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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 14 August 2026 has been entered.
Response to Arguments
Applicant’s arguments, see Remarks page 8, filed 29 July 2026, with respect to the rejections of claims 1 – 4, 8 – 11, 13, and 16 – 18 under 35 U.S.C. 103 have been fully considered and are persuasive in light of the amendments to the claims. Therefore, the rejection has been withdrawn. However, upon further consideration, a new grounds of rejection is made in view of Wu et al in view of Jung et al, and further in view of Kim et al.
Status of Claims
Applicant’s amendments to the claims filed 29 July 2026 have been entered. Applicant’s remarks filed 29 July 2026 are acknowledged.
Claims 1 and 10 are in status “Currently amended.” Claims 2 – 4, 8, 9, 11, 13 and 16 – 18 are in status “Original” or “Previously presented.” Claims 14 and 15 are withdrawn as non-elected subject matter. Claims 5 – 7 and 12 are canceled.
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 1 – 4, 8 – 11, 13, and 16 - 18 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al (US 20200376488 A1, cited on the PTO-892 form filed 16 June 2025) in view of Jung et al (US 20090215157 A1, cited on the PTO-892 form filed 21 October 2025) and further in view of Kim et al (US 20080135739 A1).
With regards to claim 1, Wu et al teaches;
The claimed “apparatus” has been read on the taught (Abstract, "Provided are microfluidic systems…");
The claimed "a first microfluidic channel fluidically coupled to a first reservoir containing a carrier fluid, the first microfluidic channel including a reaction region" has been read on the taught (Figure 1, pump 110, sorting unit 103; [0145], "…a system 100 as shown in FIG. 1 may comprise a microchip (i.e., microfluidic device) 105 with encapsulation unit 101…"; [0146], “…the terms “microfluidic device”, “microfluidic chip”, and “microchip” […] in general refers to a set of micro-channels etched or molded into a material."; [0145], "In the encapsulation unit 101, […] the carrier oil […] 107 may be injected into a second inlet with any types of pumps known to one of ordinary skill in the art…”; [0135], "…the process may comprise: providing in a microfluidic device a plurality of water-in-oil droplets […]; passing and detecting the droplets through a first point of laser-based optical detection along a channel of the microfluidic device to identify a first batch of target droplet…"; The pump and second inlet injecting carrier oil reads a fluidically coupled first reservoir containing a carrier fluid. A channel of a microfluidic device which passes droplets reads on a first channel. The first point of laser-based optical detection reads on a reaction region.);
The claimed "a fluid droplet generator including: a portion of the first microfluidic channel; and a second microfluidic channel that intersects the first microfluidic channel and is fluidically coupled to a second reservoir containing a reaction fluid" has been read on the taught ([0147], "It is expected that a person skilled in the arts can readily produce the droplets with a syringe- or pressure-pump, a microfluidic chip with a flow-focus or T-junction feature, and/or a biocompatible oil."; [0145], "In the encapsulation unit 101, one or more analytes 106 may be injected into a first inlet…"; A T-junction feature reads on the droplet generator including a portion of the first microfluidic channel and a second microfluidic channel that intersects the first microfluidic channel. The analytes in a first inlet read on a second reservoir containing a reaction fluid.);
The claimed "the reaction fluid including a plurality of cells and fluorescently-labeled capture reagents" has been read on the taught ([0145], "Cells and/or particles may co-encapsulated into droplets 108."; [0148], "It is understood that the cells can be labelled with a fluorescent dye…"; [0150], "It is further understood that particles may come as is, or pre-labelled with or functionalized for labeling with: (1) fluorophores […], (2) affinity reagents […] (3) an assay enzyme that may produce fluorescence or luminescence; (4) a chemical group; and/or (5) adaptor molecules…"); [0167], “These antibody producing cells can be encapsulated in droplets as described herein together with fluorescently-labelled antigens (i.e., “dyed antigen”) that can bind to antigen-specific antibodies (i.e., “antibody of interest”) that are secreted from an encapsulated B cell.”);
The claimed fluid droplet generator further including "a fluid ejector fluidically coupled to the first microfluidic channel and disposed downstream from the reaction region of the first microfluidic channel" has been read on the taught (Figure 1, dispensing unit 104; [0145], “… a system 100 as shown in FIG. 1 may comprise a […] downstream microfluidic tubing (capillary)-based dispensing unit 104."; [0032], “…the target droplet dispensing module may be configured to dispense the target droplets into one or more collection tubes or plates in a controlled manner.");
