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 has elected Group I (claims 2-5, 7, 8, and 33) without traverse. Applicant has added new claims 48-52 that fall within Group I. Claims 9, 10, 12, 18-21, 24-27, 29, and 31 are cancelled. Claims 2-5,7-8,33 and 48-60 are being examined herein.
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 5 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.
Claim 5 recites the limitation “further comprising: a droplet controllable” in line 2 of the claim. Claim 2, from which claim 5 depends, recites “a liquid droplet” in line 4 of the claim. It is unclear if this is the same droplet; Examiner believes the (liquid) droplets in each claim are the same. Examiner recommends amending claim 2 to read “to perform droplet operations in a droplet operations gap,” or an equivalent thereof.
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 2-3, 5, 7, and 58-59 and 52 and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Reimitz, et. al. (US 20130118900 A1) in view of Lyons, et. al. (US 4978863 A).
Regarding claim 2, Reimitz teaches a cartridge for manipulating droplets with electrodes (Abstract) to be used in a larger system (par. 0002) (for use with an instrument). Reimitz teaches an embodiment the cartridge 1 comprising a first substrate 42 with electrodes 44 individually controlled by a control unit 43 for manipulating the droplets by electrowetting in a gap 12 (Fig. 2; par. 0024, 0098) (a digital microfluidics (DMF) substrate comprising a plurality of electrowetting electrodes operative to perform droplet operations on a liquid droplet in a droplet operations gap). The cartridge further comprises a second substrate 2 parallel from the first substate 42 and contains gap 12 and pierceable bottom structure 8 to release liquid 6 from well 5, this liquid will go to form droplet 23 (Fig. 2; par. 0097-0098) (a top plate separated from the DMF substrate to form the droplet operations gap between the DMF substrate and the top plate, the top plate comprising openings for flowing liquids into the droplet operations gap).
Reimitz teaches the cartridge 1 further comprises optical fiber 21 in second substrate 2 to bring light to a droplet 23 and detect light from the droplet (Fig. 2; par. 0098) (a fiber assembly comprising a fiber optic probe…that provides excitation light from a primary illumination source to the droplet operations gap and provides emission light from the droplet operations gap to a primary optical measurement device).
Reimitz is silent to the fiber optic probe projecting into the droplet operations gap, wherein the fiber optic probe is configured to form a reflective interferometric sensor.
Lyons teaches analysis of a fluid stream using a fiber optic probe inserted within the fluid stream (Abstract). Lyons teaches a fiber optic probe 17 comprises optical fibers 18 and 19 connected to a light source 20 and light detector 21, respectively (Fig. 1). Lyons teaches fiber optic probe 17 is directly input into pipe 15 to access particles 16 within the channel of pipe 15 (Fig. 1). Lyons teaches the light source is emitted by fiber 18 into the channel, the light is reflected and by particles 16, and the reflected light is detected by fiber 19 (col. 3, lines 38-52) (the fiber optic probe projecting into the… gap). While not explicitly stated, because the fiber optic probe has both the light source and detector cables coupled to come together at the probe head and measure reflected light, it is understood that it operates as a reflective interferometric sensor (wherein the fiber optic probe is configured to form a reflective interferometric sensor). Lyons teaches inserting the fiber optic probe into the channel allows for the sensor in the probe be sensitive to the light source without having to worry about alignment (col. 2, lines 3-7) even in asymmetrical channels or with opaque fluids (col. 2, lines 38-45).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the fiber optic probe of Reimitz to be inserted into the channel as taught by Lyons in order to prevent alignment errors. Because both devices use a fiber optic probe to optically analyze a property of fluid sample, modifying the fiber optic probe to be embedded within the channel/chamber as provided by Lyons, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 3, modified Reimitz teaches fiber optic 21 is located adjacent to a set of electrodes 44 across the operations gap 12 and allows the light from the fiber optic to be "directly brought into the droplet" (Fig. 2; par. 0098), and therefore when a droplet is manipulated to be atop an electrode set, the droplet will be in contact with the fiber optic probe of modified Reimitz (wherein the fiber optic probe projecting into the droplet operations gap is situated in proximity with a set of two or more of the electrowetting electrodes such that a droplet situated atop any electrode of the set of two or more electrodes will contact the fiber optic probe).
