teaches the imaging system illuminates a first site, moving the stage to illuminate a second site, wherein the movement pattern of the stage is determined by the control system (par. 0015-0021). Further, the control system can determine what order to lyse cells within the microfluidic device based on their location within the microfluidic device based on shortest travel distance (par. 0022-0025) (a controller for controlling the microfluidic system, the controller being configured to: generate a path for the movement of the motorized stage based on those coordinates). Wheeler teaches using the control system to control stage movement allows for the shortest path to be taken by the device and reducing overall performance time (par. 0015-0025).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the stage and programming of modified Cheng to be a motorized stage to move the attached microfluidic device based on a computer program as taught by Wheeler because doing so allows for specific targets to be located and targeted in a way that minimized performance time by taking the shortest path possible (Wheeler, par. 0015-0025) with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 2, modified Cheng teaches the f-AU@SiO2 NPs are used to stabilize droplets that are dispersed in fluorocarbon oil (Cheng, pg. 21915, col. 2, lines 15-21) (wherein each of the droplets is a water-in- fluorocarbon oil droplet).
Regarding claim 3, modified Cheng teaches the f-AU@SiO2 NPs are used to stabilize droplets that are dispersed in fluorocarbon oil (Cheng, pg. 21915, col. 2, lines 15-21) (wherein the photo-responsive fluorosurfactant comprises fluorinated gold-silica core-shell NPs (f-Au@SiO2)).
Regarding claim 4, modified Cheng teaches the illumination source is a 532-nm laser (Fig. 3; pg. 21918, col. 2, lines 16-19). Cheng teaches this wavelength and laser source optimize the photothermal properties of the f-AU@SiO2 NPs (Cheng, pg. 21917-21918, section "Theoretical Model for Plasmonic Photothermal Response of Single f-Au@SiO2") (wherein the illumination source comprises a 520-540 nm laser illumination).
Regarding claim 8, modified Cheng in view of Weitz teaches wherein the flow of and path droplets take is based on flow/hydrodynamic resistance and the chamber is filled by said droplet following the principles of hydrodynamic resistance (Weitz, par. 0038) (wherein each of the plurality of traps is a hydrodynamic trap).
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng, et. al. ("Photo-responsive fluorosurfactant enabled by plasmonic nanoparticles for light-driven droplet manipulation;" as cited in IDS and references made with respect to provided copy dated 9 April 2024), Weitz, et. al. (US 20190118182 A1), and Wheeler, et. al. (US 20200016594 A1) as applied to claim 1 above, and further in view of Dimov, et. al. (US 20180353960 A1).
Regarding claim 5, modified Cheng teaches the f-AU@SiO2 NPs can further absorb fluorescent molecules to create images of fluorescently labeled droplets, wherein an excitation source is used to generate a fluorescent response on the droplet (Cheng, pg. 21922, section "Confocal Fluorescence Microscopy") (a second illumination source for exciting… fluorescence from the droplet).
Modified Cheng is silent to the second illumination source being a part of the larger optical/microfluidic system and that the fluorescence is specifically laser-induced fluorescence.
Dimov teaches sorting particles within a microchannel through an optical apparatus for laser scanning (Abstract). Dimov teaches a cassette 100 that holds a substrate 130 with microchannels (Fig. 3; par. 0137). The cassette 100 is loaded onto the optical device 1100 (Fig. 11) wherein the optical device 1100 comprises a first 1110 and second 1112 illumination source (Fig. 11, par. 0185). Dimov teaches each of the two light sources serve two purposes, one to excite the target particle and one to extract the target particle, and it is these two different functions that lead to particle sorting (par. 0045-0046). Dimov teaches the excitation beam is to generate a fluorescent response of target particles and the extraction bean is used to move/remove the targeted particles (par. 0046). Dimov teaches wherein the excitation source is a laser (par. 0053) (further comprising a second illumination source for exciting laser-induced fluorescence (LIF) from the droplet). Dimov teaches the embodiment with two or more illumination sources, one for excitation one for extraction, on the same device allows for the system to operate by first identifying the target particles by excitation and quickly follow target particle removal by extraction quickly speeding up overall operation time (par. 0045).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the fluorescent light source and microfluidic optical system of modified Cheng to include the second illumination source for exciting laser-induced fluorescence (LIF) from the droplet to be a part of the same optical system as taught by Dimov because it allows for faster instrument response and reduced operation time (Dimov, par. 0045) with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 6, Modified Cheng in view of Dimov teaches a second illumination source as applied to claim 5.
Modified Cheng is silent to wherein the second illumination source is configured to generate illumination having a wavelength of 480-500 nm.
Dimov teaches wherein the excitation wavelength of the light source is a result-effective variable. Specifically, Dimov teaches the emitted wavelength for fluorescence excitation is dependent on the fluorophore used (par. 0185). Since this particular parameter is recognized as a result-effective variable (i.e. a variable which achieves a recognized result), the determination of the optimum or workable ranges of said variable can be characterized as routine experimentation. See MPEP 2144.05 (II)(A). Therefore, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention for second illumination source that is used to generate fluorescence, to have a wavelength of 480-500 nm based on the fluorophore used.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Cheng, et. al. ("Photo-responsive fluorosurfactant enabled by plasmonic nanoparticles for light-driven droplet manipulation;" as cited in IDS and references made with respect to provided copy dated 9 April 2024), Weitz, et. al. (US 20190118182 A1), and Wheeler, et. al. (US 20200016594 A1) as applied to claim 1 above, and further in view of Baroud, et. al. (US 20200038867 A1).
Regarding claim 9, modified Cheng teaches a plurality of traps as outlined above in Claim 1.
Modified Cheng is silent to wherein each of the plurality of traps is a floating trap.
Baroud teaches a microfluidic system for handling a plurality of droplets in a plurality of trapping zones (Abstract). Baroud teaches the microfluidic system comprises a channel 9 between an upper 7 and lower 8 wall wherein the channel 9 (flow path) allows for the circulation of droplets and further comprises at least one trap 12 (par. 0265) though ideally comprises a plurality of traps within a trapping zone (par. 0122). Baroud teaches the traps can take on a wide variety of forms/geometries, including geometries that include cavities in upper or lower walls (Fig. 48) (wherein each of the plurality of traps is a floating trap). Wheeler teaches the shape of the trap/trapping zone influences the trapping force on the droplet (par. 0027) meaning trap geometry directly influenced droplet movement and isolation within the flow path.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to substitute the hydrodynamic traps of modified Cheng (in view of Weitz, see claim 8) to instead be a floating trap as taught by Baroud because various geometries can be used to impart a variety of trapping forces to selectively trap droplets (Baroud, par. 0027) yielding predictable results. The claimed limitations are obvious because the simple substitution of one known element (hydrodynamic traps, modified Cheng in view of Weitz) for another (floating traps, Baroud) is likely to be obvious when predictable results (droplet trapping) are achieved. MPEP 2143(I)(B).
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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/M.T.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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