The claimed “an optics system coupled to the reaction region and configured to provide polarized excitation light toward the reaction region” has been read on the taught ([0020], “…the system may comprise an optical assembly configured to provide a short illumination...”; [0029], “…any of the systems described herein may comprise a laser or a laser-like source. The laser or laser-like source can be configured to illuminate the first […] point of detection… In some embodiments, the optical element of the beam splitter may comprise a birefringent polarizer such as a Wollaston prism…”; The optical assembly including a laser source with birefringent polarizer to illuminate the first point of detection reads on an apparatus which includes an optics system, which is capable of providing polarized excitation light towards the reaction region.);
The claimed “a light source configured to provide excitation light toward the reaction region” has been read on the taught ([0161], “…a single-color laser beam or multiple-color laser beams may be used as an excitation source for laser-induced fluorescence detection.”; [0046], “In some embodiments, the system may further comprise one or more lasers or laser-like light sources to generate illumination at the first point of detection.”);
The claimed “a set of polarizers configured to polarize the excitation light from the light source to a first polarization” has been read on the taught ([0047], “…the system may further comprise an optical element configured to provide dual focusing along the first fluidic channel at the first point of detection. The optical element may comprise […] a birefringent polarizer.”; [0211], “Suitable birefringent polarizers are represented by Nicol prisms, Glan-Thompson prisms, Glan-Foucault prisms, Glan-Taylor prisms. Rochon prims, Senarmont prisms, and Wollaston prisms are other examples of birefringent polarizers consisting of two triangular calcite prisms that are cemented together.”);
The claimed “a bandpass filter” and wherein the filter is “configured to pass fluorescence light emitted from the reaction region within a wavelength range” has been read on the taught ([0196], “The two excitation/detection paths may use different excitation wavelengths and emission filters.”; [0281], “The fluorescent signal from the beads was detected through a 535/50 nm band pass filter by using a PMT and was output as a voltage amplitude.”; The emission filter reads on a band pass filter. This teaching is supported by the example device including a band pass filter.);
The claimed optics system including “circuitry” has been read on the taught ([0195], “Hence, by introducing a beam splitter, a detector and a light source can be fitted to each arm, respectively.” The detector fitted to the illumination/detection arm reads on circuitry);
“Circuitry configured to measure fluorescence within the reaction region over a time period” has been read on the taught ([0167], “The fluorescent focus can be optically detected as an assay readout of a positive droplet (i.e., “target droplet”), which can be sorted and dispensed in a real-time or near real-time fashion.”; a real-time or near real-time fashion reads on detection over a time period. See also [0151], which teaches an incubation period.);
“Circuitry to configured detect a change in fluorescence with the reaction region” has been read on the taught ([0241], “…signals collected from a point of detection in any one of the disclosed systems may provide informative details for each target droplet, such as […] ratios of fluorescent signals…”; Ratios of fluorescence read on a change in fluorescence with the reaction region.);
“Circuitry configured to determine a binding of one or more capture reagents to the target molecule secreted in situ by one or more of the plurality of cells” has been read on the taught ([0167], “These antibody producing cells can be encapsulated in droplets as described herein together with fluorescently-labelled antigens (i.e., “dyed antigen”) that can bind to antigen-specific antibodies (i.e., “antibody of interest”) that are secreted from an encapsulated B cell.”).
However, Wu et al does not explicitly disclose wherein the circuitry is configured to measure fluorescence anisotropy based on the polarization of the fluorescence light emitted relative to the excitation light, wherein the bandpass filter forms part of a wall of the first microfluidic channel at the reaction region and configured to pass fluorescence light emitted from the reaction region within a wavelength range, wherein the set of polarizers comprise nanowires attached to a surface of the bandpass filter, the nanowires having a line width sized to a wavelength of the fluorescence light, the set of polarizers exposed to the first microfluidic channel within the reaction region.
In the analogous art of microfluidic devices including optics systems, Jung et al teaches;
Jung et al teaches a microfluidic system (abstract) including channels ([0141]), reaction regions ([0954]), and an optics system ([0192], [0198], [0496]).
The claimed “circuitry configured to measure fluorescence anisotropy based on the polarization of the fluorescence light emitted relative to the excitation light” has been read on the taught (Claim 93, “… wherein the circuitry for analyzing the one or more samples comprises: circuitry for analyzing the one or more samples with at least one technique that includes […] fluorescence anisotropy…”).