Regarding claim 5, modified Reimitz teaches first substrate 42 that comprises an electrode array 43 with individual electrodes 44 that receive individual voltage pulses to manipulate liquid droplets by electrowetting (par. 0157) and as seen in Fig. 2, the optical fiber 21 are adjacent to electrodes 22, so the droplet can be manipulated to be in contact with the optical fiber 21 (further comprising: a droplet controllable by the electrowetting electrodes to contact the fiber optic probe).
Regarding claim 7, modified Reimitz teaches top, second substrate 2 have openings (see circles regions in provided Figure 2 below) to accommodate the fiber optic assembly to align the probe with the electrodes 44 (wherein the top plate comprises two or more grooves or openings each aligning the fiber optic probe from the fiber assembly).
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Regarding claim 58, modified Reimitz in view of Lyons teaches the sensing end of a fiber optic probe is extended into the droplet operations gap according to the limitations of claim 2 (see above).
Modified Reimitz is silent to wherein the fiber optic probe extends through the DMF substrate.
Reimitz teaches an additional embodiment of the droplet manipulation device wherein the fiber optic probe 21 is embedded in bottom substate 42 and extends to gap 12 to measure a droplet 23 (Fig. 1) (wherein the fiber optic probe extends through the DMF substrate to dispose a sensing end of the fiber optic probe in the droplet operations gap). Reimitz teaches changing the location of the optical fiber allows for different types of analysis to be performed; for example, the bottom reading system is best for fluorescent-type analysis (par. 0090).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the location of the fiber optic probe in the cartridge of modified Reimitz to be parallel to the elongated portion of the channel as taught by Li in order to provide a configuration that is robust, simple, and compact. Because both systems use fiber optic biosensors within a channel for holding fluids, modifying the location of the probe to be parallel to the cartridge top and bottom as provided by Li, provide likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 59, modified Reimitz teaches "top reading optical system" wherein the fiber optic is installed in the upper, second substrate 2 to access the operations gap 12 (Fig. 2; par. 0098) (wherein the fiber optic probe extends through the top plate to dispose a sensing end of the fiber optic probe in the droplet operations gap).
Regarding claim 52, Reimitz teaches a cartridge for manipulating droplets with electrodes (Abstract). Reimitz teaches an embodiment the cartridge 1 comprising a first substrate 42 with electrodes 44 individually controlled by a control unit 43 for manipulating the droplets by electrowetting in a gap 12 (Fig. 2; par. 0024, 0098) (a first substrate comprising one or more electrowetting electrodes for conducting droplet operations). The cartridge further comprises a second substrate 2 parallel from the first substate 42 and contains gap 12 and pierceable bottom structure 8 to release liquid 6 from well 5, this liquid will go to form droplet 23 (Fig. 2; par. 0097-0098) (a second substrate offset from the first substrate) (a droplet operations gap defined between the first substrate and the second substrate, wherein the one or more electrowetting electrodes are operative to perform droplet operations on a liquid droplet in the droplet operations gap).
Reimitz teaches the cartridge 1 further comprises optical fiber 21 in second substrate 2 to bring light to a droplet 23 and detect light emitted by the droplet through fluorescence (Fig. 2; par. 0098) (a fluorescent measurement system comprising a fiber optic probe…that provides excitation light from a primary illumination source to the droplet operations gap and emitted fluorescent light from the droplet operations gap to a primary optical measurement device).
Reimitz is silent to the fiber optic probe (being) disposed in the droplet operations gap.
