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 .
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because of the inclusion of legal phraseology such as “comprising”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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.
Claim 91 is 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.
In claim 91, the recitation of the “second polarization angle” and the “third polarization angle” is indefinite since claim 91 depends from claim 88, which does not positively recite that the energy beam has a first polarization angle. In order for the second and third polarization angles recited in claim 91 to make proper sense, claim 91 should depend from claim 90 since claim 90 positively recites that the energy beam may have a first polarization angle.
Inventorship
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.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 83-102 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Wu et al (US 2020/0376488, submitted in the IDS filed on August 29, 2024).
With regards to claims 83-84, Wu et al teach of a system for the determination of low abundance events. The system comprises a microfluidic device 105 comprising a first channel (see the horizontal channel in the microfluidic chip 105 depicted in Figure 1 of Wu et al that runs between pumps 1 and 2 to a waste outlet 116 and a target droplet outlet 117), wherein the first channel comprises a plurality of water-in-oil droplets and a droplet of the plurality of droplets comprises one or more objects therein (see paragraphs 0009-0010 and 0077 in Wu et al where it states that the system and method is for detecting droplets in bioassays by providing a plurality of water-in-oil droplets, wherein each droplet of the plurality of droplets comprises at least one cell, at least one particle, or both), a first optical detector corresponding to a first point of detection disposed along the first channel (see the laser beam 114 and “first point of detection: positioned along the horizontal channel in the microfluidic chip 105 depicted in Figure 1 of Wu et al), and a first optical element configured to provide dual focusing along the first channel at the first point of detection, wherein the dual focusing is facilitated by a first beam at a first focus and a second beam at a second focus, wherein the first focus and the second focus are on axially separate focal volumes (claim 83) and on two different focal planes (claim 84). See Figures 18A-18B and 20A-20B in Wu et al which depict an optical element that provides initial unpolarized light or light polarized at 45o, and this initial light is split into a first beam and a second beam by a Wollaston prism, wherein the first beam is focused at a focus 1 along the microfluidic channel and the second beam is focused at a focus 2 along the microfluidic channel, wherein the focus 1 and focus 2 are on axially separate focal volumes and two different focal planes of the channel. Also, see paragraphs 0030, 0047, 0062, 0064, 0073, 0211, 0279 and 0282 in Wu et al where dual focusing along the horizonal channel in the microfluidic chip 105 from a first optical element/light source at a “first point of detection” is described.
With regards to claims 85-86, Wu et al teach that an object of the one or more objects in the plurality of droplets gets excited by the first beam as it passes through the first beam and emits a first signal detectable by the optical detector, and further gets excited by the second beam as it passes through the second beam and emits a second signal detectable by the optical detector. See Figure 18B in Wu et al which depicts a droplet containing one or more objects flowing past the focus 1 and the focus 2 produced by a first beam and a second beam of light as part of the dual focusing system taught by Wu et al. Also, see paragraphs 0030, 0047, 0062, 0064, 0073, 0211, 0279 and 0282 in Wu et al where dual focusing along the horizonal channel in the microfluidic chip 105 from a first optical element/light source at a “first point of detection” is described. Also, see paragraph 0133 in Wu et al where it describes particles in the droplets as being provided with fluorescent tags for optical detection at both focus 1 and focus 2 provided by the dual focus system.
With regards to claim 87, Wu et al teach that detecting both the first and second signals from the object in a droplet increases the probability that at least one signal among the first and second signals has an optimal signal-to-noise ratio. See paragraph 0279 in Wu et al where it states “Each droplet can travel through two foci that are closely positioned one after another along the droplet flow direction, thereby improving the probability that at least one focus can yield optical signals representing intra-droplet objects with improved signal-versus-noise profile”.
With regards to claims 88-90 and 94, Wu et al teach that the first optical element comprises a laser that splits an energy beam into the first and second beams, and the first optical element comprises a beam splitter, a double refractive optical element, or a birefringent polarizer. See Figure 18A and paragraph 0211 in Wu et al where it states “a laser modulator comprising an optical device with a birefringent element can be used to efficiently provide a line-shaped laser illumination through splitting the laser light into two separate laser beams, thereby leading to dual-focusing. Such a birefringent element (i.e. birefringent polarizer) can split unpolarized light or light polarized at 45 degree angle…”.