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 apparatus of Wu et al with the circuitry configured to measure fluorescence anisotropy as taught by Jung et al. 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 includes each element claimed, with the only difference being the lack of actual combination of the elements in a single prior art reference. One of ordinary skill in the art could have combined the elements of circuitry as taught by Wu et al with the element of circuitry configured to measure fluorescence anisotropy as taught by Jung et al according to known methods. In combination, each element merely performs the same function as it does separately, and one of ordinary skill in the art would have found the combination to yield the predictable result of an apparatus which can use an optics system to take anisotropy measurements.
However, Wu et al in view of Jung et al does not explicitly disclose wherein the bandpass filter forms part of a wall of the first microfluidic channel at the reaction region and configured to pass fluorescence light emitted from the reaction region within a wavelength range, wherein the set of polarizers comprise nanowires attached to a surface of the bandpass filter, the nanowires having a line width sized to a wavelength of the fluorescence light, the set of polarizers exposed to the first microfluidic channel within the reaction region.
In the analogous art of optical devices for fluorescent measurements, Kim et al teaches;
The claimed “wherein the set of polarizers comprise nanowires attached to a surface of the bandpass filter, the nanowires having a line width sized to a wavelength of the fluorescence light” has been read on the taught ([0048], “Nanowire arrays with interwire gaps having a width of 100 nm or less, such as 30 to 100 nm, for example 50-100 nm, produce a clear bandpass filter characteristic with bandwidth of ~λ/10, where λ is the center wavelength of passband, in the visible to near IR range.”; [0147], “Thus, the devices 1 may be used as a nano-optic filter with a narrow passband width or as a polarizer. The devices 1 may also be used for wavelength separation of incident radiation… the devices may be used […] in fluorescence sensing system.”).
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 fluorescence measuring apparatus of Wu et al in view of Jung et al with the bandpass filter and polarizer as taught by Kim et al. 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 includes each element claimed, with the only difference being the lack of actual combination of the elements in a single prior art reference. One of ordinary skill in the art could have combined the elements of circuitry and optics having a generic bandpass filter/polarizer as taught by Wu et al in view of Jung et al with the specific nanowire bandpass filter and polarizer as taught by Kim et al, according to known methods (such as the embodiments taught in Kim et al [0147] – [0193]. In combination, each element merely performs the same function as it does separately, and one of ordinary skill in the art would have found the combination to yield the predictable result of an apparatus which can direct and receive a specific range of polarized light to detect fluorescence measurements.
Wu et al in view of Jung et al and further in view of Kim et al does not explicitly disclose the bandpass filter forming part of a wall of the first microfluidic channel at the reaction region and wherein the set of polarizers are exposed to the first microfluidic channel within the reaction region According to MPEP 2144.04(V)(B), making parts integral may be prima facie obvious; please see In re Larson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965). In the case of the instant invention, forming the bandpass filter and polarizers as integral to the walls of the microfluidic results in a one-piece construction is a matter of obvious engineering choice, and does not reflect an insight contrary to the understanding or expectations of the art.
As such, 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 system including a microfluidic device and an optics system as taught by Wu et al in view of Jung et al in view of Kim et al with the integrated bandpass filter and set of polarizers, for the predictable benefit of creating a microfluidic device which is easily transportable and which does not require a bandpass or polarizer attached to the light source.
With regards to claim 2, the apparatus of claim 1 is obvious over Wu et al in view of Jung et al and further in view of Kim et al.
Wu et al additionally teaches;
The claimed “wherein the fluid ejector includes a nozzle and a fluidic actuator fluidically coupled to the nozzle, the fluidic actuator to actuate to cause flow of fluid” has been read on the taught ([0010], “…a target droplet dispensing module comprising a dispensing nozzle disposed downstream of the second point of detection…”; [0289], “The sorting actuator can be triggered by setting thresholds of the fluorescent signals. Then, the sorted droplets can be directed to the second point of detection… After passing the second point of detection threshold, the dispensing unit (x-y-z moving stage) will be triggered to dispense individual droplets into PCR tubes or strips.” The module including a nozzle reads on the nozzle. The sorting actuator reads on an actuator fluidically coupled to the nozzle.).
With regards to claim 3, the apparatus of claim 2 is obvious over Wu et al in view of Jung et al and further in view of Kim et al.