Lyons teaches analysis of a fluid stream using a fiber optic probe inserted within the fluid stream (Abstract). Lyons teaches a fiber optic probe 17 comprises optical fibers 18 and 19 connected to a light source 20 and light detector 21, respectively (Fig. 1). Lyons teaches fiber optic probe 17 is directly input into pipe 15 to access particles 16 within the channel of pipe 15 (Fig. 1). Lyons teaches the light source is emitted by fiber 18 into the channel, the light is reflected and by particles 16, and the reflected light is detected by fiber 19 (col. 3, lines 38-52) (a fiber optic probe disposed in the… gap). Lyons teaches inserting the fiber optic probe into the channel allows for the sensor in the probe be sensitive to the light source without having to worry about alignment (col. 2, lines 3-7) even in asymmetrical channels or with opaque fluids (col. 2, lines 38-45).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the fiber optic probe of Reimitz to be inserted into the channel as taught by Lyons in order to prevent alignment errors. Because both devices use a fiber optic probe to optically analyze a property of fluid sample, modifying the fiber optic probe to be embedded within the channel/chamber as provided by Lyons, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G)
Regarding claim 56, modified Reimitz in view of Lyons teaches fiber optic probe 17 is directly input into pipe 15 to access particles 16 within the channel of pipe 15 (Lyons, Fig. 1). Lyons teaches the light source is emitted by fiber 18 into the channel, the light is reflected and by particles 16, and the reflected light is detected by fiber 19 (Lyons, col. 3, lines 38-52). While Lyons does not specifically state if the prob is indirect contact with the sample, but because the probe is inserted into the channel/chamber holding the fluid sample, the probe is capable of being in physical contact with the sample (wherein the fiber optic probe is in contact with the liquid droplet).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Reimitz, et. al. (US 20130118900 A1) in view of Lyons, et. al. (US 4978863 A) as applied to claim 2 above, and further in view of Tan, et. al. (EP 1645865 A1; citations made with respect to attached copy).
Regarding claim 4, modified Reimitz teaches the limitation as applied to claim 2 (see above).
Modified Reimitz is silent to wherein the fiber optic probe comprises a ligand.
Tan teaches a microfluidic biochip that uses coated optical fibers as sensors (Abstract). Tan teaches a fiber optic sensor system comprising a light source 804, a detector 818 with fiber couplers 802 to connect the light source 804 and detector 818 to fiber optic bioprobe 700 (Fig. 8; par. 0060-0063). Tan teaches the fiber optic bioprobe 700 must be in physical contact with the sample solution (par. 0067). Tan teaches a reagent 704 bonded to the end of the fiber optic bioprobe, wherein the reagent 704 can be an antibody, chemical, DNA segment, enzyme, or protein (Fig. 7a, 7b; par. 0076-0080) (wherein the fiber optic probe comprises a ligand). Tan teaches the coating reagent 704 will bind with a complimentary analyte or antibody 736 to form a layer at the end of the bioprobe 700 which alters the wavelength of the incident light (Fig. 7a, 7b; par. 0079-0082). Tan teaches a coated fiber optic bioprobe allows for analysis of complex sample to prevent nonspecific binding without the use of indicator or reagent in the sample itself that can be used on small platforms, are low cost, and have high sensitivity (par. 0020-0022).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the fiber optic probe of modified Reimitz to further include a ligand coating on the probe as taught by Tan in order to analyze complex samples by preventing nonspecific binding. Because both systems use a fiber optic probe to directly analyze a fluid sample, modifying a fiber optic probe to have a ligand coating as provided by Tan, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Reimitz, et. al. (US 20130118900 A1) in view of Lyons, et. al. (US 4978863 A) as applied to claim 2 above, and further in view of Strobbia, et. al. (Inverse Molecular Sentinel-Integrated Fiberoptic Sensor for Direct and in Situ Detection of miRNA Targets; citations made with respect to attached copy).
Regarding claim 8, Modified Reimitz teaches the limitations as applied to claim 2 (see above).
Modified Reimitz is silent to wherein a sensing end of the fiber optic probe comprises a nanoparticle sensor surface.