With regards to claim 91, Wu et al teach that the first beam of light has a second polarization angle, and the second beam has a third polarization angle different from the second polarization angle. See Figure 18A in Wu et al which depicts a laser producing unpolarized light or light polarized at 45 degree angle, a first beam of light having a polarization angle of 0o, and a second beam of light having a polarization angle of 90o.
With regards to claim 92, Wu et al teach that the system further comprises an objective, wherein the first and second beams of light pass through the objective and illuminate an excitation plane on the channel. See Figure 18 A in Wu et al which depicts an objective that each of the first and second beams of light pass through before illuminating a detection plane of the microfluidic channel.
With regards to claim 93, Wu et al teach that the first beam is located at a distance from the second beam on the channel, wherein the distance is tunable via adjusting the distance between the first optical element and the objective, via adjusting a splitting angle or both. See paragraph 0211 in Wu et al where it states “The distance between the two foci can be tuned by adjusting the distance between the objective and the optical device”.
With regards to claims 95-97, Wu et al teach that an object in a first droplet gets excited by the first beam as it passes through the first beam and emits a first signal detectable by the optical detector, a second droplet gets excited by the second beam as it passes through the second beam and emits a second signal detectable by the optical detector, wherein the first and second droplets are flowing in the same first horizontal channel in the microfluidic chip 105. See Figure 18B in Wu et al which depicts a droplet containing one or more objects flowing past the focus 1 and the focus 2 produced by a first beam and a second beam of light as part of the dual focusing system taught by Wu et al. Also, see paragraphs 0030, 0047, 0062, 0064, 0073, 0211, 0279 and 0282 in Wu et al where dual focusing along the horizonal channel in the microfluidic chip 105 from a first optical element/light source at a “first point of detection” is described. Also, see paragraph 0133 in Wu et al where it describes particles in the droplets as being provided with fluorescent tags for optical detection at both focus 1 and focus 2 provided by the dual focus system.
With regards to claims 98-99, Wu et also teach that the microfluidic system may comprise a second channel, and the optical detector corresponds to a first point of detection disposed along the first channel and the second channel, wherein a first droplet flows in the first channel and a second droplet flows in the second channel, and detecting a first signal from the first channel and a second signal from the second channel increases a throughput of the system. See paragraph 0304 in Wu et al where it states “To utilize the full field of view to increase sample throughput, the sample can be split up within the microfluidic chip into multiple channels located next to each other”.
With regards to claim 100, Wu et al teach that the system further comprises a second detector corresponding to a second point of detection. See the “second point of detection” in the dispensing unit 104 depicted in Figure 1 of Wu et al where a second optical detector is located.
With regards to claims 101-102, Wu et al teach that the one or more objects in the droplets comprise cells or particles, or both, and the droplets may further comprise a reagent for performing one or more biological events with the cells or particles. See paragraph 0310 in Wu et al.
The applied reference has a common assignee and some common inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
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.
Claim(s) 83-102 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vinogradova et al (article from Arxiv, February 4, 2008, pages 1-5, submitted in the IDS filed on April 28, 2025) in view of Wagner et al (US 2019/0187043, submitted in the IDS filed on August 29, 2024).
With regards to claims 83-84, Vinogradova et al teach of a system for detecting one or more objects (see Figure 1 in Vinogradova et al) comprising a microfluidic device comprising a first channel comprising one or more objects therein (see page 1, right column, last paragraph, page 2, left column, lines 20-26, and Figures 1 and 2 in Vinogradova et al where a microchannel MC containing fluorescently labeled latex spheres is described and depicted ), a first optical detector corresponding to a first point of detection disposed along the first channel (see ADP 1 depicted in Figure 1 of Vinogradova et al), and a first optical element configured to provide dual focusing along the first channel at the first point of detection, wherein the dual focusing is facilitated by a first beam at a first focus and a second beam at a second focus, wherein the first focus and the second focus are on axially separate focal volumes (claim 83) and on two different focal planes (claim 84). See page 2, right column of Vinogradova et al from line 2 where it states “The laser beam was split by means of a Wollaston prism. Behind the prism, the two beams are polarized perpendicularly to each other and exhibit an angular separation of 0.5 deg. After passing through two additional lenses, these beams are fed into the confocal microscope. Our alignments result in two optically equivalent, almost diffraction-limited laser foci (diameter 400 nm, height 3 microns) separated by a distance of 6.0+-0.1 microns in object space as is schematically shown in Figure 1). Also, see page 2, Figures 1-2 and the description of Figure 2 in Vinogradova et al where it states “Schematics of the basic idea of the double-focus spatial fluorescence cross-correlation method. Two laser foci are placed along the x axis separated by a distance of 6 micron. They independently record the time-resolved fluorescence intensities I1(t) and I2(t)”.