Wu et al additionally teaches;
The claimed “wherein the first microfluidic channel, the second microfluidic channel, and the fluid ejector are integrated on a microfluidic device, and the apparatus further includes a fluid dispensing device” has been read on the taught (Figure 1, system 100, microchip 105; [0145], “a system 100 as shown in FIG. 1 may comprise a microchip (i.e., microfluidic device) 105 with encapsulation unit 101, incubation unit 102, sorting unit 103, and a downstream microfluidic tubing (capillary)-based dispensing unit 104.”; Microchip 105 reads on a microfluidic device with integrated components. System 100 reads on a fluid dispensing device.);
The limitation “configured to house the microfluidic device” is functional language and has been given the appropriate patentable weight. Please see MPEP 2114(II), and Hewlett-Packard Co.v.Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990). As Wu et al teaches all of the structural limitations of the apparatus as defined in claim 3, this additional limitation does not define the instant application over the prior art.
The claimed wherein the apparatus further includes “a controller communicatively coupled to the fluid ejector configured to selectively actuate the fluidic actuator of the fluid ejector to cause flow of the carrier fluid coordinated with flow of the reaction fluid to generate fluid droplets of the reaction fluid” has been read on the taught (Figure 1, sorting controller 125; [0154], “The sorting controller 125 may then activate the sorting actuator 115 to redirect a moving target droplet 117 to a target collection channel in the microfluidic device. When the sorting actuator 115 is not triggered, the moving droplets in the channel may continue their motion and enter the waste channel 116.”).
With regards to claim 4, the apparatus of claim 3 is obvious over Wu et al in view of Jung et al and further in view of Kim et al.
Wu et al additionally teaches;
The claimed “the apparatus further including: a substrate, wherein the fluid ejector is to selectively eject the fluid droplets of the reaction fluid from the microfluidic device to a plurality of regions of the substrate” and “a stage coupled to the substrate, wherein the controller is communicatively coupled to the stage to instruct the stage to move the substrate relative to the fluid ejector, such that the fluid ejector is aligned with a select region of the plurality of regions of the substrate” have been read on the taught ([0032], “… the target droplet dispensing module may be configured to dispense the target droplets into one or more collection tubes or plates in a controlled manner. The one or more collection tubes or plates may comprise a 96-well plate, a 384-well plate, or a multi-well plate. In some embodiments, the dispensing module may comprise an x-y-z moving dispenser, a rotatory dispenser, or the combination thereof.”; [0158], “The dispensing Module 122 with nozzle 123 can comprise an x-y-z moving stage or a rotating moving stage configured to move nozzle 123 to dispensing collector 124 (e.g., to a specific well of a multi-well plate collector 124).”; A multi-well plate reads on a substrate with a plurality of regions. The dispensing module comprising an x-y-z moving dispenser reads on stage. The dispensing nozzle configured to move to a specific well of the multi-well plate collector reads on the stage coupled to the substrate.).
With regards to claim 8, the apparatus of claim 1 is obvious over Wu et al in view of Jung et al and further in view of Kim et al.
Wu et al additionally teaches;
The claimed “the apparatus further including a waste chamber fluidically coupled to the first microfluidic channel” has been read on the taught ([0010], “The system comprises a microfluidic device comprising a first channel connected to a second channel and a waste channel by a first sorting junction…”; A waste channel connected to the first channel reads on a waste chamber fluidically coupled to the first microfluidic channel.);
With regards to claim 9, the apparatus of claim 1 is obvious over Wu et al in view of Jung et al and further in view of Kim et al.
Wu et al additionally teaches;
The claimed “the target molecule is a protein selected from the group consisting of: an antibody, an enzyme, a cytokine, a hormone, a metabolic product, a metabolite, a synthetic precursor, and a toxin” has been read on the taught (Abstract, “The systems and methods described herein […] will make relevant microfluidic based tools available for a variety of applications in biotechnology including antibody discovery…”; Antibody discovery reads on a target molecule being an antibody);
The claimed “the fluorescently-labeled capture reagents is a molecule selected from the group consisting of: an antibody, an aptamer, and an antigen molecule specific to the target molecule” has been read on the taught ([0167], “These antibody producing cells can be encapsulated in droplets as described herein together with fluorescently-labelled antigens (i.e., “dyed antigen”) that can bind to antigen-specific antibodies (i.e., “antibody of interest”) that are secreted from an encapsulated B cell.”; the dyed antigen reads on a fluorescently-labeled capture reagent consisting of an antigen).