Strobbia teaches a fiber optic sensor that targets nucleic acid targets with a nanoparticle coating when in direct contact with the sample solution (Abstract). Strobbia teaches the optical detection system comprises an optical fiber with one end that directly contacts the sample and another end that has coupled fibers leading to light source and a detector (Fig. 1A). On the sample end of the optical fiber, the fiber is coated with silver-coated gold nanostars (Fig. 1A, 1B; pg. 6348, section "Fiber-Optrode Fabrication") (wherein a sensing end of the fiber optic probe comprises a nanoparticle sensor surface). Strobbia teaches coating the optical fiber in the nanoparticles allows for non-invasive sample analysis without the need for extensive sample preparation steps while additionally creating a sensitive and specific sensor that can be reused (pg. 6346, col. 1, par. 03 - col. 2, par. 01).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the fiber optic probe of modified Reimitz to further include a nanoparticle coating on the probe as taught by Strobbia in order to analyze complex samples without invasive preparation steps through sensitive and specific binding. Because both systems use a fiber optic probe to directly analyze a fluid sample, modifying a fiber optic probe to have a nanoparticle coating as provided by Strobbia, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Claim 57 is rejected under 35 U.S.C. 103 as being unpatentable over Reimitz, et. al. (US 20130118900 A1) in view of Lyons, et. al. (US 4978863 A) as applied to claim 2 above, and further in view of Li, et. al. (Integrated multichannel all-fiber optofluidic biosensing platform for sensitive and simultaneous detection of trace analytes; citations made with respect to attached copy).
Regarding claim 57, modified Reimitz in view of Lyons teaches the sensing end of a fiber optic probe is extended into the droplet operations gap according to the limitations of claim 2 (see above).
Modified Reimitz is silent to wherein the fiber optic probe extends into the droplet operations gap between the DMF substrate and the top plate substantially parallel to the DMF substrate and the top plate.
Li teaches an integrated multichannel fiber optic biosensing platform (Abstract). Li teaches the platform comprises a fluidic systema light source, fiber outports from the light source leading to fluidic channels, a detector with fiber outports leading from the fluidic channels to the detector and bundled with the light source fiber (Fig. 1). Li teaches the fiber optic biosensor is inserted to the side of the fluidic channel to be in the center of the channel/parallel to all elongated sides of the channel (Fig. 1) (wherein the fiber optic probe extends into the droplet operations gap between the DMF substrate and the top plate substantially parallel to the DMF substrate and the top plate). Li teaches this configuration of the fiber optic in the fluidic channel prevents misalignment of the optical elements, and keeps the device simple, small/compact, and flexible (pg. 118; col. 1; par. 02).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the location of the fiber optic probe in the cartridge of modified Reimitz to be parallel to the elongated portion of the channel as taught by Li in order to provide a configuration that is robust, simple, and compact. Because both systems use fiber optic biosensors within a channel for holding fluids, modifying the location of the probe to be parallel to the cartridge top and bottom as provided by Li, provide likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Claim 60 is rejected under 35 U.S.C. 103 as being unpatentable over Reimitz, et. al. (US 20130118900 A1) in view of Lyons, et. al. (US 4978863 A) as applied to claim 2 above, and further in view of Dong, et. al. (US 20200108387 A1; with a priority date of 19 Jan. 2018 from CN 107607475 A).
Regarding claim 60, modified Reimitz teaches upper substrate 2 is made of a material like glass (par. 0074).
Modified Reimitz is silent to wherein the DMF substrate and the top plate comprise a material sufficiently transparent to allow excitation light from a secondary illumination source to pass through the DMF substrate to the droplet operations gap and emission light from the droplet operations gap to pass through the top plate onto a secondary optical measurement device.
Dong teaches a micro-total analysis system with optical units and corresponding detection units (Abstract). Dong teaches the analysis system comprises a microfluidic device 10 with a first substrate 101 and a second substrate 121 that form a space 1020 and electrodes for manipulating droplets (Fig. 1; par. 0055, 0066). Dong teaches the microfluidic system comprises at least two lights L1, L2 from light source 201, the light pass through droplets 131 and space 1020 to reach detectors 301 beneath substrate 301 (Fig. 1; par. 0055). Dong teaches first 101 and second 121 substrates are made of glass (par. 0055) (wherein the DMF substrate and the top plate comprise a material sufficiently transparent to allow excitation light from a secondary illumination source to pass through the DMF substrate to the droplet operations gap and emission light from the droplet operations gap to pass through the top plate onto a secondary optical measurement device). Dong teaches the multiple lights allow for multiple types of analyses to be performed at once on a single device (par. 0057-0058) which saves times and resources.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the cartridge material of modified Reimitz to be optically transparent as taught by Dong in order to allow multiple light sources and detectors to be used simultaneously for multiple types of analyses. Because both cartridges use optical system to measure liquid droplets, modifying the cartridge substrates to be transparent as provided by Dong, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Examiner notes the secondary illumination source and secondary optical measurement device are not positively recited elements for the cartridge of claim 2.