Vinogradova et al fail to teach that the microfluidic channel MC in the system comprises a plurality of water-in-oil droplets, wherein the droplets each comprise one or more objects therein.
Wagner et al teach of a microfluidic system for analyzing objects such as sperm cells contained within liquid droplets. The microfluidic system comprises a microfluidic chip 900 having one or more channels 904 therein. A portion of the channels 904 comprises a measurement region 908 where beams of light produced from one or more quantum cascade lasers are focused and transmitted through the channels 904. Cells contained in water-in-oil droplets (see paragraph 0349 in Wagner et al) are passed through the measurement region 908 and produce an optical signal as they pass by one or more focal regions. See paragraph 0198 and Figures 1, 8-9 and 12 of Wagner et al. Wagner et al teach that in one embodiment depicted in Figure 44, light from an array of multiple lasers 4402 is focused by a lens 4404, then treated with a phase delay element 4408, and passed through another lens 4410 that focuses multiple light beams onto the microfluidic channel 4412. The laser array is imaged onto the microchannel such that a series of volumes are illuminated along the axis of flow in the microchannel. The transmitted portions of the light beams are then delivered to a detector 4418 via one or more lenses 4414. In this configuration, different points along the channel are sampled by each laser focus such that cells in a sample flowing in the microchannel pass through each beam of light at each focus one after the next to produce different signals, and the changes in the signals are processed to determine a chemical concentration in the cells. See Figure 44 and paragraph 0357 in Wagner et al.
Based upon a combination of Vinogradova et al and Wagner et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the double-focusing microfluidic system taught by Vinogradova et al to detect one or more objects (i.e. cells) in a plurality of water-in-oil droplets flowing along a microchannel because Vinogradova et al teach that objects flowing in a microfluidic channel are effectively detected by the use of a dual focusing optical element that irradiates a first and a second beam of light at the channel at two different focal points, and Wagner et al teach that cells located in water-in-oil droplets flowing along a microfluidic channel can also be effectively measured by passing through multiple focal points of light imaged onto the channel.
With regards to claims 85-86, Vinogradova et al teach that an object of the one or more objects gets excited by the first beam as it passes through the first beam and emits a first signal detectable by the optical detector, and further gets excited by the second beam as it passes through the second beam and emits a second signal detectable by the optical detector. See page 2, right column of Vinogradova et al from line 2 where it states “The laser beam was split by means of a Wollaston prism. Behind the prism, the two beams are polarized perpendicularly to each other and exhibit an angular separation of 0.5 deg. After passing through two additional lenses, these beams are fed into the confocal microscope. Our alignments result in two optically equivalent, almost diffraction-limited laser foci (diameter 400 nm, height 3 microns) separated by a distance of 6.0+-0.1 microns in object space as is schematically shown in Figure 1). Also, see page 2, Figures 1-2 and the description of Figure 2 in Vinogradova et al where it states “Schematics of the basic idea of the double-focus spatial fluorescence cross-correlation method. Two laser foci are placed along the x axis separated by a distance of 6 micron. They independently record the time-resolved fluorescence intensities I1(t) and I2(t)”.
With regards to claim 87, one of ordinary skill in the art would inherently expect that detecting both the first and second signals from the objects flowing through the microfluidic channel taught by Vinogradova et al would increase the probability that at least one signal among the first and second signals has an optimal signal-to-noise ratio since the double-focus fluorescence system taught by Vinogradova et al contains all of the same physical elements as the dual focus system recited in the instant claims.