With regards to claim 10, Wu et al teaches;
The claimed “a first microfluidic channel fluidically coupled to a first reservoir containing a carrier fluid, the first microfluidic channel including a reaction region” has been read on the taught (Figure 1, pump 110, sorting unit 103, laser beam 114; [0145], "…a system 100 as shown in FIG. 1 may comprise a microchip (i.e., microfluidic device) 105 with encapsulation unit 101…"; [0146], “…the terms “microfluidic device”, “microfluidic chip”, and “microchip” […] in general refers to a set of micro-channels etched or molded into a material."; [0145], "In the encapsulation unit 101, […] the carrier oil […] 107 may be injected into a second inlet with any types of pumps known to one of ordinary skill in the art…”; [0135], "…the process may comprise: providing in a microfluidic device a plurality of water-in-oil droplets […]; passing and detecting the droplets through a first point of laser-based optical detection along a channel of the microfluidic device to identify a first batch of target droplet…"; The pump and second inlet injecting carrier oil reads a fluidically coupled first reservoir containing a carrier fluid. A channel of a microfluidic device which passes droplets reads on a first channel. The first point of laser-based optical detection reads on a reaction region);
The claimed “a second microfluidic channel that intersects the first microfluidic channel and is fluidically coupled to a second reservoir containing a reaction fluid” has been read on the taught ([0147], "It is expected that a person skilled in the arts can readily produce the droplets with a syringe- or pressure-pump, a microfluidic chip with a flow-focus or T-junction feature, and/or a biocompatible oil."; [0145], "In the encapsulation unit 101, one or more analytes 106 may be injected into a first inlet…"; A T-junction feature reads on a second microfluidic channel that intersects the first microfluidic channel. The analytes in a first inlet read on a second reservoir containing a reaction fluid. See also Figure 1, encapsulation unit 101.);
The claimed “the reaction fluid including a plurality of cells and fluorescently-labeled capture reagents to form reaction products with a target molecule secreted by the plurality of cells” has been read on the taught ([0145], "Cells and/or particles may co-encapsulated into droplets 108."; [0148], "It is understood that the cells can be labelled with a fluorescent dye…"; [0150], "It is further understood that particles may come as is, or pre-labelled with or functionalized for labeling with: (1) fluorophores […], (2) affinity reagents […] (3) an assay enzyme that may produce fluorescence or luminescence; (4) a chemical group; and/or (5) adaptor molecules…");
The claimed “wherein a fluid droplet generator is formed at the intersection of the first microfluidic channel and the second microfluidic channel” has been read on the taught ([0147], "It is expected that a person skilled in the arts can readily produce the droplets with a syringe- or pressure-pump, a microfluidic chip with a flow-focus or T-junction feature, and/or a biocompatible oil."; the T-junction feature which forms droplets reads on a droplet generator being formed at the intersection of the first and second microfluidic channel);
The claimed “a bandpass filter” has been read on the taught ([0196], “The two excitation/detection paths may use different excitation wavelengths and emission filters.”; [0281], “The fluorescent signal from the beads was detected through a 535/50 nm band pass filter by using a PMT and was output as a voltage amplitude.”; The emission filter reads on a band pass filter. This teaching is supported by the example device including a band pass filter.);
The claimed “a set of polarizers” has been read on the taught ([0030], “…the system may further comprise an optical element configured to provide dual focusing along the first channel at the first point of detection. The optical element may comprise an optical fiber splitter or a birefringent polarizer configured to […] direct the first and second beams to the first point of detection.”; [0195], “Since the arrangement of the first and second objectives can be symmetric, either objective lens can serve for illumination or detection. Hence, by introducing a beam splitter, a detector and a light source can be fitted to each arm, respectively.”);
The claimed “a fluid ejector fluidically coupled to and disposed within the first microfluidic channel and downstream from the reaction region and configured to eject droplets of the reaction fluid from the first microfluidic channel” has been read on the (Figure 1, dispensing unit 104; [0145], “… a system 100 as shown in FIG. 1 may comprise a […] downstream microfluidic tubing (capillary)-based dispensing unit 104."; [0032], “…the target droplet dispensing module may be configured to dispense the target droplets into one or more collection tubes or plates in a controlled manner.");
The claimed “circuitry coupled to the bandpass filter” has been read on the taught ([0154], “In some embodiments, detection signals may be sent to a data acquisition & processing unit 126 for signal processing.”);
“A controller to configured detect a change in fluorescence with the reaction region” has been read on the taught ([0241], “…signals collected from a point of detection in any one of the disclosed systems may provide informative details for each target droplet, such as […] ratios of fluorescent signals…”; Ratios of fluorescence read on a change in fluorescence with the reaction region.);
“A controller configured to determine a binding of one or more capture reagents to the target molecule secreted in situ by one or more of the plurality of cells” has been read on the taught ([0167], “These antibody producing cells can be encapsulated in droplets as described herein together with fluorescently-labelled antigens (i.e., “dyed antigen”) that can bind to antigen-specific antibodies (i.e., “antibody of interest”) that are secreted from an encapsulated B cell.”).