Claims 33, 48, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Reimitz, et. al. (US 20130118900 A1) in view of Lyons, et. al. (US 4978863 A) and Carlson (WO 2005036175 A2; citations made with respect to attached copy).
Regarding claim 33, Reimitz teaches a cartridge for manipulating droplets with electrodes (Abstract) to be used in a larger system (par. 0002). Reimitz teaches an embodiment the cartridge 1 comprising a first substrate 42 with electrodes 44 individually controlled by a control unit 43 for manipulating the droplets by electrowetting in a gap 12 (Fig. 2; par. 0024, 0098) (a cartridge, comprising: digital microfluidics (DMF) substrate comprising a plurality of electrowetting electrodes operative to perform droplet operations on a liquid droplet in a droplet operations gap). The cartridge further comprises a second substrate 2 parallel from the first substate 42 and contains gap 12 and pierceable bottom structure 8 to release liquid 6 from well 5, this liquid will go to form droplet 23 (Fig. 2; par. 0097-0098).
Reimitz teaches the cartridge 1 further comprises optical fiber 21 in second substrate 2 to bring light to a droplet 23 and detect light emitted by the droplet through fluorescence (Fig. 2; par. 0098). Reimitz teaches fiber optic 21 is located adjacent to a set of electrodes 44 across the operations gap 12 and allows the light from the fiber optic to be "directly brought into the droplet" (Fig. 2; par. 0098), and therefore when a droplet is manipulated to be atop an electrode set, the droplet will be in contact with the fiber optic probe of modified Reimitz (fiber optic probe is positioned in proximity with a set of two or more of the electrowetting electrodes such that a droplet situated atop any electrode of the set of two or more electrodes will contact at least one… fiber optic probe).
Reimitz teaches a control unit that controls individual electrodes for droplet manipulation by electrowetting (par. 0024) and other contact points on the substrate (par. 0156) (a controller operationally coupled to the electrowetting electrodes and the… fiber optic probes). The device further comprises an excitation light that illuminates the droplet through the fiber optic (one or more illumination sources optically coupled to the… fiber optic probe to provide excitation light to the droplet operations gap) and a detector connected to the fiber optic reading system (one or more optical measurement devices optically coupled to the fiber optic probe to receive optical signals from the plurality of fiber optic probes) (par. 0090).
Reimitz is silent to the fiber optic probe (being) disposed in the droplet operations gap.
Lyons teaches analysis of a fluid stream using a fiber optic probe inserted within the fluid stream (Abstract). Lyons teaches a fiber optic probe 17 comprises optical fibers 18 and 19 connected to a light source 20 and light detector 21, respectively (Fig. 1). Lyons teaches fiber optic probe 17 is directly input into pipe 15 to access particles 16 within the channel of pipe 15 (Fig. 1). Lyons teaches the light source is emitted by fiber 18 into the channel, the light is reflected and by particles 16, and the reflected light is detected by fiber 19 (col. 3, lines 38-52) (projecting into the… gap). Lyons teaches inserting the fiber optic probe into the channel allows for the sensor in the probe be sensitive to the light source without having to worry about alignment (col. 2, lines 3-7) even in asymmetrical channels or with opaque fluids (col. 2, lines 38-45).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the fiber optic probe of Reimitz to be inserted into the channel as taught by Lyons in order to prevent alignment errors. Because both devices use a fiber optic probe to optically analyze a property of fluid sample, modifying the fiber optic probe to be embedded within the channel/chamber as provided by Lyons, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Modified Reimitz is silent to a plurality of fiber optic probes, the plurality of fiber optic probes comprising at least two different probe types.