With regards to claims 88-90 and 94, Vinogradova et al teach that the first optical element comprises a laser that splits an energy beam into the first and second beams, and the first optical element comprises a beam splitter, a double refractive optical element, or a birefringent polarizer. See the HeNe laser and the Wollaston prism that splits an energy beam from the laser into a first beam 1 and a second beam 2 depicted in Figure 1 of Vinogradova et al.
With regards to claim 91, Vinogradova et al teach that the first beam of light has a second polarization angle, and the second beam has a third polarization angle different from the second polarization angle. See Figure 1 and page 2, right column of Vinogradova et al from line 2 where it states “The laser beam was split by means of a Wollaston prism. Behind the prism, the two beams are polarized perpendicularly to each other and exhibit an angular separation of 0.5 deg.”.
With regards to claim 92, Vinogradova et al teach that the system further comprises an objective, wherein the first and second beams of light pass through the objective and illuminate an excitation plane on the microchannel. See the objective in Figure 1 of Vinogradova et al.
With regards to claim 93, Vinogradova et al teach that the first beam is located at a distance from the second beam on the microchannel, and the distance would inherently be tunable via adjusting the distance between the first optical element and the objective, via adjusting a splitting angle, or both in the same manner as the instant invention since the double-focus fluorescence system taught by Vinogradova et al contains all of the same physical elements as the dual focus system recited in the instant claims.
With regards to claims 95-97, in the combination of the systems taught by Vinogradova et al and Wagner et al, an object in a first droplet gets excited by the first beam as it passes through the first beam and emits a first signal detectable by the optical detector, a second droplet containing an object gets excited by the second beam as it passes through the second beam and emits a second signal detectable by the optical detector, wherein the first and second droplets flow in the same microchannel MC of the system depicted in Figure 1 of Vinogradova et al.
With regards to claims 98-99, Vinogradova et al fail to teach that the microfluidic system may comprise a second channel, and the optical detector corresponds to a first point of detection disposed along the first channel and the second channel, wherein a first droplet flows in the first channel and a second droplet flows in the second channel, and that detecting a first signal from the first channel and a second signal from the second channel increases a throughput of the system. However, Wagner et al teach that a similar microfluidic system for analyzing objects located in droplets may comprise multiple fluidic channels located in parallel for analyzing droplets contained in multiple flowing streams, wherein a laser-generated light from an optical detector passes through a first point of detection disposed along all of the multiple fluidic channels. Wagner et a teach that this multiplexed embodiment containing parallel channels allows for higher system throughput. See paragraph 0200 in Wagner et al. Therefore, based upon a combination of Vinogradova et al and Wagner et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide the system taught by Vinogradova et al with multiple parallel microfluidic channels, wherein a first droplet flows in the first channel and a second droplet flows in the second channel, and an optical detector that corresponds to a first point of detection disposed along the first channel and the second channel, because Wagner et al teach that this multiplexed configuration in a microfluidic system is advantageous since it allows for higher system throughput.
With regards to claim 100, Vinogradova et al teach that the system further comprises a second detector APD-2 corresponding to a second point of detection in the microfluidic channel. See Figure 1 in Vinogradova et al.
With regards to claims 101-102, Wagner et al teach that the one or more objects in the droplets comprise cells or particles, or both, and the droplets may further comprise a reagent for performing one or more biological events with the cells or particles. See paragraphs 0155 and 0416-0418 in Wagner et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the double-focusing microfluidic system taught by Vinogradova et al to detect one or more objects (i.e. cells) and to perform chemical reactions in a plurality of water-in-oil droplets flowing along a microchannel because Vinogradova et al teach that objects flowing in a microfluidic channel are effectively detected by the use of a dual focusing optical element that irradiates a first and a second beam of light at the channel at two different focal points, and Wagner et al teach that cells and reagents for chemical reactions located in water-in-oil droplets flowing along a microfluidic channel can also be effectively measured by passing through multiple focal points of light imaged onto the channel.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Please make note of: Bharadwaj et al (US 2021/0293693) who teach of a method and a device for detecting and sorting droplets; and Wu (US 2018/0321130) who teaches of a method and a device for reference-assisted droplet detection.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAUREEN M WALLENHORST whose telephone number is (571)272-1266. The examiner can normally be reached on Monday-Thursday from 6:30 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander, can be reached at telephone number 571-272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MAUREEN WALLENHORST/Primary Examiner, Art Unit 1797 December 8, 2025