The claimed wherein the apparatus further includes “a controller communicatively coupled to the circuitry and the fluid ejector, the controller configured to cause flow of fluid, including the fluid droplets of the reaction fluid as carried by the carrier fluid, toward the reaction region of the first microfluidic channel” and “selectively eject the fluid droplets of the reaction fluid responsive to determining the binding of the one or more capture reagents to the target molecule secreted in situ by one or more of the plurality of cells” have been read on the taught (Figure 1, sorting controller 125; [0154], “The sorting controller 125 may then activate the sorting actuator 115 to redirect a moving target droplet 117 to a target collection channel in the microfluidic device. When the sorting actuator 115 is not triggered, the moving droplets in the channel may continue their motion and enter the waste channel 116.”; [0154], “Upon detecting a signal indicative of a positive droplet (i.e., “target droplet”), the acquisition and processing unit 126 may deliver a trigger signal to a sorting controller 125.”; [0010] of Wu et al makes clear that the system relates to the selective ejection of particles based on detection based on optical signals.);
However, Wu et al does not explicitly disclose wherein the circuitry is configured to provide a fluorescence anisotropy measurement based on the polarization of the fluorescence light emitted from the reaction region through the set of polarizers relative to excitation light passed through the reaction region from a light source, wherein the set of polarizers are attached to a surface of the bandpass filter and extending into the reaction region, wherein the set of polarizers comprise nanowire attached to the surface of the bandpass filter, the nanowires having a line width sized to a wavelength of the fluorescence light, the set of polarizers exposed to the first microfluidic channel within the reaction region.
In the analogous art of microfluidic devices including optics systems, Jung et al teaches;
Jung et al teaches a microfluidic system ([abstract]) including channels ([0141]), reaction regions ([0954]), and an optics system ([0192], [0198], [0496]). Jung et al additionally teaches the arrangement of the optical components for fluorescence anisotropy (see, i.e., [0198], [0246], [0252], [0298]);
The claimed “circuitry coupled to the bandpass filter and configured to provide a fluorescence anisotropy measurement of the reaction region over a time period based on the polarization of the fluorescence light emitted from the reaction region through the set of polarizers relative to excitation light passed through the reaction region from a light source” has been read on the taught (Claim 93, “… wherein the circuitry for analyzing the one or more samples comprises: circuitry for analyzing the one or more samples with at least one technique that includes […] fluorescence anisotropy…”).
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 apparatus of Wu et al with the circuitry configured to measure fluorescence anisotropy as taught by Jung et al. 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 includes each element claimed, with the only difference being the lack of actual combination of the elements in a single prior art reference. One of ordinary skill in the art could have combined the elements of circuitry as taught by Wu et al with the element of circuitry configured to measure fluorescence anisotropy as taught by Jung et al according to known methods. In combination, each element merely performs the same function as it does separately, and one of ordinary skill in the art would have found the combination to yield the predictable result of an apparatus which can use an optics system to take anisotropy measurements.
However, Wu et al in view of Jung et al does not explicitly disclose wherein the bandpass filter forms part of a wall of the first microfluidic channel at the reaction region, wherein the set of polarizers are attached to a surface of the bandpass filter and extending into the reaction region, wherein the set of polarizers comprise nanowire attached to the surface of the bandpass filter, the nanowires having a line width sized to a wavelength of the fluorescence light, the set of polarizers exposed to the first microfluidic channel within the reaction region.
In the analogous art of optical devices for fluorescent measurements, Kim et al teaches;
The claimed “the set of polarizers are attached to a surface of the bandpass filter and extending into the reaction region, wherein the set of polarizers comprise nanowire attached to the surface of the bandpass filter, the nanowires having a line width sized to a wavelength of the fluorescence light” has been read on the taught ([0048], “Nanowire arrays with interwire gaps having a width of 100 nm or less, such as 30 to 100 nm, for example 50-100 nm, produce a clear bandpass filter characteristic with bandwidth of ~λ/10, where λ is the center wavelength of passband, in the visible to near IR range.”; [0147], “Thus, the devices 1 may be used as a nano-optic filter with a narrow passband width or as a polarizer. The devices 1 may also be used for wavelength separation of incident radiation… the devices may be used […] in fluorescence sensing system.”).