Carlson teaches a sensor system comprising a detector system and artificial receptor (pg. 2, line17-22). Carlson teaches the artificial receptors can be used with fiber optic technology for optical detection (pg. 20, line 30-34). Carlson teaches one such fiber optic sensing system 300 where multiple fibers can make up the sensing system (a plurality of fiber optic probes) and the different probes can detect light, or other reflected, refracted, or fluoresced radiation from the different receptors 310 (the plurality of fiber optic probes comprising at least two different probe types) (pg. 22, lines 4-18). Carlson teaches multiple fibers with multiple detection options results in different parts of the substate being analyzed simultaneously.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the fiber optic probe of modified Reimitz to comprise a plurality of fiber optic probes as taught by Carlson in order to analyze multiple locations simultaneously. Because both systems use fiber optic probes to perform optical analysis, modifying the system to include a plurality of different optical fiber probes as provided by Carson, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 48, modified Reimitz in view of Carlson teaches the plurality of fiber optic probes can detected radiation that is reflected, refracted, or fluoresced (pg. 22, lines 4-18) (wherein the different probe types are selected from the group consisting of fluorescent probes… and reflectance probes).
Regarding claim 51, modified Reimitz teaches fiber optic 21 is located adjacent to a set of electrodes 44 across the operations gap 12 and allows the light from the fiber optic to be "directly brought into the droplet" (Fig. 2; par. 0098), and therefore when a droplet is manipulated to be atop an electrode set, the droplet will be in contact with the fiber optic probe of modified Reimitz (wherein the controller is to control the electrowetting electrodes to oscillate the liquid droplet from one of the electrowetting electrodes to another of the electrodes while the liquid droplet remains in contact with the at least one of the plurality of fiber optic probes).
Claim 49 is rejected under 35 U.S.C. 103 as being unpatentable over Reimitz, et. al. (US 20130118900 A1) in view of Lyons, et. al. (US 4978863 A) and Carlson (WO 2005036175 A2 as applied to claim 33 above, and further in view of Li, et. al. (Integrated multichannel all-fiber optofluidic biosensing platform for sensitive and simultaneous detection of trace analytes).
Regarding claim 49, modified Reimitz in view of Carlson teaches one such fiber optic sensing system 300 where multiple fibers can make up the sensing system as applied to claim 33 (see above).
Modified Reimitz is silent to wherein the one or more illumination sources comprise a single illumination source optically coupled to multiple optical probes of different probe types, and the one or more optical measurement devices comprise a single optical measurement device optically coupled to multiple optical probes of different probe types
Li teaches Li teaches an integrated multichannel fiber optic biosensing platform (Abstract). Li teaches the platform comprises a fluidic system light source, fiber outports from the light source leading to fluidic channels, a detector with fiber outports leading from the fluidic channels to the detector and bundled with the light source fiber (Fig. 1). As seen in Figure 1, the fibers are coupled together so only a singular light source and singular detector are needed for multiple fibers (wherein the one or more illumination sources comprise a single illumination source optically coupled to multiple optical probes of different probe types, and the one or more optical measurement devices comprise a single optical measurement device optically coupled to multiple optical probes of different probe types). Li teaches this configuration of the coupled fibers in the keeps the device simple, small/compact, and flexible (pg. 118; col. 1; par. 02).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the light source and detection source of modified Reimitz to allow for multiple fibers to be connected to a singular light source and detector as taught by Li in order to keep the full device simple and compact. Because both devices are optical systems that use a fiber optic biosensor embedded in a sample containing channel, modifying the system to have multiple fibers connected to a single light source and detector as provided by Li, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Reimitz, et. al. (US 20130118900 A1) in view of Lyons, et. al. (US 4978863 A) and Carlson (WO 2005036175 A2 as applied to claim 33 above, and further in view of Dong, et. al. (US 20200108387 A1; with a priority date of 19 Jan. 2018 from CN 107607475 A).
Regarding claim 50, modified Reimitz teaches the limitation as applied to claim 33 (see above).