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 fluorescence measuring apparatus of Wu et al in view of Jung et al with the bandpass filter and polarizer as taught by Kim et al. 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 includes each element claimed, with the only difference being the lack of actual combination of the elements in a single prior art reference. One of ordinary skill in the art could have combined the elements of circuitry and optics having a generic bandpass filter/polarizer as taught by Wu et al in view of Jung et al with the specific nanowire bandpass filter and polarizer as taught by Kim et al, according to known methods (such as the embodiments taught in Kim et al [0147] – [0193]. In combination, each element merely performs the same function as it does separately, and one of ordinary skill in the art would have found the combination to yield the predictable result of an apparatus which can direct and receive a specific range of polarized light to detect fluorescence measurements.
However, Wu et al in view of Jung et al and further in view of Kim et al does not explicitly disclose wherein the bandpass filter forms part of a wall of the first microfluidic channel at the reaction region and a set of polarizers attached to a surface of the bandpass filter and extending into the reaction region. According to MPEP 2144.04(V)(B), making parts integral may be prima facie obvious; please see In re Larson, 340 F.2d 965, 968, 144 USPQ 347, 349 (CCPA 1965). In the case of the instant invention, forming the bandpass filter and polarizers as integral to the walls of the microfluidic results in a one-piece construction is a matter of obvious engineering choice, and does not reflect an insight contrary to the understanding or expectations of the art.
As such, 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 system including a microfluidic device and an optics system as taught by Wu et al in view of Jung et al and further in view of Kim et al with the integrated bandpass filter and set of polarizers, for the predictable benefit of creating a microfluidic device which is easily transportable and which does not require a bandpass or polarizer attached to the light source.
With regards to claim 11, the system of claim 10 is obvious over Wu et al in view of Jung et al and further in view of Kim et al.
Wu et al further teaches;
The claimed “wherein the first microfluidic channel is configured to pass the excitation light through and toward the reaction region from the light source” has been read on the taught ([0047], “…the system may further comprise an optical element configured to provide dual focusing along the first fluidic channel at the first point of detection.);
The claimed “the bandpass filter is configured to block the excitation light and pass the fluorescence light emitted from the reaction region” has been read on the taught ([0196], “The two excitation/detection paths may use different excitation wavelengths and emission filters.”);
Neither Wu et al nor Kim et al explicitly disclose wherein the set of polarizers are configured to selectively select the polarization of the fluorescence light emitted from the reaction region as illuminated by the excitation light to a first polarization and to a second polarization.
Jung et al additionally teaches;
The claimed “wherein the set of polarizers are configured to selectively select the polarization of the fluorescence light emitted from the reaction region as illuminated by the excitation light to a first polarization and to a second polarization” has been read on the taught (Claim 93, “… wherein the circuitry for analyzing the one or more samples comprises: circuitry for analyzing the one or more samples with at least one technique that includes […] fluorescence anisotropy…”; one of ordinary skill in the art will recognize that fluorescence anisotropy requires polarization. See also [0298] which describes the arrangement of optical elements for such measurement.).
According to MPEP 2143(I)(D), applying a known technique to a known device ready for improvement to yield predictable results may be prima facie obvious. In the case of the instant invention, the prior art of Wu et al contains a “base” device upon which the claimed invention can be seen as an improvement. The prior art of Jung et al contains a known technique of detecting particles via fluorescence anisotropy measurements that is applicable to the base device. One of ordinary skill in the art would recognize that applying the known technique would yield the predictable result of an improved system which can sort molecules using fluorescence anisotropy measurements.
With regards to claim 13, the system of claim 10 is obvious over Wu et al in view of Jung et al and further in view of Kim et al.
Wu et al additionally teaches;
The claimed “wherein the circuitry includes a set of diodes coupled to the bandpass filter and signal processing circuitry coupled to the set of diodes” has been read on the taught ([0014], “…the optical detector may comprise […] an avalanche photodiode detector (APD).”; The photodiode detector reads on a set of diodes; [0306], “Optical filters can be added to the detection path to select for specific wavelength bands.”; An optical filter added to the detection path reads on the diodes coupled to the band pass filter. See also [0281] which recites a band pass filter specifically; [0232], “The detection signals are sent to the data acquisition and processing unit 255 for data analysis.”; The data acquisition and processing unit receiving the detection signals from the detector reads on the signal processing circuitry coupled to the diodes.).