Modified Reimitz is silent to one or more additional illumination sources to provide excitation light to the droplet operations gap via free-space optics.
Dong teaches a micro-total analysis system with optical units and corresponding detection units (Abstract). Dong teaches the analysis system comprises a microfluidic device 10 with a first substrate 101 and a second substrate 121 that form a space 1020 and electrodes for manipulating droplets (Fig. 1; par. 0055, 0066). Dong teaches the microfluidic system comprises at least two lights L1, L2 from light source 201, the light pass through droplets 131 and space 1020 to reach detectors 301 beneath substrate 301 (Fig. 1; par. 0055) (one or more additional illumination sources to provide excitation light to the droplet operations gap via free-space optics). Dong teaches the multiple lights allow for multiple types of analyses to be performed at once on a single device (par. 0057-0058) which saves times and resources.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the optical system of modified Reimitz to further include an additional illumination source as taught by Dong in order to allow multiple light sources and detectors to be used simultaneously for multiple types of analyses. Because both systems use optical system to measure liquid droplets, modifying the system to include multiple illumination sources as provided by Dong, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Claims 53-55 are rejected under 35 U.S.C. 103 as being unpatentable over Reimitz, et. al. (US 20130118900 A1) in view of Lyons, et. al. (US 4978863 A) as applied to claim 52 above, and further in view of Li, et. al. (Integrated multichannel all-fiber optofluidic biosensing platform for sensitive and simultaneous detection of trace analytes; citations made with respect to attached copy).
Regarding claim 53, Modified Reimitz teaches the fiber optic probes within the cartridge are capable of analyzing a fluorescent sample (par. 0090).
Modified Reimitz is silent to wherein the fiber optic probe comprises a probe tip with fluorophores immobilized thereon.
Li teaches Li teaches an integrated multichannel fiber optic biosensing platform (Abstract). Li teaches the platform comprises a fluidic system light source, fiber outports from the light source leading to fluidic channels, a detector with fiber outports leading from the fluidic channels to the detector and bundled with the light source fiber (Fig. 1). Li teaches fluorescence-labeled antibody are bound to immobilized conjugates on the sensor surface (pg. 115, section "4.1 Characteristic of M-AOB platform") (wherein the fiber optic probe comprises a probe tip with fluorophores immobilized thereon). Li teaches adding the immobilized fluorophore conjugates create a biosensor surface that is reusable, sensitive, and accurate for small molecules (pg. 115, col. 2, par. 02).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the fiber optic probe of modified Reimitz to further include immobilized fluorophores as taught by Li in order to have a sensor surface that is sensitive and accurate for small molecules. Because both systems use fiber optic probes for liquid samples, modifying the probe surface to have an immobilized fluorophore as provided by Li, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 54, Modified Reimitz in view of Li teaches fluorophores on the probe as applied to claim 53 (see above).
Modified Reimitz is silent to wherein the fluorophores include multiple different fluorophores used in conjunction on the probe tip simultaneously.
Li teaches a second embodiment and operation of the fiber optic biosensor that has multiple conjugates immobilized on the surface (pg. 115, section "4.2. Biosensing mechanism for the simultaneous detection of small molecules) (wherein the fluorophores include multiple different fluorophores used in conjunction on the probe tip simultaneously). Li teaches this allows for detection of multiple analytes at the same time (pg. 115, section "4.2. Biosensing mechanism for the simultaneous detection of small molecules).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the fiber optic probe of modified Reimitz to include multiple immobilized fluorophores as taught by Li in order to have a sensor surface that is sensitive and accurate for different small molecules simultaneously. Because both systems use fiber optic probes for liquid samples, modifying the probe surface to have multiple immobilized fluorophore as provided by Li, provides likewise sought functionality with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 55, modified Reimitz in view of Li teaches the fiber optic biosensor is silanized to pre-treat the probe for immobilizing the fluorophores to the surface (Li, pg. 115, section "3.2. Biosensor functionalization") (wherein the probe tip further comprises a coating that modifies emissive properties of the fluorophores).
Conclusion
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/M.T.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758