With regards to claim 16, the apparatus of claim 1 is obvious over Wu et al in view of Jung et al and further in view of Kim et al.
Wu et al additionally teaches;
The claimed “wherein the circuitry is further configured to: activate the fluid ejector responsive to determining the binding based on the detected change in fluorescent anisotropy within the reaction region” has been read on the taught ([0021], “A processor may be configured to synchronize the sorting and/or dispensing mechanism with one or more of the first and the second detectors or sensors based on one or more of the first and the second signals/images.”).
With regards to claim 17, the apparatus of claim 1 is obvious over Wu et al in view of Jung et al and further in view of Kim et al.
Wu et al does not explicitly disclose wherein the circuitry is configured to measure the fluorescence anisotropy within the reaction region over the time period by: measuring the fluorescence anisotropy within the reaction region over the time period by receiving, via the bandpass filter and the set of polarizers, first and second fluorescence intensity components having polarization states respectively parallel and perpendicular to the first polarization of the excitation light; and computing, from the first and second fluorescence intensity components, a fluorescence anisotropy value at each of a plurality of times within the time period.
Jung et al further teaches;
The claimed “wherein the circuitry is configured to measure the fluorescence anisotropy within the reaction region over the time period by: measuring the fluorescence anisotropy within the reaction region over the time period by receiving, via the bandpass filter and the set of polarizers, first and second fluorescence intensity components having polarization states respectively parallel and perpendicular to the first polarization of the excitation light; and computing, from the first and second fluorescence intensity components, a fluorescence anisotropy value at each of a plurality of times within the time period” has been read on the taught (Please see [0198], which describes the calculation method for fluorescence anisotropy.).
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 apparatus of Wu et al with the circuitry configured to measure fluorescence anisotropy as taught by Jung et al. 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 includes each element claimed, with the only difference being the lack of actual combination of the elements in a single prior art reference. One of ordinary skill in the art could have combined the elements of circuitry as taught by Wu et al with the element of circuitry configured to measure fluorescence anisotropy as taught by Jung et al according to known methods. In combination, each element merely performs the same function as it does separately, and one of ordinary skill in the art would have found the combination to yield the predictable result of an apparatus which can use an optics system to take anisotropy measurements.
With regards to claim 18, the apparatus of claim 1 is obvious over Wu et al in view of Jung et al and further in view of Kim et al.
Wu et al further teaches;
Circuitry configured to distinguish between successive testing values, as read on the taught ([0267], “The detection signals from the second point of detection will also be sent to the data acquisition & processing for data analysis where a decision may be made on dispensing of target droplets based on analyzing all data received from both first and second points of detection, in comparison with the threshold values set by the operator per assay application.”).
Wu et al does not explicitly disclose wherein the circuitry is configured to detect the change in fluorescent anisotropy within the reaction region by: detecting a difference between successive fluorescence anisotropy values computed from the first and second fluorescence intensity components.
Jung et al further teaches;
The claimed “wherein the circuitry is configured to detect the change in fluorescent anisotropy within the reaction region by: detecting a difference between successive fluorescence anisotropy values computed from the first and second fluorescence intensity components” has been read on the taught (Please see [0198], which describes the calculation method for fluorescence anisotropy, including first and second intensity components.).
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 apparatus of Wu et al with the circuitry configured to measure fluorescence anisotropy as taught by Jung et al. 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 includes each element claimed, with the only difference being the lack of actual combination of the elements in a single prior art reference. One of ordinary skill in the art could have combined the elements of circuitry as taught by Wu et al with the element of circuitry configured to measure fluorescence anisotropy as taught by Jung et al according to known methods. In combination, each element merely performs the same function as it does separately, and one of ordinary skill in the art would have found the combination to yield the predictable result of an apparatus which can use an optics system to take anisotropy measurements.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Shkolnikov et al (US 20260132445 A1, effectively filed 28 September 2026), teaches the use of a nanowire bandpass filter in a fluidic device.
Holmes et al (WO 2013052318 A1) teaches a variety of analysis techniques including anisotropic measurements.
Chen et al (US 20160230210 A1) teaches bandpass filters joined with components of a fluidic system.
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/ALISON CLAIRE GERHARD/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797
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